A/0
No
A/0
SOTA_Literature excluded
reason
Date
2024.04.15
Document No.
Revised Reason
First Issued
HK-T100QPCE-18-03-05
Revised Content
ALL
Excluded due to duplicate
(2021). "[Diagnostic and treatment recommendations from the FACME ad-hoc expert
working group on the management of cerebral venous sinus thrombosis associated with
COVID-19 vaccination]." Neurologia 36(6): 451-461.
INTRODUCTION: Cases of cerebral venous sinus thrombosis
have been reported in individuals vaccinated against COVID-19
with non-replicating adenoviral vector vaccines. We issue our
recommendations on the diagnosis and management of patients
presenting this complication. METHOD: The multidisciplinary
working group, led by the Spanish Federation of Medical and
Scientific Associations and including representatives of several
scientific societies, reviewed the available evidence from the
literature and reports of the European Medicines Agency. We
establish a definition for suspected cases and issue diagnostic and
treatment recommendations regarding vaccine-induced immune
thrombotic thrombocytopaenia. RESULTS: We define suspected
cases as those cases of cerebral venous sinus thrombosis
occurring between 3 and 21 days after the administration of nonreplicating adenoviral vector vaccines, in patients with a platelet
count below 150,000/μL or presenting a decrease of 50% with
respect to the previous value. Findings suggestive of vaccineinduced immune thrombotic thrombocytopaenia include the
presence of antibodies to platelet factor 4, D-dimer levels 4 times
greater than the upper limit of normal, and unexplained
thrombosis. The recommended treatment includes intravenous
administration of non-specific human immunoglobulin or
alternatively plasmapheresis, avoiding the use of heparin, instead
employing argatroban, bivalirudin, fondaparinux, rivaroxaban, or
apixaban for anticoagulation, and avoiding platelet transfusion.
CONCLUSIONS: Non-replicating adenoviral vector vaccines
may be associated with cerebral venous sinus thrombosis with
thrombocytopaenia; it is important to treat the dysimmune
Alam, A., et al. (2013). "The Prevention of Transfusion-Associated Circulatory Overload."
Transfusion Medicine Reviews 27(2): 105-112.
Transfusion-associated circulatory overload (TACO) is an
important and potentially injurious complication of transfusion
that is underappreciated by clinicians. Risk factors for TACO
include being at an extreme of age, having preexisting cardiac
and/or (potentially) renal dysfunction, acute myocardial
infarction, and individuals receiving plasma. Keys to preventing
TACO, aside from identifying high-risk individuals, should be
multifaceted. We advocate for the widespread use of
pretransfusion checklists and implementation of nonemergent
transfusion protocols. We suggest the regular use of
pretransfusion diuretics in high-risk individuals. When a
transfusion is required, we believe that “critical” nursing
supervision and leadership are instrumental in the coordination of
slow transfusion rates on computerized infusion pumps and
ensuring patients are appropriately monitored. We believe that
using these methodologies on a global scale will prevent many
Cavallini, A., D. Marcer and S. Ferrari Ruffino (2014). "Endovenous Ablation of Incompetent
Saphenous Veins with a New 1,540-Nanometer Diode Laser and Ball-Tipped Fiber." Annals
of Vascular Surgery 28(3): 686-694.
Background Endovenous laser ablation (EVLA) is an efficient
method to treat incompetent saphenous veins with high occlusion
rates. The major side effects are postoperative pain and bruising.
Laser systems with higher wavelengths, associated with new
energy delivery devices, have recently shown excellent short-term
results, while reducing the previously reported side effects. The
aim of this study is to show the first outcome after EVLA of
incompetent saphenous veins with a newly developed ball-tipped
fiber and a new wavelength 1,540-nm diode laser. Methods Fortyfive incompetent saphenous veins in 35 patients (27 women) were
treated: 33 great saphenous veins, 6 short saphenous veins, and 6
anterior saphenous veins. The gravity of chronic venous disease
was determined according to the clinical-etiology-anatomypathophysiology (CEAP) classification, and the severity of
symptoms was scored according to the revised Venous Clinical
Severity Score. Patient satisfaction was assessed on a 0–3 scale.
Results The average linear endovenous energy density was 63.5
J/cm of vein length. Patients returned to daily activities after a
mean of 1.7 days (SD: 2) after treatment. The modified CEAP
clinical severity score improved drastically from a preintervention
mean of 4.9 (SD: 2.6) to 0.17 (SD: 0.38) at day 30. During the
follow-up period (mean: 168 days [range: 90–240 days]), all the
veins were occluded. All patients except 1 were satisfied or very
satisfied with the method. No severe complications occurred. Two
patients (5%) developed mild paresthesia in the treated area,
which spontaneously resolved after 3 months. Postoperative
ecchymoses are frequent (83%). Sixteen patients (43%)
experienced pain, but only 5 patients (14%) described it as quite
Corcoran, P. C., et al. (2010). "Surgical and Nonsurgical Complications of a Pig to Baboon
Heterotopic Heart Transplantation Model." Transplantation Proceedings 42(6): 2149-2151.
A modified immunosuppressive regimen, developed at the
National Institutes of Health, has been employed in a large animal
model of heterotopic cardiac xenotransplantation. Graft survival
has been prolonged, but despite this, our recipients have
succumbed to various surgical or nonsurgical complications.
Herein, we have described different complications and
management strategies. The most common complication was
hypercoagulability (HC) after transplantation, causing thrombosis
of both small and large vasculature, ultimately leading to graft
loss. While managing this complication we discovered that there
was a delicate balance between HC and consumptive
coagulopathy (CC). CC encountered in some recipient baboons
was not able to be reversed by stopping anticoagulation and
administering multiple blood transfusions. Some complications
had iatrogenic components. To monitor the animals, a solid state
left ventricular telemetry probe was placed directly into the
transplanted heart via the apex. Induction of hypocoagulable
states by continuous heparin infusion led to uncontrollable intraabdominal bleeding in 1 baboon from this apical site. This
occurrence necessitated securing the probe more tightly with
multiple purse strings and 4-quadrant pledgeted stay sutures. One
instance of cardiac rupture originated from a lateral wall
infarction site. Earlier studies have shown infections to be
uniformly fatal in this transplant model. However, owing to the
telemetry placement, infections were identified early by
temperature spikes that were treated promptly with antibiotics.
We had several cases of wound dehiscence due to recipients
disrupting the suture line. These complications were promptly
Kim, C. Y., S. B. Choi and E. S. Lee (2024). "Prevalence and predisposing factors of poststroke complex regional pain syndrome: Retrospective case-control study." Journal of Stroke
and Cerebrovascular Diseases 33(2): 107522.
Abstracts Introduction Poststroke complex regional pain
syndrome (CRPS) is an important complication in stroke
survivors. The identification of factors associated with post-stroke
CRPS is important for preventive measures and early diagnosis.
Methods A total of 141 first-ever stroke survivors in the subacute
stage were retrospectively analyzed. Demographic data, diagnosis
time, duration of hospitalization, location of brain lesion,
etiology, comorbidities, and blood test findings were investigated.
Clinical data included Medical Research Council (MRC) grade,
Fugl-Meyer assessment (FMA), National Institute for Health
Stroke Scale (NIHSS), Berg Balance Scale (BBS). Results Among
141 patients with subacute stroke, 22 were diagnosed with CRPS,
with a prevalence of 15.6 %. The mean time to diagnosis was 38.6
(±16.5) days. The prevalence according to the degree of paralysis
was 33.3 % in MRC grades 0 and 1, 8.6 % in grade 2, and 0 % in
grade 3 or higher. The incidence rates within 1 month after stroke
were 1.42 % and 22.47 % between 1 and 3 months after stroke,
respectively. The independent risk factors for CRPS were
hospitalization duration and FMA, NIHSS, and BBS scores. The
sensitivity and specificity of the NIHSS score for predicting poststroke CRPS were 86.4 % and 59.7 %, respectively, with an
optimal cutoff value of 7.5. Conclusions CRPS of the affected
upper limb in stroke patients is associated with stroke severity,
including paralysis, and the incidence increases over time during
the subacute phase. Additionally, having sufficient strength to
move through a full range of motion against gravity had a
Lee, K. J., et al. (2022). "Performance comparison of intraosseous devices and setups for
infusion of whole blood in a cadaveric swine bone model." The American Journal of
Emergency Medicine 54: 58-64.
Objectives Intraosseous (IO) access can provide a critical bridge
for blood product infusion when peripheral venous access is not
obtainable. Successful pressurized IO infusion requires flow rates
sufficient to preserve life, but with infusion pressures low enough
to avoid clinical complications (e.g., hemolysis, bone damage, fat
emboli). However, the optimal method for pressured IO delivery
of blood was unknown. Methods Three trained physicians infused
500 mL of whole blood through a 15-gauge, 45 mm IO catheter
into fresh, high bone density cadaveric swine proximal humeri.
Participants applied eight different pressure infusion strategies:
(1) gravity, (2) pressure bag, (3) pressure bag actively maintained
at or above 300 mmHg, (4) hand pump, (5) hand pump with
pressure bag, (6) push-pull with 10 mL syringe, (7) push-pull with
60 mL syringe, and a (8) Manual Rapid Infuser in a randomized
within-subjects design (30 trials per method, 240 trials total). The
primary outcomes of flow rates, mean and peak pressures, and
user ratings were contrasted using ANOVA at p < 0.05. Results
The Manual Rapid Infuser conferred the highest flow rates (199 ±
3 mL/min) and most favorable user ratings, but also the highest
mean and peak pressures. Push-pull conferred the next highest
flow rates (67 ± 5 mL/min for 60 mL, 56 ± 2 mL/min for 10 mL)
and pressures, with intermediate-to-high user ratings. Hand pump
flow rates were essentially identical with (45 ± 4 mL/min) or
without (44 ± 3 mL/min) pressure bag, with high user ratings
without a pressure bag. Pressure bag and gravity methods
conferred low flow rates and user ratings. Conclusions Some
pressured IO infusion methods can achieve flow rates adequate to
serve as a resuscitative bridge in the massively hemorrhaged
Pires, M. P. O., et al. (2021). "Effect of warming and infusion of red blood cell concentrates
on markers of haemolysis: An ex vivo simulation study." Australian Critical Care 34(3): 235240.
Background Transfusion of red blood cell (RBC) concentrates is a
common procedure to restore blood volume and tissue oxygen
delivery in patients with trauma. Although RBC warmers may
prevent hypothermia, some warming or infusion equipment may
lead to haemolysis and patient injury. Objectives The aim of this
study was to test the effect of (i) RBC warming and (ii)
administration via manual vs. pump infusion on haemolysis.
Methods This experimental ex vivo study studied haemolysis
markers of RBC injury. The sample consisted of 90 RBC
infusions in two simulations, randomly, 45 warmed RBC
infusions and 45 nonwarmed RBC infusions, in two or three
stages: before the intervention (baseline—warming, N= 45;
nonwarming, N= 45), after water bath warming at 42 °C (warmed,
N= 45), and then after the warmed or nonwarmed RBCs were
infused by manual or pump infusion at a rate of 100 mL/h
(infusion—warming, N= 45; nonwarming, N= 45). Results
Warmed RBCs showed significantly lower total haemoglobin
(Hb) and haematocrit levels and increase in free Hb levels,
haemolysis levels, and lactate dehydrogenase (LDH) activity (all
p<0.05) than baseline RBCs. Pump infusion RBCs were
associated with reduced total Hb and increased free Hb,
haemolysis, and potassium (K) levels (all p<0.05) compared with
warmed RBCs. In contrast, manual infusion of warmed RBCs
resulted in significantly reduced total Hb levels and increased
LDH activity (both <0.05). After infusion, total Hb, free Hb,
haematocrit, haemolysis, and LDH values were significantly
different for warmed vs. nonwarmed RBCs (p<0.05). Conclusions
Haemolysis biomarkers increase with RBC warming and infusion,
Rauck, R., et al. (2010). "Accuracy and efficacy of intrathecal administration of morphine
sulfate for treatment of intractable pain using the Prometra® Programmable Pump."
Neuromodulation: Technology at the Neural Interface 13(2): 102-108.
Objectives Intrathecal infusion pumps are increasingly used to
deliver analgesics for chronic intractable pain. This trial evaluated
the accuracy and efficacy of the new Prometra® Programmable
Pump System for intrathecal administration of morphine sulfate to
treat chronic intractable pain. Methods One hundred and ten
patients were given continuous intrathecal morphine sulfate and
assessed monthly for up to six months. Accuracy was determined
as the ratio of delivered to programmed drug volume (DP ratio).
Efficacy was assessed using the visual analog and numeric rating
scales and the Oswestry Disability Index. Results The mean
accuracy of the Prometra pump was 97.1%, with a 90%
confidence interval of 96.2–98.0%. Decreases in pain and
disability were reported at 68.4% of patient visits. No
unanticipated adverse events or device complications were
reported. Conclusions The Prometra pump provides an accurate,
effective, and safe system for intrathecal administration of
Tatsumi, K., et al. (2020). "New device for sperm preparation involving migration-gravity
sedimentation without centrifugation compared with density-gradient centrifugation for
normozoospermic intrauterine insemination." F&S Reports 1(2): 106-112.
Objective To investigate the efficacy of a new device for sperm
preparation involving migration-gravity sedimentation without
centrifugation (MIGLIS), compared with density-gradient
centrifugation (DGC) for normozoospermic intrauterine
insemination (IUI). Design Retrospective cohort study. Setting
Not applicable. Patients A total of 10,318 cases of IUI (3,015
MIGLIS and 7,303 DGC) between October 2013 and
September 2019. Interventions None. Main Outcome Measures
Sperm analysis, subsequent pregnancy outcomes, and
complications. Results MIGLIS was associated with a lower
sperm recovery rate and fewer injected sperm compared with
DGC. However, the overall pregnancy rates following MIGLIS
and DGC were similar (MIGLIS 8.8%, DGC 9.3%). In a
subanalysis according to age, the pregnancy rate was higher for
MIGLIS among women 40–41 years of age (8.6% vs. 5.9%).
Peritonitis was the only recorded complication, with similar
frequencies in the MIGLIS and DGC groups (MIGLIS two cases,
DGC four cases). No cases became severe, and all improved after
antibiotic treatment. There were no cases of uterine cramping or
pain symptoms. Conclusions MIGLIS is a new sperm preparation
method that does not require centrifugation. Its use was associated
with pregnancy rates similar to those with DGC and a higher
pregnancy rate in older women. MIGLIS is a novel sperm
preparation method for selecting spermatozoa with high motility
and good fertilization ability in patients undergoing IUI, in vitro
Turgutoğlu Yılmaz, A., et al. (2023). "Does the use of infusion pumps increase hemolysis
during blood transfusion in patients with thalassemia?" Transfusion and Apheresis Science
62(3): 103623.
Background Patients with thalassemia need regular blood
transfusions to maintain normal growth and suppression of
ineffective erythropoiesis. Packed red blood cell (RBC) units can
be delivered by infusion pumps (IPs); however, IPs may cause
mechanical stress-induced RBC lysis. This study aimed to
investigate the biomarkers of hemolysis related to transfusion
techniques in patients with thalassemia. Material and methods
Eighty-one thalassemia patients compared to those 42 healthy
controls in terms of hemolysis markers (hemoglobin, plasma free
hemoglobin (Hb), haptoglobin, potassium (K), lactate
dehydrogenase (LDH)) before transfusion. Considering the age
and peripheral venous diameter of the patient, the physician
decided on the caliber of vascular access device (22 G or 24 G)
for transfusion and the method to be used (gravitational method
[GM] or IP). Hemolysis markers were repeated after transfusion
in thalassemia patients. Results Packed RBC units were
transfused to 24 (30 %) patients by IP and 57 (70 %) patients by
GM. Plasma free Hb was significantly increased from
4.76 ± 7.92 mg/dL to 9.01 ± 7.66 mg/dL following transfusion
(p < 0.001). There was no significant difference between IP and
GM in terms of plasma free Hb increase. Post-transfusion plasma
free Hb, LDH, and K levels significantly increased in patients
who were transfused with 24 G catheters compared to those
transfused with 22 G. Conclusion An elevation in LDH levels was
detected after transfusion with volumetric IPs; however, plasma
free Hb or K levels were not affected by the transfusion method.
Studies are needed to determine the factors associated with
Excluded due to animal study, case report
(2021). "Diagnostic and treatment recommendations from the FACME ad-hoc
expert working group on the management of cerebral venous sinus thrombosis
associated with COVID-19 vaccination." Neurologia (Engl Ed) 36(6): 451-461.
(2023). "Erratum: Generation of a Mouse Spontaneous Autoimmune Thyroiditis
Model." J Vis Exp(196).
INTRODUCTION: Cases of cerebral venous sinus thrombosis have been reported in
individuals vaccinated against COVID-19 with non-replicating adenoviral vector vaccines.
We issue our recommendations on the diagnosis and management of patients presenting this
complication. METHODS: The multidisciplinary working group, led by the Spanish
Federation of Medical and Scientific Associations (FACME) and including representatives of
several scientific societies, reviewed the available evidence from the literature and reports of
the European Medicines Agency. We establish a definition for suspected cases and issue
diagnostic and treatment recommendations regarding vaccine-induced immune thrombotic
thrombocytopaenia. RESULTS: We define suspected cases as those cases of cerebral venous
sinus thrombosis occurring between 3 and 21 days after the administration of non-replicating
adenoviral vector vaccines, in patients with a platelet count below 150 000/μL or presenting a
decrease of 50% with respect to the previous value. Findings suggestive of vaccine-induced
immune thrombotic thrombocytopaenia include the presence of antibodies to platelet factor 4,
D-dimer levels 4 times greater than the upper limit of normal, and unexplained thrombosis.
The recommended treatment includes intravenous administration of non-specific human
immunoglobulin or alternatively plasmapheresis, avoiding the use of heparin, instead
employing argatroban, bivalirudin, fondaparinux, rivaroxaban, or apixaban for
anticoagulation, and avoiding platelet transfusion. CONCLUSIONS: Non-replicating
adenoviral vector vaccines may be associated with cerebral venous sinus thrombosis with
An erratum was issued for: Generation of a Mouse Spontaneous Autoimmune Thyroiditis
Model. The Protocol section was updated. Step 3.1.1 of the Protocol was updated from: After
the induction, anesthetize the mice with a volume of 0.01 mL/g anesthetic by intraperitoneal
injection. Prepare the anesthetic by mixing midazolam (40 µg/100 µL for sedation),
medetomidine (7.5 µg/100 µL for sedation), and butorphanol tartrate (50 µg/100 µL for
analgesia) in phosphate-buffered saline (PBS). to After the induction, anesthetize the mice
with a volume of 0.01 mL/g anesthetic by intraperitoneal injection. Prepare the anesthetic by
mixing midazolam (40 µg/100 µL for sedation), medetomidine (7.5 µg/100 µL for sedation),
and butorphanol tartrate (50 µg/100 µL for analgesia) in phosphate-buffered saline (PBS).
NOTE: The specific concentrations of each component in the anesthesia mixture are:
midazolam 13.33µg/100µL, medetomidine 2.5µg/100µL, and butorphanol 16.7µg/100µL. For
specific dosages used in mice, the doses are: midazolam 4µg/g, medetomidine 0.75µg/g, and
butorphanol 1.67µg/g. Anesthesia depth was confirmed when the mouse's limb muscles
relaxed, the whiskers had no touch response, and there was loss of pedal reflex. Step 3.1.2 of
the Protocol was updated from: After the mice are anesthetized, cut off their whiskers with
ophthalmic scissors to prevent blood from flowing down the whiskers and causing hemolysis.
Fix the mouse with one hand and press the skin of the eye to make the eyeball protrude.
Quickly remove the eyeball and draw 1 mL of blood into the microcentrifuge tube via a
capillary tube. to After the mice are anesthetized, prepare the peripheral blood samples, by
fixing the mouse with one hand and pressing the eye skin to protrude the eyeball. Then, insert
the capillary tube into the inner corner of the eye and penetrate at a 30-45 degree angle to the
plane of the nostril. Apply pressure while gently rotating the capillary tube. Blood will flow
into the tube via capillary action. Step 3.2.1 of the Protocol was updated from: Dissect the
chest wall to expose the heart, cut open the right atrium, and infuse saline into the left
ventricle by an intravenous infusion needle attached to a 20 mL syringe until the tissue turns
white. to Humanely euthanize the animal according to the institutional policies. Then, dissect
the chest wall to expose the heart, cut open the right atrium, and infuse saline into the left
ventricle by an intravenous infusion needle attached to a 20 mL syringe until the tissue turns
Ahmad, M. S. M., M. R. Iqbal and J. S. Refson (2021). "Acute mesenteric ischaemia
due to superior mesenteric vein (SMV) thrombosis." BMJ Case Rep 14(4).
Aibinder, W. R., et al. (2021). "Outcomes of nonoperative management of displaced
olecranon fractures in medically unwell patients." JSES International 5(2): 291-295.
A 77-year-old male patient presented with a 5-day history of abdominal pain, coffee ground
vomiting and blood-stained diarrhoea. CT scan of the abdomen and pelvis demonstrated a
long segment thrombotic occlusion of the superior mesenteric vein (SMV) extending up to
the proximal portion of the portal vein causing significant acute small bowel ischaemia.
Patient's deteriorating clinical condition warranted surgical management. Successful surgical
management required multidisciplinary teamwork between emergency, vascular surgeons,
anaesthetists and intensivists. Emergency laparotomy revealed gangrene of an estimated
120 cm of small bowel segment starting from duodenojejunal junction and a long segment
thrombotic occlusion of the SMV extending up to the portal confluence. Resection of
gangrenous small bowel without anastomosis and thrombo-embolectomy of SMV along with
laparostomy was done at the initial operation. Patient was admitted in the intensive care unit
on systemic heparinisation through intravenous administration of unfractionated heparin.
Second relook exploration was done after 48 hours followed by anastomosis of the small
bowel and closure of the abdomen. Patient made a good recovery following anticoagulation
therapy and was discharged on postoperative day 10.
Background Surgical treatment of displaced olecranon fractures in the elderly has a high rate
of complications, including wound breakdown and fixation failure. The purpose of this study
was to assess the clinical, radiographic, and functional outcomes of nonsurgical management
of displaced olecranon fractures in low-demand elderly and medically unwell patients.
Methods A retrospective review of 28 patients with displaced closed olecranon fractures was
performed with an average follow-up of 11 months. The mean age at the time of injury was
79 ± 10 years. The average Charlson Comorbidity Index was 6.4 ± 2.6. Treatment modalities
were at the discretion of the treating surgeon. A sling alone was used in 3 cases, an extension
circumferential cast in 9, or a plaster or thermoplastic splint in 16. The mean period of
immobilization was 5 ± 1 weeks. Outcomes included range of motion, ability to perform
active overhead extension, as well as radiographic and functional outcomes. Results At final
follow-up, the mean elbow range of motion for the cohort was from 28° ± 21° extension to
127° ± 15° flexion. Active overhead elbow extension against gravity was noted or
documented in 24 (86%) patients. Two patients (7%) were unable to perform active
extension. No pain was noted in 18 elbows, severe pain was present in 1 elbow, and the
remainder reported mild occasional pain. All olecranon fractures in this cohort were
displaced on the initial lateral radiograph. The mean displacement was 11 ± 7 mm. Nonunion
at final radiographic outcome was observed in 23 (82%) elbows. Two (7%) patients
developed skin complications related to posteriorly placed splints; one of which was severe.
Discussion This study adds to the growing literature that supports nonoperative management
of displaced olecranon fractures in elderly and medically unwell patients with low upper
extremity demand. Patients can be counseled that they have a good chance of obtaining
overhead extension, with minimal pain. Posteriorly based splints should not be used to
Akkerman, R. D. L., et al. (2020). "Opiate Intoxication Caused by Epidural Infusion
of Morphine: A Case Report of a Near Fatal Medication Error." Pain Pract 20(3): 321324.
INTRODUCTION: Epidural infusion of local anesthetics with opioids is widely used for pain
control during the perioperative-and peripartum-periods. Selection of the opioid, appropriate
dosing, and follow-up by the acute pain service are critical in providing safe postoperative
epidural analgesia. CASE REPORT SUMMARY: A 71-year-old man was scheduled for a
parastomal hernia repair with midline laparotomy. The parastomal hernia was a complication
from a previously performed colectomy for ulcerative colitis. Preoperatively, the patient
received a lower thoracic epidural catheter. The epidural infusate (0.2% ropivacaine with
0.5 µg/mL sufentanil) was prepared and double-checked by holding area nurses. The fact that
the right prescription medication label partially covered a morphine label went unnoticed.
The intraoperative phase was characterized by stable parameters. Postoperatively, it was not
possible to demonstrate an epidural nerve block. No pain was reported, and the patient could
be transferred to the ward. The patient developed coma and delayed respiratory depression
after discharge to the surgical ward, requiring intensive care unit admission and naloxone
administration. Analysis of the syringe content revealed the presence of morphine (1 mg/mL).
DISCUSSION: Color-coded prefilled syringes combined with the use of an epidural specific
syringe connector to prevent cross-connections should become standard practice. In addition,
delayed respiratory depression should be considered after epidural administration of
Alamger, et al. (2015). "Evaluation of anti-inflammatory, analgesic and antipyretic
activities of Thymus serphyllum Linn. in mice." Acta Pol Pharm 72(1): 113-118.
The present study was conducted to evaluate the analgesic, anti-inflammatory and antipyretic
activities of Thymus serphyllum Linn. in mice. Anti-inflammatory activity was evaluated by
carrageenan and egg albumin induced paw edema in mice, while analgesic activity was
assessed using formalin induced paw licking and acetic acid induced abdominal writhing in
mice. For determination of antipyretic activity, pyrexia was induced by subcutaneous
injection of 20% yeast. All the extracts produced significant anti-inflammatory effect
however, ether extract produced maximum effect 34% inhibition (p < 0.001) against
carrageenan and 22% (p < 0.01) inhibition against egg albumin induced paw edema in mice at
the end of 3 h. Ether extract produced prominent analgesic effect 77% (p < 0.001) inhibition
in acetic acid induced abdominal writhing and 59% inhibition in formalin induced paw
licking model in mice, respectively. Ether extract also demonstrated significant (p < 0.001)
antipyretic activity against yeast induced pyrexia. The plant showed no sign of toxicity up to
the dose of 2000 mg/kg in mice. This study supports the use of Thymus serphyllum in
traditional medicine for inflammation accompanied by pain and fever.
Al-Anii, F. M., et al. (2023). "Vancomycin flushing syndrome in orthopaedic practice:
A case report." World J Orthop 14(10): 771-775.
Alayan, J. and S. Ivanovski (2018). "A prospective controlled trial comparing
xenograft/autogenous bone and collagen-stabilized xenograft for maxillary sinus
augmentation-Complications, patient-reported outcomes and volumetric analysis."
Clin Oral Implants Res 29(2): 248-262.
BACKGROUND: Vancomycin flushing syndrome (VFS), also known as red man syndrome,
is an allergic reaction to vancomycin. It typically presents as a rash on the face, neck, and
upper torso after intravenous administration of vancomycin. VFS is blamed on rapid
intravenous infusion of vancomycin during management and rarely happens after local use. A
review of the literature showed that in the last 23 years, 4 such cases have been reported.
Here, we add another case of VFS developed after slow local absorption of vancomycin in
cement beads. CASE SUMMARY: A 44-year-old male with a known case of hypertension,
no history of allergies to medications, and a history of chronic osteomyelitis of the right tibia
with discharging sinus over the anterolateral aspect of the leg. The pus culture grew
Staphylococcus aureus, which was sensitive to clindamycin and vancomycin. The patient
underwent irrigation and debridement with the placement of vancomycin cement beads made
from 4 g of vancomycin powder and 40 g of polymethyl methacrylate. Three hours
postoperatively, the patient developed a pruritic, erythematous, macular rash predominantly
on his face, neck, chest, and lower extremities and to a lesser extent his upper extremities. A
diagnosis of VFS was made and was successfully treated with cetirizine (10 mg, oral) and
methylprednisolone sodium succinate (125 mg, intravenous). The patient continued to have
itching with a facial rash for 12 h with gradual improvement. A decision was made to not
remove the beads as the patient continued to improve. Gradually, the rash disappeared after
96 h with no further sequela. CONCLUSION: VFS can occur not only after rapid intravenous
injection of vancomycin but also with local release, as in our case. As orthopaedic surgeons
routinely use vancomycin with polymethyl methacrylate in chronic osteomyelitis and revision
arthroplasty, they should be aware of such a complication occurring.
OBJECTIVE: Compare maxillary sinus augmentation (MSA) using two different materialsanorganic bovine bone mineral (ABBM) + autogenous bone (AB) (control group) vs.
collagen-stabilized ABBM (test group) in terms of complications, patient-reported outcome
measures (PROMs) and volumetric analysis. MATERIALS AND METHODS: Sixty patients
underwent sinus augmentation (30 control + 30 test group). Intra- and postoperative
complications were recorded. PROMs measured the impact of grafting on daily activities,
pain and morbidity. CT scans were used to measure graft volume, ridge height, material
selection and degree of contact of graft-to-surrounding sinus walls. Dental implant placement
parameters were also recorded. RESULTS: All complications were minor and did not prevent
completion of the augmentation or subsequent implant placement. Schneiderian membrane
perforation was the most frequently encountered complication. Both treatment groups
reported moderate limitation in the 1st 48 hr post-surgery but little or none by day 3 or 4. Jaw
opening, chewing and bruising were significantly higher in the control group. The impact on
work and social life was moderate initially but reduced to little or none by the 2nd day. Mild
to moderate pain and interference to daily activities were reported for the first 3 days
requiring the use of NSAIDs only. A mean graft volume of 1.46 cm(3) (±0.77) was calculated
in the control group and 1.27 cm(3) (±0.65) in the test group. Extent of contact between graft
and surrounding sinus walls had a significant impact on bone volume. Shorter (8 mm)
implants were utilized more frequently in the test group, which was also more likely to
require additional vertical augmentation, but this was not statistically significant.
CONCLUSION: MSA using a lateral wall approach is safe and associated with mild to
moderate pain and restrictions to daily activities for 48-72 hr. Patients' reports of morbidity
were greater with autogenous bone harvesting. Collagen-stabilized ABBM provides
comparable bone volume to AB + ABBM that is sufficient for placement of implants of
adequate size with no need for further vertical augmentation. Engaging the surrounding sinus
Alhalabi, M., et al. (2021). "Subcutaneous golimumab induced and maintained
clinical response in a child with a biological-experienced steroid-refractory flare of
ulcerative colitis: A case report." Medicine (Baltimore) 100(38): e27283.
INTRODUCTION: Golimumab is a fully human antitumor necrosis monoclonal antibody that
can be administered by either subcutaneous injection or intravenous infusion. Golimumab is
approved for the treatment of the adults with rheumatic diseases, and ulcerative colitis,
Whereas in children, golimumab is indicated only for the treatment of active polyarticular
juvenile idiopathic arthritis. We have written on the off-label use of subcutaneous
golimumab, which helped to induce and maintain remission on a low-weight biologically
experienced child with steroid-refractory ulcerative colitis flare. PATIENT CONCERNS: A
13-year-old pancolitis Syrian boy presented with abdominal pain and six to seven times
bloody diarrhea. The child had treated with mesalamine 80 mg/kg/day, azathioprine
2.5 mg/kg/day, infliximab with an induction dose of 5 mg/kg at weeks 0, 2, and 6 followed by
5 mg/kg every 8 weeks. Infliximab did not maintain remission as the patient suffered from two
flares that required hospital admission, intravenous corticosteroids, and infliximab escalation.
Initial tests disclosed leukocytosis, anemia, hypoalbuminemia, an elevation in C-reactive
protein and fecal calprotectin. All Stool studies were negative including routine stool
cultures, Clostridium difficile toxin, Escherichia coli O157:H7, Cryptosporidium, and
microscopy for ova and parasites. A sigmoidoscopy revealed multiple large ulcerations and
spontaneous bleeding, colon biopsies were negative for Clostridium difficile and
Cytomegalovirus. Cyclosporine, tacrolimus, and adalimumab were unavailable in Syria.
Child's parents opposed colectomy as a treatment option. DIAGNOSIS: Ulcerative colitis
flare. INTERVENTIONS: A subcutaneous golimumab with a loading dose of 200 mg at week
0, followed by 100 mg at week 2, then 50 mg every 4 weeks. OUTCOMES: The patient
achieved clinical remission by week sixth and maintained the remission for the next 90 weeks.
At the time of last evaluation, tests, including C-reactive protein and fecal calprotectin, were
within normal limits, complete colonoscopy revealed erythema, edema, mucosal friability,
loss of vascular patterns, and pseudo-polyps. The Pediatric Ulcerative Colitis Activity Index
and Mayo scores were 5 and 2 points, respectively. No adverse events were documented.
CONCLUSION: Golimumab has shown potential efficacy and safety in the treatment of
ulcerative colitis in children which may indicate a significant future role for subcutaneous
Altan, A. (2020). "Accidental injection of ethylenediaminetetraacetic acid (EDTA)
instead of an anaesthetic solution: a case report." J Stomatol Oral Maxillofac Surg
121(1): 77-79.
The accidental use of drugs is an unacceptable mistake in medicine, but the misuse of
different agents has been reported frequently in the literature. While performing local
anesthesia before starting dental treatment, the injection of a wrong agent, as a result of
confusing the liquid in the syringe may cause local and systemic complications. Sudden
swelling, intense pain, and severe allergic reactions may develop in the patient. A
complication causing soft tissue necrosis is presented in this case report in which
Ethylenediaminetetraacetic acid (EDTA) was accidentally injected instead of an anesthetic
solution. This case report is unique because it is the first to report an inadvertent injection of
EDTA in dentistry.
Altuntas, C. Z., et al. (2012). "Autoimmunity to uroplakin II causes cystitis in mice: a
novel model of interstitial cystitis." Eur Urol 61(1): 193-200.
BACKGROUND: The pathophysiology of interstitial cystitis (IC) is unknown. Deficits in
urothelial cell layers and autoimmune mechanisms may play a role. OBJECTIVE: To
examine whether immunization of mice with recombinant mouse uroplakin II (rmUPK2), a
bladder-specific protein, would provoke an autoimmune response sufficient to create an IC
phenotype. DESIGN, SETTING, AND PARTICIPANTS: RmUPK2 complementary DNA
was generated, transferred into a bacterial expression vector, and the generated protein was
purified. Eight-week-old SWXJ female mice were immunized with rmUPK2 protein via
subcutaneous injection of 200μg of rmUPK2 protein in 200μl of an emulsion.
MEASUREMENTS: Mice were euthanized 5 wk after immunization. Axillary and inguinal
lymph node cells were tested for antigen-specific responsiveness and cytokine production,
serum isotype antibody titers against rmUPK2 were determined, and gene expression of
inflammatory mediators was measured in the bladder and other organs. For functional
analysis, mice were placed in urodynamic chambers for 24-h micturition frequency and total
voided urine measurements. RESULTS AND LIMITATIONS: Immunization with rmUPK2
resulted in T-cell infiltration of the bladder urothelium and increased rmUPK2-specific serum
antibody responses in the experimental autoimmune cystitis (EAC) mice models compared
with controls. The ratio of bladder to body weight was increased in EAC mice. Quantitative
reverse transcriptase polymerase chain reaction analysis showed elevated gene expression of
tumor necrosis factor α, interferon γ, interleukin (IL)-17A, and IL-1β in bladder urothelium
but not in other organs. Evaluation of 24-h micturition habits of EAC mice showed
significantly increased urinary frequency (p<0.02) and significantly decreased urine output
per void (p<0.021) when compared with control mice. CONCLUSIONS: Our study showed
that a bladder-specific autoimmune response sufficient to induce inflammation and EAC
occurs in mice following immunization with rmUPK2. EAC mice displayed significant
evidence of urinary frequency and decreased urine output per void. Further phenotype
characterization of EAC mice should include evidence for pain and/or afferent
Ankichetty, S., et al. (2013). "Case report: Rhabdomyolysis in morbidly obese
patients: anesthetic considerations." Can J Anaesth 60(3): 290-293.
PURPOSE: We report the presentation and management of rhabdomyolysis involving
shoulder girdle and upper arm muscles in a morbidly obese patient after prolonged
laparoscopic surgery. CLINICAL FEATURES: A 41-yr-old morbidly obese woman presented
for laparoscopic abdominal hysterectomy. She had hypertension and type II diabetes which
were controlled on regular medications. She also had obstructive sleep apnea. Her clinical
examination and investigations revealed no abnormality except morbid obesity (body mass
index 54 kg·m(-2)) and left ventricular hypertrophy on transthoracic echocardiogram.
Standard general anesthesia was administered under baseline non-invasive monitors.
Succinylcholine was used to secure the airway during anesthetic induction. Surgery was
performed with the patient positioned with a 15° head-down tilt, and it took six hours to
complete the procedure as technical difficulty was encountered due to her body habitus. Her
trachea was extubated and she was transferred to the postanesthetic care unit (PACU) without
incident. In the PACU, the patient complained of severe bilateral arm pain and weakness an
hour after surgery. On physical examination, she exhibited limited movement of her arms
against gravity while complaining of tenderness in her shoulder girdle muscles and both arms.
Clinical suspicion of rhabdomyolysis based on her signs and symptoms was confirmed by an
elevated serum creatinine kinase (CK) of 18,392 IU·L(-1) and serum potassium of 5.3
mmol·L(-1). Intravenous crystalloids and mannitol were administered for 24 hr for renal
protection, and her clinical symptoms and serum CK levels improved over seven days. The
patient was discharged to home on the tenth postoperative day, and she continued to improve
over the three-month follow-up period. CONCLUSIONS: Morbidly obese patients who
undergo prolonged surgery are at risk for rhabdomyolysis, and early diagnosis and therapy
Asabella, A. N., et al. (2011). "(18)F-FDG positron emission tomography/computed
tomography and (99m)Tc-MDP skeletal scintigraphy in a case of Erdheim-Chester
disease." Hell J Nucl Med 14(3): 311-312.
Erdheim-Chester disease (ECD), first described by Jakob Erdheim and William Chester in
1930, is a rare form of non-Langerhan's cell histiocytosis with unknown aetiology, is
charaterized by systemic xanthogranulomatous infiltrative disease. To date, about 350 cases
of ECD have been described in the medical literature. The typical ECD diagnostic triad is
bone pain, diabetes insipidus and bilateral exophthalmos. A 24 years old man came at our
attention for polydipsia with nocturnal and diurnal polyuria, anorexia, febrile episodes
(38(o)C), and arthromyalgia especially in the knees. Physical examination showed bilateral
periorbital xanthelasma. Blood exams showed increase of plasma osmolarity, haematocrit,
sodium and urea and decrease of potassium. Urine exams showed just decreased urine
specific gravity, (1.001;normal range: 1.010-1.030) suggestive for central diabetes insipidus
(CDI). Brain magnetic resonance with gadolinium enhancement showed the presence of
multiple hyperintense lesions expecially in neurohypophysis (swollen and with markedly
contrast enhancement). All these data raised the suspision of neurosarcoidosis, so a chest and
abdomen contrast enhancement computed tomography was performed, which didn't show
abnormalities, making less possible the diagnosis of sarcoidosis. Two weeks later, wholebody (from head to pelvis) plus lower limbs 18-fluorine-labelled 2-deoxy-2-fluoro-D-glucose
positron emission tomography/computed tomography ((18)F-FDG PET/CT) was performed.
Uptake of (18)F-FDG was observed in the upper portion of the midbrain area (SUV(max)
7.1) and the pituitary gland (SUV(max) 7.3), and diffuse bone marrow uptake of (18)F-FDG
in the proximal epiphysis and metaphysis of both humeri and thigh bones (SUV(max) 6.5),
shoulder blades, pelvis bones and the L2 vertebral body (SUV(max) 3.9). This (18)F-FDG
PET/CT confirmed the presence of brain lesion seen in MRI , the absence of visceral lesions,
but also showed the presence of an atypical bone uptake of (18)F-FDG, leading to the
suspision of ECD. A technetium-99m-methyl-diphosphonate skeletal scintigraphy ((99m)TcMDP) scan showed diffuse uptake of the radiopharmaceutical, in the diaphysis of long bones
and in the left portion of the body and the spinous process of L2. Considering the difficulties
of an osteomedullary or brain biopsy, biopsy was performed on a right anterior thoracic
cutaneous xanthelasma. Histology showed lipid-laden histiocytes (CD1a-, CD68+, S-100
Aschoff, A. T., et al. (2017). "[Unclear Abdominal Pain - Not Always a
Gastroenterological Emergency]." Dtsch Med Wochenschr 142(7): 530-533.
History and admission findings An 84-year old patient with persistent atrial fibrillation and
chronic renal failure received a subcutaneous injection with low molecular weight heparin
(LMWH) during a hospital stay. Over the course of her hospitalization, the patient developed
abdominal pain. There was a marked hematoma at the injection site. A large tumor was
palpable in the right abdominal quadrant. Examinations Due to the significant reduction in
hemoglobin, we performed a CT-angiogram of the abdomen. Diagnosis We were able to
visualize an intramuscular hematoma within the rectus abdominis muscle. Therapy and
clinical course After visualization with digital subtraction angiography and application of
microcoils and histoacryl-glue, we were able to stop bleeding. After implantation of left atrial
appendage occluder, oral anticoagulation therapy could be stopped. Conclusion LMWHtreated patients with nonspecific abdominal pain should be meticulously examined to exclude
iatrogenic abdominal muscle hematoma.
Azevedo, C., et al. (2021). "Prevention of diabetes-associated fibrosis: Strategies in
FcRn-targeted nanosystems for oral drug delivery." Adv Drug Deliv Rev 175: 113778.
Başer Can, E. D., M. Karapınar Kazandağ and R. F. Kaptan (2015). "Inadvertent
apical extrusion of sodium hypochlorite with evaluation by dental volumetric
tomography." Case Rep Dent 2015: 247547.
Diabetes mellitus is a chronic disease with an elevated risk of micro- and macrovascular
complications, such as fibrosis. To prevent diabetes-associated fibrosis, the symptomatology
of diabetes must be controlled, which is commonly done by subcutaneous injection of
antidiabetic peptides. To minimize the pain and distress associated with such injections, there
is an urgent need for non-invasive oral transmucosal drug delivery strategies. However, orally
administered peptide-based drugs are exposed to harsh conditions in the gastrointestinal tract
and poorly cross the selective intestinal epithelium. Thus, targeting of drugs to receptors
expressed in epithelial cells, such as the neonatal Fc receptor (FcRn), may therefore enhance
uptake and transport through mucosal barriers. This review compiles how in-depth studies of
FcRn biology and engineering of receptor-binding molecules may pave the way for design of
new classes of FcRn-targeted nanosystems. Tailored strategies may open new avenues for
oral drug delivery and provide better treatment options for diabetes and, consequently,
fibrosis prevention.
This case report describes the tissue injury caused by inadvertently extruded NaOCl through
the apical constriction. A 56-year-old female patient with complaints of pain, swelling, and
ecchymosis on the left side of her face was referred to our clinic. The symptoms had emerged
following root canal treatment of the maxillary left first premolar, and a soft tissue
complication due to apical extrusion of NaOCl was diagnosed. Antibiotics and analgesics
were prescribed. DVT images revealed that the buccal root apex had perforated the maxillary
bone. The patient was followed up every other day and became asymptomatic on the 10th
day. Endodontic therapy was completed with routine procedures. Determining working length
precisely and following irrigation protocols meticulously are indispensable to prevent this
type of complication. 3D visualization of the affected area may reveal the cause of the
Bedner, K. and E. Crago (2022). "What a Rat Race: A Case Study of Rat Bite Fever in
an Emergency Department." Journal of Emergency Nursing 48(5): 583-585.
Benlabed, M., et al. (2019). "Clinical implications of intravenous drug
incompatibilities in critically ill patients." Anaesthesia Critical Care & Pain Medicine
Rat bite fever is an acute illness caused by bacteria from rodents. In the United States, rat bite
fever is considered rare; however, actual incidence is unknown because of lack of mandatory
disease reporting requirements. Risk of development of rat bite fever after being bitten by a
rat is approximately 10%. Early treatment is imperative as death is a potential complication.
The following case study demonstrates the gravity of the syndrome.
Objective The aim of this review is to analyse the clinical consequences of intravenous drug
incompatibilities in critically ill patients, especially the incidence of organ dysfunctions and
mortality. Methods A review of literature was conducted according to the PRISMA statement
in June 2017, using Medline, ISI Web of Science and Clinicaltrials.gov. Data extraction
Eligible studies were case reports and randomised controlled trials (RCTs) that assessed the
effects of drug incompatibilities in critically ill patients on morbidity or mortality as primary
or secondary outcomes, or adverse events. Two investigators independently reviewed the
eligibility of the study from abstracts or manuscript data. Data synthesis Twelve articles met
the selection criteria. The six articles reporting RCTs concern only four RCTs. RCTs were
single-centre studies comparing infusion with or without filter. One of them included adult
patients. The others included paediatric and neonatal intensive care unit patients. Primary
endpoints were SIRS, organ failure, overall complication rate, bacteraemia, sepsis, phlebitis
and length of stay. The results are mixed with one RCT reporting a reduction in SIRS, organ
failure and overall complication rate, two studies in disagreement over the occurrence of
sepsis and one study reporting no impact on length of hospital stay. The six articles on case
reports show different drug incompatibility situations. They report pulmonary toxicity.
Conclusion Little data is available on this topic. Infused particles may induce organ failure, in
particular pulmonary toxicity and SIRS. Further studies are needed to establish a link
Blasi-Brugué, C., et al. (2021). "Quantitative assessment of infusion pump-mediated
haemolysis in feline packed red blood cell transfusions." J Feline Med Surg 23(12):
1149-1154.
OBJECTIVES: Haemolysis caused by the use of peristaltic infusion pumps (PIPs) has been
described in human and canine packed red blood cells (pRBCs). The aim of this study was to
evaluate the effects of two different linear PIPs on the haemolysis of feline pRBC units stored
for a long time. METHODS: Feline pRBC units stored with adenine, dextrose, mannitol and
sodium chloride (SAGM) were manufactured. After 35-42 days of storage at 2-4°C, a line
administration system with a 180 µm filter was attached to every pRBC bag, the system was
drained by gravity alone (8 drops/min) and a 1.3 ml sample was collected (G). A NIKI V4
pump was then used at a flow rate of 25 ml/h, the flow was stopped when the infusion system
was filled with blood coming from the infusion pump and another 1.3 ml sample was
collected (NK). Finally, an Infusomat FmS pump was evaluated, collecting another 1.3 ml
sample (IM). Packed cell volume (PCV) was measured in all samples by microhaematocrit
centrifugation, total haemoglobin (HGB) was measured using a specific haemoglobin
analyser and, after centrifugation, free HGB was determined by spectrophotometry. The
percentage of haemolysis was calculated. Friedman's test was used to compare the samples.
RESULTS: Fifteen feline pRBC units were evaluated. The average degree of haemolysis for
sample G (gravity-assisted) was 1.12%. Comparison of the degree of gravity-assisted
haemolysis with haemolysis in PIP NK (1.13%) and IM (1.14%) samples revealed no
significant differences, with differences of only 0.01% and 0.02%, respectively.
CONCLUSIONS AND RELEVANCE: The results of this study demonstrate that the use of
two common PIPs in veterinary hospitals does not produce levels of haemolysis that are
significantly different than that caused by gravity alone during transfusion of feline pRBCs at
Brace, C. L., J. L. Hinshaw and M. G. Lubner (2011). "Thermal ablation for the
treatment of abdominal tumors." J Vis Exp(49).
Percutaneous thermal ablation is an emerging treatment option for many tumors of the
abdomen not amenable to conventional treatments. During a thermal ablation procedure, a
thin applicator is guided into the target tumor under imaging guidance. Energy is then applied
to the tissue until temperatures rise to cytotoxic levels (50-60 °C). Various energy sources are
available to heat biological tissues, including radiofrequency (RF) electrical current,
microwaves, laser light and ultrasonic waves. Of these, RF and microwave ablation are most
commonly used worldwide. During RF ablation, alternating electrical current (~500 kHz)
produces resistive heating around the interstitial electrode. Skin surface electrodes (ground
pads) are used to complete the electrical circuit. RF ablation has been in use for nearly 20
years, with good results for local tumor control, extended survival and low complication
rates. Recent studies suggest RF ablation may be a first-line treatment option for small
hepatocellular carcinoma and renal-cell carcinoma. However, RF heating is hampered by
local blood flow and high electrical impedance tissues (eg, lung, bone, desiccated or charred
tissue). Microwaves may alleviate some of these problems by producing faster, volumetric
heating. To create larger or conformal ablations, multiple microwave antennas can be used
simultaneously while RF electrodes require sequential operation, which limits their
efficiency. Early experiences with microwave systems suggest efficacy and safety similar to,
or better than RF devices. Alternatively, cryoablation freezes the target tissues to lethal levels
(-20 to -40 °C). Percutaneous cryoablation has been shown to be effective against RCC and
many metastatic tumors, particularly colorectal cancer, in the liver. Cryoablation may also be
associated with less post-procedure pain and faster recovery for some indications.
Cryoablation is often contraindicated for primary liver cancer due to underlying coagulopathy
and associated bleeding risks frequently seen in cirrhotic patients. In addition, sudden release
of tumor cellular contents when the frozen tissue thaws can lead to a potentially serious
condition known as cryoshock. Thermal tumor ablation can be performed at open surgery,
laparoscopy or using a percutaneous approach. When performed percutaneously, the ablation
procedure relies on imaging for diagnosis, planning, applicator guidance, treatment
monitoring and follow-up. Ultrasound is the most popular modality for guidance and
Braun, R. K., et al. (2016). "Cardiopulmonary and histological characterization of an
acute rat lung injury model demonstrating safety of mesenchymal stromal cell
infusion." Cytotherapy 18(4): 536-545.
BACKGROUND AIMS: In the field of cellular therapy, potential cell entrapment in the lungs
following intravenous administration in a compromised or injured pulmonary system is an
important concern that requires further investigation. We developed a rat model of
inflammatory and fibrotic lung disease to mimic the human clinical condition of obliterative
bronchiolitis (OB) and evaluate the safety of intravenous infusion of mesenchymal stromal
cells (MSCs). This model was used to obtain appropriate safety information and functional
characterization to support the translation of an ex vivo-generated cellular product into
human clinical trials. To overcome spontaneous recovery and size limitations associated with
current animal models, we used a novel multiple dose bleomycin strategy to induce lasting
lung injury in rats. METHODS: Intratracheal instillation of bleomycin was administered to
rats on multiple days. MSCs were intravenously infused 7 days apart. Detailed pulmonary
function tests including forced expiratory volume, total lung capacity, and invasive
hemodynamic measurements were conducted to define the representative disease model and
monitor cardiopulmonary hemodynamic consequences of the cell infusion. Post-euthanasia
assessments included a thorough evaluation of lung morphology and histopathology.
RESULTS: The double dose bleomycin instillation regimen resulted in severe and
irreversible lung injury and fibrosis. Cardiopulmonary physiological monitoring reveled that
no adverse events could be attributed to the cell infusion process. DISCUSSION: Although
our study did not show the infusion of MSCs to result in an improvement in lung function or
Brewer, D. J., et al. (2022). "Toxicity of zoledronic acid after intravenous
administration: A retrospective study of 95 dogs." J Vet Intern Med 36(1): 253-258.
BACKGROUND: There is a paucity of veterinary literature on the safety or outcome of
zoledronic acid (ZA) use in dogs for either bone pain or hypercalcemia.
HYPOTHESIS/OBJECTIVES: The primary aim was to report the adverse events in dogs
receiving intravenous administration of ZA. ANIMALS: Ninety-five dogs with ZA use.
METHODS: A retrospective cohort study was performed; all dogs that received at least 1
dose of ZA and had a serum biochemistry profile performed before and after treatment were
reviewed. Diagnosis, indication for treatment, adverse events and survival times were
recorded. RESULTS: Ninety-five dogs met the inclusion criteria. Thirty-one (33%) received
multiple intravenous infusions of ZA (range, 2-7), making a total of 166 administrations in all
dogs. The dose range was 0.13 to 0.32 mg/kg, given at intervals of 4 to 6 weeks. Thirteen
adverse events were recorded in 10 dogs: azotemia (n = 8), vomiting (n = 2), pancreatitis
(n = 1), cutaneous ulceration (n = 1), and diarrhea (n = 1). Zoledronic acid could not be
confirmed as the cause of azotemia in any case. The change in serum creatinine concentration
from dose to dose was not related to the total dose received (P = .46). Five dogs (5%)
changed Veterinary Comparative Oncology Group Common Terminology Criteria (VCOGCTAE) renal/genitourinary grade after administration of ZA; their total dose 0.4 mg/kg
(range, 0.26-0.66) was not significantly different to the group which did not change VCOGCTAE renal/genitourinary grade 0.35 mg/kg (range, 0.2-1.50; P = .93). CONCLUSIONS
AND CLINICAL IMPORTANCE: Multiple doses of ZA were well tolerated in dogs within
this study. A small number of dogs developed progressive azotemia which was not associated
Brustoloni, Y. M., et al. (2010). "Treatment of visceral leishmaniasis in children in the
Central-West Region of Brazil." Infection 38(4): 261-267.
BACKGROUND: Detailed reports on the treatment of visceral leishmaniasis (VL) are scarce,
particularly with regard to the utilization of antimoniate of N-methylglucamine. The aim of
this study was to analyze the treatment of children admitted to a reference hospital, focusing
in particular on the use of antimoniate of N-methylglucamine and on the supportive measures
adopted. MATERIALS AND METHODS: Medical records of children treated for VL from
January 1998 to February 2005 in the Hospital of the University of Mato Grosso do Sul,
Central-West Region of Brazil, were reviewed retrospectively. RESULTS: A total of 116
children were treated, and 111 received antimoniate as the first therapeutic choice. The drug
was highly efficient (96.9%) in patients with no signs of gravity on admission, in cases
presenting warning signs of potential evolution to gravity, and even in some severely ill
children. The most common adverse effects were increases in transaminase (22.5%) and
amylase (17.5%) levels, and generally reversible electrocardiogram changes (18%). Some
problems were detected during the treatment, such as inadequate prescription (causing an
under- or overdose) or inappropriate change to a second-line scheme. Of the 116 children,
80% were given antibiotics, 71.5% needed a transfusion of red blood cells, 10.3% required a
transfusion of platelets, fresh frozen plasma was given to 4.3%, albumin was administered in
3.4, and 8.6% needed intensive care support. The mortality rate was about 2.6%.
CONCLUSION: Antimoniate of N-methylglucamine remains highly efficient and well
tolerated in pediatric patients, which allows its utilization as a first-line therapy in Brazilian
children until a better drug for widespread use becomes available; however, it should be used
with caution, and special attention is required during its prescription and for the management
of adverse effects. The low mortality rate obtained confirms that, in addition, successful
treatment demands the correction of serious anemia and thrombocytopenia, the vigorous use
of antibiotics to fight intercurrent bacterial infections, and sometimes the availability of
Buonora, M. J. E. (2019). "Management of Gravity Intravenous Infusions in an
Austere Environment Using the DripAssist Infusion Rate Monitor." Aana j 87(1): 6570.
The US Army's 541st Forward Surgical Team (FST) deployed in support of Operation
Inherent Resolve- Syria in 2017. Throughout the deployment the 541st FST provided surgical
and anesthesia services to US, coalition, and partner forces in numerous austere
environments. Following an enemy attack, the FST received multiple casualties and provided
a total of 7 critical medication infusions to 3 patients without the aid of electronic-controlled
intravenous (IV) infusion pumps or syringes for 10 hours while the wounded soldiers waited
for evacuation to a higher level of care. The team administered propofol, norepinephrine,
tranexamic acid, and ketamine by individual gravity infusions relying solely on counting
drops. An infusion rate monitor (DripAssist, Shift Labs Inc) was used to assist in initial IV
rate setup and maintenance. The medics and nurses of the 541st FST found that the infusion
rate monitor improved the speed of setting the IV infusion rate, drop counting accuracy, and
the team's ability to monitor the continuous delivery of gravity IV infusions.
Cao, W., et al. (2020). "Early diagnosis and precision treatment of right ovarian vein
and inferior vena cava thrombosis following caesarean section: A case report." Exp
Ther Med 19(4): 2923-2926.
Cashman, G. and R. Attariwala (2014). "Influence of MRI field strength on clinical
decision making in knee cartilage injury - A case study." J Can Chiropr Assoc 58(4):
395-400.
Ovarian vein thrombosis (OVT) is a rare medical complication that is most often diagnosed
in the post-partum period. OVT can lead to conditions, including sepsis, inferior vena cava
(IVC), pulmonary emboli and mortality. The current study outlines a case of a patient who
experienced pain in the lower abdomen and waist without fever postpartum following
caesarean section (CS). Plasma FDP, D-Dimer and fibrinogen levels were markedly increased
following CS and this was an indicator of the rapid progression of blood coagulation and
fibrinolysis. Increased maternal lipid may be one of the risk factors for thrombosis. Based on
the clinical presentation, a CT scan demonstrated thrombosis of the right ovarian vein and
inferior vena cava, and a diagnosis of OVT and IVC thrombosis was subsequently made. In
the current case, an anticoagulant therapy was started with a subcutaneous injection low
molecular weight heparin calcium, an intravenous urokinase drip as a thrombolytic agent and
implantation of inferior vena cava filters as a novel method of treatment for thrombosis. The
patient was discharged from hospital 20 days following treatment in a good condition. The
current study reports a case of OVT associated with IVC that was successfully managed
without complication.
OBJECTIVE: To increase clinicians' awareness of the differences in image resolution and
potential diagnostic accuracy between small and large-field MR Scanners. To present an
example of a clinical decision making challenge in how to proceed when knee MRI and
clinical findings don't agree. CLINICAL FEATURES: A 38 year old female mountain biker
presented with knee pain and clinical features strongly suggestive of a torn meniscus or loose
bodies. An initial MRI using a small field strength (0.18T) scanner was reported as normal.
Her clinical presentation was suspicious enough that a repeat MRI on a high-field (1.5T)
scanner was ordered. The second MRI included high resolution 3D volumetric imaging which
revealed cartilage damage and loose bodies. INTERVENTION AND OUTCOME: The
patient was treated with arthroscopic surgery which confirmed the presence of meniscal and
chondral injury and resulted in notable improvement in the patient's symptoms.
CONCLUSION: Clinicians should consider scanner quality and diagnostic accuracy before
discounting strongly suggestive clinical history and examination findings when MRIs are
reported as normal.
Chen, D., et al. (2021). "Laparoscopic Uterine Artery Occlusion Combined with
Uterine-sparing Pelvic Plexus Block and Partial Adenomyomectomy for
Adenomyosis: A Video Case Report." J Minim Invasive Gynecol 28(10): 1681-1684.
OBJECTIVE: Adenomyosis usually causes dysmenorrhea and anemia. Clinically, it is
difficult to be treated with medicine or by traditional surgery, however, hysterectomy is
always performed for radical treatment. In this article, we introduce a new method that could
control the dysmenorrhea and the anemia through laparoscopic uterine artery occlusion
(LUAO) combined with uterine-sparing pelvic plexus block and partial adenomyomectomy
for uterus preservation. DESIGN: Surgical video article. Local institutional review board
approval for the video reproduction was obtained. SETTING: A 42-year-old patient, who had
a history of a previous cesarean delivery, was admitted to our department with complaints of
progressive dysmenorrhea for more than 5 years and aggravated with anemia for 1 year. The
patient had failed treatment with traditional Chinese medicine and gonadotropin-releasing
hormone and had to take painkillers for nearly half a year. The patient had no desire for
another pregnancy. After careful consideration, the patient strongly rejected hysterectomy
and demanded the preservation of the uterus, insisting on the integrity of the organs. A
gynecologic examination showed that the uterus was hard and enlarged similar to one that is
more than 8 gestational weeks, without tender nodules in the rectouterine pouch. The visual
analog scale pain score was 7, and her hemoglobin was 93 g/L (after correction). The
preoperative magnetic resonance imaging implied that there was 1 lesion in the posterior wall
and the maximum diameter of the lesion was 7.8 cm. INTERVENTIONS: We performed
laparoscopic partial adenomyomectomy combined with occlusion of uterine artery to limit the
amount of intraoperative bleeding, dissected the uterine branch of pelvic plexus nerve, and
performed electrocoagulation blocking to relieve the dysmenorrhea. The specific operation
procedures are as follows (Video): Firstly, we opened the peritoneum through Cheng's
triangle, which contained the external iliac blood vessels, the round ligament, and the
infundibulopelvic ligament (Fig. 1). Secondly, we separated the lateral rectal space and
exposed the ureter, the internal iliac artery, the uterine artery, and the deep uterine vein.
Thirdly, we found that the pelvic plexus was located on the outside of the sacral ligament and
was approximately 2 to 3 cm below the ureter, going against the sacral ligament and passing
through below the deep uterine vein (Supplemental Video 1). Fourthly, we separated the 4
Chen, L., et al. (2013). "Multiple cell transplantation based on an intraparenchymal
approach for patients with chronic phase stroke." Cell Transplant 22 Suppl 1: S83-91.
Stroke is the third leading cause of death worldwide and a huge perpetrator in adult disability.
This pilot clinical study investigates the possible benefits of transplanting multiple cells in
chronic stroke. A total of 10 consecutive stroke patients were treated by combination cell
transplantation on the basis of an intraparenchymal approach from November 2003 to April
2011. There were six males and four females. Their age ranged from 42 to 87 years, and the
course of disease varied from 6 months to 20 years. Six patients suffered cerebral infarction,
and four patients suffered a brain hemorrhage. The olfactory ensheathing cells, neural
progenitor cells, umbilical cord mesenchymal cells, and Schwann cells were injected through
selected routes including intracranial parenchymal implantation, intrathecal implantation, and
intravenous administration, respectively. The clinical neurological function was assessed
carefully and independently before treatment and during a long-term follow-up using the
Clinic Neurologic Impairment Scale and the Barthel index. All patients were followed up
successfully from 6 months to 2 years after cell transplantation. Every subject achieved
neurological function amelioration including improved speech, muscle strength, muscular
tension, balance, pain, and breathing; most patients had an increased Barthel index score and
Clinic Neurologic Impairment Scale score. These preliminary results demonstrate the novel
strategy of combined multiple cell therapy based on intraparenchymal delivery: it appears to
be relatively clinically safe and at least initially beneficial for chronic stroke patients. This
manuscript is published as part of the International Association of Neurorestoratology
Chen, S., H. Wang and L. Huang (2020). "The presence of De Winter
electrocardiogram pattern following elective percutaneous coronary intervention in a
patient without coronary artery occlusion: A case report." Medicine (Baltimore)
99(5): e18656.
RATIONALE: The De Winter electrocardiogram (ECG) pattern is considered as a ST
elevated myocardial infarction (STEMI)-equivalent pattern. Due to its rare nature, it is
unclear whether this ECG pattern suggests the presence of some other condition. PATIENT
CONCERNS: We reported a 47-year-old man with new-onset chest discomfort several hours
after the second-stage percutaneous coronary intervention (PCI). DIAGNOSES: An
emergency coronary angiogram (CAG) did not show any abnormality. However, the dynamic
changes in the ECG and myocardial biomarkers indicated perioperative myocardial
infarction. INTERVENTION: The patient was monitored in the cardiac care unite (CCU),
and was administered an intravenous infusion of diltiazem and subcutaneous injection of low
molecular weight heparin. OUTCOMES: After a few hours, his symptoms were alleviated.
The patient was discharged after 6 days of hospitalization without any complications.
LESSONS: The De Winter ECG pattern can be observed in patients without significantly
coronary arteries occlusion. The newly onset De Winter ECG pattern after PCI procedure
may indicate perioperative myocardial infarction caused by impaired microvascular
Chen, Y., et al. (2019). "Intravenous administration of adenosine triphosphate and
phosphocreatine combined with fluoxetine in major depressive disorder: protocol for
a randomized, double-blind, placebo-controlled pilot study." Trials 20(1): 34.
BACKGROUND: Major depressive disorder (MDD) is a common psychiatric disorder. With
systematic antidepressant treatment, 50-75% of patients have a treatment response but require
4-6 weeks to have their symptoms alleviated. Therefore, researchers anticipate the
development of novel fast-acting antidepressants. Previous studies have revealed that the
decrease of bio-energetic metabolism may contribute to the occurrence of depression, while
our team has found adenosine triphosphate (ATP) and phosphocreatine (PCr) to be fast-acting
antidepressants in the depressed-animal model. ATP and PCr have already been widely
prescribed clinically as energy supplements for cells. This will be the first clinical attempt of
the intravenous administration of ATP and PCr combined with orally administered fluoxetine
in MDD. METHODS: This is a single-center, randomized, double-blind, placebo-controlled
pilot study. A total of 42 patients will be divided randomly into three groups. Patients will
receive an intravenous administration of ATP or PCr or saline twice daily combined with
orally administered fluoxetine (20 mg/day) for the first 2 weeks and fluoxetine monotherapy
for the following 4 weeks. Follow-up assessment will be completed at week 10. Feasibility
outcomes will include percentages of patient eligibility, intention to use medication,
willingness to participate, drug adherence, completion of the scheduled assessment, retention,
drop-out, etc. Physical examination results, Side Effect Rating Scale, adverse events, results
from blood tests, electroencephalogram, and electrocardiograph will be recorded for safety
evaluation of the augmentation therapy. The trends of efficacy will be evaluated by the
reduction rate of the Hamilton Depression Rating Scale, the mean change of the Clinical
Global Impression Scale, and the Patients Health Questionaire-9 items. DISCUSSION: In our
study, ATP and PCr will be given by intravenous infusion. Thus patients will be hospitalized
for the initial 2 weeks for safety concern. Hospitalization will be an impact factor for the
recruitment, participation, drop-out, efficacy, results, etc. The evaluation of our feasibility
outcomes, study setting, safety of augmentation therapy and possible efficacy trends among
groups, will facilitate a full-scale trial design and sample size calculation. TRIAL
Chen, Y., et al. (2023). "Integration of genetically engineered virus nanofibers and
fibrin to form injectable fibrous neuron-rich hydrogels and enable neural
differentiation." J Mater Chem B 11(4): 802-815.
Peripheral nerve injury (PNI) results in persistent pain, a burning sensation, tingling, or
complete loss of sensation. Treating large nerve defects is a major challenge, and the use of
autologous nerve grafts (ANGs) cannot overcome this challenge. Hence, substitutes for
ANGs that can serve as artificial nerve fibers are urgently needed in the clinical treatment of
PNI. To develop such substitutes, we genetically engineered a virus nanofiber (M13 phage)
that displays a high density of RGD peptide on its sidewall, producing an RGD-displaying
phage (R-phage). In the presence of neural stem cells (NSCs), the resultant negatively
charged R-phage nanofibers were electrostatically bound to a complex (with a net positive
charge) of negatively charged fibrin and positively charged polyethyleneimine (PEI). The
biocompatible injectable fibrin gel (FG) was integrated with R-phage and seeded with NSCs,
forming a hydrogel termed R-phage/FG, which is further extruded through a syringe to form a
fiber. The developed fiber-shaped hydrogel exhibited the desired excellent physical-chemical
properties, and controllable and appropriate mechanical properties (170-240 kPa) similar to
native nerve. The R-phage/FG not only promoted NSC adhesion, infiltration, and
proliferation, but also induced efficient preferential differentiation of NSCs into neurons in
the hydrogels in a non-differentiating medium within only 4 days. After the NSC-seeded Rphage/FG was injected into the long-gap (10 mm) defect of a rat's sciatic nerve, a solid
neuron-rich hydrogel fiber was formed as an artificial nerve fiber graft that stimulated
neurogenesis in the transplanted area within 60 days for nerve regeneration. These results
suggest that the R-phage/FG fiber represents a potential substitute ANG for repairing large
nerve injuries. This work demonstrates a new phage-based biomaterial that can be used as a
Chen, Y., et al. (2023). "Toward Automated Detection of Silent Cerebral Infarcts in
Children and Young Adults With Sickle Cell Anemia." Stroke 54(8): 2096-2104.
BACKGROUND: Silent cerebral infarcts (SCI) in sickle cell anemia (SCA) are associated
with future strokes and cognitive impairment, warranting early diagnosis and treatment.
Detection of SCI, however, is limited by their small size, especially when neuroradiologists
are unavailable. We hypothesized that deep learning may permit automated SCI detection in
children and young adults with SCA as a tool to identify the presence and extent of SCI in
clinical and research settings. METHODS: We utilized UNet-a deep learning model-for fully
automated SCI segmentation. We trained and optimized UNet using brain magnetic
resonance imaging from the SIT trial (Silent Infarct Transfusion). Neuroradiologists provided
the ground truth for SCI diagnosis, while a vascular neurologist manually delineated SCI on
fluid-attenuated inversion recovery and provided the ground truth for SCI segmentation.
UNet was optimized for the highest spatial overlap between automatic and manual
delineation (dice similarity coefficient). The optimized UNet was externally validated using
an independent single-center prospective cohort of SCA participants. Model performance was
evaluated through sensitivity and accuracy (%correct cases) for SCI diagnosis, dice similarity
coefficient, intraclass correlation coefficient (metric of volumetric agreement), and Spearman
correlation. RESULTS: The SIT trial (n=926; 31% with SCI; median age, 8.9 years) and
external validation (n=80; 50% with SCI; age, 11.5 years) cohorts had small median lesion
volumes of 0.40 and 0.25 mL, respectively. Compared with the neuroradiology diagnosis,
UNet predicted SCI presence with 100% sensitivity and 74% accuracy. In magnetic
resonance imaging with SCI, UNet reached a moderate spatial agreement (dice similarity
coefficient, 0.48) and high volumetric agreement (intraclass correlation coefficient, 0.76; ρ
=0.72; P<0.001) between automatic and manual segmentations. CONCLUSIONS: UNet,
trained using a large pediatric SCA magnetic resonance imaging data set, sensitively detected
small SCI in children and young adults with SCA. While additional training is needed, UNet
Cheng, Y., et al. (2015). "Intravenously delivered neural stem cells migrate into
ischemic brain, differentiate and improve functional recovery after transient ischemic
stroke in adult rats." Int J Clin Exp Pathol 8(3): 2928-2936.
Stem cell transplantation may provide an alternative therapy to promote functional recovery
after various neurological disorders including cerebral infarct. Due to the minimal
immunogenicity and neuronal differentiation potential of neural stem cells (NSCs), we tested
whether intravenous administration of mice-derived C17.2 NSCs could improve neurological
function deficit and cerebral infarction volume after ischemic stroke in rats. Additionally, we
evaluated the survival, migration, proliferation, and differentiation capacity of transplanted
NSCs in the rat brain. Intravenous infusion of NSCs after middle cerebral artery occlusion
(MCAO) showed better performance in neurobiological severity scores after MCAO
compared to control. However, the volume of cerebral infarction was not different at 7 days
after MCAO compared with control. Transplanted NSCs were detected in the ischemic region
but not in the contralateral hemisphere. NSCs differentiated into neurons or astrocytes after
MCAO. These data suggest that intravenously transplanted NSCs can migrate, proliferate,
and differentiate into neurons and astrocytes in the rat brain with focal ischemia and improve
functional recovery.
Chiancone, F., et al. (2016). "Spondylodiscitis: a rare complication following
percutaneous nephrostomy." Urologia: 0.
Spondylodiscitis is an inflammation of the intervertebral disc and the adjacent vertebral
bodies. The spondylodiscitis can not only be a complication of medical interventions such as
an operation near spinal column but also urogenital and vascular interventions and
intravenous catheter use. A 71-year-old man was admitted to our emergency department with
fever and severe abdominal pain. Antibiotic therapy had been performed with intravenous
administration of 2 g of ceftriaxone and the patient underwent the placement of a
percutaneous nephrostomy according to Seldinger technique. After 1 week, the patient
experienced a severe pain at the lumbar tract of the vertebral column associated with a
moderate abdominal pain and septic fever. A magnetic resonance imaging (MRI) of the
lumbar spine showed widespread impregnation of the upper portion of L3 and the lower
portion of L2 compressing the spinal roots as well as the ileopsoas muscle such as a
spondylodiscitis. Liquor culture showed an increase of liquor immunoglobulin G, total liquor
protein and was positive for Extended-spectrum beta-lactamases (ESBL) - producing
Escherichia coli. After the antibiotic therapy, the spondylodiscitis resolves without important
sequelae. In the present case report, we describe a very rare complication of percutaneous
nephrostomy tube placement, despite of the prophylactic antibiotic therapy according to the
most recent guidelines. Predisposing factors to spondylodiscitis include the very young and
elderly, the immunosuppressed, diabetic individuals and a general debilitating disease such as
renal failure. This case suggests the importance of remembering spondylodiscitis when septic
fever and back pain occurs following the placement of a percutaneous nephrostomy in a
Cicero, A. F., A. Colletti and C. Borghi (2015). "Profile of evolocumab and its
potential in the treatment of hyperlipidemia." Drug Des Devel Ther 9: 3073-3082.
Cicero, A. F., E. Tartagni and S. Ertek (2014). "Efficacy and safety profile of
evolocumab (AMG145), an injectable inhibitor of the proprotein convertase
subtilisin/kexin type 9: the available clinical evidence." Expert Opin Biol Ther 14(6):
863-868.
Despite the proven efficacy of statins, they often fail to achieve low-density lipoprotein
(LDL) cholesterol goals, especially in high-risk patients. Moreover, a large number of
subjects cannot tolerate statins or full doses of these drugs, in particular patients with familial
hypercholesterolemia. Thus, there is a need for additional effective LDL cholesterol-reducing
agents. Evolocumab (AMG145) is a monoclonal antibody inhibiting proprotein convertase
subtilisin/kexin type 9 that binds to the liver LDL receptor and prevents it from normal
recycling by targeting it for degradation. Phase I, II, and III trials revealed that, on
subcutaneous injection, either alone or in combination with statins, evolocumab is able to
reduce high LDL cholesterol levels from 54% to 80%, apolipoprotein B100 from 31% to
61%, and lipoprotein(a) from 12% to 36%, in a dose-dependent manner. The incidence of
side effects seems to be low and mainly limited to nasopharyngitis, injection site pain,
arthralgia, and back pain. Evolocumab is an innovative powerful lipid-lowering drug, additive
to statins and/or ezetimibe, with a large therapeutic range associated with a low rate of mild
adverse events. If the available data are confirmed in long-term trials with strong outcome
measures, evolocumab will become an essential tool in the treatment of a large number of
high-risk patients, such as those affected by familial hypercholesterolemia, those who are
unable to tolerate an efficacious statin dosage, and those at very high cardiovascular risk and
unable to achieve their target LDL cholesterol levels with currently available lipid-lowering
Cillo, U., et al. (2015). "Totally Laparoscopic Microwave Ablation and Portal Vein
Ligation for Staged Hepatectomy : A New Minimally Invasive Two-Stage
Hepatectomy." Ann Surg Oncol 22(8): 2787-2788.
INTRODUCTION: Despite the proven efficacy of statins, they are often reported to be
inadequate to achieve low-density lipoprotein cholesterol (LDL-C) goals (especially in highrisk patients). Moreover, a large number of subjects cannot tolerate statins or full doses of
these drugs. Thus, there is a need for additional effective LDL-C reducing agents. AREAS
COVERED: Evolocumab (AMG145) is a monoclonal antibody inhibiting the proprotein
convertase subtilisin/kexin type 9 that binds to the liver LDL receptor and prevents it from
normal recycling by targeting it for degradation. Phase I and II trials revealed that its
subcutaneous injection, either alone or in combination with statins, is able to reduce LDL-C
from 40 to 80%, apolipoprotein B100 from 30 to 59% and lipoprotein(a) from 18 to 36% in a
dose-dependent manner. The incidence of side effects seems to be low and mainly limited to
nasopharyngitis, injection site pain, arthralgia and back pain. EXPERT OPINION:
Evolocumab is an innovative powerful lipid-lowering drug, additive to statins and with an
apparently large therapeutic range associated to a low rate of mild adverse events. If available
data will be confirmed in long-term trials with strong outcomes, Evolocumab will provide an
essential tool to treat high-risk patients who need to reach ambitious LDL-C target.
BACKGROUND: Laparoscopic microwave ablation and portal vein ligation for staged
hepatectomy (LAPS) is a new technique with a first laparoscopic step available in cases of
unresectable right liver masses and inadequate future liver remnant (FLR). METHODS: In
Step 1, laparoscopic right portal vein occlusion is performed with microwave ablation on the
future transection plane and in the FLR. Step 2 consists of a totally laparoscopic right
trisectionectomy. RESULTS: Duration of the Step 1 operation was 170 min, without the need
for blood transfusions and intensive care unit admission. The postoperative liver volumetric
computed tomography scan was performed on postoperative day 9 and revealed a satisfactory
left hepatic hypertrophy (FLR 666 cm(3); FLR to body weight ratio 0.96; FLR increase
90.4 %; daily FLR hypertrophy 35 cm(3)/day). Duration of the Step 2 operation was 630 min
(liver transection time 240 min). Blood loss was 700 cc, with no need for transfusion. The
specimen was extracted through a 10-cm Pfannenstiel incision, and pathology revealed a
tumor-free resection margin (R0). The patient was discharged on postoperative day 7 without
complications (total hospital stay for Step 1 + Step 2: 10 days). CONCLUSIONS: Totally
LAPS is a technically feasible and safe procedure. It could provide benefit in selected
patients with primarily non-resectable liver cancer, making extreme liver surgery easy and
Clements, B. M., et al. (2023). "Biodistribution of Agmatine to Brain and Spinal Cord
after Systemic Delivery." J Pharmacol Exp Ther 387(3): 328-336.
Conde-Estévez, D., et al. (2010). "Successful dexrazoxane treatment of a potentially
severe extravasation of concentrated doxorubicin." Anticancer Drugs 21(8): 790-794.
Agmatine, an endogenous polyamine, has been shown to reduce chronic pain behaviors in
animal models and in patients. This reduction is due to inhibition of the GluN2B subunit of
the N-methyl-D-aspartate receptor (NMDAR) in the central nervous system (CNS). The
mechanism of action requires central activity, but the extent to which agmatine crosses
biologic barriers such as the blood-brain barrier (BBB) and intestinal epithelium is
incompletely understood. Determination of agmatine distribution is limited by analytical
protocols with low sensitivity and/or inefficient preparation. This study validated a novel
bioanalytical protocol using high-performance liquid chromatography tandem mass
spectrometry (HPLC-MS/MS) for quantification of agmatine in rat biologic matrices. These
protocols were then used to determine the plasma pharmacokinetics of agmatine and the
extent of distribution to the CNS. Precision and accuracy of the protocol met US Food and
Drug Administration (FDA) standards in surrogate matrix as well as in corrected
concentrations in appropriate matrices. The protocol also adequately withstood stability and
dilution conditions. Upon application of this protocol to pharmacokinetic study, intravenous
agmatine showed a half-life in plasma ranging between 18.9 and 14.9 minutes. Oral
administration led to a prolonged plasma half-life (74.4-117 minutes), suggesting flip-flop
kinetics, with bioavailability determined to be 29%-35%. Intravenous administration led to a
rapid increase in agmatine concentration in brain but a delayed distribution and lower
concentrations in spinal cord. However, half-life of agmatine in both tissues is substantially
longer than in plasma. These data suggest that agmatine adequately crosses biologic barriers
in rat and that brain and spinal cord pharmacokinetics can be functionally distinct.
SIGNIFICANCE STATEMENT: Agmatine has been shown to be an effective nonopioid
therapy for chronic pain, a significantly unmet medical necessity. Here, using a novel
bioanalytical protocol for quantification of agmatine, we present the plasma
pharmacokinetics and the first report of agmatine oral bioavailability as well as variable
pharmacokinetics across different central nervous system tissues. These data provide a
distributional rationale for the pharmacological effects of agmatine as well as new evidence
Dexrazoxane is now authorized for the treatment of anthracycline extravasations. Several
clinical cases of doxorubicin extravasation treated with dexrazoxane have been reported to
date, but detailed cases have not been published. We report a case of a successful
dexrazoxane treatment for a potentially severe extravasation of concentrated doxorubicin. We
also describe objective outcome of this treatment, drug tolerance to dexrazoxane and long
follow-up. A 29-year-old man diagnosed with Hodgkin's lymphoma was prescribed a regimen
including 90 mg of doxorubicin in a 50 ml infusion using a reduced occlusion infusion pump.
After this infusion, the patient complained of pain around the site of injection and presented a
10x6-cm swollen area with erythema and inflammation. A significant portion of doxorubicin
was extravasated. Dexrazoxane was prescribed as an antidote. Side effects of dexrazoxane
were restricted to reversible hematological toxicity, nausea, and vomiting. The next day, the
inflammation of the extravasation area was reduced. On day 7, a painless mild induration in
the extravasated area was the only remaining sign of the extravasation. On day 40, an arm
nuclear magnetic resonance image showed no focal injuries. At 6-month follow-up, the
patient has no sequelae. The two risk factors that could have increased the severity of the
extravasation are the use of an infusion pump and the high drug concentration. Dexrazoxane
proved to be effective and moderately well tolerated. A dexrazoxane stock in oncological
facilities could help to promptly handle emergencies like this. Anthracyclines can be
administered using reduced occlusion infusion pumps, but it seems preferable to always
Conversy, B., et al. (2013). "Comparison of gravity collection versus suction
collection for transfusion purposes in dogs." J Am Anim Hosp Assoc 49(5): 301-307.
Blood donation is an essential step in transfusion medicine that must take into account the
donor's welfare, collection effectiveness, and blood product quality. This prospective study
enrolled 13 canine blood donors, each subjected to both gravity and suction collection
methods, in a randomized order. Clinical parameters, including heart rate (HR), respiratory
rate (RR), systolic blood pressure (SBP), and rectal temperature (RT), were evaluated at four
time points, including when the donor was on the floor and on the collection table, and before
and after blood donation. The number of times the donor and needle required repositioning,
the duration of the donation, the noise created by the apparatus, and the presence of a
hematoma were evaluated. The weight, index of hemolysis, and hematocrit of each unit of
blood were recorded. There was no significant difference between collection methods for
either the clinical parameters at each time point or the prevalence of hematoma formation, the
frequency of needle repositioning, the hemolysis index, or hematocrit. Collection by suction
was noisier (P < 0.0001), faster (P = 0.004), and associated with significantly less donor
repositioning (P = 0.007). Suction appears to be a safe and cost-effective method that should
be considered to optimize blood donation.
Cooley-Lock, K. M., et al. (2019). "Assessment of erythrocyte damage and in-line
pressure changes associated with simulated transfusion of canine blood through
microaggregate filters." Am J Vet Res 80(9): 852-861.
Corcoran, P. C., et al. (2010). "Surgical and nonsurgical complications of a pig to
baboon heterotopic heart transplantation model." Transplant Proc 42(6): 2149-2151.
OBJECTIVE: To determine whether passage of whole blood through a microaggregate filter
by use of a syringe pump would damage canine erythrocytes. SAMPLE: Blood samples
obtained from 8 healthy client-owned dogs. PROCEDURES: Whole blood was passed
through a standard microaggregate filter by use of a syringe pump at 3 standard
administration rates (12.5, 25, and 50 mL/h). Prefilter and postfilter blood samples were
collected at the beginning and end of a simulated transfusion. Variables measured at each
time point included erythrocyte osmotic fragility, mean corpuscular fragility, RBC count,
hemoglobin concentration, RBC distribution width, and RBC morphology. In-line pressure
when blood passed through the microaggregate filter was measured continuously throughout
the simulated transfusion. After the simulated transfusion was completed, filters were
visually analyzed by use of scanning electron microscopy. RESULTS: Regardless of
administration rate, there was no significant difference in mean corpuscular fragility, RBC
count, hemoglobin concentration, or RBC distribution width between prefilter and postfilter
samples. Additionally, there were no differences in in-line pressure during the simulated
transfusion among administration rates. Echinocytes were the erythrocyte morphological
abnormality most commonly observed at the end of the transfusion at administration rates of
12.5 and 25 mL/h. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that
regardless of the administration rate, the microaggregate filter did not alter fragility of canine
RBCs, but may have altered the morphology. It appeared that the microaggregate filter would
A modified immunosuppressive regimen, developed at the National Institutes of Health, has
been employed in a large animal model of heterotopic cardiac xenotransplantation. Graft
survival has been prolonged, but despite this, our recipients have succumbed to various
surgical or nonsurgical complications. Herein, we have described different complications and
management strategies. The most common complication was hypercoagulability (HC) after
transplantation, causing thrombosis of both small and large vasculature, ultimately leading to
graft loss. While managing this complication we discovered that there was a delicate balance
between HC and consumptive coagulopathy (CC). CC encountered in some recipient baboons
was not able to be reversed by stopping anticoagulation and administering multiple blood
transfusions. Some complications had iatrogenic components. To monitor the animals, a solid
state left ventricular telemetry probe was placed directly into the transplanted heart via the
apex. Induction of hypocoagulable states by continuous heparin infusion led to uncontrollable
intra-abdominal bleeding in 1 baboon from this apical site. This occurrence necessitated
securing the probe more tightly with multiple purse strings and 4-quadrant pledgeted stay
sutures. One instance of cardiac rupture originated from a lateral wall infarction site. Earlier
studies have shown infections to be uniformly fatal in this transplant model. However, owing
to the telemetry placement, infections were identified early by temperature spikes that were
treated promptly with antibiotics. We had several cases of wound dehiscence due to
recipients disrupting the suture line. These complications were promptly resolved by either
re-approximating the wound or finding distractions for the baboon. A few of the most
common problems we faced in our earlier experiments were related to the jacket, tether, and
infusion pumps. It was difficult to keep the jackets on some baboons and the tether had to be
modified several times before we assured long-term success. Infusion catheter replacement
resulted in transplant heart venous obstruction and thrombosis from a right common femoral
venous line. Homeostatic perturbations such as HC and CC and baboon-induced wound
complications comprised most complications. Major bleeding and death due to telemetry
implantation and infarct rupture occurred in 2 baboons. Despite the variety of complications,
Csete, J., et al. (2016). "Public health and international drug policy." Lancet
387(10026): 1427-1480.
In September 2015, the member states of the United Nations endorsed sustainable
development goals (SDG) for 2030 that aspire to human rights-centered approaches to
ensuring the health and well-being of all people. The SDGs embody both the UN Charter
values of rights and justice for all and the responsibility of states to rely on the best scientific
evidence as they seek to better humankind. In April 2016, these same states will consider
control of illicit drugs, an area of social policy that has been fraught with controversy, seen as
inconsistent with human rights norms, and for which scientific evidence and public health
approaches have arguably played too limited a role. The previous UN General Assembly
Special Session (UNGASS) on drugs in 1998 – convened under the theme “a drug-free world,
we can do it!” – endorsed drug control policies based on the goal of prohibiting all use,
possession, production, and trafficking of illicit drugs. This goal is enshrined in national law
in many countries. In pronouncing drugs a “grave threat to the health and well-being of all
mankind,” the 1998 UNGASS echoed the foundational 1961 convention of the international
drug control regime, which justified eliminating the “evil” of drugs in the name of “the health
and welfare of mankind.” But neither of these international agreements refers to the ways in
which pursuing drug prohibition itself might affect public health. The “war on drugs” and
“zero-tolerance” policies that grew out of the prohibitionist consensus are now being
challenged on multiple fronts, including their health, human rights, and development impact.
The Johns Hopkins – Lancet Commission on Drug Policy and Health has sought to examine
the emerging scientific evidence on public health issues arising from drug control policy and
to inform and encourage a central focus on public health evidence and outcomes in drug
policy debates, such as the important deliberations of the 2016 UNGASS on drugs. The Johns
Hopkins-Lancet Commission is concerned that drug policies are often colored by ideas about
drug use and drug dependence that are not scientifically grounded. The 1998 UNGASS
declaration, for example, like the UN drug conventions and many national drug laws, does
not distinguish between drug use and drug abuse. A 2015 report by the UN High
Commissioner for Human Rights, by contrast, found it important to emphasize that “[d]rug
use is neither a medical condition nor does it necessarily lead to drug dependence.” The idea
Dahdal, S., et al. (2013). "A rare case of a large spinal meningioma with mediastinal
extension and malignant behavior classified histologically as benign." Recent Results
Cancer Res 194: 443-455.
AIM: To report a rare case of a spinal WHO grade I meningioma extending through
intervertebral foramina C7 to D4 with an extensive mediastinal mass and infiltration of the
vertebrae, and to discuss the malignant behavior of a tumor classified as benign. METHODS:
(Clinical Presentation, Histology, and Imaging): A 54-year-old man suffered from increasing
lower back pain with gait difficulties, weakness and numbness of the lower extremities, as
well as urge incontinence. CT scan of the thorax and MRI scan of the spine revealed a large
prevertebral tumor, which extended to the spinal canal and caused compression of the spinal
cord at the levels of C7 to D4 leading to myelopathy with hyperintense signal alteration on
T2-weighted MRI images. The signal constellation (T1 with and without contrast, T2, TIR)
was highly suspicious for infiltration of vertebrae C7 to D5. Somatostatin receptor
SPECT/CT with (111)In-DTPA-D: -Phe-1-octreotide detected a somatostatin receptorpositive mediastinal tumor with infiltration of multiple vertebrae, dura, and intervertebral
foramina C7-D4, partially with Krenning score >2. Percutaneous biopsies of the mediastinal
mass led to histopathological findings of WHO grade I meningioma of meningothelial
subtype. RESULTS: (Therapy): C7 to D4 laminoplasty was performed, and the intraspinal,
extradural part of the tumor was microsurgically removed. Postoperative stereotactic
radiation therapy was done using the volumetric modulated arc therapy (VMAT) technique
(RapidArc). No PRRNT with (90)Y-DOTA-TOC was done. CONCLUSIONS: Due to the
rare incidence and complex presentation of this disease not amenable to complete surgical
resection, an individualized treatment approach should be worked out interdisciplinarily. The
treatment approach should be based not only on histology but also on clinical and imaging
Dai, M. G., et al. (2022). "Acute pancreatitis as a rare complication of gastrointestinal
endoscopy: A case report." World J Clin Cases 10(13): 4185-4189.
BACKGROUND: Acute pancreatitis is an uncommon complication of gastrointestinal
endoscopy, especially if the patient has none of the common risk factors associated with
pancreatitis; such as alcoholism, gallstones, hypertriglyceridemia, hypercalcemia or the use of
certain drugs. CASE SUMMARY: A 56-year-old female patient developed abdominal pain
immediately after the completion of an upper gastrointestinal endoscopy. The pain was
predominantly in the upper and middle abdomen and was persistent and severe. The patient
was diagnosed with acute pancreatitis. Treatment included complete fasting, octreotide
injection prepared in a prefilled syringe to inhibit pancreatic enzymes secretion, ulinastatin
injection to inhibit pancreatic enzymes activity, esomeprazole for gastric acid suppression,
fluid replacement and nutritional support. Over the next 3 d, the patient's symptoms
improved. The patient remained hemodynamically stable throughout hospitalization and was
discharged home in a clinically stable state. CONCLUSION: Pancreatitis should be
considered in the differential diagnosis of abdominal pain after upper and lower
gastrointestinal endoscopy.
de Andrade, A. R. B., et al. (2021). "Levobupivacaine-Loaded Liposome Associated
with Thermogel for Prolonged Analgesia." AAPS PharmSciTech 22(3): 104.
Pain is a phenomenon present in the majority of the population, affecting, among others, the
elderly, overweight people, and especially recently operated patients, analgesia being
necessary. In the specific case of relief of postoperative pain, different kinds of anesthetics
are being used, among them bupivacaine, a widely used drug which promotes long-lasting
analgesic effects. However, cardiotoxicity and neurotoxicity are related to its repetitive use.
To overcome these shortcomings, Novabupi® (a racemic mixture) was developed and is
marketed as an injectable solution. This formulation contains an enantiomeric excess of the
levogyre isomer, which has reduced toxicity effects. Seeking to rationalize its use by
extending the duration of effect and reducing the number of applications, the objectives of
this work were to develop and evaluate liposomes containing Novabupi (LBPV), followed by
incorporation into thermogel. Liposomes were prepared using the lipid hydration method,
followed by size reduction using sonication, and the developed formulations were
characterized by hydrodynamic diameter, polydispersity index (PDI), surface zeta potential,
and encapsulation efficiency. The selected optimal liposomal formulation was successfully
incorporated into a thermogel without loss of thermoresponsive properties, being suitable for
administration as a subcutaneous injection. In the ex vivo permeation studies with fresh
rodent skin, the thermogel with liposomes loaded with 0.5% LBPV (T-gel formulation 3)
showed higher permeation rates compared to the starting formulation, thermogel with 0.5%
LBPV (T-Gel 1), which will probably translate into better therapeutic benefits for treatment
Del Vecchio Blanco, G., et al. (2020). "Contrast-enhanced endoscopic ultrasound
diagnosis of the intraductal papillary mucinous neoplasm." Clin J Gastroenterol 13(1):
120-126.
Delavan, J. A., et al. (2016). "Confidence in Assessment of Lumbar Spondylolysis
Using Three-Dimensional Volumetric T2-Weighted MRI Compared With Limited
Field of View, Decreased-Dose CT." Sports Health 8(4): 364-371.
Pancreatic cystic neoplasms (PCNs) are a frequent incidental finding during an ultrasound or
other radiological investigations. As PCNs may have a potential of malignancy, a precise
differential diagnosis between a malignant and benign lesion is crucial to define appropriate
management of patients with this kind of lesions. Radiology, with computed tomography
(CT) and magnetic resonance imaging, may not be conclusive in the diagnostic assessment of
PCNs. Endoscopic ultrasound (EUS), a simple and relatively low invasive technique, is able
to identify intra-cystic worrisome features suggesting malignancy. Fine-needle aspiration
(FNA) of the cystic fluid or of intra-cystic tissue nodule during EUS is an adjunctive
procedure for reaching a conclusive diagnosis. As EUS-FNA is burdened by complications,
the use of intravenous contrast may increase the diagnostic accuracy of EUS allowing in
many cases a correct diagnosis of PCN at high risk of malignancy, without additional risk of
complication during the procedure. The present report deals with the case of a cystic lesion
found by CT scan in the pancreatic head of a 59-year-old woman suffering from mild
epigastric pain. Once submitted to EUS, malignant nature of PCN was suspected due to the
finding of a typical worrisome feature, the presence of a mural nodule. The intravenous
administration of contrast medium during the EUS confirmed malignancy and the patient was
immediately sent to the surgeon for pancreatic resection. Histology revealed an intraductal
papillary mucinous neoplasm, with areas of high-grade dysplasia in the main and secondary
BACKGROUND: Limited z-axis-coverage computed tomography (CT) to evaluate for
pediatric lumbar spondylolysis, altering the technique such that the dose to the patient is
comparable or lower than radiographs, is currently used at our institution. The objective of
the study was to determine whether volumetric 3-dimensional fast spin echo magnetic
resonance imaging (3D MRI) can provide equal or greater diagnostic accuracy compared with
limited CT in the diagnosis of pediatric lumbar spondylolysis without ionizing radiation.
HYPOTHESIS: Volumetric 3D MRI can provide equal or greater diagnostic accuracy
compared with low-dose CT for pediatric lumbar spondylolysis without ionizing radiation.
STUDY DESIGN: Clinical review. LEVEL OF EVIDENCE: Level 2. METHODS: Three
pediatric neuroradiologists evaluated 2-dimensional (2D) MRI, 2D + 3D MRI, and limited
CT examinations in 42 pediatric patients who obtained imaging for low back pain and
suspected spondylolysis. As there is no gold standard for the diagnosis of spondylolysis
besides surgery, interobserver agreement and degree of confidence were compared to
determine which modality is preferable. RESULTS: Decreased-dose CT provided a greater
level of agreement than 2D MRI and 2D + 3D MRI. The kappa for rater agreement with 2D
MRI, 2D + 3D MRI, and CT was 0.19, 0.32, and 1.0, respectively. All raters agreed in 31%,
40%, and 100% of cases with 2D MRI, 2D + 3D MRI, and CT. Lack of confidence was
significantly lower with CT (0%) than with 2D MRI (30%) and 2D + 3D MRI (25%).
CONCLUSION: For diagnosing spondylolysis, radiologist agreement and confidence trended
toward improvement with the addition of a volumetric 3D MRI sequence to standard 2D MRI
sequences compared with 2D MRI alone; however, agreement and confidence remain
significantly greater using decreased-dose CT when compared with either MRI acquisition.
CLINICAL RELEVANCE: Decreased-dose CT of the lumbar spine remains the optimal
examination to confirm a high suspicion of spondylolysis, with dose essentially equivalent to
radiographs. If clinical symptoms are not classic for spondylolysis, 2D MRI is still very good
at detecting spondylolysis while remaining sensitive for detection of alternative diagnoses
such as disc abnormalities and pars stress reaction. The data suggest that standard 2D MRI
sequences should not be entirely replaced by a volumetric T2-weighted 3D sequence (despite
Demircan, C., N. Akdogan and L. Elmas (2023). "Nicolau Syndrome Secondary to
Subcutaneous Glatiramer Acetate Injection." Int J Low Extrem Wounds 22(1): 149151.
Nicolau syndrome, also known as embolia cutis medicamentosa, is a rare complication of
injectable drugs. Patients present with pain at injection site, followed by swelling, erythema,
purple, hemorrhagic patches and lastly ulcer formation. A variety of intramuscular agents
have been implicated as responsible. We report a case of a 26-year-old woman with a history
of a purple lesion on her thigh who was diagnosed with Nicolau syndrome due to
subcutaneous administration of glatiramer acetate. The patient was followed up with topical
mupirocin. On follow-up, although the patient stated that she continued using glatiramer
acetate, no new lesions appeared and the existing lesion continued to shrink. Nicolau
syndrome seems to have an unpredictable and unavoidable course. This case suggests that
physicians should have a high index of suspicion for the presence of Nicolau syndrome in
patients presenting with necrotic or ulcerative lesions with a history of using injectable drugs.
Deng, S., et al. (2023). "Analgesic Effect of Intraoperative Intravenous S(+)-Ketamine
During Total Knee Arthroplasty Surgery: Study Protocol for a Randomized
Controlled Clinical Trial." JMIR Res Protoc 12: e53063.
BACKGROUND: Total knee arthroplasty (TKA) is currently the main treatment for endstage knee disease. The number of cases of TKA in China increased from 53,880 in 2011 to
374,833 in 2019, representing a 5.9-fold increase. Moderate to severe pain often occurs after
TKA, which seriously affects postoperative rehabilitation, patient satisfaction, and overall
outcome. Multimodal analgesia is considered the ideal solution. Adequate postoperative
analgesia can not only reduce pain, opioid consumption, and, consequently, opioid-related
adverse events, but can also reduce the length of hospital stay and costs and improve
rehabilitation and patient satisfaction. OBJECTIVE: Effective multimodal pain management
in the early postoperative period is essential for anesthesiologists. Additional studies have
demonstrated that a low-dose intravenous infusion of ketamine can be administered as an
adjuvant drug to alleviate acute postoperative pain. Therefore, we aim to appraise the efficacy
and safety of intraoperative intravenous injection of S(+)-ketamine to relieve acute pain after
TKA in older patients. METHODS: This is a protocol for a randomized, placebo-controlled
trial. A total of 144 participants aged 65 years and older undergoing TKA will be randomly
allocated into the S(+)-ketamine and placebo groups in a 1:1 ratio. S(+)-ketamine or the
placebo will be intravenously administered at 0.3 mg/kg/h during the operation by
anesthesiologists. Blinded evaluation by trained investigators will be completed at 2 hours, 24
hours, and 48 hours after surgery. The primary outcome measure will be the numeric rating
scale score at rest and movement at 24 hours after surgery. The secondary outcomes will
include the numeric rating scale scores at rest and movement at 2 hours and 48 hours after
surgery, the number of patients who require additional analgesics during the first 48 hours
after operation, the total consumption of opioids or nonsteroid anti-inflammatory drugs
during the first 48 hours after operation, and adverse events at 2, 24, and 48 hours after
operation. RESULTS: The protocol was registered at Clinical Trials.gov on February 26,
2022. It was performed in accordance with the approved guidelines and regulations of the
participating institutions. Recruitment began in April 2022. Data collection is expected to
conclude in September 2024. Study completion is expected in December 2024.
CONCLUSIONS: A randomized, controlled, clinical study was designed to observe the
Dimopoulos, M. A., et al. (2016). "Carfilzomib and dexamethasone versus bortezomib
and dexamethasone for patients with relapsed or refractory multiple myeloma
(ENDEAVOR): a randomised, phase 3, open-label, multicentre study." Lancet Oncol
17(1): 27-38.
BACKGROUND: Bortezomib with dexamethasone is a standard treatment option for
relapsed or refractory multiple myeloma. Carfilzomib with dexamethasone has shown
promising activity in patients in this disease setting. The aim of this study was to compare the
combination of carfilzomib and dexamethasone with bortezomib and dexamethasone in
patients with relapsed or refractory multiple myeloma. METHODS: In this randomised, phase
3, open-label, multicentre study, patients with relapsed or refractory multiple myeloma who
had one to three previous treatments were randomly assigned (1:1) using a blocked
randomisation scheme (block size of four) to receive carfilzomib with dexamethasone
(carfilzomib group) or bortezomib with dexamethasone (bortezomib group). Randomisation
was stratified by previous proteasome inhibitor therapy, previous lines of treatment,
International Staging System stage, and planned route of bortezomib administration if
randomly assigned to bortezomib with dexamethasone. Patients received treatment until
progression with carfilzomib (20 mg/m(2) on days 1 and 2 of cycle 1; 56 mg/m(2) thereafter;
30 min intravenous infusion) and dexamethasone (20 mg oral or intravenous infusion) or
bortezomib (1·3 mg/m(2); intravenous bolus or subcutaneous injection) and dexamethasone
(20 mg oral or intravenous infusion). The primary endpoint was progression-free survival in
the intention-to-treat population. All participants who received at least one dose of study drug
were included in the safety analyses. The study is ongoing but not enrolling participants;
results for the interim analysis of the primary endpoint are presented. The trial is registered at
ClinicalTrials.gov, number NCT01568866. FINDINGS: Between June 20, 2012, and June 30,
2014, 929 patients were randomly assigned (464 to the carfilzomib group; 465 to the
bortezomib group). Median follow-up was 11·9 months (IQR 9·3-16·1) in the carfilzomib
group and 11·1 months (8·2-14·3) in the bortezomib group. Median progression-free survival
was 18·7 months (95% CI 15·6-not estimable) in the carfilzomib group versus 9·4 months
(8·4-10·4) in the bortezomib group at a preplanned interim analysis (hazard ratio [HR] 0·53
[95% CI 0·44-0·65]; p<0·0001). On-study death due to adverse events occurred in 18 (4%) of
464 patients in the carfilzomib group and in 16 (3%) of 465 patients in the bortezomib group.
Serious adverse events were reported in 224 (48%) of 463 patients in the carfilzomib group
Dreischalück, J., et al. (2010). "Vascular infarction by subcutaneous application of
tissue factor targeted to tumor vessels with NGR-peptides: activity and toxicity
profile." Int J Oncol 37(6): 1389-1397.
tTF-NGR consists of the extracellular domain of the (truncated) tissue factor (tTF), a central
molecule for coagulation in vivo, and the peptide GNGRAHA (NGR), a ligand of the surface
protein aminopeptidase N (CD13). After deamidation of the NGR-peptide moiety, the fusion
protein is also a ligand for integrin αvβ3 (CD51/CD61). Both surface proteins are upregulated
on endothelial cells of tumor vessels. tTF-NGR showed binding to specific binding sites on
endothelial cells in vitro as shown by flow cytometry. Subcutaneous injection of tTF-NGR
into athymic mice bearing human HT1080 fibrosarcoma tumors induced tumor growth
retardation and delay. Contrast enhanced ultrasound detected a decrease in tumor blood flow
in vivo after application of tTF-NGR. Histological analysis of the tumors revealed vascular
disruption due to blood pooling and thrombotic occlusion of tumor vessels. Furthermore, a
lack of resistance was shown by re-exposure of tumor-bearing mice to tTF-NGR after
regrowth following a first cycle of treatment. However, after subcutaneous (s.c.) push
injection with therapeutic doses (1-5 mg/kg bw) side effects have been observed, such as skin
bleeding and reduced performance. Since lethality started within the therapeutic dose range
(LD10 approximately 2 mg/kg bw) no safe therapeutic window could be found. Limiting
toxicity was represented by thrombo-embolic events in major organ systems as demonstrated
by histology. Thus, subcutaneous injection of tTF-NGR represents an active, but toxic
Dychter, S. S., et al. (2014). "Tolerability and pharmacokinetic properties of
ondansetron administered subcutaneously with recombinant human hyaluronidase in
minipigs and healthy volunteers." Clin Ther 36(2): 211-224.
BACKGROUND: Subcutaneous ondansetron facilitated by recombinant human
hyaluronidase PH20 (rHuPH20) is an alternative for treating nausea/vomiting in patients who
cannot receive ondansetron by other routes of administration. OBJECTIVE: Based on
preclinical results in minipigs, a Phase I study was designed to assess the tolerability and
pharmacokinetic properties of subcutaneous ondansetron + rHuPH20 compared with
intramuscular, intravenous, or oral ondansetron monotherapy in healthy volunteers.
METHODS: In a crossover design, 3 minipigs were dosed with subcutaneous ondansetron
0.08 mg/kg + rHuPH20, or as intramuscular or intravenous monotherapy, for the evaluation
of plasma ondansetron concentrations and local tolerability. In a randomized, open-label, 4way crossover study, subjects received a randomized sequence of SC ondansetron 4 mg +
rHuPH20, or ondansetron monotherapy IM (4 mg), IV (4 mg), or PO (8 mg), over 4 daily
visits. Study participants included healthy volunteers aged 19 to 65 years with adequate
venous access in both upper extremities and no history of QT-interval prolongation. Primary
tolerability end points (administration-site observations, systemic adverse events [AEs], and
subject-assessed pain) were assessed, and pharmacokinetic parameters (AUC, Cmax, Tmax,
t½) were computed to compare relative rate and extent of systemic exposure. Results were
described using summary statistics, and bioequivalence was determined with a linear mixedeffects model. RESULTS: In the preclinical study, no adverse events or significant local
reactions were observed. The Cmax (45.8 ng/mL at 0.08 hour) with subcutaneous
administration + rHuPH20 was 83% greater and was achieved 68% faster than with
intramuscular administration (Cmax = 25 ng/mL at 0.25 hour). In the clinical study, a total of
12 subjects (7 women, 5 men; white majority; mean age, 44.8) were randomized. The
majority of AEs were at the injection site, mild in severity, and transient. After subcutaneous
administration of ondansetron + rHuPH20, geometric mean Cmax was 35% higher than with
intramuscular ondansetron, 43% lower than with intravenous ondansetron, and 126% higher
than with oral ondansetron (corrected for dose). Bioequivalence tests demonstrated that
systemic exposure after subcutaneous administration was similar to that after intramuscular
or intravenous administration and significantly greater than that after oral administration.
El-Ekiaby, M., et al. (2015). "Minipool caprylic acid fractionation of plasma using
disposable equipment: a practical method to enhance immunoglobulin supply in
developing countries." PLoS Negl Trop Dis 9(2): e0003501.
BACKGROUND: Immunoglobulin G (IgG) is an essential plasma-derived medicine that is
lacking in developing countries. IgG shortages leave immunodeficient patients without
treatment, exposing them to devastating recurrent infections from local pathogens. A simple
and practical method for producing IgG from normal or convalescent plasma collected in
developing countries is needed to provide better, faster access to IgG for patients in need.
METHODOLOGY/PRINCIPAL FINDINGS: IgG was purified from 10 consecutive
minipools of 20 plasma donations collected in Egypt using single-use equipment. Plasma
donations in their collection bags were subjected to 5%-pH5.5 caprylic acid treatment for 90
min at 31°C, and centrifuged to remove the precipitate. Supernatants were pooled, then
dialyzed and concentrated using a commercial disposable hemodialyzer. The final preparation
was filtered online by gravity, aseptically dispensed into storage transfusion bags, and frozen
at <-20°C. The resulting preparation had a mean protein content of 60.5 g/L, 90.2%
immunoglobulins, including 83.2% IgG, 12.4% IgA, and 4.4% IgM, and residual albumin.
There was fourfold to sixfold enrichment of anti-hepatitis B and anti-rubella antibodies.
Analyses of aggregates (<3%), prekallicrein (5-7 IU/mL), plasmin (26.3 mU/mL), thrombin
(2.5 mU/mL), thrombin-like activity (0.011 U/g), thrombin generation capacity (< 223 nM),
and Factor XI (<0.01 U/mL) activity, Factor XI/XIa antigen (2.4 ng/g) endotoxin (<0.5
EU/mL), and general safety test in rats showed the in vitro safety profile. Viral validation
revealed >5 logs reduction of HIV, BVDV, and PRV infectivity in less than 15 min of
caprylic acid treatment. CONCLUSIONS/SIGNIFICANCE: 90% pure, virally-inactivated
immunoglobulins can be prepared from plasma minipools using simple disposable equipment
and bag systems. This easy-to-implement process could be used to produce immunoglobulins
from local plasma in developing countries to treat immunodeficient patients. It is also
relevant for preparing hyperimmune IgG from convalescent plasma during infectious
Ensikat, H. J., et al. (2021). "Distribution, Ecology, Chemistry and Toxicology of
Plant Stinging Hairs." Toxins (Basel) 13(2).
Plant stinging hairs have fascinated humans for time immemorial. True stinging hairs are
highly specialized plant structures that are able to inject a physiologically active liquid into
the skin and can be differentiated from irritant hairs (causing mechanical damage only).
Stinging hairs can be classified into two basic types: Urtica-type stinging hairs with the
classical "hypodermic syringe" mechanism expelling only liquid, and Tragia-type stinging
hairs expelling a liquid together with a sharp crystal. In total, there are some 650 plant species
with stinging hairs across five remotely related plant families (i.e., belonging to different
plant orders). The family Urticaceae (order Rosales) includes a total of ca. 150 stinging
representatives, amongst them the well-known stinging nettles (genus Urtica). There are also
some 200 stinging species in Loasaceae (order Cornales), ca. 250 stinging species in
Euphorbiaceae (order Malphigiales), a handful of species in Namaceae (order Boraginales),
and one in Caricaceae (order Brassicales). Stinging hairs are commonly found on most aerial
parts of the plants, especially the stem and leaves, but sometimes also on flowers and fruits.
The ecological role of stinging hairs in plants seems to be essentially defense against
mammalian herbivores, while they appear to be essentially inefficient against invertebrate
pests. Stinging plants are therefore frequent pasture weeds across different taxa and
geographical zones. Stinging hairs are usually combined with additional chemical and/or
mechanical defenses in plants and are not a standalone mechanism. The physiological effects
of stinging hairs on humans vary widely between stinging plants and range from a slight itch,
skin rash (urticaria), and oedema to sharp pain and even serious neurological disorders such
as neuropathy. Numerous studies have attempted to elucidate the chemical basis of the
physiological effects. Since the middle of the 20th century, neurotransmitters (acetylcholine,
histamine, serotonin) have been repeatedly detected in stinging hairs of Urticaceae, but recent
analyses of Loasaceae stinging hair fluids revealed high variability in their composition and
content of neurotransmitters. These substances can explain some of the physiological effects
of stinging hairs, but fail to completely explain neuropathic effects, pointing to some yet
unidentified neurotoxin. Inorganic ions (e.g., potassium) are detected in stinging hairs and
could have synergistic effects. Very recently, ultrastable miniproteins dubbed "gympietides"
Eom, K. S. and T. Y. Kim (2012). "Percutaneous vertebroplasty-induced adjacent
vertebral compression fracture." Pain Physician 15(4): E527-532.
BACKGROUND: The risks associated with percutaneous vertebroplasty (PV) are low.
Patients show marked improvement and are able to rapidly resume normal activities after PV.
The sudden development of postoperative vertebral compression fracture (VCF) is a common
complication, and additional PV is frequently performed in these cases. However, there have
been no studies reporting acute compression fractures of an adjacent vertebra immediately
after PV. OBJECTIVE: This case report presents a rare case in which the patient had to
undergo a second PV because of PV-induced adjacent VCF. Further, we review previous
studies and discuss the possible pathogenesis of this rare complication. STUDY DESIGN:
Case report. SETTING: Pain management clinic. METHODS: A 62-year-old woman
presented with a severe pain in the lower back, which started after she slipped. A radiograph
showed severe vertebral collapse with a vertebral vacuum cleft in the T12 vertebral body. T1weighted magnetic resonance imaging showed low signal intensity in T12, suggesting acute
VCF, but the signals from the other vertebrae were normal. RESULTS: The patient
underwent PV at T12. When the cannula was inserted into the fracture line of the vertebral
body, reduction of the collapsed T12 was developed. Although the postoperative course was
uneventful, the patient's pain did not resolve. Postoperative radiographic image obtained 4
hours after the PV showed reduction of T12 and adjacent acute VCF in T11. We performed a
second PV at T11. However, 2 weeks later, adjacent acute VCF in L1 was developed and PV
was performed. LIMITATIONS: This report describes a single case. CONCLUSION: To the
best of our knowledge, this is the first case report of adjacent VCF that developed almost
immediately after PV. Although the exact mechanism underlying this rare complication
remains unclear, we assume that the VCF was induced by PV, although this was not proven.
However, we suggest that the insertion of the cannula into the fracture line induced the
iatrogenic dynamic mobility of the fractured vertebra. Reduction was caused by the cannula
and positional gravity. The upward reduction may have had an effect on the upper and
Epperson, L. C., S. T. Weiss and D. J. Cao (2021). "A Case Report of a Severe,
Unusually Delayed Anaphylactoid Reaction to Intravenous N-Acetylcysteine During
Treatment of Acute Acetaminophen Toxicity in an Adolescent." J Med Toxicol 17(1):
75-79.
INTRODUCTION: Anaphylactoid reactions are well-documented adverse events associated
with the intravenous administration of N-acetylcysteine (NAC) in patients with
acetaminophen overdose. Most reactions are mild, occurring within the first 1-5 hours of
initiation. This report presents the case of an adolescent with a delayed, life-threatening
anaphylactoid reaction 24.5 hours after starting NAC, where discontinuing NAC could have
resulted in fulminant hepatic failure (FHF) and death. CASE REPORT: A 17-year-old
previously healthy female presented with nausea, vomiting, and abdominal pain 10 hours
after an acute acetaminophen ingestion. Her 11-hour serum acetaminophen concentration was
above the treatment line (149 μg/mL), and she had elevated transaminases (AST = 202 U/L,
ALT = 284 U/L). She was treated with intravenous NAC, which was suspended for 3 hours
after she developed an apparent life-threatening anaphylactoid reaction with angioedema and
respiratory distress 24.5 hours after treatment initiation. Given her high risk of progression to
FHF, NAC was resumed at double the previous rate along with scheduled corticosteroids and
antihistamines after resolution of her symptoms. Her AST increased to 10,927 U/L, and INR
peaked at 3.6, but she had no further anaphylactoid symptoms. She was discharged in her
normal state of health after 6 days. DISCUSSION: Discontinuing NAC in this case of severe,
delayed anaphylactoid reaction could have resulted in FHF requiring liver transplant. The
reason for her reaction is unclear but could be related to patient risk factors or medication
error. Guidelines for reinitiation of NAC after development of delayed anaphylactoid
reactions are not well-established. Close observation beyond the first 1-5 hours of NAC
Familiar Casado, C., et al. (2020). "Single-session treatment of benign thyroid nodules
with radiofrequency ablation: Results at 6 months in 24 patients." Endocrinol
Diabetes Nutr (Engl Ed) 67(3): 164-171.
OBJECTIVE: To evaluate the efficacy and safety of one single-session of radiofrequency
ablation (RFA) performed in thyroid benign and predominantly solid nodules. PATIENTS
AND METHOD: Unicentric retrospective study in usual clinical setting that included patients
with solid and benign thyroid nodules treated with one single session of RFA and with
folllow-up of at at least 6 months after the procedure. RFA was performed as an alternative to
surgery in cases of pressure symptoms or nodular growth evidence. Patients were evaluated
basally and at one, 3 and 6 months after RFA and also at 12 months if the follow-up was
available. In each evaluation efficacy variables were recorded (percentual change from basal
volume, percentage of nodules reaching a volume reduction above 50% from baseline,
patients with disappearance of pressure symptoms and the possibility of antithyroid drug
withdrawal) and safety variables were also registered including minor complications (pain
needing analgesic drugs, hematoma) and major complications (voice changes, braquial plexus
injury, nodule rupture and thyroid dysfunction). RESULTS: Twenty-four patients with a
follow-up of at least 6 months after RFA were included, 16 of them with more than 12
months of follow-up. Mean nodule volume changed from 25.4±15.5ml basally to 10.7±9.9ml
at month 6 (P<.05) and to 9.9±10,4ml at month 12 in 16 nodules. Six months after RFA mean
volumetric reduction was 57.5±24% and 65% of the nodules reached a volume reduction
above 50% from baseline. Median percentage of reduction at month 6 was 50.4±25.8% for
nodules with a basal volume above 20ml (n=13) and 65.3±20.1% for nodules with a lower
basal volume (n=11). Pressure symptoms reported in 12 patients disappeared in all cases.
Antithyroid drugs could be stopped in 3 of 4 cases treated before RFA. A mild and transient
pain responsive to conventional analgesic drugs was recorded in 9 patients during the 24h
after the procedure and in 7 a small perithyroid and transient hematoma was observed in the
48 following hours. One major complication was described as a nodule rupture that recovered
spontaneously. There were no changes in hormonal values in euthyroid cases.
CONCLUSION: A single session of RFA seems to be an effective and safe procedure in
patients with solid thyroid nodules with pressure symptoms or relevant growth evidence. As
an outpatient and scarless procedure with no need of general anaesthesia it could become an
Fateha, M. J. and P. Willsie (2023). "Epinephrine-Containing Topical Anesthetic Gel
Inducing Systemic Epinephrine Toxicity: A Case Report." Cureus 15(9): e44844.
Systemic epinephrine toxicity is a rare complication following inadvertent, excessively large,
rapid subcutaneous, intramuscular, or intravenous administration. Signs and symptoms of
epinephrine toxicity include the rapid onset of transient agitation, hypertension, tachycardia,
lactic acidosis, and dysrhythmias with potentially fatal consequences. This is a case report of
a 33-year-old female who experienced epinephrine toxicity following the use of a topical
anesthetic cream containing lidocaine and epinephrine. The patient had multiple applications
to her chest before and during tattoo placement, which led to tachycardia, elevated blood
pressure, headaches, chest pain, nausea, vomiting, and anxiety. The patient was brought into
the ED, where her vital signs had begun to normalize, but laboratory analysis was concerning
for severe lactic acidosis and non-ST elevation myocardial infarction. After admission to the
hospital, the patient's symptoms quickly improved, the lactic acidosis resolved, and further
workup was unrevealing. This case report explains the potential adverse outcome of topical
epinephrine use to help create awareness of the possibility of systemic epinephrine toxicity.
Faure, A., et al. (2016). "Postural therapy for renal stones in children: A Rolling
Stones procedure." Journal of Pediatric Urology 12(4): 252.e251-252.e256.
Summary Introduction Despite many advances, the management of renal stones – especially
lower caliceal stones (LCS) – remains a challenge. The gravity-dependent location of the
lower calices hinders the spontaneous clearance of fragments, which can be a nidus for future
growth and symptomatic recurrence. Currently, there is no standard adjunctive therapy to
facilitate fragment passage. Objectives To report the safety and effectiveness of mechanical
percussion diuresis and inversion (PDI) therapy for eliminating renal stones in children.
Patients and Methods Since November 2013, children with residual fragments (after shock
wave lithotripsy or flexible ureteroscopy) or native symptomatic renal stones were
prospectively included in a protocol of four PDI sessions. After giving written consent,
the children drank 10 ml/kg of water 30 min before therapy. They then laid in a prone
Trendelenburg position on a couch angled at 45° and received continuous 10-min mechanical
percussion applied over the affected flank by a physiotherapist (Figure summary). Tolerance
stone burden reduction and stone clearance were documented with ultrasound 4 weeks after
the last session. Results Seventeen participants, with a median age of 10.8 years (range 18
months to 18 years), received 82 PDI sessions performed over 22 months. The median stone
diameter was 5 mm (range 3–9). All children tolerated the PDI therapy well. Over a median
follow-up of 11 months (range 3–18), no significant adverse effects were noted. The overall
stone-free rate was 65%. Four of the six patients with residual fragment passed their
fragments. The patients who did not become stone free by PDI experienced a decrease in
fragment size of 57% (range 34–71). The observance rate was 100%. Discussion Many
studies have demonstrated that the gravity-dependent position of the lower calyces appears to
be an important factor limiting the clearance of LCS. Positioning patients with a degree of
inversion in order to put the collecting system beyond the horizontal plane affected the LCS
through gravitational force. Complications were rare. PDI appeared to save costs and have
similar success rates as shock wave lithotripsy for native small renal stones in children.
Conclusion PDI is safe and effective for facilitating gravity-dependent drainage of renal
stones and provides an opportunity to treat children in a quick, non-invasive, economic,
painless, non-radiative and diverting fashion. This therapy is a valuable alternative in the
Ferenz, K. B., et al. (2014). "Safety of poly (ethylene glycol)-coated perfluorodecalinfilled poly (lactide-co-glycolide) microcapsules following intravenous administration
of high amounts in rats." Results Pharma Sci 4: 8-18.
The host response against foreign materials designates the biocompatibility of intravenously
administered microcapsules and thus, widely affects their potential for subsequent clinical
use as artificial oxygen/drug carriers. Therefore, body distribution and systemic parameters,
as well as markers of inflammation and indicators of organ damage were carefully evaluated
after administration of short-chained poly (vinyl alcohol, (PVA)) solution or poly (ethylene
glycol (PEG))-shielded perfluorodecalin-filled poly (d,l-lactide-co-glycolide, PFD-filled
PLGA) microcapsules into Wistar rats. Whereas PVA infusion was well tolerated, all animals
survived the selected dose of 1247 mg microcapsules/kg body weight but showed marked
toxicity (increased enzyme activities, rising pro-inflammatory cytokines and complement
factors) and developed a mild metabolic acidosis. The observed hypotension emerging
immediately after start of capsule infusion was transient and mean arterial blood pressure
restored to baseline within 70 min. Microcapsules accumulated in spleen and liver (but not in
other organs) and partly occluded hepatic microcirculation reducing sinusoidal perfusion rate
by about 20%. Intravenous infusion of high amounts of PFD-filled PLGA microcapsules was
tolerated temporarily but associated with severe side effects such as hypotension and organ
damage. Short-chained PVA displays excellent biocompatibility and thus, can be utilized as
Ferrari-Light, D., et al. (2019). "Pseudoaneurysm formation after Pasteurella
multocida lower extremity vascular bypass graft infection." J Vasc Surg Cases Innov
Tech 5(3): 232-234.
Fischer, D., et al. (2016). "Novel method to leukoreduce murine blood for transfusion:
how to reduce animal usage." Transfusion 56(1): 146-152.
Prosthetic vascular bypass graft infection is a rare complication requiring prompt
identification and isolation of the organism. A 66-year-old woman developed left lower
extremity pain and a pulsatile pseudoaneurysm 7 months after left common femoral to
peroneal artery bypass with prosthetic polytetrafluoroethylene graft, requiring re-exploration
and a jump graft. Pasteurella multocida was isolated from blood and tissue culture specimens,
and the patient admitted to a new kitten that frequently bit her lower extremities. Treatment
included intravenous administration of ertapenem for 6 weeks followed by lifelong oral
antibiotic suppression, which may offer the best chance for limb salvage when total graft
explantation would result in amputation.
BACKGROUND: Basic research on the pathomechanisms of transfusion-related adverse
events depends on murine transfusion models, in which leukoreduction (LR) is a prevalent
standard. The commonly used neonatal LR filter (LRF) is associated with considerable
animal numbers. A more efficient method would help support the guiding principles of
"replacement, reduction, refinement" (3Rs). STUDY DESIGN AND METHODS: Blood
from C57BL/6 and C57BL/6-Tg(UBC-GFP)30Scha/J mice was leukoreduced using (1) a
neonatal LRF, (2) a syringe LRF, or (3) CD45 microbeads. Product quality was assessed
according to US Food and Drug Administration (FDA) standards. White blood cell numbers
were analyzed by flow cytometry; hemoglobin concentrations and hematocrit were measured
and in vivo posttransfusion recoveries were determined after 2 weeks of storage. RESULTS:
Using the neonatal filter, a LR of 99.56% was achieved with wastage of 12.4 mL in
comparison to 99.68% and 1-mL hold-up volume with the syringe filter and 99.11 ± 0.24%
LR and 0.1-mL wastage using microbeads. All techniques achieved FDA quality standards,
apart from posttransfusion recovery rate, which was only reached by the microbeads-based
technique. CONCLUSION: LR with CD45 microbeads not only reduces animal usage but
also provides a more efficacious method regarding posttransfusion red blood cell recovery
Franco, C., et al. (2021). "Long Term Rigid Retained Foreign Object After Breast
Augmentation: A Case Report and Literature Review." Front Surg 8: 725273.
Franco Marques, G., et al. (2018). "The management of livedoid vasculopathy focused
on direct oral anticoagulants (DOACs): four case reports successfully treated with
rivaroxaban." Int J Dermatol 57(6): 732-741.
Introduction: Retained foreign object (RFO) is a rare iatrogenic complication. This article
presents an unprecedented case of a plastic RFO post-augmentation mammoplasty. Case
Presentation: We present the case of a 32-year-old woman, 8 years after breast augmentation
surgery, with a 4 year history of a palpable migrating mass in the superior lateral quadrant of
her right breast with fluctuating levels of pain. Imaging studies included mammography tests,
sonographic examinations, a Magnetic Resonance Imaging scan, and a Computed
Tomography scan, all of which did not identify any pathological findings. Exploratory
surgery discovered a syringe-tip cover in the implant pocket. Conclusion: Persistent
complaints and symptoms accompanied by non-specific imaging studies warrant escalation of
diagnostic methods, in line with a high awareness for the possibility of an RFO. As pocket
lavage is a common practice in various surgeries, this report can serve as a valuable reminder
for surgical teams to account for syringe covers and other disposable items at the end of all
Livedoid vasculopathy (LV) is a thrombotic skin disease characterized by episodic painful
ulcerations of the distal aspects of the legs. Its healing process typically leaves small
porcelain-white scars called atrophie blanche as a result of the occlusion of cutaneous
microcirculation. The main goals of the treatment are pain management and the prevention of
ulceration and of progressive scarring in the malleolar area. The therapeutic management is
still a challenge, however, and most treatments were based on anecdotal off-label protocols.
Over such context, direct oral anticoagulants (DOACS) arise as a potential treatment for this
disease. This class of medications became an alternative from initial large studies applied on
different pathologic scenarios regarding thromboembolic events. In that line, recent case
series using DOACS, including rivaroxaban, started to emerge in the literature related to LV
and reported successful prevention of cutaneous infarctions and ulcerations, providing
physicians with a new promising alternative. The current report describes four cases of longterm recalcitrant LV, in which rivaroxaban monotherapy effectively reduced pain and
cutaneous ulcerations in a few weeks of treatment without relevant side effects. The authors
also review therapy management of the disease, focused on DOACS, and suggest a step-bystep approach to treat these patients, taking into consideration different resource profiles of
Fu, J., et al. (2014). "Targeted delivery of pulmonary arterial endothelial cells
overexpressing interleukin-8 receptors attenuates monocrotaline-induced pulmonary
vascular remodeling." Arterioscler Thromb Vasc Biol 34(7): 1539-1547.
OBJECTIVE: Interleukin-8 (IL-8) receptors IL8RA and IL8RB (IL8RA/B) on neutrophil
membranes bind to IL-8 with high affinity and play a critical role in neutrophil recruitment to
sites of injury and inflammation. This study tested the hypothesis that administration of rat
pulmonary arterial endothelial cells (ECs) overexpressing IL8RA/B can accelerate the
adhesion of ECs to the injured lung and inhibit monocrotaline-induced pulmonary
inflammation, arterial thickening and hypertension, and right ventricular hypertrophy.
APPROACH AND RESULTS: The treatment groups included 10-week-old ovariectomized
Sprague-Dawley rats that received subcutaneous injection of PBS (vehicle), a single injection
of monocrotaline (monocrotaline alone, 60 mg/kg, SC), monocrotaline followed by
intravenous transfusion of ECs transduced with the empty adenoviral vector (null-EC), and
monocrotaline followed by intravenous transfusion of ECs overexpressing IL8RA/B (1.5 ×
10(6) cells/rat). Two days or 4 weeks after monocrotaline treatment, endothelial nitric oxide
synthase, inducible nitric oxide synthase, cytokine-induced neutrophil chemoattractant-2β
(IL-8 equivalent in rat), and monocyte chemoattractant protein-1 expression, neutrophil and
macrophage infiltration into pulmonary arterioles, and arteriolar and alveolar morphology
were measured by histological and immunohistochemical techniques. Proinflammatory
cytokine/chemokine protein levels were measured by Multiplex rat-specific magnetic beadbased sandwich immunoassay in total lung homogenates. Transfusion of ECs overexpressing
IL8RA/B significantly reduced monocrotaline-induced neutrophil infiltration and
proinflammatory mediator (IL-8, monocyte chemoattractant protein-1, inducible nitric oxide
synthase, cytokine-induced neutrophil chemoattractant, and macrophage inflammatory
protein-2) expression in lungs and pulmonary arterioles and alveoli, pulmonary arterial
pressure, and pulmonary arterial and right ventricular hypertrophy and remodeling.
CONCLUSIONS: These provocative findings suggest that targeted delivery of ECs
Gaertner, J. and T. Fusi-Schmidhauser (2022). "Dexmedetomidine: a magic bullet on
its way into palliative care-a narrative review and practice recommendations." Ann
Palliat Med 11(4): 1491-1504.
BACKGROUND AND OBJECTIVE: Dexmedetomidine is a potent adrenergic alpha-2
receptor agonist. It was first approved for sedation for mechanically ventilated patients. Being
a sedative medication that is not associated with respiratory depression and holding analgesic
properties fosters the interest for this drug in the palliative care field. The primary objectives
of this review were to identify the key indications for the real-world use of dexmedetomidine
in palliative care and other disciplines. METHODS: A narrative review after extensive
PubMed search was performed from 1950 to present on October 21st 2021. The language of
the publications was restricted to English, German, French and Italian. KEY CONTENT
AND FINDINGS: (I) Current dexmedetomidine use. There is a growing body of evidence
that dexmedetomidine may reduce the incidence and severity of delirium, reduce opioidconsumption and postoperative nausea in intensive care settings. It is also used to facilitate
withdrawal from different substances (alcohol, opioids, heroin). Concerning safety aspects of
the drug, some studies reported an increased rate of serious cardiovascular events in patients
with pre-existing heart conditions due to bradycardia and arterial hypo- and hypertension.
Since the drug has a main hepatic metabolism, dose reduction is mandatory in patients with
hepatic impairment. (II) Dexmedetomidine and palliative care. There have been sporadic case
reports about the successful use of dexmedetomidine in palliative care. Indications for
symptom control included sedation for hyperactive delirium, cancer pain, opioid-inducedhyperalgesia, dystonia, cough, vomiting, shivering and dyspnea. It is mainly applied via the
intravenous (i.v.), subcutaneous, but also nasal and, buccal routes. Admixture ("syringedriver") studies showed that dexmedetomidine is compatible with morphine, hydromorphone,
hyoscine and haloperidol. In 2021, a first prospective cohort study became available. Here,
the authors reported promising result for dexmedetomidine use in hyperactive terminal
delirium for reducing delirium intensity and agitation. Especially the unique "conscious
sedation" or "awake sedation" that allows patients to arouse easily under sedation and report
comfort or distress was discussed by the authors. CONCLUSIONS: In this review, we present
the main findings for dexmedetomidine from palliative care settings and other disciplines.
The potential benefits and criticalities of the drug are discussed and practical
Galié, E., et al. (2016). "Paraneoplastic Morvan's syndrome following surgical
treatment of recurrent thymoma: A case report." Oncol Lett 12(4): 2716-2719.
Morvan's syndrome (MoS) is a rare, complex neurological disorder characterized by
neuromyotonia, neuropsychiatric features, dysautonomia and neuropathic pain. The majority
of MoS cases have a paraneoplastic aetiology, usually occurring prior to the diagnosis of the
underlying tumour and showing improvement following its treatment. The present study
reports the case of a 35-year-old Caucasian male patient who was diagnosed with stage IVA
thymoma. Thymectomy, lung resection, diaphragmatic pleurectomy and pericardiophrenectomy were performed 6 months after neoadjuvant chemotherapy. The pathological
evaluation revealed a type B2-B3 thymoma with focal squamous differentiation. Two years
later, the patient underwent new surgical treatment for a local recurrence of the same
histological type, and 4 weeks later, the patient presented with complex neurological
symptoms compatible with MoS, including neuromyotonia, neuropsychiatric features,
dysautonomia and neuropathic pain. Electromyography was compatible with a diagnosis of
neuromyotonia. Brain magnetic resonance imaging scan and tests for serum antiacetylcholine receptor, anti-striated muscle antibodies and anti-30-kDa titin fragment
antibodies were all negative, whereas tests for anti-voltage-gated potassium channel
(VGKC)-complex antibodies (333.3 pmol/l), anti-leucine-rich glioma inactivated protein 1
and anti-contactin-associated protein-like 2 antibodies were positive. The patient underwent 3
cycles of intravenous administration of immunoglobulins (0.4 g/kg/day for 5 days every 4
weeks) with little clinical and electrophysiological improvement. We speculated that the late
onset of the symptoms in the present patient may have been triggered by an increase in the
serum level of anti-VGKC antibody, which was caused by the surgery performed for the
treatment of recurrent thymoma. To the best of our knowledge, the present report is the first
case of MoS associated with this histological type of thymoma uncommonly occurring upon
García-Arredondo, A., et al. (2015). "Systemic toxic effects induced by the aqueous
extract of the fire coral Millepora complanata and partial purification of thermostable
neurotoxins with lethal effects in mice." Comp Biochem Physiol C Toxicol Pharmacol
169: 55-64.
Millepora complanata is a cnidarian widely distributed in the coral reefs of the Mexican
Caribbean. This species is popularly known as "fire coral", since contact with it causes severe
pain, skin eruptions and blisters. Intravenous administration of of M. complanata aqueous
extract induces violent convulsions and death in mice within 1 min (LD50=4.62µgprotein/g
of body weight). Doses less than the LD50 produced histopathological damage in kidneys and
lungs. Such histopathological damage was completely eliminated after incubation of the
extract in heat denaturing conditions. Unexpectedly, the denatured extract conserved its lethal
effect. These findings demonstrated that the extract contained hemolytic and phospholipase
activities that might be responsible for the histopathological damage, and additionally it
contained other unidentified thermostable toxins with lethal effects in mice. Chromatographic
analysis of the extract led to the isolation of a 61 kDa vasoconstrictor protein. Furthermore,
several non-peptidic vasoconstrictor fractions were separated. Particularly interesting was the
fraction MC1-IIA obtained as a result of three-step chromatography processes (ion exchange,
gel filtration and reverse phase). Like the original crude extract, this fraction induced
vasoconstriction and delayed hemolysis and lethal effects in mice. A subsequent
chromatographic analysis of MC1-IIA showed that this fraction contained at least four nonpeptidic compounds. MS and NMR spectroscopic data analyses indicated that these
metabolites were poly-oxygenated alkylbenzenes. The present study constitutes the first
report of the presence of non-peptidic lethal toxins in an organism of the class Hydrozoa, and
Geng, C., et al. (2010). "Cholinergic signal activated renin angiotensin system
associated with cardiovascular changes in the ovine fetus." J Perinat Med 38(1): 7176.
AIM: Cholinergic regulation is important in the control of cardiovascular and endocrine
responses. The mechanisms behind cardiovascular responses induced by cholinergic
activation are explored by studying hormonal systems, including renin-angiotensin and
vasopressin (VP). RESULTS: In chronically prepared fetal sheep, intravenous infusion of the
cholinergic agonist carbachol increased fetal systolic, diastolic, and mean arterial pressure
accompanied with bradycardia at near-term. Although intravenous administration of
carbachol had no effect on plasma VP concentrations, this agonist increased angiotensin I and
angiotensin II levels in fetal plasma. Fetal blood values, including sodium, osmolality, nitric
oxide, hemoglobin, and hematocrit were unchanged by intravenous carbachol.
CONCLUSION: Cholinergic activation by carbachol controls fetal blood pressure and heart
rate in utero. An over-activated fetal renin-angiotensin-system (RAS) is associated with
changes in vascular pressure following intravenous administration of carbachol, indicating
that the cholinergic stimulation-mediated hormonal mechanism in the fetus might play a
critical role in the regulation of cardiovascular homeostasis.
Golse, M., et al. (2021). "Case 294." Radiology 299(3): 727-729.
Golse, M., et al. (2021). "Case 294: Catastrophic Antiphospholipid Syndrome."
Radiology 301(1): 242-246.
History A 50-year-old woman presented to the emergency department of our hospital with a
2-day history of lower limb pain associated with unusual asthenia and diffuse arthralgia over
the past 3 weeks. She was a native of Guinea and had lived in France for most of her life,
working as a personal care assistant. Her only medical history of note was an occurrence of
fetal death at 12 weeks gestation when she was 35 years old. She had bilateral lower limb
swelling, without changes in skin temperature or color. All proximal and distal arterial pulses
were felt. General physical examination findings were otherwise unremarkable. Her
laboratory tests showed a decreased hemoglobin concentration of 8.9 g/dL (normal range, 1216 g/dL), a decreased platelet count of 45 × 10(9)/L (normal range, 150-400 × 10(9)/L), a Creactive protein level of 158 mg/L (normal range, <5 mg/L) and a d-dimer level of 2000 mg/L
(normal range, <500 mg/L). Compression US of the lower limbs revealed bilateral calf vein
thrombosis involving the fibular and posterior tibial veins. Curative anticoagulation using
low-molecular-weight heparin (enoxaparin, subcutaneous injection of 100 units per kilogram
of body weight twice a day) was started. The day after the start of anticoagulation therapy,
the patient reported dyspnea and acute chest and abdominal pain. Her vital signs were
assessed, and she had elevated blood pressure and increased heart rate and respiratory rate,
but she remained afebrile. Her cardiac auscultation was unremarkable, besides tachycardia.
Skin examination revealed small areas of necrosis on the fingertips of her right hand.
Laboratory studies were repeated and showed an increase in serum creatinine level from a
baseline value of 0.49 mg/dL to a new value of 1.01 mg/dL (normal range, 0.6-1.1 mg/dL), an
apparition of low-grade proteinuria of 0.43 g per day (normal range, <0.3 g/day), and a high
serum troponin level of 1066 ng/L (normal range, <14 ng/L), whereas electrocardiography
showed no ST segment modification and echocardiography revealed a moderately altered left
ventricular ejection fraction (45%). There was no coronary occlusion seen at emergency
coronarography. Contrast-enhanced CT of the chest, abdomen, and pelvis was performed
History A 50-year-old woman presented to the emergency department of our hospital with a
2-day history of lower limb pain associated with unusual asthenia and diffuse arthralgia over
the past 3 weeks. She was a native of Guinea and had lived in France for most of her life,
working as a personal care assistant. Her only medical history of note was an occurrence of
fetal death at 12 weeks gestation when she was 35 years old. She had bilateral lower limb
swelling, without changes in skin temperature or color. All proximal and distal arterial pulses
were felt. General physical examination findings were otherwise unremarkable. Her
laboratory tests showed a decreased hemoglobin concentration of 8.9 g/dL (normal range, 1216 g/dL), a decreased platelet count of 45 × 10(9)/L (normal range, [150-400] × 10(9)/L), a
C-reactive protein level of 158 mg/L (normal range, <5 mg/L), and a d-dimer level of 2000
mg/L (normal range, <500 mg/L]). Compression US of the lower limbs revealed bilateral calf
vein thrombosis involving the fibular and posterior tibial veins. Curative anticoagulation
using low-molecular-weight heparin (enoxaparin, subcutaneous injection of 100 units per
kilogram of body weight twice a day) was started. The day after the start of anticoagulation
therapy, the patient reported dyspnea and acute chest and abdominal pain. Her vital signs
were assessed, and she had elevated blood pressure and increased heart rate and respiratory
rate, but she remained afebrile. Her cardiac auscultation was unremarkable, besides
tachycardia. Skin examination revealed small areas of necrosis on the fingertips of her right
hand. Laboratory studies were repeated and showed an increase in serum creatinine level
from a baseline value of 0.49 mg/dL to a new value of 1.01 mg/dL (normal range, 0.6-1.1
mg/dL), an apparition of low-grade proteinuria of 0.43 g per day (normal range, <0.3 g/ day),
and a high serum troponin level of 1066 ng/L (normal range, <14 ng/L), whereas
electrocardiography showed no ST segment modification and echocardiography revealed a
moderately altered left ventricular ejection fraction (45%). There was no coronary occlusion
seen at emergency coronarography. Contrast-enhanced CT of the chest, abdomen, and pelvis
Gomes, J. P. P., et al. (2018). "Three-Dimensional Volume Imaging to Increase the
Accuracy of Surgical Management in a Case of Recurrent Chordoma of the Clivus."
Am J Case Rep 19: 1168-1174.
BACKGROUND The clivus is a depression in the anterior occipital bone of the skull base,
posterior to the dorsum sellae, at the junction with the sphenoid bone. Chordoma is a rare
tumor arising from embryonic remnants of the notochord and can be locally aggressive with a
tendency to recur. The optimal management of this rare tumor remains controversial. A report
of a case of recurrent chordoma of the clivus is presented to illustrate the value of volumetric
three-dimensional (3-D) reconstruction with computed tomography (CT) and magnetic
resonance imaging (MRI) to determine optimal surgical management. CASE REPORT A 53year-old man presented with pain in the right orbital cavity, right proptosis, swelling of the
right cheek, and bilateral loss of vision. He also had adrenal insufficiency. CT and contrastenhanced (gadolinium) T1-weighted MRI with multiplanar acquisition were performed with
volumetric 3-D reconstruction of the tumor, to increase the chances of treatment success.
Surgical resection was performed to remove the tumor and reduce the risk of recurrence.
Histology of the tumor was consistent with chordoma, supported by positive
immunohistochemical staining for S-100 and epithelial membrane antigen (EMA).
CONCLUSIONS This report highlighted the value of 3-D volume imaging in the diagnosis
and treatment planning in a rare case of recurrent chordoma of the clivus. Analysis of tumor
volume may be an indicator of the efficacy of surgery, complementing the Response
Evaluation Criteria In Solid Tumors (RECIST) system and as a valuable tool to predict
Greenberg, R. N., et al. (2016). "A Randomized, Double-Blind, Placebo-Controlled
Phase II Trial Investigating the Safety and Immunogenicity of Modified Vaccinia
Ankara Smallpox Vaccine (MVA-BN®) in 56-80-Year-Old Subjects." PLoS One
11(6): e0157335.
BACKGROUND: Modified Vaccinia Ankara MVA-BN® is a live, highly attenuated, viral
vaccine under advanced development as a non-replicating smallpox vaccine. In this Phase II
trial, the safety and immunogenicity of Modified Vaccinia Ankara MVA-BN® (MVA) was
assessed in a 56-80 years old population. METHODS: MVA with a virus titer of 1 x 108
TCID50/dose was administered via subcutaneous injection to 56-80 year old vacciniaexperienced subjects (N = 120). Subjects received either two injections of MVA (MM group)
or one injection of Placebo and one injection of MVA (PM group) four weeks apart. Safety
was evaluated by assessment of adverse events (AE), focused physical exams,
electrocardiogram recordings and safety laboratories. Solicited AEs consisted of a set of predefined expected local reactions (erythema, swelling, pain, pruritus, and induration) and
systemic symptoms (body temperature, headache, myalgia, nausea and fatigue) and were
recorded on a memory aid for an 8-day period following each injection. The immunogenicity
of the vaccine was evaluated in terms of humoral immune responses measured with a
vaccinia-specific enzyme-linked immunosorbent assay (ELISA) and a plaque reduction
neutralization test (PRNT) before and at different time points after vaccination. RESULTS:
Vaccinations were well tolerated by all subjects. No serious adverse event related to MVA
and no case of myopericarditis was reported. The overall incidence of unsolicited AEs was
similar in both groups. For both groups immunogenicity responses two weeks after the final
vaccination (i.e. Visit 4) were as follows: Seroconversion (SC) rates (doubling of titers from
baseline) in vaccine specific antibody titers measured by ELISA were 83.3% in Group MM
and 82.8% in Group PM (difference 0.6% with 95% exact CI [-13.8%, 15.0%]), and 90.0%
for Group MM and 77.6% for Group PM measured by PRNT (difference 12.4% with 95% CI
of [-1.1%, 27.0%]). Geometric mean titers (GMT) measured by ELISA two weeks after the
final vaccination for Group MM were 804.1 and 605.8 for Group PM (with ratio of GMTs of
1.33 with 95% CI of [0.96, 1.84]). Similarly, GMTs measured by PRNT were 210.3 for
Group MM and 126.7 for Group PM (with ratio 1.66 and 95% CI [0.95, 2.90]).
CONCLUSIONS: One or two doses of MVA were safe and immunogenic in a 56-80 years
old vaccinia-experienced population. No cases of myopericarditis were observed following
Gul, S., et al. (2023). "Intravenous whole blood transfusion results in faster recovery
of vascular integrity and increased survival in experimental cerebral malaria." Mem
Inst Oswaldo Cruz 117: e220184.
BACKGROUND: Cerebral malaria is a lethal complication of Plasmodium falciparum
infections in need of better therapies. Previous work in murine experimental cerebral malaria
(ECM) indicated that the combination of artemether plus intraperitoneal whole blood
improved vascular integrity and increased survival compared to artemether alone. However,
the effects of blood or plasma transfusion administered via the intravenous route have not
previously been evaluated in ECM. OBJECTIVES: To evaluate the effects of intravenous
whole blood compared to intravenous plasma on hematological parameters, vascular
integrity, and survival in artemether-treated ECM. METHODS: Mice with late-stage ECM
received artemether alone or in combination with whole blood or plasma administered via the
jugular vein. The outcome measures were hematocrit and platelets; plasma angiopoietin 1,
angiopoietin 2, and haptoglobin; blood-brain barrier permeability; and survival. FINDINGS:
Survival increased from 54% with artemether alone to 90% with the combination of
artemether and intravenous whole blood. Intravenous plasma lowered survival to 18%.
Intravenous transfusion provided fast and pronounced recoveries of hematocrit, platelets,
angiopoietins levels and blood brain barrier integrity. MAIN CONCLUSIONS: The outcome
of artemether-treated ECM was improved by intravenous whole blood but worsened by
intravenous plasma. Compared to prior studies of transfusion via the intraperitoneal route,
Guo, J. L., et al. (2022). "Time to Occurrence of Phlebitis After Continuous Infusion
of Total Nutrient Admixture Through Peripheral Veins: An Experimental Animal
Study." J Inflamm Res 15: 205-215.
OBJECTIVE: To study the limit time of phlebitis caused by continuous infusion of
Kabiven(TM) Pl and TNA (Kabiven(TM) Pl+ alanyl glutamine + potassium aspartate)
through a peripheral vein, and to provide a reference for clinical formulation of preventive
measures for phlebitis. METHODS: White rabbits (n = 72) were randomly divided into three
groups: group A (Normal saline), group B (Kabiven™ Pl), and group C (TNA). Blood was
collected from the ear margin vein before administration and after three hours, four hours,
five hours, and six hours of administration. CRP and TNF-ɑ were measured by enzymelinked immunosorbent assay. Hematoxylin and eosin staining and immunohistochemical
staining were performed on tissue samples taken from the insertion point of the indwelling
needle, the tip of the indwelling needle, and 1 cm from the tip of the indwelling needle, closer
to the heart, to analyze early pathological changes in blood vessels. RESULTS: (1) There
were no visible inflammatory symptoms in groups A, B, or C within 6 hours. (2) Four hours
after starting intravenous administration, the levels of inflammatory markers in groups B and
C were higher than in group A, and (3) the degree of inflammatory cell infiltration in groups
B and C was more severe than in group A. (4) In all groups, the inflammatory reaction at the
tip of the indwelling needle was more severe than at the other two sites. CONCLUSION:
When the emulsions TNA and Kabiven™ Pl are infused through a peripheral vein, (1) four
hours may be considered as the maximum time for continuous intravenous infusion in the
same vein before inflammatory changes become evident, and (2) systematic assessment of the
tip of the indwelling needle should be considered for inclusion in the nursing plan for
Habnouny, J. E. L., et al. (2020). "Hypocalcemia secondary to hypomagnesemia in a
patient on liraglutide." Ann Med Surg (Lond) 60: 327-329.
Haruki, R., et al. (2015). "Safety Evaluation of Hemoglobin-Albumin Cluster
"HemoAct" as a Red Blood Cell Substitute." Sci Rep 5: 12778.
A 73-year-old man with type 2 diabetes on Liraglutide with a history of coronary artery
disease. Admitted to emergency for abdominal pain, severe diarrhea and episodes of tetany
attacks. Laboratory workup reveals hypomagnesemia, hypocalcemia and normal
parathormone (PTH). After intravenous administration of magnesium and calcium, the blood
ionogram quickly normalized. In addition, plasma levels of intact parathyroid hormone
increased immediately after magnesium administration. Strongly suggests that hypocalcemia
resulted from a disruption of adequate parathyroid hormone secretion caused by
hypomagnesemia which in turn was caused by severe diarrhea under treatment with
Liraglutide.
A hemoglobin (Hb) wrapped covalently by human serum albumins (HSAs), a core-shell
structured hemoglobin-albumin cluster designated as "HemoAct", is an O2-carrier designed
for use as a red blood cell (RBC) substitute. This report describes the blood compatibility,
hemodynamic response, and pharmacokinetic properties of HemoAct, and then explains its
preclinical safety. Viscosity and blood cell counting measurements revealed that HemoAct
has good compatibility with whole blood. Intravenous administration of HemoAct into
anesthetized rats elicited no unfavorable increase in systemic blood pressure by
vasoconstriction. The half-life of (125)I-labeled HemoAct in circulating blood is markedly
longer than that of HSA. Serum biochemical tests conducted 7 days after HemoAct infusion
yielded equivalent values to those observed in the control group with HSA. Histopathologic
inspections of the vital organs revealed no marked abnormality in their tissues. All results
indicate that HemoAct has sufficient preclinical safety as an alternative material for RBC
transfusion.
Hatun, Ş., et al. (2016). "Evaluation of therapeutics management patterns and
glycemic control of pediatric type 1 diabetes mellitus patients in Turkey: A
nationwide cross-sectional study." Diabetes Research and Clinical Practice 119: 32-
Aims To evaluate the management strategies, glycemic control and complications of pediatric
type 1 diabetes mellitus (T1DM) patients in Turkey. Methods Study included 498 patients
with T1DM between the ages 1–18. Data provided from patients’ hospital files were recorded
on standard case report forms by applicant clinicians within the 3months of data collection
period between October 2012 and July 2013. Results Mean age of patients was
11.3±3.8years. Mean duration of DM was determined as 3.7±3.1years. Majority of patients
(85.5%) used basal/bolus injection (BBI), and 6.5% used continuous subcutaneous insulin
infusion pump. Assessment of glycemic control based on HbA1c levels showed that 29.1% of
patients had an HbA1c value <7.5% (58mmol/mol), 16.1% had a value between 7.5%
(58mmol/mol) and 8% (64mmol/mol), 19.1% had a value between 8.1% (64mmol/mol) and
9%(75mmol/mol) and 35.7% a value >9%(75mmol/mol). Hypoglycemia was reported in 145
(29.1%) patients and the number of severe hypoglycemic attacks in the last 3months was
1.0±2.4. Taking into consideration the carbohydrate count and insulin correction dose and
parents with high socioeconomic status was related to have better glycemic control. The most
common comorbidities were Hashimoto’s thyroiditis/hypothyroidism (6.2%) followed by
celiac disease (3.8%), epilepsy(1.2%), and asthma(1.0%). Conclusions BBI insulin therapy is
widely used among pediatric T1DM patients in Turkey. However, despite improvements in
treatment facilities and diabetic care, glycemic control is not at a satisfactory level.
Therefore, new and comprehensive initiatives require for pediatric T1DM patients with poor
glycemic control. Promoting use of carbohydrate count and insulin correction doses may
Hayakawa, N., et al. (2019). "Efficacy of three-dimensional roadmapping by fusion of
computed tomography angiography with volumetric data from an angiography
machine in endovascular therapy for iliac chronic total occlusion: a case report."
CVIR Endovasc 2(1): 32.
He, J. W., et al. (2011). "Simultaneous absolute measures of glabrous skin
hemodynamic and light-scattering change in response to formalin injection in rats."
Neurosci Lett 492(1): 59-63.
BACKGROUND: The usefulness of endovascular therapy (EVT) for the iliac artery has been
established. However, difficult cases such as a long total occlusion and tortuous vessels are
sometimes encountered. We recently performed rotational angiography with an angiography
machine immediately before EVT and fused three-dimensional (3D) anatomical information
obtained from preoperative enhanced computed tomography (CT) that had been performed in
advance to create a 3D roadmap. We termed this method the CT fusion 3D roadmap (CTf3DRM) technique and used it for treatment of iliac occlusive disease. CASE PRESENTATION:
A 73-year-old man presented with pain in his left leg while resting. CT showed total
occlusion from the ostium of the common iliac artery (CIA) to the distal part of the external
iliac artery (EIA). A guiding sheath was inserted from the left common femoral artery using
the CTf3D-RM technique, and the occlusive vessel was clearly observed. The guidewire
could be passed retrogradely without bidirectional wiring. The time taken to pass the
guidewire was only about 9 min despite the long and hard chronic total occlusion (CTO).
Intravascular ultrasound showed that all of the guidewire followed the intraplaque route.
After ballooning the entire lesion, we deployed two stent grafts and three bare nitinol stents
from the left CIA ostium to the distal EIA. Final angiography showed good expansion and
sufficient flow to the left leg. CONCLUSIONS: The use of a 3D roadmap by fusion of CT
angiography with volumetric data from an angiography machine in EVT for iliac CTO was
Hernández-Matehuala, R., et al. (2015). "Cytolytic and systemic toxic effects induced
by the aqueous extract of the fire coral Millepora alcicornis collected in the Mexican
Caribbean and detection of two types of cytolisins." J Venom Anim Toxins Incl Trop
Dis 21: 36.
Subcutaneous injection of formalin is a well-known model to study the nature of
inflammatory pain. One of the cardinal signs of inflammation is redness, as a result of
increased blood perfusion. We used an optical technology, light reflectance spectroscopy, to
noninvasively obtain absolute measures of cutaneous hemodynamic components, including
the concentrations of oxy- ([HbO]), deoxy- ([Hb]), total-hemoglobin ([HbT]), oxygen
saturation (SO(2)), and the reduced light-scattering coefficient (μs'). The objective is to
assess the effect of formalin-induced skin inflammation on the aforementioned parameters.
Six rats were injected with formalin (50 μl, 3%) into left hind paw under pentobarbital
anesthesia. Our results indicate prolonged increases in [HbO], [HbT], and SO(2) post
injection only in the ipsilateral side. No statistically significant changes in [Hb] and μ(s)'
occurred in either side. The arterial blood influx tends to be the major attribute of local
hyperemia during inflammation. Thereby, [HbO] appears to be superior to [Hb] in measuring
inflammation. In conclusion, the needle-probe-based light reflectance can be a feasible means
to obtaining absolute measures of skin hemodynamic and light-scattering parameters when
studying inflammatory pain.
BACKGROUND: Millepora alcicornis is a branching hydrocoral common throughout the
Caribbean Sea. Like other members of this genus, this species is capable of inducing skin
eruptions and blisters with severe pain after contact. In the present study, we investigated the
toxicity of the M. alcicornis aqueous extract on several animal models. Considering that some
cnidarian hemolysins have been associated to local tissue damage, since they also induce
lysis of other cell types, we also made a partial characterization of the hemolytic activity of
M. alcicornis aqueous extract. This information is important for understanding the defense
mechanisms of the "fire corals". METHODS: The effects of pH, temperature, and some
divalent cations on the hemolytic activity of the extract were assayed, followed by a
zymogram analysis to detect the cytolysins and determine their approximate molecular
weight. The toxicity of the aqueous extract was assayed in mice, by intravenous
administration, and histopathological changes on several tissues were analyzed by light
microscopy. The toxicity of the extract was also tested in Artemia salina nauplii, and the
damages caused on the crustaceans were analyzed by transmission and scanning electron
microscopy. RESULTS: The hemolytic activity of the hydrocoral extract was enhanced in the
presence of Ca(2+) (≥2 mM), Mg(2+) (≥6 mM), and Ba(2+) (≥0.1 mM); however, it was
reduced in the presence of Cu(2+) (≥0.1 mM), Zn(2+) (≥6 mM), and EDTA (≥0.34 mM).
Differences in the pH did not affect the hemolytic activity, but it was temperature-sensitive,
since preincubation at ≥ 50 °C sharply reduced hemolysis. The zymogram showed the
presence of two types of hemolysins: ~ 28-30 kDa proteins with phospholipase A2 activity
and ~ 200 kDa proteins that do not elicit enzymatic activity. The aqueous extract of this
cnidarian was lethal to mice (LD50 = 17 μg protein/g), and induced kidney, liver, and lung
damages. Under denaturing conditions, the aqueous extract completely lost its toxic and
hemolytic activities. CONCLUSIONS: The results showed that the M. alcicornis aqueous
extract contains two types of thermolabile hemolysins: proteins of approximately 28-30 kDa
with PLA2 activity, while the others are larger proteins of approximately 200 kDa, which do
not possess PLA2 activity. Those thermolabile cytolysins, which are stable to pH changes and
whose activity is calcium dependent, are capable of inducing damage in lung, kidney and
Higashida-Konishi, M., et al. (2023). "Giant cell arteritis successfully treated with
subcutaneous tocilizumab monotherapy." Rheumatol Int 43(3): 545-549.
Glucocorticoid remains the mainstay for treatment of large vessel vasculitis (LVV) including
giant cell arteritis (GCA); however, the disease affects the elderly for whom the adverse
effects of glucocorticoid are problematic. Recently, some reports have suggested that
intravenous tocilizumab (TCZ) monotherapy is effective for this disease. To date, it remains
unknown whether subcutaneous TCZ monotherapy is also effective. Here, we present a first
case of GCA successfully treated with subcutaneous TCZ monotherapy. A 75-year-old
woman presented with shoulder and hip pain. She was diagnosed with polymyalgia
rheumatica (PMR) and treated with low-dose prednisolone (15 mg daily); however, she
discontinued glucocorticoid therapy at her discretion due to the psychiatric adverse effect
(cognitive dysfunction). Seven months later, her shoulder and hip pain relapsed. Furthermore,
(18)F-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed
tomography (CT) revealed uptake in the descending thoracic aorta, indicating a complication
of LVV. She refused to take glucocorticoid for fear of psychiatric adverse effects and chose
subcutaneous TCZ monotherapy (162 mg weekly) for treating this life-threatening urgent
condition. Nine months later, her shoulder and hip pain resolved and FDG-PET/CT
demonstrated no uptake in the descending thoracic aorta, indicating a successful treatment
with subcutaneous TCZ monotherapy for the disease. No adverse events and disease relapse
were found during observation period. Our case and the literature review suggest that not
only intravenous injection but also subcutaneous injection of TCZ monotherapy can serve as
an alternative treatment for patients with GCA who have comorbidities or refuse to take
Hirose, S., et al. (2022). "Intramedullary spinal cord abscess associated with right-toleft shunt via right superior vena cava draining into left atrium: A case report."
Medicine (Baltimore) 101(26): e29740.
RATIONALE: Intramedullary spinal cord abscess (ISCA) is a rare but treatable bacterial
infection of the central nervous system, and the etiology in no less than 40% of the cases is
cryptogenic. Although a few cases of ISCA in individuals with a right-to-left shunt (RL
shunt) have been reported, only few arguments focused on the association between RL shunt
and ISCA have been provoked. The right superior vena cava (RSVC) draining into the left
atrium (LA) is an uncommon systemic venous anomaly that results in an RL shunt, and this
anomaly causes several types of neurological complication such as stroke or brain abscess.
We report the first case of ISCA associated with RSVC-LA RL shunt. PATIENT
CONCERNS: A 36-year-old man developed progressive paraparesis, dysuria, and
spontaneous pain in the lumbar region and lower extremities. Spinal magnetic resonance
imaging revealed an intramedullary lesion extended from Th12 to L2 with ring-shaped
gadolinium enhancement. Cerebrospinal fluid (CSF) study exhibited a marked pleocytosis,
and CSF culture grew Streptococcus intermedius. Cardiovascular computed tomography
angiography identified RSVC-LA RL shunt, which caused transient acute cardiac syndrome
due to air embolus. DIAGNOSES: The patient was diagnosed with ISCA associated with an
RSVC-LA RL shunt. INTERVENTIONS: The patient was treated with a combination of
intravenous administration of meropenem and vancomycin in a daily dose of 6 and 2.5 g,
respectively, followed by intravenous administration of ampicillin in a daily dose of 750 mg.
The intravenous antibiotic therapy was continued for 37 days. OUTCOMES: A favorable
neurological outcome was obtained by the intravenous antibiotic therapy, and recurrence of
infection was prevented by continuous oral antibiotic therapy for 18 months. LESSONS:
With a literature review of ISCA associated with RL shunt, we insist that screening for
RSVC-LA is beneficial to patients who are diagnosed with cryptogenic ISCA as its
Hocking, A., et al. (2020). "The Safety and Exploration of the Pharmacokinetics of
Intrapleural Liposomal Curcumin." Int J Nanomedicine 15: 943-952.
BACKGROUND: Malignant pleural effusion (MPE) is the accumulation of fluid in the
pleural cavity as a result of malignancies affecting the lung, pleura and mediastinal lymph
nodes. Curcumin, a compound found in turmeric, has anti-cancer properties that could not
only treat MPE accumulation but also reduce cancer burden. To our knowledge, direct
administration of curcumin into the pleural cavity has never been reported, neither in animals
nor in humans. PURPOSE: To explore the compartmental distribution, targeted
pharmacokinetics and the safety profile of liposomal curcumin following intrapleural and
intravenous administration. METHODS: Liposomal curcumin (16 mg/kg) was administered
into Fischer 344 rats by either intrapleural injection or intravenous infusion. The
concentration of curcumin in plasma and tissues (lung, liver and diaphragm) were measured
using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). Blood and
tissues were examined for pathological changes. RESULTS: No pleural or lung pathologies
were observed following intrapleural liposomal curcumin administration. Total curcumin
concentration peaked 1.5 hrs after the administration of intrapleural liposomal curcumin and
red blood cell morphology appeared normal. A red blood cells abnormality (echinocytosis)
was observed immediately and at 1.5 hrs after intravenous infusion of liposomal curcumin.
CONCLUSION: These results indicate that liposomal curcumin is safe when administered
directly into the pleural cavity and may represent a viable alternative to intravenous infusion
Hosztafi, S. (2011). "[Heroin addiction]." Acta Pharm Hung 81(4): 173-183.
Heroin is an illicit, highly addictive drug. It is either the most abused or the most rapidly
acting member of opioids. Abusers describe a feeling of a surge of pleasurable sensation,
named as "rush" or "high". Repeated administration of high doses of heroin results in the
induction of physical dependence. Physical dependence refers to an altered physiological
state produced by chronic administration of heroin which necessitates the continued
administration of the drug to prevent the appearance of a characteristic syndrome, the opioid
withdrawal or abstinence syndrome. Withdrawal symptoms may occur within a few hours
after the last administration of heroin. Symptoms of the withdrawal include restlessness,
insomnia, drug craving, diarrhea, muscle and bone pain, cold flashes with goose bumps, and
leg movements. Major withdrawal symptoms peak between 48 and 72 hours after the last
dose of heroin and subside after about a week. At this time, weakness and depression are
pronounced and nausea and vomiting are common. Nevertheless, some chronic addicts have
shown persistent withdrawal signs for many months or even years. Heroin addiction is
considered as a behavioural state of compulsive drug use and a high tendency to relapse after
periods of abstinence. It is generally accepted that compulsive use and relapse are typically
associated with the status of heroin craving or heroin hunger that are difficult to define but
appear to be powerful motivational significance in the addiction process. The route of
administering heroin varies largely and may indicate the degree of seriousness of the
individual's addiction. Intravenous administration seems to be the predominant method of
heroin use, but recently a shift in heroin use pattern has been found, i.e. from injection to
sniffing and smoking. Frequent injections coupled with widespread sharing of syringes
increase the risk of contracting HIV, hepatitis B, C and other blood-borne infectious diseases.
Long-term use of heroin has also severe medical consequences such as scarred veins,
Hoy, S. M. (2013). "Lacosamide: a review of its use as adjunctive therapy in the
management of partial-onset seizures." CNS Drugs 27(12): 1125-1142.
Lacosamide (Vimpat(®)) is a functionalized amino acid available orally (as a syrup or tablet)
and as an intravenous infusion. It is believed to exert its antiepileptic effect by selectively
enhancing the slow inactivation of voltage-gated sodium channels. Lacosamide is approved in
several countries worldwide as an adjunctive therapy for the treatment of partial-onset
seizures; however, prescribing regulations differ between countries. This article reviews the
use of lacosamide as indicated in adults and adolescents (aged 16-18 years) in the EU, where
it is approved in this patient population as an adjunctive therapy to other AEDs in the
treatment of partial-onset seizures, with or without secondary generalization. In three
randomized, double-blind, placebo-controlled, multicentre studies in adults and adolescents
(aged 16-18 years) with partial-onset seizures, adjunctive therapy with oral lacosamide
(administered for an initial titration period followed by 12 weeks' maintenance therapy)
generally reduced the frequency of seizures to a significantly greater extent than placebo,
with antiepileptic efficacy sustained following longer-term treatment (up to 8 years) in this
patient population. Oral and intravenous lacosamide were generally well tolerated in clinical
studies, with the majority of adverse events being mild or moderate in severity. Very common
adverse reactions following adjunctive therapy with oral lacosamide included diplopia,
dizziness, headache and nausea; the tolerability profile of intravenous lacosamide appeared
consistent with that of oral lacosamide, although intravenous administration was associated
with local adverse events, such as injection site discomfort or pain, irritation and erythema.
Thus, oral and intravenous lacosamide as an adjunctive therapy to other AEDs provides a
Hurley, T., et al. (2021). "Bisphosphonate use in children with cerebral palsy."
Cochrane Database Syst Rev 7(7): Cd012756.
BACKGROUND: Cerebral palsy (CP) is a heterogeneous group of non-progressive disorders
of posture or movement, caused by a lesion of the developing brain. Osteoporosis is common
in children with cerebral palsy, particularly in children with reduced gross motor function,
and leads to an increased risk of fractures. Gross motor function in children with CP can be
categorised using a tool called the Gross Motor Function Classification System (GMFCS).
Bisphosphonate increases bone mineral density (BMD) and reduces fracture rates.
Bisphosphonate is used widely in the treatment of adult osteoporosis. However, the use of
bisphosphonate in children with CP remains controversial, due to a paucity of evidence and a
lack of recent trials examining the efficacy and safety of bisphosphonate use in this
population. OBJECTIVES: To examine the efficacy and safety of bisphosphonate therapy in
the treatment of low BMD or secondary osteoporosis (or both) in children with cerebral palsy
(GMFCS Levels III to V) who are under 18 years of age. SEARCH METHODS: In
September 2020, we searched CENTRAL, MEDLINE, Embase, six other databases, and two
trial registers for relevant studies. We also searched the reference lists of relevant systematic
reviews, trials, and case studies identified by the search, and contacted the authors of relevant
studies in an attempt to identify unpublished literature. SELECTION CRITERIA: All
relevant randomised controlled trials (RCTs), and quasi-RCTs, comparing at least one
bisphosphonate (given at any dose, orally or intravenously) with placebo or no drug, for the
treatment of low BMD or osteoporosis in children up to 18 years old, with cerebral palsy
(GMFCS Levels III to V). DATA COLLECTION AND ANALYSIS: We used standard
methodological procedures expected by Cochrane. We were unable to conduct any metaanalyses due to insufficient data, and therefore provide a narrative assessment of the results.
MAIN RESULTS: We found two relevant RCTs (34 participants). Both studies included
participants with non-ambulatory CP or CP and osteoporosis. Participants in both studies
were similar in severity of CP, age distribution, and sex distribution. The two trials used
different bisphosphonate medications and different intervention durations, but further
comparison of the interventions was not possible due to a lack of published data from one
trial. One trial received funding and support from research, academic, and hospital
Hwang, J. H. (2023). "Single-Dose Toxicity Study of Intramuscular NeuralgiaPharmacopuncture Injection in Rats." J Pharmacopuncture 26(4): 348-356.
OBJECTIVES: Neuralgia-pharmacopuncture (NP) was recently developed as a water-soluble
type of pharmacopuncture inspired by CS (care special pain)-pharmacopuncture. I aimed to
evaluate the toxic response and approximate lethal dose of when NP when administered
intramuscularly to Sprague Dawley rats. METHODS: The experimental group was divided
into the NP test substance group and the saline control group and administered at a dose of
1.0 mL/animal to the posterior thigh muscles on both sides using a 1 mL syringe; each group
consisted of five males and five females. Each rat was monitored for clinical signs and
changes in body weight for 14 days after a single intramuscular injection. After completing
observation, necropsy findings and localized tolerance at the injection site were assessed via
gross necropsy and histopathological examination. RESULTS: No deaths occurred in the NP
or control group, regardless of sex. During the observation period, no changes (such as
general symptoms, weight change, or visual observation results at the time of autopsy) were
judged to be due to the test substance. Histopathological examination showed no changes at
the administration site judged to be caused by the test substance in either the male or female
test substance administration groups. In addition, mononuclear cell infiltration of the outer
membrane of the femoris muscle at the administration site was observed at the same
frequency and extent in the control and NP groups, and was judged to be caused by physical
stimulation by the injection needle; therefore, it had no toxicological significance.
CONCLUSION: Based on the above results, the approximate lethal dose for a single
intramuscular administration of the test substance NP in Sprague-Dawley rats was judged to
be > 1.0 mL/animal, and there were no findings that were judged to be due to the test
Ibey, A. A. M., C. Ciarniello and S. Gorelik (2015). "Inadvertent overinfusion of
norepinephrine using infusion pump loading dose." Intensive and Critical Care
Nursing 31(6): 375-379.
Summary Programming infusion pumps has been recognised as a high-risk step and a source
of adverse events (Nuckols et al., 2008, Hyman, 2010). Literature describing infusion pump
loading dose errors and NORepinephrine complications is scarce (Girard et al., 2010). This
case study presents the first ever report of an inadvertent overinfusion of NORepinephrine
due to the loading dose option on the infusion pump, and resulting cardiac arrest of the
patient. A patient was admitted to the emergency room and started on a NORepinephrine
infusion inadvertently as a loading dose rather than a primary infusion. Historical values for
the loading dose volume to be infused (VTBI) and primary rate were not adjusted during the
setup. Eight hours and 58minutes later, the loading dose VTBI reached 0mL and the pump
reverted to the historical primary rate of 999mL/hour. The event log showed that 37.1mL of
NORepinephrine was infused resulting in an equivalent calculated bolus dose of 1.8mg
administered in two minutes. The patient suffered a cardiac arrest and the infusion was
stopped. No faults were found with the pump. Herein, we discuss our analysis of the pump
event logs and propose further safety strategies and interventions.
Jain, A. K., et al. (2015). "Validating hyperbilirubinemia and gut mucosal atrophy
with a novel ultramobile ambulatory total parenteral nutrition piglet model." Nutrition
Research 35(2): 169-174.
Total parenteral nutrition (TPN) provides all nutrition intravenously. Although TPN therapy
has grown enormously, it causes significant complications, including gut and hepatic
dysfunction. Current models use animal tethering which is unlike ambulatory human TPN
delivery and is cost prohibitive. We hypothesize that using ultramobile infusion pumps, TPN
can be delivered cost-effectively, resulting in classical gut and hepatic injury, and we thus
aim to establish a new model system. Neonatal pigs (n=8) were implanted with jugular vein
and duodenal catheters. Animals were fitted in dual-pocket jackets. An ultramobile
ambulatory pump was placed in one pocket and connected to the jugular vein or duodenal
catheter. Isocaloric TPN or swine formula was placed in the other pocket. Rigorous Wifibased video and scheduled monitoring was performed. After 14days, the animals were
euthanized. The mean (±SD) daily weight gain (in grams) for enteral-fed control (EN) vs
TPN animals was 102.4±10.8 and 91.03±12.1 respectively (P<.05). Total parenteral nutrition
resulted in significant conjugated bilirubin elevation and hepatomegaly. Mean (±SD) serum
conjugated bilirubin (in μmol/L) was 1.5±0.7 for EN and 6.3±2.8 for TPN (P<.05). Marked
gut atrophy was noted with TPN. The mean (±SD) gut weight as a percent of body weight
was 4.30±0.26 for EN and 2.62±0.48 for TPN (P<.05). Surgical sites healed well. All animals
remained completely mobile. We thus established that TPN can be successfully delivered
using ultramobile pumps and believe that this remains the first such description of an
ambulatory piglet TPN model system. In addition to cholestasis and gut atrophy, classical
Jain, R. S., et al. (2015). "Purple glove syndrome occurring after oral administration
of phenytoin in therapeutic doses: mechanism still a dilemma." Am J Emerg Med
33(1): 123.e125-126.
Jankowski, G. and J. Nevarez (2010). "Evaluation of a pediatric blood filter for whole
blood transfusions in domestic chickens (Gallus gallus)." J Avian Med Surg 24(4):
272-278.
Jeon, D. H., et al. (2016). "Rhabdomyolysis associated with single-dose intravenous
esomeprazole administration: A case report." Medicine (Baltimore) 95(29): e4313.
Purple glove syndrome is a rare and poorly understood complication of phenytoin use,
occurring almost always with its intravenous formulation. This syndrome comprises of pain,
purple discoloration, and edema distal to the site of intravenous administration of phenytoin.
We hereby report an unusual case, wherein purple glove syndrome was seen on oral
formulation of phenytoin in its therapeutic dose.
Blood filters that prevent clots, microaggregates, and other debris from being passed from the
donor blood into the recipient are an essential component of blood transfusions in
mammalian species but have not been consistently recommended in avian transfusions. To
evaluate the hemolytic effect of an 18-microm filter in chickens, 9 mL of blood was collected
from each of 30 chickens (Gallus gallus) into a syringe containing 1 mL of citrate phosphate
dextrose adenine (CPDA-1) to obtain a 1:9 dilution of CPDA-1 to blood. One half of each
sample was then run through a pediatric blood filter before separating the plasma. The level
of hemolysis in both filtered and unfiltered portions was determined by measuring the
concentration of free hemoglobin in the plasma. All samples had low hemoglobin
concentrations (less than 30 mg/dL) with no significant difference between the unfiltered and
filtered portions. Based on these results, an 18-microm blood filter can be used safely for
blood transfusions in domestic chickens as it does not cause significant hemolysis.
BACKGROUND: Proton pump inhibitors are usually safe, although serious adverse effects
can occur. We report the first case of rhabdomyolysis associated with single-dose intravenous
esomeprozole administration. METHODS: A 45-year-old Korean male visited our emergency
room because of persistent lower chest discomfort that started 10 hours before. He had been
diagnosed with diabetes and coronary heart disease, but discontinued oral hypoglycemic
agents 1 month earlier. He continued to take medications for coronary heart disease. There
was no abnormality on an electrocardiogram or in cardiac enzymes. Initial laboratory findings
did not show abnormalities for muscle enzymes. Esomeprozole 40 mg was administrated
intravenously for the control of his ambiguous chest discomfort. Then, 12 hours later, he
complained of abrupt severe right buttock pain. An area of tender muscle swelling 8 cm in
diameter was seen on his right buttock area. Creatine kinase and lactate dehydrogenase were
elevated to 40,538 and 1326 U/L, respectively. A bone scan using 20 mCi of Tchydroxymethylene diphosphonate was compatible with rhabdomyolysis. RESULTS: His
muscular symptoms, signs, and laboratory findings improved markedly with conservative
management, including hydration and urine alkalinization. He is being followed in the
outpatient department with no evidence of recurrence. CONCLUSION: We should keep in
Ji, B. B., et al. (2020). "[Study on efficacy specificity of electroacupuncture at
"Zusanli "(ST36) and "Baihui" (GV20) in cerebral ischemia and inflammatory pain
rats]." Zhen Ci Yan Jiu 45(10): 823-828.
OBJECTIVE: To explore the efficacy difference between electroacupuncture (EA) at
"Zusanli" (ST36) and "Baihui" (GV20) for inflammatory pain and cerebral ischemiareperfusion injury (CIRI) in rats. METHODS: In 1st part of this study, 90 male SD rats were
randomly divided into sham-operation, model (induced by occlusion of the middle cerebral
artery and reperfusion), GV20 EA, ST36 EA，and sham EA groups (n=16 in each group). In
the 2nd part of the study, 40 male SD rats were randomized into saline injection (control),
inflammatory pain model (subcutaneous injection of complete Freund's adjuvant ［CFA］
into the right paw), ST36 EA, GV20 EA, and sham EA groups (n=8 in each group). In these
two parts, EA (2 Hz/15 Hz, 1 mA) was applied to ST36 or GV20. The mechanical withdrawal
threshold (MWT) and thermal withdrawal latency （TWL） were detected 2.5 h after
administration of CFA by using Von Frey and plantar tester, respectively. The neurological
deficit scores (NDS) were assessed by using Longa's method and the infarct size of the brain
assessed after staining with 2% triphenyltetrazolium chloride (TTC). The expression of c-fos
protein in the dorsal horns (DHs) of the spinal cord was detected by immunohistochemistry.
RESULTS: (1) Twenty-four hours following CIRI, the NDS and infarct volume were
significantly increased in the model group compared with the sham-operation group (P<0.01),
and obviously decreased in the GV20 EA and ST36 EA groups relevant to the CIRI model
group (P<0.05, P<0.01). There were no significant differences between the two EA groups in
the NDS and infarct volume levels (P>0.05). (2) After administration of CFA, both the MPT
and TPT were notably decreased in the inflammatory pain model group in contrast to the
saline-injection group (P<0.01), but were considerably increased in both ST36 EA and GV20
EA groups (P<0.05), rather than in the sham EA group (P>0.05). The number of c-fos
positive cells was significantly increased in the medial half of I-II and III-IV lamina of DHs
in the L4-L6 segments of spinal cord in the inflammatory pain model group relevant to the
saline-injection group (P<0.01,P<0.05), and was remarkably decreased in the lamina I-II (not
in the deeper lamina) in both ST36 EA and GV20 EA groups (P<0.01), rather than in the
sham EA group (P>0.05). No significant differences were found in the number of c-fos
positive cells between the ST36 EA and GV20 EA groups (P>0.05). CONCLUSION: Our
Joret, M. O. and F. El-Haddawi (2021). "Intraperitoneal migration of a hookwire
following wide local excision of a breast lesion presenting as a spontaneous
pneumothorax." BMJ Case Rep 14(8).
Hookwire migration is a rare complication of wide local excision surgery for breast
neoplasia. We report the case of a 64-year-old woman who presented to hospital with acute
on chronic left upper quadrant and left scapular pain. She had undergone a hookwire-guided
wide local excision of a right breast neoplasm 5 years previously. Her vital signs, clinical
examination and blood test were unremarkable. A CT scan revealed a left-sided
pneumothorax and a 20 cm metallic intraperitoneal foreign body transpiercing the diaphragm.
A review of the patient's clinical record revealed that she experienced a vagal collapse during
hookwire implantation. This article underlines the importance of clear communication
between members of a multidisciplinary team involved in a staged surgical intervention and
exemplifies that foreign bodies can migrate across large distances, sometimes against gravity,
to cross multiple anatomical compartments and cause iatrogenic injuries multiple years after
an index intervention.
Kakita, K., et al. (2018). "Local subcutaneous injection of chlorogenic acid inhibits
the nociceptive trigeminal spinal nucleus caudalis neurons in rats." Neurosci Res 134:
49-55.
Acute administration of chlorogenic acid (CGA) in vitro was recently shown to modulate
potassium channel conductance and acid-sensing ion channels (ASICs) in the primary
sensory neurons; however, in vivo peripheral effects of CGA on the nociceptive mechanical
stimulation of trigeminal neuronal activity remains to be determined. The present study
investigated whether local administration of CGA in vivo attenuates mechanical stimulationinduced excitability of trigeminal spinal nucleus caudalis neuronal (SpVc) activity in rats.
Extracellular single-unit recordings were made of SpVc wide-dynamic range (WDR)
neuronal activity elicited by non-noxious and noxious orofacial mechanical stimulation in
pentobarbital anesthetized rats. The mean number of SpVc WDR neuronal firings responding
to both non-noxious and noxious mechanical stimuli were significantly and dose-dependently
inhibited by local subcutaneous administration of CGA (0.1-10mM), with the maximal
inhibition of discharge frequency revealed within 10min and reversed after approximately
30min. The mean frequency of SpVc neuronal discharge inhibition by CGA was comparable
to that by a local anesthetic, the sodium channel blocker, 1% lidocaine. These results suggest
that local CGA injection into the peripheral receptive field suppresses the excitability of
SpVc neurons, possibly via the activation of voltage-gated potassium channels and
modulation of ASICs in the nociceptive nerve terminal of trigeminal ganglion neurons.
Therefore, local injection of CGA could contribute to local anesthetic agents for the treatment
Kakuta, M., et al. (2013). "Efficacy of a single intravenous administration of
laninamivir (an active metabolite of laninamivir octanoate) in an influenza virus
infection mouse model." Antiviral Res 100(1): 190-195.
Kamimura, D. and M. Murakami (2019). "Neural stimulations regulate the infiltration
of immune cells into the CNS." J Intern Med 286(3): 259-267.
Laninamivir, a potent neuraminidase (NA) inhibitor, is an active metabolite of laninamivir
octanoate (code name: CS-8958) which is a long acting NA inhibitor and is commercially
available under the brand name Inavir in Japan to complete the treatment of influenza by a
single inhalation. It is supposed that the long acting character is provided by the long
retention of laninamivir in the respiratory tract after intranasal administration of laninamivir
octanoate in mice and with stable binding of laninamivir to NA of various influenza viruses
such as N1, N2 subtypes and NA of B virus. Peramivir, another NA inhibitor, is also
approved in Japan as a single intravenous infusion. In spite of the quick disappearance of
peramivir from the blood after injection, the reason treatment can be completed by a single
administration is thought to be that peramivir showed stable binding to NA with N9 subtype.
Therefore, the stable binder, laninamivir is possibly effective by a single intravenous
administration in the mouse model infected with influenza viruses. A single intravenous
administration of laninamivir and peramivir at 30mg/kg significantly prolonged mice survival
at a comparable level in the mouse lethal model infected with the A/PR/8/34 (H1N1) virus.
Also, a single intravenous administration of laninamivir and peramivir significantly
suppressed virus proliferation in the lungs of mice infected with influenza B virus. Thus,
The systemic regulation of immune reactions by the nervous system is well studied and
depends on the release of hormones. Some regional regulations of immune reactions, on the
other hand, depend on specific neural pathways. Better understanding of these regulations
will expand therapeutic applications for neuroimmune and organ-to-organ functional
interactions. Here, we discuss one regional neuroimmune interaction, the gateway reflex,
which converts specific neural inputs into local inflammatory outputs in the CNS.
Neurotransmitters released by the inputs stimulate specific blood vessels to express
chemokines, which serve as a gateway for immune cells to extravasate into the target organ
such as the brain or spinal cord. Several types of gateway reflexes have been reported, and
each controls distinct CNS blood vessels to form gateways that elicit local inflammation,
particularly in the presence of autoreactive immune cells. For example, neural stimulation by
gravity creates the initial entry point to the CNS by CNS-reactive pathogenic CD4+ T cells at
the dorsal vessels of fifth lumbar spinal cord, while pain opens the gateway at the ventral side
of blood vessels in the spinal cord. In addition, it was recently found that local inflammation
by the gateway reflex in the brain triggers the activation of otherwise resting neural circuits to
dysregulate organ functions in the periphery including the upper gastrointestinal tract and
heart. Therefore, the gateway reflex represents a novel bidirectional neuroimmune interaction
Kane, I., et al. (2016). "Arteriovenous Fistula Formation After Intra-articular Injection
Following Total Joint Arthroplasty." Orthopedics 39(5): e976-979.
Intra-articular joint capsule injection is a common method used to control postoperative pain
as a result of primary total knee arthroplasty (TKA). It is generally considered a safe practice
and is highly effective in reducing the need for postoperative opioid administration as well as
decreasing recovery time through early mobilization. However, any injection into the
posterior knee space has the potential to injure the vascular structures surrounding the knee.
Iatrogenic formation of an arteriovenous fistula is a rare complication after TKA, and there
are no reported cases of arteriovenous fistula formation as a direct result of intra-articular
injection. This case report describes this complication that occurred several days after TKA.
The patient had acute pain and swelling in the treated leg. An arteriovenous fistula of the
popliteal artery and vein was identified with bilateral Doppler ultrasound and confirmed by
angiogram. The most likely inciting event for the formation of the arteriovenous fistula was
intra-articular injection of bupivacaine, which likely pierced the popliteal artery and vein,
allowing the formation of the patent channel. The patient was treated successfully with stent
placement through interventional radiology. Orthopedic surgeons performing intra-articular
injections of the knee should refamiliarize themselves with the anatomy and location of the
popliteal artery, use smaller-gauge needles, and aspirate the syringe before the injection to
decrease the risk of iatrogenic damage to the vasculature or fistula formation.
Kaneko, K., et al. (2023). "Early treatment with Fibrinogen γ-chain peptide-coated,
ADP-encapsulated Liposomes (H12-(ADP)-liposomes) ameliorates post-partum
hemorrhage with coagulopathy caused by amniotic fluid embolism in rabbits." AJOG
Glob Rep 3(4): 100280.
BACKGROUND: Amniotic fluid embolism is an unpredictable and sometimes lethal
complication of childbirth. Fibrinogen γ-chain peptide-coated, ADP-encapsulated Liposomes
(H12-(ADP)-liposomes), which were developed as a platelet substitute, may be useful to
control postpartum hemorrhage with consumptive coagulopathy. OBJECTIVE: This study
aimed to establish a hemodynamically stable amniotic fluid embolism animal model and
evaluate the efficacy of H12-ADP-liposome infusion in the initial management of postpartum
hemorrhage complicated with amniotic fluid embolism-involved coagulopathy. STUDY
DESIGN: Pregnant New Zealand white rabbits (28th day of pregnancy or normal gestation
period of 29-35 days) underwent cesarean delivery, followed by intravenous administration of
amniotic fluid (a total of 3.0 mL administered in 4 doses over 9 minutes). Thereafter,
uncontrolled postpartum hemorrhage was induced by transecting the right midartery and
concomitant vein in the myometrium. After initial bleeding for 5 minutes, rabbits received
isovolemic fluid resuscitation through the femoral vein with an equivalent volume of blood
loss every 5 minutes for 60 minutes. The transfusion regimens included platelet-rich plasma,
platelet-poor plasma, and a bolus administration of H12-ADP-liposomes followed by plateletpoor plasma transfusion (8 rabbits per group). Moreover, 60 minutes after initiation of
bleeding, rabbits received surgical hemostasis by ligation of bleeding vessels, except in cases
with spontaneous hemostasis. RESULTS: The administration of amniotic fluid caused
thrombocytopenia (56±3 × 10(3)/μL) and prolonged both clotting time (before administration:
130.0±3.0 to 171.0±5.0 seconds) and prothrombin time (4.5±0.1 to 4.7±0.1 seconds). After
the initial 5-minute bleeding in the rabbits, the mean arterial pressure fell to 43±2 mm Hg.
Platelet-poor plasma transfusion alone further prolonged clotting time and prothrombin time
at 60 minutes (192.0±10.0 and 5.2±0.1 seconds, respectively) with decreasing mean arterial
pressure to <40 mm Hg. By contrast, the administration of H12-ADP-liposomes followed by
platelet-poor plasma transfusion reduced the prolonged clotting time (153.0±5.0 seconds) and
prothrombin time (4.9±0.1 seconds) similar to platelet-rich plasma transfusion (154.0±11.0
and 4.9±0.1 seconds, respectively) at 60 minutes. These rabbits maintained a mean arterial
pressure of >45 mm Hg throughout the experiment. H12-ADP-liposome infusion and plateletKang, H. J., et al. (2014). "Cancer pain control for advanced cancer patients by using
autonomic nerve pharmacopuncture." J Pharmacopuncture 17(3): 62-69.
OBJECTIVES: The purpose of this study is to report a case series of advanced cancer
patients whose cancer pain was relieved by using autonomic nerve pharmacopuncture (ANP)
treatment. ANP is a subcutaneous injection therapy of mountain ginseng pharmacopuncture
(MGP) along the acupoints on the spine (Hua-Tuo-Jia-Ji-Xue; 0.5 cun lateral to the lower
border of the spinous processes of vertebrae) to enhance the immune system and to balance
autonomic nerve function. METHODS: Patients with three different types of cancer (gastric
cancer, lung cancer, colon cancer with distant metastases) with cancer pain were treated with
ANP. 1 mL of MGP was injected into the bilateral Hua-Tuo-Jia-Ji-Xue on the T1-L5 sites
(total 12 ─ 20 mL injection) of each patient's dorsum by using the principle of symptom
differentiation. During ANP treatment, the visual analogue scale (VAS) for pain was used to
assess their levels of cancer pain; also, the dosage and the frequency of analgesic use were
measured. RESULTS: The cancer pain levels of all three patients improved with treatment
using ANP. The VAS scores of the three patients decreased as the treatment progressed. The
dosage and the frequency of analgesics also gradually decreased during the treatment period.
Significantly, no related adverse events were found. CONCLUSION: ANP has shown benefit
in controlling cancer pain for the three different types of cancer investigated in this study and
in reducing the dosage and the frequency of analgesics. ANP is expected to be beneficial for
Kato, K., et al. (2013). "Intravenous administration of granulocyte colony-stimulating
factor for treating neuropathic pain associated with compression myelopathy: a phase
I and IIa clinical trial." Eur Spine J 22(1): 197-204.
OBJECTIVE: To confirm the feasibility and safety of granulocyte colony-stimulating factor
(G-CSF) for treating spinal neuropathic pain associated with compression myelopathy, we
have initiated an open-label single-center prospective clinical trial. METHODS: Between
January 2009 and February 2011, 17 patients were accrued and were divided into two groups.
One group included 7 patients who complained of pain associated with worsening symptoms
of myelopathy (progressing myelopathy-related pain group). The other group included 10
patients who complained of pain that persisted after surgery for compression myelopathy
(post-operative persistent pain group). All patients underwent intravenous administration of
G-CSF (10 μg/kg/day) for 5 consecutive days. Pain severity was evaluated using a visual
analog scale (VAS) before and after G-CSF administration. RESULTS: In 14 of the 17
patients, pain was relieved within several days after G-CSF administration. Pain disappeared
completely in 3 patients. In the progressing myelopathy-related pain group, the mean VAS
score was 71.4/100 before G-CSF administration, and decreased to 35.9/100 at 1 week after
G-CSF administration (p < 0.05). In the post-operative persistent pain group, the mean VAS
score was 72.0/100 before G-CSF administration, and decreased to 51.7/100 at 1 week after
G-CSF administration (p < 0.05). No severe adverse events occurred during or after G-CSF
administration. CONCLUSIONS: The present results provide us with the possibility that GCSF has a pain-relieving effect for neuropathic pain in patients with compression
Kien, N. T., et al. (2019). "Successful intralipid-emulsion treatment of local anesthetic
systemic toxicity following ultrasound-guided brachial plexus block: case report." Int
Med Case Rep J 12: 193-197.
BACKGROUND: Local anesthetic systemic toxicity (LAST) is a life-threatening
complication that may follow application of LAs through various routes. Despite increasing
usage of LA techniques in a large number of health-care settings, contemporary awareness of
LAST and understanding of its management are inadequate. CASE PRESENTATION: We
report two cases who suffered LAST following brachial plexus block for surgery on the upper
extremity. The first patient received an ultrasound-guided supraclavicular block with 300 mg
lidocaine (6 mg/kg) and 50 mg ropivacaine (1 mg/kg) in 25 mL without epinephrine, and the
second patient received an ultrasound guided interscalene block with 200 mg lidocaine (4.5
mg/kg) and 45 mg ropivacaine (1 mg/kg) supplemented with epinephrine 1:200,000. Both
patients presented with symptoms of central nervous and respiratory system depression, the
first roughly 10 minutes after injection, and the second immediately after withdrawal of the
needle. In both cases, thorough recovery was obtained using lipid-emulsion therapy.
CONCLUSION: The complication of LAST following ultrasound-guided brachial plexus
block could be treated successfully applying the American Society of Regional Anesthesia
and Pain Medicineprotocol of intravenous administration of lipid emulsion.
Kim, C. Y., S. B. Choi and E. S. Lee (2024). "Prevalence and predisposing factors of
post-stroke complex regional pain syndrome: Retrospective case-control study." J
Stroke Cerebrovasc Dis 33(2): 107522.
King, J. N., et al. (2016). "Clinical safety of robenacoxib in feline osteoarthritis:
results of a randomized, blinded, placebo-controlled clinical trial." J Feline Med Surg
18(8): 632-642.
INTRODUCTION: Poststroke complex regional pain syndrome (CRPS) is an important
complication in stroke survivors. The identification of factors associated with post-stroke
CRPS is important for preventive measures and early diagnosis. METHODS: A total of 141
first-ever stroke survivors in the subacute stage were retrospectively analyzed. Demographic
data, diagnosis time, duration of hospitalization, location of brain lesion, etiology,
comorbidities, and blood test findings were investigated. Clinical data included Medical
Research Council (MRC) grade, Fugl-Meyer assessment (FMA), National Institute for Health
Stroke Scale (NIHSS), Berg Balance Scale (BBS). RESULTS: Among 141 patients with
subacute stroke, 22 were diagnosed with CRPS, with a prevalence of 15.6 %. The mean time
to diagnosis was 38.6 (±16.5) days. The prevalence according to the degree of paralysis was
33.3 % in MRC grades 0 and 1, 8.6 % in grade 2, and 0 % in grade 3 or higher. The incidence
rates within 1 month after stroke were 1.42 % and 22.47 % between 1 and 3 months after
stroke, respectively. The independent risk factors for CRPS were hospitalization duration and
FMA, NIHSS, and BBS scores. The sensitivity and specificity of the NIHSS score for
predicting post-stroke CRPS were 86.4 % and 59.7 %, respectively, with an optimal cutoff
value of 7.5. CONCLUSIONS: CRPS of the affected upper limb in stroke patients is
associated with stroke severity, including paralysis, and the incidence increases over time
during the subacute phase. Additionally, having sufficient strength to move through a full
OBJECTIVES: The objective of this study was to evaluate the clinical safety of the nonsteroidal anti-inflammatory drug (NSAID) robenacoxib in cats with osteoarthritis.
Degenerative joint disease, including osteoarthritis, is highly prevalent in cats and many cases
have associated pain and impaired mobility. Although NSAIDs are used routinely to control
pain and inflammation in cats with osteoarthritis, there are safety concerns because of the
high concurrent prevalence of chronic kidney disease (CKD) and the paucity of data on the
safety of these drugs in target clinical populations. METHODS: A total of 194 cats with
osteoarthritis were recruited and randomly allocated to receive either robenacoxib at a dosage
of 1.0-2.4 mg/kg (n = 95) or placebo (n = 99) tablets PO q24h for 28 days. Safety was
assessed in 193 cats, including a subgroup of 40 animals with concurrent CKD, defined as
serum creatinine concentration ⩾ 1.6 mg/dl and urine specific gravity <1.030. Safety
endpoints included reports of adverse events, results of clinical examinations, including body
weight, and clinical chemistry and hematology variables. RESULTS: In all 193 cats and the
subgroup of 40 animals with concurrent CKD, there were no differences between groups in
frequencies of reported adverse events, body weight change or results of serum or urine
chemistry or hematology variables. CONCLUSIONS AND RELEVANCE: Robenacoxib was
well tolerated when administered daily for 1 month in cats with osteoarthritis, including cats
with evidence of concurrent CKD. There was no clinical indication of damage to the
Kivett, L., J. Taintor and J. Wright (2014). "Evaluation of the safety of a combination
of oral administration of phenylbutazone and firocoxib in horses." J Vet Pharmacol
Ther 37(4): 413-416.
Simultaneous administration of a nonselective COX inhibitor and a COX-2 specific NSAID
has not been previously reported in horses. The goal of this study was to determine the safety
of a 10-day dosage regimen of phenylbutazone and firocoxib, both at their standard dosages,
in horses. Six horses were administered 2.2 mg/kg of phenylbutazone and 0.1 mg/kg of
firocoxib by mouth, daily for 10 days. Horses were assessed daily for changes in behavior,
appetite, fecal consistency, signs of abdominal pain, and oral mucous membrane ulceration.
Horses were assessed prior to and on the last day of treatment for changes in serum
creatinine, albumin, total protein, and urine-specific gravity. Horses underwent endoscopic
examination of the esophagus, stomach, and pylorus prior to and 24 hours after the last
treatment. A significant change in serum creatinine and total protein was observed on day 10
of treatment. No other significant findings were noted during the experiment. Results
indicated that co-administration of phenylbutazone and firocoxib may cause renal disease.
Klerx, S. P., et al. (2022). "Associations between primary motor cortex organization,
motor control and sensory tests during the clinical course of low back pain. A protocol
for a cross-sectional and longitudinal case-control study." Contemporary Clinical
Trials Communications 30: 101022.
Kogan, L. R. and K. A. Cooney (2023). "Defining a "Good Death": Exploring
Veterinarians' Perceptions of Companion Animal Euthanasia." Animals (Basel)
13(13).
Background In people with low back pain (LBP), altered motor control has been related to
reorganization of the primary motor cortex (M1). Sensory impairments in LBP have also been
suggested to be associated with reorganization of M1. Little is known about reorganization of
M1 over time in people with LBP, and whether it relates to changes in motor control and
sensory impairments and recovery. This study aims to investigate 1) differences in
organization of M1 of trunk muscles between people with and without LBP, and whether the
organization of M1 relates to motor control and sensory impairments (cross-sectional
component) and 2) reorganization of M1 over time and its relation with changes in motor
control and sensory impairments and experienced recovery (longitudinal component).
Methods A case-control study with a cross-sectional and five-week longitudinal component is
conducted in participants with LBP (N = 25) and participants without LBP (N = 25).
Participants with LBP received usual care physiotherapy. Various tests were administered at
baseline and follow-up. Following an anatomical MRI, organization of M1 (Center of Gravity
and Area of the cortical representation of trunk muscles) was determined using transcranial
magnetic stimulation. Quantitative sensory testing, a spiral-tracking motor control test,
graphesthesia, two-point discrimination threshold and various self-reported questionnaires
were also assessed. Multivariate multilevel analysis will be used for statistical analysis.
Conclusion We will address the gaps in knowledge about the association between
reorganization of M1 and motor control and sensory tests during the clinical course of LBP.
This study was designed to determine how veterinarians define a good euthanasia experience.
This information is used to generate a working definition of companion animal euthanasia
that aligns with animal welfare standards and pet owners' expectations. An electronic survey
distributed via veterinary-related social media (Facebook, Instagram) and listservs were
completed by 249 veterinarians who perform feline and/or canine euthanasia. Our results
suggest that very few veterinarians feel their veterinary school training adequately prepared
them for euthanasia. When veterinarians were asked to rank a list of physiologic conditions
and anatomical traits in order of euthanasia-related concerns, respiratory distress was ranked
the highest, while the most concerning physical changes were reported to be indications or
impressions of seizures or pain. The most commonly reported euthanasia injection technique
performed by participants was intravenous administration of pentobarbital sodium (97%), and
most veterinarians preferred having owners present (57%) or having no preference (38%)
during euthanasia. Results suggest that veterinarians want a pain-free, anxiety-free experience
for the patient, appreciate the use of sedatives before euthanasia, and feel that when available
and appropriate, home euthanasia offers several benefits. This understanding of the numerous
aspects involved in a good euthanasia experience can help inform the creation of an updated
definition of companion animal euthanasia that strives to prioritize the welfare of the patient
Kolosov, A., C. S. Goodchild and I. Cooke (2010). "CNSB004 (Leconotide) causes
antihyperalgesia without side effects when given intravenously: a comparison with
ziconotide in a rat model of diabetic neuropathic pain." Pain Med 11(2): 262-273.
OBJECTIVE: Leconotide is an omega-conotoxin that blocks neuronal voltage sensitive
calcium channels. This study compared the antihyperalgesic potencies of leconotide and
ziconotide given intravenously alone and in combinations with a potassium channel
modulator flupirtine, given intraperitoneally, in a rat model of diabetic neuropathic pain.
DESIGN: Rats were given streptozotocin (150 mg/kg ip) to induce diabetic neuropathy and
hyperalgesia. Experiments were performed on diabetic rats with >or=30% hyperalgesia to
noxious heat. Rats were given each conopeptide alone and with flupirtine. Open field activity
monitoring and non-invasive blood pressure measurements were used to define the maximum
doses and combinations that caused no side effects. Doses in a range up to maximum no side
effect doses were tested for antihyperalgesic effects in rats with hyperalgesia. RESULTS:
The maximum no side effect dose of leconotide (2 mg/kg intravenously) caused 51.7%
reversal of hyperalgesia compared with 0.4% for the highest no side effect dose of ziconotide
(0.02 mg/kg; P < 0.001, one-way anova). Leconotide caused dose-related antihyperalgesic
effects that were potentiated by coadministration with flupirtine at doses that were ineffective
when given alone. Leconotide (0.02 mg/kg) and flupirtine (5 mg/kg) caused 25.3 +/- 7.6 and 6 +/- 9.5% reversal of hyperalgesia, respectively when given alone but in combination they
caused 84.1 +/- 7.2% reversal of hyperalgesia (P < 0.01; one-way anova). No such interaction
occurred with ziconotide. CONCLUSION: Leconotide could have wider clinical applications
than ziconotide. Unlike ziconotide, powerful antihyperalgesia without side effects can be
achieved by intravenous administration of leconotide thus avoiding the need for an intrathecal
Korah, M. C., et al. (2023). "Pharmacological safety of dimethoxy curcumin-human
serum albumin conjugate for potential therapeutic purpose." Can J Physiol Pharmacol
101(6): 304-315.
Medicinal properties of curcumin are widely published. Previously, researchers used
curcuminoid mixture comprising three chemical forms, out of which, the highest quantity is
the most active molecule-dimethoxy curcumin (DMC). Reduced bioavailability, poor aqueous
solubility, and quick hydrolytic degradation of DMC have projected challenges limiting its
therapeutic value. However, selective conjugation of DMC with human serum albumin
(HSA) enhances drug stability and solubility by several folds. Studies using animal models
demonstrated potential anti-cancer/anti-inflammatory effects of DMCHSA; both studies
showed results of local administration in peritoneal cavity and rabbit knee joint. DMC has
prospects as intravenous therapeutic agent because carrier is HSA. However, before in vivo
testing, important preclinical data required are toxicological safety and bioavailability of
soluble forms of DMC. This study evaluated absorption, distribution, metabolism, and
excretion of DMCHSA. Imaging technology and molecular analysis proved bio-distribution.
The study also assessed the pharmacological safety of DMCHSA in mice in terms of its acute
and sub-acute toxicity, complying with regulatory toxicology. Overall, the study
demonstrated the safety pharmacology of DMCHSA upon intravenous infusion. This is a
novel study establishing the safety of highly soluble and stable formulation of DMCHSA,
Ladeb, S., et al. (2018). "Plasmodium falciparum infection transmitted by transfusion:
A cause of hemophagocytic syndrome after bone marrow tranplantation in a nonendemic country." Transpl Infect Dis 20(3): e12887.
A 27-year-old man with severe aplastic anemia underwent bone marrow transplantation from
his HLA identical brother in July 2016. Conditioning included ATGAM 30 mg/kg for 3 days
and Cyclophosphamide 50 mg/kg for 4 days. The patient received several platelet and red
blood cell transfusions before and after the conditioning. The patient received broad spectrum
antibiotics and caspofungin because persistant febrile neutropenia without bacteriological or
mycological documentation. Hemophagocytic syndrome was diagnosed on day +12. Steroids
at 1 mg/kg were started on day +12. Fever resolved the same day but resumed 3 days later
associated to intravascular hemolysis with no schizocytes on blood smears and negative
DAT. Thick blood film smears performed on day +26 revealed Plasmodium falciparum
parasites (parasitemia = 20%). Except the level of parasitemia, there were no signs of gravity.
Quinine was started on day 26 at a loading dose of 15 mg/kg followed by 8 mg/kg three times
a day for 20 doses. Fever vanished after 2 days. Parasitemia cleared in 3 days and remained
negative thereafter. Investigations revealed that the patient was transfused by a red cell unit
harvested in a voluntary donor native of a malaria endemic country. PCR for P. falciparum
performed in this donor in the frame of investigations was positive. The patient is alive with a
Lee, I. H., H. S. Shin and D. J. Ahn (2022). "A forgotten double-J ureteral stent
resulting in an emphysematous perinephric abscess: A case report." Medicine
(Baltimore) 101(25): e29418.
Lee, K. J., et al. (2022). "Performance comparison of intraosseous devices and setups
for infusion of whole blood in a cadaveric swine bone model." Am J Emerg Med 54:
58-64.
RATIONALE: Double-J stents (DJSs) are urologic devices widely used for urinary tract
obstruction treatment. Perinephric abscess is a condition with purulent accumulation resulting
from urinary tract infection retained between the renal capsule and Gerota's fascia.
Emphysematous urinary tract infection in patients with a forgotten DJS is extremely rare.
Herein, we report a case of emphysematous perinephric abscess as a complication in a 56year-old non-diabetic woman who neglected a 10-year-old DJS placed for obstructive
uropathy treatment. PATIENT CONCERNS: The patient presented with fever and abdominal
pain that persisted for 4 days. Laboratory examinations showed leukocytosis,
hypoalbuminemia (2.3 g/dL), and elevated C-reactive protein level (305.5 mg/L) with no
azotemia. DIAGNOSIS: Abdominal computed tomography scan revealed a DJS with
encrustation and multiple stones in the right kidney as well as a perinephric abscess with gas
formation. INTERVENTIONS: Intravenous administration of piperacillin/tazobactam was
initiated immediately and percutaneous catheter drainage was performed. Extended-spectrum
beta-lactamase-producing Escherichia coli was identified on abscess culture and antibiotics
were switched to meropenem, resulting in gradual improvement of the inflammatory lesion.
The patient was referred to the urology department for retained DJS removal and
vesicolitholapaxy. A piece of fractured stent was removed via open ureterolithotomy.
OUTCOMES: Since discharge on hospital day 42, she has been under regular follow-up, and
the surgical wound has been healing with no significant sequelae. LESSONS: Prompt
medical therapy for inflammation and thorough urologic correction of the stent-induced
structural deformities are crucial in long-term neglected DJS and resulting emphysematous
perinephric abscess. Patients who undergo DJS placement should be systematically followed
OBJECTIVES: Intraosseous (IO) access can provide a critical bridge for blood product
infusion when peripheral venous access is not obtainable. Successful pressurized IO infusion
requires flow rates sufficient to preserve life, but with infusion pressures low enough to avoid
clinical complications (e.g., hemolysis, bone damage, fat emboli). However, the optimal
method for pressured IO delivery of blood was unknown. METHODS: Three trained
physicians infused 500 mL of whole blood through a 15-gauge, 45 mm IO catheter into fresh,
high bone density cadaveric swine proximal humeri. Participants applied eight different
pressure infusion strategies: (1) gravity, (2) pressure bag, (3) pressure bag actively
maintained at or above 300 mmHg, (4) hand pump, (5) hand pump with pressure bag, (6)
push-pull with 10 mL syringe, (7) push-pull with 60 mL syringe, and a (8) Manual Rapid
Infuser in a randomized within-subjects design (30 trials per method, 240 trials total). The
primary outcomes of flow rates, mean and peak pressures, and user ratings were contrasted
using ANOVA at p < 0.05. RESULTS: The Manual Rapid Infuser conferred the highest flow
rates (199 ± 3 mL/min) and most favorable user ratings, but also the highest mean and peak
pressures. Push-pull conferred the next highest flow rates (67 ± 5 mL/min for 60 mL, 56 ± 2
mL/min for 10 mL) and pressures, with intermediate-to-high user ratings. Hand pump flow
rates were essentially identical with (45 ± 4 mL/min) or without (44 ± 3 mL/min) pressure
bag, with high user ratings without a pressure bag. Pressure bag and gravity methods
conferred low flow rates and user ratings. CONCLUSIONS: Some pressured IO infusion
methods can achieve flow rates adequate to serve as a resuscitative bridge in the massively
hemorrhaged trauma victim, but flow rates and pressures vary greatly across IO pressurized
infusion methods. Manual Rapid Infuser and push-pull methods conferred high flow rates but
also relatively high pressures, highlighting the importance of using in vivo models in future
research to assess the possible clinical complications of using these promising methods.
Combined, present findings highlight the importance of studying pressurized IO methods
Lee, N. A., et al. (2022). "Antiphospholipid syndrome with renal and splenic
infarction after blunt trauma: A case report." World J Clin Cases 10(26): 9404-9410.
BACKGROUND: In trauma patients, bleeding is an immediate major concern. At the same
time, there are few cases of acute vascular occlusion after blunt trauma, and it is unclear what
assessment and diagnosis should be considered for these cases. Herein, we describe a patient
diagnosed with antiphospholipid syndrome after a hypercoagulable workup for acute renal
and splenic vascular occlusion due to blunt trauma. CASE SUMMARY: A 20-year-old man
was admitted to the emergency department with abdominal pain after hitting a tree while
riding a sled 10 h ago. He had no medical history. Radiological investigations revealed
occlusion of the left renal artery with global infarction of the left kidney and occlusion of
branches of the splenic artery with infarction of the central portion of the spleen. Attempted
revascularization of the left renal artery occlusion through percutaneous transluminal
angioplasty failed due to difficulty in passing the wire through the total occlusion.
Considering the presence of acute multivascular occlusions in a young man with low
cardiovascular risk, additional laboratory tests were performed to evaluate
hypercoagulability. The results suggested a high possibility of antiphospholipid syndrome.
Treatment with a subcutaneous injection of enoxaparin was started and changed to oral
warfarin after two weeks. The diagnosis was confirmed, and he continued to visit the
rheumatology outpatient clinic while taking warfarin. CONCLUSION: A hypercoagulable
workup can be considered in trauma patients with acute multivascular occlusion, especially in
Lesniak, W. G., et al. (2019). "A Distinct Advantage to Intraarterial Delivery of
(89)Zr-Bevacizumab in PET Imaging of Mice With and Without Osmotic Opening of
the Blood-Brain Barrier." J Nucl Med 60(5): 617-622.
Glioblastoma multiforme (GBM) is the most aggressive and common type of brain cancer.
Five-year survival rates are below 12%, even with the most aggressive trimodal therapies.
Poor blood-brain barrier (BBB) permeability of therapeutics is a major obstacle to efficacy.
Intravenous administration of bevacizumab is the standard treatment for GBM. It has been
recently demonstrated that a single intraarterial infusion of bevacizumab provides superior
therapeutic outcomes in patients with recurrent GBM. Further GBM treatment benefits can be
achieved through opening of the BBB before intraarterial infusion of bevacizumab. However,
a rationale for intraarterial delivery and BBB opening when delivering antibodies is lacking.
A method facilitating quantification of intraarterial delivery of bevacizumab is needed for
more effective and personalized GBM treatment. Here, we demonstrate such a method using
PET imaging of radiolabeled bevacizumab. Methods: Bevacizumab was conjugated with
deferoxamine and subsequently radiolabeled with (89)Zr. (89)Zr-bevacizumab deferoxamine
((89)Zr-BVDFO) was prepared with a specific radioactivity of 81.4 ± 7.4 MBq/mg (2.2 ± 0.2
μCi/mg). Brain uptake of (89)Zr-BVDFO on carotid artery and tail vein infusion with an
intact BBB or with BBB opening with mannitol was initially monitored by dynamic PET,
followed by whole-body PET/CT at 1 and 24 h after infusion. Th ex vivo biodistribution of
(89)Zr-BVDFO was also determined. Results: Intraarterial administration of (89)Zr-BVDFO
resulted in gradual accumulation of radioactivity in the ipsilateral hemisphere, with 9.16 ±
2.13 percentage injected dose/cm(3) at the end of infusion. There was negligible signal
observed in the contralateral hemisphere. BBB opening with mannitol before intraarterial
infusion of (89)Zr-BVDFO resulted in faster and higher uptake in the ipsilateral hemisphere
(23.58 ± 4.46 percentage injected dose/cm(3)) and negligible uptake in the contralateral
hemisphere. In contrast, intravenous infusion of (89)Zr-BVDFO and subsequent BBB
opening did not lead to uptake of radiotracer in the brain. The ex vivo biodistribution results
validated the PET/CT studies. Conclusion: Our findings demonstrate that intraarterial
delivery of bevacizumab into the brain across an osmotically opened BBB is effective, in
Li, W., et al. (2017). "LC-MS/MS determination of a human mAb drug candidate in
rat serum using an isotopically labeled universal mAb internal standard." J
Chromatogr B Analyt Technol Biomed Life Sci 1044-1045: 166-176.
We report the application of a liquid chromatography-tandem mass spectrometry (LCMS/MS) bioanalytical method for the determination of a recombinant human
immunoglobulin G1 (hIgG1), NVSMAb-1, in rat serum. A stable isotopically labeled
universal monoclonal antibody (SILuMab), instead of stable isotopically labeled surrogate
peptide, was employed as the internal standard. The internal standard was added to the
sample matrix in the first step of the sample preparation process, which involved protein
precipitation and pellet digestion. The digestion of the resulting pellet with trypsin was
performed prior to analysis of surrogate peptides of both NVSMAb-1 and SILuMab using
LC-MS/MS. Precipitation reagents (1% TCA in IPA, 75% MeOH and 14% PEG) and
digestion conditions (50°C for 2h and 60°C for 0.5h) were evaluated by monitoring LCMS/MS responses of GPS and VVS in the resulting sample extracts. Overall, the use of 1%
TCA in IPA appeared to be more effective as compared to 75% methanol in protein
precipitation and removal of unwanted matrix components, e.g., albumin, and more appealing
than 14% PEG as it avoided additional steps that are necessary to remove PEG or reduce
PEG to a negligible level. The yield (LC-MS/MS response) of GPS is less sensitive than VVS
to the changes of digestion conditions (time and temperature). The results obtained using
SILuMab over SIL surrogate peptide as the internal standard appeared unaffected by the
suboptimal sample processing method. For the current assay, surrogate peptide
GPSVFPLAPSSK (GPS) was selected as surrogate peptide over VVSVLTVLHQDWLNGK
(VVS) for quantitative analysis of NVSMAb-1. The optimal chromatographic separation was
achieved on a Waters Cortecs C18 (100×2.1mm, 2.7μm) column using gradient elution with a
total cycle time of approximately 8min. The mobile phases were water containing 0.1%
formic acid (mobile phase A) and acetonitrile containing 0.1% formic acid (mobile phase B).
The current method was validated for specificity, sensitivity, matrix effect, recovery,
linearity, accuracy and precision, dilution integrity, and stability. The validated assay
dynamic range was 10-5000μg/mL using 20μL of rat serum. The accuracy and precision for
the LLOQs (10μg/mL) were within ±6.0% bias and ≤6.5% CV, respectively. From the intraday and inter-day assay performance evaluations, the precision of the other QC sample (30,
Lim, A. S. L., A. A. B. Sali and J. P. Y. Cheung (2020). "Iatrogenic biological fracture
of the cervical spine during gradual halo traction for kyphotic deformity correction:
case report." BMC Musculoskelet Disord 21(1): 318.
BACKGROUND: Severe kyphotic deformities carry high risk for neurological injuries as
osteotomies are often required for correction. Surgeons often utilize a staged approach for
dealing with these conditions starting with a period of halo traction to stretch tight soft tissues
and partially correct the deformity, followed by surgery. Halo traction is a relatively safe
procedure and complications are uncommon. We report a unique case of iatrogenic fracture
of the cervical spine during gradual halo traction for deformity correction of a severe cervical
kyphosis. CASE PRESENTATION: An 80-year-old female with previous cervical spine
tuberculosis infection and C5-C6 anterior spinal fusion developed severe cervical kyphosis of
64° from C2-C6 and neck pain requiring deformity correction surgery. Gradual increase in
traction weight was applied, aiming for a maximum traction weight of 45 pounds or half body
weight. During the 1st stage halo-gravity traction, sudden neck pain and a loud cracking
sound was witnessed during increase of the traction weight to 14 pounds. Imaging revealed a
fracture through the C4 and reduction in kyphosis deformity to 11° from C2-C6. There was
no neurological deficit. No further traction was applied and the patient underwent an in-situ
occipital to T3 fusion without osteotomies. At 3-year follow-up, the patient was symptomfree and radiographs showed solid fusion and maintenance of alignment. CONCLUSIONS:
Iatrogenic fracture may occur with halo traction. Elderly patients with osteoporotic and
diseased bone should be closely monitored during the treatment. A fracture without
complications was a fortunate complication as the patient was able to avoid any high-risk
Lin, Y. H., et al. (2016). "Significant symptoms alleviation and tumor volume
reduction after combined simultaneously integrated inner-escalated boost and
volumetric-modulated arc radiotherapy in a patient with unresectable bulky
hepatocellular carcinoma: A care-compliant case report." Medicine (Baltimore)
95(34): e4717.
BACKGROUND: Clinically, elderly patients with unresectable bulky hepatocellular
carcinoma (HCC) are difficult to manage, especially in those with co-infections of hepatitis B
and C virus. Herein, we reported such a case treated with radiotherapy (RT) by using
combined simultaneously integrated inner-escalated boost and volumetric-modulated arc
radiotherapy (SIEB-VMAT). After RT, significant symptoms alleviation and durable tumor
control were observed. CASE SUMMARY: At presentation, an 85-year-old male patient
complained abdominal distention/pain, poor appetite, and swelling over bilateral lower limbs
for 1 month. On physical examination, a jaundice pattern was noted. Laboratory studies
showed impaired liver and renal function. Abdominal computed tomography (CT) revealed a
12.5-cm bulky tumor over the caudate lobe of the liver. Biopsy was done, and hepatocellular
carcinoma (HCC) was reported histopathologically. As a result, AJCC stage IIIA
(cT3aN0M0) and BCLC stage C were classified. Surgery, radiofrequency ablation (RFA),
trans-catheter arterial chemoembolization (TACE), and sorafenib were not recommended
because of his old age, central bulky tumor, and a bleeding tendency. Thus, RT with SIEBVMAT technique was given alternatively. RT was delivered in 26 fractions, with dose
gradience as follows: 39 Gy on the outer Plan Target Volume (PTV), 52 Gy in the middle
PTV, and 57.2 Gy in the inner PTV. Unexpectedly, cyproheptadine (a newly recognized
potential anti-HCC agent) was retrospectively found to be prescribed for alleviating skin
itching and allergic rhinitis since the last 2 weeks of the RT course (2 mg by mouth Q12h for
24 months).After RT, significant symptoms alleviation and tumor volume reduction were
observed for 32 months till multiple bone metastases. Before and after RT, a large tumor
volume reduction rate of 88.7% was observed (from 608.4 c.c. to 68.7 c.c.). No severe
treatment toxicity was noted during and after RT. The patient died due to aspiration
pneumonia with septic shock at 4 months after bone metastases identified. CONCLUSIONS:
SIEB-VMAT physically demonstrated double benefits of intratumor dose escalation and
extra-tumor dose attenuation. Significant tumor regression and symptoms alleviation were
observed in this elderly patient with unresectable bulky HCC. Further prospective
randomized trials are encouraged to demarcate effective size of SIEB-VMAT with or without
Linguanti, F., et al. (2022). "Metabolic Imaging in B-Cell Lymphomas during CAR-T
Cell Therapy." Cancers (Basel) 14(19).
Chimeric antigen receptor-engineered (CAR) T cells are emerging powerful therapies for
patients with refractory/relapsed B-cell lymphomas. [(18)F]FDG PET/CT plays a key role
during staging and response assessment in patients with lymphoma; however, the evidence
about its utility in CAR-T therapies for lymphomas is limited. This review article aims to
provide an overview of the role of PET/CT during CAR-T cell therapy in B-cell lymphomas,
focusing on the prognostic value of metabolic parameters, as well as on response assessment.
Data from the literature report on the use of [(18)F]FDG PET/CT at the baseline with two
scans performed before treatment started focused on the time of decision (TD) PET/CT and
time of transfusion (TT) PET/CT. Metabolic tumor burden is the most studied parameter
associated with disease progression and overall survival, making us able to predict the
occurrence of adverse effects. Instead, for post-therapy evaluation, 1 month (M1) PET/CT
seems the preferable time slot for response assessment and in this setting, the Deauville 5point scale (DS), volumetric analyses, SUVmax, and its variation between different time
points (∆SUVmax) have been evaluated, confirming the usefulness of M1 PET/CT,
especially in the case of pseudoprogression. Additionally, an emerging role of PET/CT brain
scans is reported for the evaluation of neurotoxicity related to CAR-T therapies. Overall,
PET/CT results to be an accurate method in all phases of CAR-T treatment, with particular
interest in assessing treatment response. Moreover, PET parameters have been reported to be
Liu, J., et al. (2022). "The rare complication caused by thrombus shedding during
arteriovenous fistula thrombolysis: a case report." Ann Palliat Med 11(9): 3014-3019.
BACKGROUND: Arteriovenous fistula is the lifeline of maintenance for patients requiring
hemodialysis, with thrombosis being a common complication of this procedure. Traditionally,
thrombi have been removed via thrombectomy. In recent years, it has been reported that
newly occurring thrombi can be treated by urokinase thrombolysis. However, the thrombus
shedding in the process should be valued, which may cause the distal limb ischemia
syndrome. The complication of thrombolysis is rare but serious. Patients will experience pain
and numbness, and possibly even extremity necrosis may occur without diagnosed or treated
timely. There are not any reports about the occurrence or treatment of distal limb ischemia
syndrome caused by thrombus shedding during thrombolysis. CASE DESCRIPTION:
Considering the thrombosis volume and texture of this case, we attempted to use urokinase
thrombolysis to resolve the thrombus in fistula. During thrombolysis, thrombus shedding
occurred in the distal limb. The patient's fingers of the limbs on the side of the internal fistula
were pale, numb, and painful in the case. Fortunately, we solved the problem ultimately by
continuously pumping urokinase. The heparin, urokinase, infusion pumps, ultrasound, and
infrared therapy devices were obtained from the Affiliated Hospital of Chuanbei Medical
College. Their usage and dosage are described in the relevant literature and China's 2020
blood purification standard operating procedures. CONCLUSIONS: In the process of
thrombolysis of arteriovenous fistula, attention should be paid to thrombus shedding. Distal
limb ischemia syndrome is a rare but serious complication of thrombus shedding. Continued
Liu, P., et al. (2011). "Continuous intravertebral injection of fasudil hydrochloride in
the treatment of cerebral vasospasm." Neurol India 59(2): 161-167.
BACKGROUND AND OBJECTIVE: Cerebral vasospasm is a serious complication of
subarachnoid hemorrhage (SAH) and is associated with clinical deterioration and mortality.
The objective of this study is to investigate the effect of continuous intravertebral artery
(cIVA) injection of fasudil hydrochloride on delayed cerebral vasospasm (CVS).
MATERIAL AND METHODS: Forty white rabbits were alloted into groups: (i) seven-day
(cIVA injection of fasudil hydrochloride for seven days after injection of blood) group, (ii)
five-day (cIVA injection of fasudil hydrochloride for five days from the third day after
injection of blood) group, (iii) intravenous treatment (intravenous infusion of fasudil
hydrochloride after the first blood injection twice a day) group, and (iv) control group. All the
rabbits in all the four groups underwent selective vertebrobasilar angiography. The
pathological changes in the basal artery were observed by light and electron microscopy.
Fasudil hydrochloride injection (2ml:30mg) was provided by Tianjin Chase Sun
Pharmaceutical Company Limited. RESULTS: Severe CVS occurred after subarachnoid
hemorrhage (SAH) in the control group, whereas, it was significantly lower after
intravertebral artery and intravenous injection of fasudil hydrochloride. The difference
between the intravenous and intravertebral artery groups was statistically significant on the
seventh day. CONCLUSIONS: The effect of cIVA injection of fasudil hydrochloride in
Lu, H. F., C. T. Yue and W. M. Kung (2022). "Salmonella Group D1 Subdural
Empyema Mimicking Subdural Hematoma: A Case Report." Infect Drug Resist 15:
6357-6363.
Subdural empyema is caused by various pathogens. The most typical clinical presentation
may include fever, headache, seizures, and altered consciousness. However, Salmonella
infections are relatively rare. Representative features of Salmonella infection include fever
and gastrointestinal symptoms such as diarrhea, vomiting, and abdominal cramping pain.
Extra-gastrointestinal invasion of Salmonella in the central nervous system is unusual. We
present the case of an afebrile 58-year-old male who presented with a headache and a
progressive dull response for a week. He had a closed head injury approximately 1 week
before this visit. A tentative diagnosis led to a subdural hematoma (SDH), and he underwent
urgent burr hole surgery. Intraoperative findings showed a large amount of brown-yellow pus
in the subdural space instead of the pathognomonic bloody serosanguinous or thick motor oil,
which is typical of SDH. The intraoperative culture yielded Salmonella group D1. After
initial brain surgery and 52 days of effective intravenous administration of a third-generation
cephalosporin (Ceftriaxone 2000 mg per day), the patient recovered fully without
neurological deficits. His consciousness and mentality remained normal without focal
weakness of the limbs for over 5 years of follow-up. This is a unique case with an atypical
initial presentation that leads to a final unexpected diagnosis. Ongoing treatment strategies
Lu, W. D., et al. (2022). "Pharmacodynamics, toxicology and toxicokinetics of
ropivacaine oil delivery depot." BMC Anesthesiol 22(1): 113.
BACKGROUND: Ropivacaine oil delivery depot (RODD) can be used to treat postoperative
incision pain. The aim was to study pharmacodynamics, toxicity and toxicokinetics of
RODD. METHODS: The base research of RODD were conducted. Thirty rabbits were
randomly divided into saline, solvent, ropivacaine aqueous injection (RAI) 0.9 mg, RODD
0.9 mg and RODD 3 mg groups. The sciatic nerve of rabbits were isolated, dripped with
RODD and the effect of nerve block were observed. In toxicity study, the rats were divided
into saline, solvent and RODD 75, 150 and 300 mg/kg groups, 30 rats per group. In
toxicokinetics, rats were divided into RODD 75, 150 and 300 mg/kg groups, 18 rats per
group. The rats were subcutaneously injected drugs. RESULTS: The analgesic duration of
RODD 3 mg and RAI 0.9 mg blocking ischiadic nerve lasted about 20 h and 2 h, respectively,
and their blocking intensity was similar. The rats in RODD 75 mg/kg did not show any
toxicity. Compared with saline group, in RODD 150 mg/kg group neutrophils and
mononuclear cells increased, lymphocytes decreased and albumin decreased(P < 0.05), and
pathological examination showed some abnormals. In RODD 300 mg/kg group, 10 rats died
and showed some abnormalities in central nerve system, hematologic indexes, part of
biochemical indexes, and the weights of spleen, liver, and thymus. However, these abnormal
was largely recovered on 14 days after the dosing. The results of toxicokinetics of RODD
75 mg/kg group showed that the C(max) was 1.24 ± 0.59 µg/mL and the AUC((0-24 h)) was
11.65 ± 1.58 h·µg/mL. CONCLUSIONS: Subcutaneous injection RODD releases ropivacaine
Lu, X., et al. (2019). "G-CSF-induced severe thrombocytopenia in a healthy donor: A
rare case report." Medicine (Baltimore) 98(12): e14786.
RATIONALE: Granulocyte colony-stimulating factor (G-CSF) is most frequently used in
healthy donors to mobilize progenitor cells into the peripheral blood for collection. While
mild thrombocytopenia is common in allogeneic peripheral blood stem cell transplant donors
after G-CSF mobilization, serious thrombocytopenia is rarely reported. Herein, we report a
case of severe thrombocytopenia caused by G-CSF in a 14-year-old healthy donor and review
the relevant literature. To our knowledge, this is the first reported case of severe
thrombocytopenia caused by G-CSF in a healthy adolescent donor. PATIENT CONCERNS:
A 14-year-old sister of a girl with T lymphocyte leukemia was selected as a matched donor
for transplantation. The donor was healthy with normal blood parameters. DIAGNOSES: The
donor received 10 μg/kg/day G-CSF via subcutaneous injection. On day 4 of G-CSF
administration, blood tests before stem cell collection indicated that platelets dropped to
51 g/L. Abdominal ultrasound showed that the spleen was mildly enlarged.
INTERVENTIONS: In order to prevent blood loss and other effects caused by a too low
platelet count after collection, the donor's peripheral blood hematopoietic stem cells were
collected after platelet transfusion. OUTCOMES: Checkups for 1 year after G-CSF
administration showed normal blood parameters. LESSONS: Due to the rare risk of severe
thrombocytopenia in G-CSF mobilization, it is necessary to routinely monitor blood
Lucatelli, P., et al. (2019). "Polyethylene Glycol Epirubicin-Loaded Transcatheter
Arterial Chemoembolization Procedures Utilizing a Combined Approach with 100
and 200 μm Microspheres: A Promising Alternative to Current Standards." J Vasc
Interv Radiol 30(3): 305-313.
PURPOSE: To report clinical effectiveness, toxicity profile, and prognostic factors of
combined 100 μm ± 25 and 200 μm ± 50 epirubicin-loaded polyethylene glycol (PEG)
microsphere drug-eluting embolic transcatheter arterial chemoembolization protocol in
patients with hepatocellular carcinoma. MATERIALS AND METHODS: In this prospective,
single-center, single-arm study with 18 months of follow-up, 36 consecutive patients (mean
age 69.9 y ± 10.8; 26 men, 10 women; 54 naïve lesions) were treated. Embolization was
initiated with 100 μm ± 25 microspheres, and if stasis (10 heart beats) was not achieved, 200
μm ± 50 microspheres were administered. Each syringe (2 mL) of PEG microsphere was
loaded with 50 mg of epirubicin. Results were evaluated using Modified Response Evaluation
Criteria In Solid Tumors with multidetector computed tomography/magnetic resonance
imaging at 1, 3-6, 9-12, and 15-18 months. Toxicity profile was assessed by laboratory testing
before and after the procedure. Complications were recorded. Postembolization syndrome
(PES) was defined as onset of fever/nausea/pain after the procedure. Patient/lesion
characteristics and treatment results were correlated with predicted outcome using regression
analysis. Child-Pugh score was A in 86.1% of patients (31/36) and B in 13.9% (5/36).
RESULTS: In 10 of 21 lesions, < 2 cm in diameter (47.5%) stasis was achieved with 100 μm
± 25 microspheres only, whereas all other lesions required adjunctive treatment with 200 μm
± 50 microspheres. Reported adverse events were grade 1 acute liver bile duct injury (3/39
cases, 7.7%) and PES (grade 2; 3/39 cases, 7.7%). Complete response (CR) at 1, 3-6, 9-12,
and 15-18 months was 61.1%, 65.5%, 63.63%, and 62.5%. Objective response (CR + partial
response) at 1, 3-6, 9-12, and 15-18 months was 83.3%, 65.85%, 63.63%, and 62.5%. No
single factor (laboratory testing, etiology, patient status, hepatic status, tumor characteristics,
administration protocol) predicted outcomes except for albumin level at baseline for CR (P <
.05, odds ratio = 1.09). CONCLUSIONS: The combined microsphere sizing strategy was
Lundberg, J., et al. (2017). "Safety of Intra-Arterial Injection With Tumor-Activated T
Cells to the Rabbit Brain Evaluated by MRI and SPECT/CT." Cell Transplant 26(2):
283-292.
Glioblastoma multiforme (GBM) is the most common and most severe form of malignant
gliomas. The prognosis is poor with current combinations of pharmaceutical, radiotherapy,
and surgical therapy. A continuous search for new treatments has therefore been ongoing for
many years. Therapy with tumor-infiltrating lymphocytes (TILs) is a clinically promising
strategy to treat various cancers, including GBM. An endovascular intra-arterial injection of
TILs as a method of delivery may, instead of intravenous infusion, result in better retention of
effector cells within the tumor. Prior to clinical trials of intra-arterial injections with any
cells, preclinical safety data with special emphasis on embolic-ischemic events are necessary
to obtain. We used native rabbits as a model for intra-arterial injections with routine clinical
catheter material and a clinical angiography suite. We selectively infused a total dose of 20
million activated T cells at a cell concentration of 4,000 cells/μl over 8 min of injection time.
The rabbits were evaluated for ischemic lesions by 9.4 T magnetic resonance imaging (MRI)
(n = 6), and for tracking of injected cells, single-photon emission computed
tomography/computed tomography (SPECT/CT) was used (n = 2). In this study, we show that
we can selectively infuse activated T cells to a CNS volume of 3.5 cm3 (estimated from the
volumetric MRI) without catastrophic embolic-ischemic adverse events. We had one adverse
event with a limited basal ganglia infarction, probably due to catheter-induced mechanical
occlusion of one of the lateral lenticulostriatal arteries. The cells pass through the native brain
without leaving SPECT signals. The cells then, over the first hours, end up in the liver to a
large extent and to a lesser degree by the spleen, pancreas, and kidneys. Virtually no uptake
could be detected in the lungs. This indicates a difference in biodistribution as opposed to
Magnani, H. N. (2010). "An analysis of clinical outcomes of 91 pregnancies in 83
women treated with danaparoid (Orgaran)." Thromb Res 125(4): 297-302.
Danaparoid case reports of 91 pregnancies in 83 patients with a history of thrombophilia
and/or intra-uterine growth retardation have been analysed. All had intolerance to the
heparins including HIT and acute or past thromboses or a history of repeated pregnancy loss
(RPL). Danaparoid was started in the first, second and third trimesters in 60.2%, 19.3% and
20.5% pregnancies respectively at a dosing intensity of 1000 to 7500 U/day. Subcutaneous
and/or intravenous administration was continued for a median 105 days (range 1-252) during
pregnancy and 7 days (range 2 to 56) post-partum. The live birth rate was 90.4% (75/81) and
danaparoid was restarted after 37 deliveries. Maternal adverse events in 46.2% of the
pregnancies included 2 post cesarean deaths (a failed post-operative resuscitation and a major
bleed in a patient refusing transfusion), 3 non-fatal major bleeds (associated with cesarean
section and faulty placental implantation), 3 thrombo-embolic events unresponsive to
danaparoid dose increase and 10 recurrent rashes. Seven early miscarriages, 1 therapeutic
termination and 1 neonatal death occurred. In 13 reports a maternal, but no fetal, adverse
event was attributed to danaparoid. Anti-Xa activity levels in maternal plasma were between
0.1 and 1.2 U/mL, absent from 6 fetal cord blood samples and 0 - 0.07 U/mL in the 5
maternal breast milk samples tested. CONCLUSION: The successful birth rate and adverse
event profile indicates that danaparoid can be an effective and safe alternative anti-thrombotic
Mahboubi-Fooladi, Z., et al. (2021). "Parenteral Anticoagulation and Retroperitoneal
Hemorrhage in COVID-19: Case Report of Five Patients." SN Compr Clin Med 3(10):
2005-2010.
Since coronavirus disease 2019 (COVID-19) is associated with a hypercoagulable state,
especially in critical patients, anticoagulation is used for thromboprophylaxis. Hemorrhagic
complications, even uncommon ones such as retroperitoneal hemorrhage, can occur following
anticoagulant administration. We present 5 patients with COVID-19 whose clinical course
was complicated by spontaneous retroperitoneal hemorrhage. The patients were initially
presented with respiratory manifestations of the infection. There was no history or evidence
suggestive for traumatic injury. After hospitalization, the patients received supplemental
oxygen, antibiotics, enoxaparin or heparin, interferon beta-1b (in three patients), and
anticoagulation with subcutaneous injection of enoxaparin (three patients) or heparin (two
patients). During the course of hospitalization, the patients showed sudden-onset abdominal
pain (three cases), hypotension (three cases), and an acute drop in hemoglobin level. CT scan
of the abdomen and pelvis revealed retroperitoneal hemorrhage. For one patient, owing to
unstable vital signs and an expanding hematoma, surgical intervention was performed. Others
were managed conservatively with discontinuation of anticoagulants, intravenous (IV) fluid
resuscitation, and packed red blood cells transfusion. Three patients died due to worsening of
the infection and respiratory failure. Retroperitoneal hemorrhage could be a potential
complication in COVID-19 patients receiving anticoagulation. Careful monitoring of the vital
Malekzadeh-Milani, S., et al. (2014). "Percutaneous valvulation of failing Fontan:
Rationale, acute effects and follow-up." Archives of Cardiovascular Diseases 107(11):
599-606.
Summary Background Fontan circulation is fragile and unfavourable evolution is frequent.
Fontan physiology largely depends on respiration and gravity. The hypothesis for valvulation
is that valvulation of the circuit reduces the effects of respiration and the proclive position,
and increases anterograde flow towards the systemic circulation, with increasing exercise
capacity and benefits for enteropathy. Because it originates from the bovine jugular vein, the
Melody® valve (Medtronic, Minneapolis, MN, USA) is naturally designed to work in a lowpressure environment. Aims To report our experience of percutaneous valvulation of
refractory failing Fontan circulation. Methods We reviewed all patients who received a
Melody valve in Fontan circulation in our unit. Results Four patients were included: two had
severe and refractory protein-losing enteropathy; one had severe oedema and ascites; and one
had very severe lower limb venous insufficiency. The Melody valve was successfully
implanted in all patients. Central venous pressure and inferior vena cava pressure did not
change after valvulation. There were no early complications. At follow-up, no acute or midterm thrombosis was noted. Two patients had intracardiac echocardiography 6 and 24months
after valvulation: the Melody valve was found not to be functioning in both cases. One
patient died 3months after valvulation; the cause was unrelated to the procedure. Conclusion
Percutaneous valvulation of Fontan circulation is technically feasible. More clinical studies
are needed before considering this treatment as an option. Résumé Contexte La circulation de
Fontan est fragile avec une évolution emaillée de nombreuses complications. Sa physiologie
est unique et dépend beaucoup de la respiration et de la gravité. L’hypothèse de l’effet
favorable de la valvulation est que la mise en place d’une valve dans le circuit réduit les
effets de la respiration et de la position proclive. Ce faisant, la valvulation augmente le débit
antérograde de la circulation systémique améliorant la capacité à l’effort et peut également
diminuer les signes d’entéropathie exsudative. La valve Mélody® (Medtronic, Minneapolis,
MN, États-Unis) qui est issue de la jugulaire de bœuf est, de par son origine, naturellement
faite pour fonctionner dans un environnement à basse pression. Objectif Nous rapportons
notre expérience de la valulation percutanée de circuits de Fontan défaillants et réfractaires
au traitement médical conventionnel. Méthodes Tous les patients ayant reçu une valve
Matsuura, W., S. Harada and S. Tokuyama (2016). "Effects of Adjuvant Analgesics
on Cerebral Ischemia-Induced Mechanical Allodynia." Biol Pharm Bull 39(5): 856862.
Central post-stroke pain (CPSP), a potential sequela of stroke, is classified as neuropathic
pain. Although we recently established a CPSP-like model in mice, the effects of adjuvant
analgesics as therapeutic drugs for neuropathic pain in this model are unknown. Hence, the
aim of the present study was to assess the usefulness of our model by evaluating the effects of
adjuvant analgesics used for treating neuropathic pain in this mouse model of CPSP. Male
ddY mice were subjected to 30 min of bilateral carotid artery occlusion (BCAO). The
development of hind paw mechanical allodynia was measured after BCAO using the von Frey
test. The mechanical allodynia was significantly increased on day 3 after BCAO compared
with that during the pre-BCAO assessment. BCAO-induced mechanical allodynia was
significantly decreased by intraperitoneal injections of imipramine (a tricyclic
antidepressant), mexiletine (an antiarrhythmic), gabapentin (an antiepileptic), or a
subcutaneous injection of morphine (an opioid receptor agonist) compared with that
following vehicle treatment in BCAO-mice. By contrast, milnacipran (a serotonin and
norepinephrine reuptake inhibitor), paroxetine (selective serotonin reuptake inhibitor),
carbamazepine (antiepileptic), and indomethacin (nonsteroidal anti-inflammatory drug) did
not affect the BCAO-induced mechanical allodynia. Our results show that BCAO in mice
may be useful as an animal model of CPSP. In addition, BCAO-induced mechanical allodynia
Matsuzawa, R., et al. (2019). "Autologous Transfusion of Blood Aspirated during
Suction Decompression in Clipping of Large or Giant Cerebral Aneurysm." Neurol
Med Chir (Tokyo) 59(9): 351-356.
The suction decompression (SD) method, which proactively aspirates the blood flowing into
the aneurysm and reduces the internal pressure of the aneurysm, is useful for clipping surgery
of large and giant cerebral aneurysm. However, there has been little discussion on reutilization of blood aspirated during SD. This study aimed to examine the safety,
convenience, and usefulness of autologous transfusion of aspirated blood using a transfusion
bag. At the time of craniotomy, the cervical carotid artery is fully exposed. An angiocatheter
sheath was inserted into the carotid artery and placed in the internal carotid artery. In SD,
blood was aspirated from the sheath at a constant speed and quickly stored in a blood
transfusion storage bag. Blood aspiration was repeated with a new syringe; once the
transfusion bag was full, the blood was re-administered to the patient. Changes in vital sign
and hemoglobin/hematocrit values before and after SD were examined in five cases
performed in this procedure. The aspirated blood volumes of five cases ranged from 130 to
400 mL, and all aspirated blood was successfully re-transfused. There was no critical change
in vital sign, and no significant decrease in the hemoglobin/hematocrit value. No findings
suggestive of complications of thrombus formation, infection, and hemolysis were noted. Retransfusion of aspirated blood during SD using a transfusion bag is a simple and safe method,
which can minimize potential risk of re-utilizing aspirated blood, and enables the safe and
Mebazaa, M. S., et al. (2011). "Is magnesium sulfate by the intrathecal route efficient
and safe?" Ann Fr Anesth Reanim 30(1): 47-50.
Merrill, T. L., et al. (2013). "A hemolysis study of an intravascular blood cooling
system for localized organ tissue cooling." Perfusion 28(1): 6-13.
The polypharmacological approach to the treatment of postoperative pain has become routine
in an attempt to minimize the adverse side effects of opioids. Magnesium sulphate is a
noncompetitive antagonist of the N-methyl-d-aspartate (NMDA) receptor and thus can
modify nociceptive modulation. Intravenous administration of magnesium sulphate can
improve postoperative analgesia and decrease the requirement for postoperative opiates, but
the effects are inconsistent and have not been reliably accompanied by a reduction in the
incidence of morphine-related adverse events. Several studies have shown that the
administration of magnesium by the intrathecal route is safe and, in combination with opiates,
extends the effect of spinal anaesthesia in both animal and human studies. The analysis of
these studies justifies further investigation of the use of magnesium sulphate by the
intrathecal route.
Therapeutic hypothermia can reduce both ischemic and reperfusion injury arising after
strokes and heart attacks. New localized organ cooling systems offer a way to reduce tissue
damage more effectively with fewer side effects. To assess initial blood safety of our new
organ cooling system, the CoolGuide Cooling System (CCS), we investigated safe operating
conditions and configurations from a hemolysis perspective. The CCS consists of a peristaltic
pump, a custom-built external heat exchanger, a chiller, biocompatible polyvinyl cellulose
(PVC) tubing, and a control console. The CCS cools and circulates autologous blood
externally and re-delivers cooled blood to the patient through a conventional catheter inserted
directly into the organ at risk. Catheter configurations used included: a 7F guide catheter
only, a 7F guide with a 0.038" wire inserted through the center and advanced 2 cm distal to
the catheter distal tip, a 6F guide catheter only and a 6F guide with a 0.014" guidewire
similarly inserted through the center. Using porcine blood, an in vitro test rig was used to
measure the degree of hemolysis generation, defined as the percentage change in free
hemoglobin, adjusted for total hemoglobin and hematocrit, between exiting and entering
blood. The highest degree of hemolysis generation was 0.11±0.04%, based on the average
behavior with a 6F catheter and a 0.014" guidewire configuration at a blood flow rate of
approximately 130 mL/min. In terms of average percentage free hemoglobin exiting the
system, based on total hemoglobin, the highest value measured was 0.17%±0.03%, using this
6F and 0.014" guidewire configuration. This result is significantly below the most stringent
European guideline of 0.8% used for blood storage and transfusion. This study provides
initial evidence showing hemolysis generation arising from the CoolGuide Cooling System is
Min, B. M. and J. H. Kim (2013). "Epidural catheterization with a subcutaneous
injection port for the long-term administration of opioids and local anesthetics to treat
zoster-associated pain -a report of two cases." Korean J Anesthesiol 65(5): 462-467.
Continuous epidural analgesia has been used for decades to treat acute herpes zoster pain and
to prevent postherpetic neuralgia. However, many technical problems can arise during
chronic treatment with epidural medications. These complications include catheter
dislodgement, infection, injection pain, leakage, and occlusion. Epidural catheter placement
utilizing subcutaneous injection port implantation has gained widespread acceptance as a
method to overcome such complications. The technique reduces the risk of infection, the
most feared complication, compared to the use of a percutaneous epidural catheter. Herein,
we present 2 cases in which the continuous thoracic epidural administration of opioids and
local anesthetics through an implantable subcutaneous injection port for over 2 months
successfully treated zoster-associated pain without any technique- or medication-related
complications in patients with risk factors for epidural abscess.
Minowa, K., et al. (2014). "Romiplostim treatment allows for platelet transfusion-free
liver transplantation in pediatric thrombocytopenic patient with primary sclerosing
cholangitis." Pediatr Transplant 18(6): E212-215.
Moassas, F., M. S. Nweder and H. Murad (2019). "Hb Knossos (HBB: c.82G > T), βglobin CD 5 (-CT) (HBB: c.17_18delCT) and δ-globin CD 59 (-a) (HBD: c.179delA)
mutations in a Syrian patient with β-thalassemia intermedia." BMC Pediatr 19(1): 61.
Thrombocytopenia is a major risk factor for cirrhotic liver disease. Patients with
thrombocytopenia may have esophageal or gastric varices secondary to portal hypertension,
leading to variceal bleeding which exposes the liver to further damage. Here, we present a
female pediatric patient with PSC and CD, whose progressive thrombocytopenia was
successfully controlled by romiplostim, a TPO receptor agonist. The patient developed
bloody diarrhea at four yr of age, and was subsequently diagnosed with PSC and CD when
seven yr old. While CD was well-controlled by immunomodulators, the patient's
thrombocytopenia gradually progressed resulting in petechiae (platelet count of 11 × 10(9)
/L) when she was 10 yr and four months old. She responded poorly to immunoglobulin and
corticosteroids. Weekly subcutaneous injection of romiplostim was therefore initiated, and
platelet counts were maintained over at 50 × 10(9) /L. She was able to undergo successful
LDLT without platelet transfusion seven months after the initiation of romiplostim.
Romiplostim was not required after LDLT with improved platelet counts. This case report
suggests that romiplostim may be effective in the treatment of thrombocytopenic children
with liver cirrhosis and portal hypertension, and in eliminating the need for platelet
BACKGROUND: Beta thalassemia (β-thal) is an inherited hemoglobin disorder characterized
by reduced synthesis of the hemoglobin that results in microcytic hypochromic anemia. βThalassemia intermedia (TI) is a clinical term of intermediate gravity between the carrier
state and β-thalassemia major (β -TM). CASE PRESENTATION: We describe a 12-year-old
male proband originating from Al-Quneitra province - southwest Syria. Hematological
investigations revealed, pallor and anemia (Hb 9 g/dl). The mean cell volume (MCV) 64 fL;
mean cell hemoglobin (MCH) 21.8 pg. Capillary electrophoresis (CE) electropherogram
revealed low level of Hb A1 (36.2%), high level of Hb F (62.2%) and low level of Hb A2
(1.6%). The proband requires blood transfusion occasionally. Direct DNA sequencing and
Polymerase chain reaction-restriction fragment length polymorphism (PCR/RFLP) for
mutations detection were used. The molecular analysis revealed the presence of rare β(+) Hb
Knossos codon 27 (G > T) (HBB: c.82G > T) variant associated with β(0) codon 5 [-CT]
(HBB: c.17_18delCT) mutation in beta-globin (β-globin) gene and δ(0) codon 59 [-A] (HBD:
c.179delA) mutation in delta-globin (δ-globin) gene. The proband tested negative for the
common deletional forms of alpha thalassemia (α-thal). Polymorphism of the Xmn-I locus
(HBG2: c.-211C > T) revealed that the proband had a homozygous [TT] for Xmn-1 locus.
CONCLUSIONS: To our knowledge, this is the first report of beta thalassemia intermedia
due to combination of Hb Knossos /codon 5 [-CT] associated with δ(0) codon 59 [-A] in
Syrian patient. On the other hand, in Syria, β-thal carriers who have low level of Hb A2 due
to decreased δ-chain production, different δ-thal gene mutations must be screened to avoid
Mochizuki, K., A. Sawada and N. Katsumura (2010). "Case of lacrimal gland
inflammation associated with ulcerative colitis." Int Ophthalmol 30(1): 109-111.
Mott, S. E., et al. (2016). "Nicolau syndrome and localized panniculitis: a report of
dual diagnoses with an emphasis on morphea profunda-like changes following
injection with glatiramer acetate." J Cutan Pathol 43(11): 1056-1061.
We report a case of lacrimal gland pseudotumor as the presenting sign of ulcerative colitis. A
25-year-old woman presented with a right upper eyelid swelling and pain. Intravenous
administration of prednisolone was initiated on suspicion of lacrimal gland inflammation
(pseudotumor). Although the treatment markedly reduced her ocular symptoms, she
developed lower abdominal cramping and diarrhea with the 5 mg/day of oral prednisolone.
Sigmoid colonoscopy and colon biopsy led to make a diagnosis of ulcerative colitis.
Ulcerative colitis improved significantly with increased dose of steroid and additive
mesalazine therapy. Ulcerative colitis should be included in the differential diagnosis of
lacrimal gland pseudotumor.
Glatiramer acetate, given as a 40 mg subcutaneous injection thrice weekly, was recently
approved by the FDA based on data suggesting better compliance and a more favorable side
effect profile compared to lower dose, daily dosing. The most commonly reported adverse
events are transient injection site reactions involving redness and pain at the site; however,
more pronounced panniculitis and lipoatrophy have also been reported. Here, we present the
case of a 51-year-old female treated with higher dose glatiramer acetate who presented with a
cutaneous injection site reaction consistent with Nicolau syndrome. The excised specimen
revealed typical glatiramer acetate-associated panniculitis, alongside subcutaneous sclerosis.
This case shows the spectrum of cutaneous complications possible with glatiramer acetate
injections, the finding of sclerosis being relatively infrequently reported. Given the relatively
short duration of trials leading to FDA approval of thrice weekly dosing of glatiramer acetate,
clinicians should perform careful clinical and histopathological evaluation and reporting of
patients who experience injection site reactions.
Nahrwold, D. A., et al. (2021). "Rupture of an epidural filter connector during bolus
administration of local anesthetic: a case report." BMC Anesthesiol 21(1): 143.
BACKGROUND: Epidural catheters are routinely placed for many surgical procedures and
to treat various pain conditions. Known complications arising from epidural catheter
equipment malfunction include epidural pump failure, epidural catheter shearing, epidural
catheter connector failure, epidural filter connector cracking, and loss-of-resistance syringe
malfunction. Practitioners need to be aware of these potentially dangerous complications and
take measures to mitigate the chances of causing significant patient harm. We report on the
complete breakage of an epidural filter connector during epidural bolus administration of
local anesthetic by hand with a syringe. CASE PRESENTATION: A B. Braun Perifix®
epidural catheter was placed in a 73-year-old male scheduled for radical prostatectomy.
During the operation, a continuous infusion of local anesthetic was administered through the
epidural catheter in addition to general endotracheal anesthesia. At the conclusion of surgery
and after extubation, the patient endorsed incisional pain. The epidural filter connector broke
in half as a bolus of local anesthetic was administered by hand with a syringe. The local
anesthetic sprayed widely throughout the room as the fragmented epidural filter connector
became a projectile object that recoiled and struck the patient. CONCLUSIONS: This
incident placed the patient and surrounding healthcare providers at substantial risk for injury
and infection from the fractured epidural filter connector becoming a projectile object and
from the local anesthetic spray. The most plausible cause of this event was from a large
amount of pressure being applied to the filter connector. This may have occurred by
excessive force being applied by hand to the syringe, by the presence of a clogged filter, or by
the catheter being kinked or blocked proximal to the filter. Being aware of this deleterious
complication and potentially modifying existing epidural bolus techniques, such as using
smaller syringes with less applied force and checking all epidural components vigilantly prior
to and during bolus administration, can help anesthesia providers deliver the safest possible
Narang, S., et al. (2016). "Upper Antero-Medial Thigh as an Alternative Site for
Implantation of Intrathecal Pumps: A Case Series." Neuromodulation: Technology at
the Neural Interface 19(6): 655-663.
Introduction Neuraxial drug delivery via intrathecal drug delivery systems (IDDS) is
becoming an increasingly common mode of treating intractable cancer-related pain, chronic
pain, or severe spasticity. An implanted infusion pump delivers medication into the
intrathecal (subarachnoid) space via a thin catheter. These pumps are commonly placed in the
anterior abdominal wall. Certain conditions may render it difficult or unsafe for an IDDS to
be implanted at the traditional site; thus, alternative sites have been explored. We report on
the use of the upper antero-medial thigh as a safe alternative site for this purpose. Methods
and Materials Nine patients between 22 and 69 years of age underwent placement of an IDDS
infusion pump in the upper antero-medial aspect of one thigh. In each patient, the anterior
abdominal wall was precluded for implantation due to various reasons, such as extensive
abdominal scar tissue from previous surgeries, placement of feeding tubes and ostomies, large
ventral hernia or metastatic masses protruding from the abdomen. Results Nine patients, with
ages ranging from 22 to 69 years old, had IDDS implantation in the upper thigh. The first
patient experienced wound dehiscence (antero-lateral location) and after explantation,
another pump was placed successfully in the opposite thigh (antero-medial location). One
patient has had pump replacement due to end-of-battery life. She also needed an unrelated
catheter revision. Seven patients have expired from their disease progression after living for
an average of 142.7 days (range 50 days to 354 days) while two patients continue to
experience relief from pain and spasticity years later (see Table 1). No neurovascular
damage, infections, or other complications occurred in our series. Conclusion The upper
Neuwirth, R. S. and A. Singer (2013). "Evaluation of a silver nitrate endometrial
ablation fluid delivery system as a chemical treatment for menorrhagia." J Minim
Invasive Gynecol 20(5): 627-630.
STUDY OBJECTIVE: To explore the safety, feasibility, and effectiveness of silver nitratedextran paste delivered through the cervix as a simple and inexpensive endometrial ablation
therapy for menorrhagia. DESIGN: Safety, feasibility, and effectiveness trials (Canadian
Task Force classification II-3). SETTING: The trials were performed at the Whittington
Hospital in London. PATIENTS: Seven women were treated for menorrhagia after
prehysterectomy trials on 10 patients. Studies were first performed on rats and rabbits and
human uterine specimens. INTERVENTION: We dissolved 10 g 75% silver nitrate/25%
potassium nitrate and 15 g dextran 70 in 10 mL distilled water and delivered this paste
through the cervix with a pressure-controlled syringe under fluroscopic monitoring. We
planned silver nitrate doses of 500 mg in a 50-kg woman to remain in the uterus for 8 minutes
after injection and then to be neutralized with normal saline and washed out. In uterine
specimens, 8-minute treatment produced local necrosis to 4 mm. LD50 (lethal dose, 50%)
studies in rats and mice ranged from 1100 to 2000 mg/kg. Prehysterectomy trials on 10
patients to evaluate safety revealed no penetration into the tubes and normal complete blood
count, renal, cardiac, and liver tests with plasma silver rising to 20 to 30 μmoles/L and
returning to baseline after 4 weeks. Finally, 7 patients were treated and followed for 6
months. We followed blood values, complications, and degree of flow reduction. Six patients
were well and discharged the same day; of those, all blood values were similar to the safety
studies, 5 reported varying degrees of flow reduction, and 1 patient continued with
menorrhagia. The seventh patient had passage of paste into the left fallopian tube and
peritoneal cavity producing immediate pain. Laparoscopy showed several burns on the back
of the uterus, sigmoid colon, and cul de sac. After neutralization with saline, she made a
complete, uneventful recovery and became oligoamenorrheic. CONCLUSION: Silver nitrate
could be a simple, inexpensive, safe, and potentially effective agent for endometrial ablation.
However, to ensure safety, the fluid delivery system described herein must be abandoned. An
alternative delivery system is needed, one which precisely controls the locus of caustic
Nikenina, E. V., A. Y. Abramova and A. Y. Kozlov (2012). "Nociceptive sensitivity
and lymphocytic index of peripheral blood in rats with different behavioral activity in
model of inflammatory pain provoked by injection of freund's complete adjuvant and
bovine serum albumin." Bull Exp Biol Med 153(5): 631-633.
Nociceptive thresholds decreased in rats at the early stage of inflammatory reaction induced
by subcutaneous injection of BSA and complete Freund's adjuvant. At the later stage of this
reaction, there was a trend of restoring nociceptive parameters in behaviorally passive rats in
contrast to active animals, which demonstrated further decrease in the nociceptive thresholds.
During the late inflammatory period, the lymphocytic index (by Shaganin) changed
unidirectionally in the rats with different behavioral parameters. Probably, the changes in
nociceptive thresholds were not triggered by the shift in lymphocyte/segmented neutrophil
ratio, but resulted from production of yet not established biologically active agents with
proalgesic and analgesic nature.
Noh, K., et al. (2011). "Determination of a novel low-voltage-activated calcium
channel blocker (HYP-10) in rat plasma by liquid chromatography-mass
spectrometry." J Pharm Biomed Anal 54(3): 568-571.
Ntoulia, A., et al. (2024). "Safety of Ultrasound Contrast Agents in Pediatric Patients
With Sickle Cell Disease and Trait." J Ultrasound Med 43(1): 189-200.
A novel T-type calcium channel blocker, 4-amino-1-{4-[(4-chloro-phenyl)-phenyl-methyl]piperazin-1-yl}-butan-1-one (HYP-10) has been synthesized, and the compound has shown
promise as both a nociceptive and inflammatory pain reliever as well as an analgesic in a rat
neuropathic pain model. A quantification method was developed for the determination of
HYP-10 in rat plasma. After simple protein precipitation with methanol, HYP-10 and the
internal standard, methaqualone were chromatographed on a reversed-phase column and
detected by liquid chromatography/tandem mass spectrometry with electrospray ionization.
The accuracy and precision of the assay were in accordance with FDA regulations for
validation of bioanalytical methods. This method was applied to measure the plasma HYP-10
concentration after a single intravenous administration of the compound in rats.
Ultrasound contrast agent (UCA) use is increasing. Recent isolated reports observed a rise in
pain-related adverse events with the intravenous administration of the UCA Definity in adults
with sickle cell disease. To date, no studies have investigated the incidence of similar adverse
events with UCA Lumason or Optison. We describe our experience regarding the safety of
Lumason and Optison in children with sickle cell disease and trait who underwent contrastenhanced ultrasound exams in our department with intravenous, intravesical, and other
intracavitary routes. No pain-related or other adverse events were observed in this pediatric
population with any route of UCA administration.
Nukui, T., et al. (2014). "[A case of neuro-Sweet disease showing the close
association between disease activity and levels of soluble IL-2 receptor]." Rinsho
Shinkeigaku 54(11): 876-881.
Nyborg, A. C., et al. (2016). "A Therapeutic Uricase with Reduced Immunogenicity
Risk and Improved Development Properties." PLoS One 11(12): e0167935.
A 76-year-old man was admitted to our hospital presenting with fever, redness and pain in
both the periocular regions, and disturbance of consciousness. He had neck stiffness, and
cerebrospinal fluid analysis suggested aseptic meningoencephalitis. Laboratory tests showed
increased levels of C-reactive protein, soluble IL-2 receptor (sIL-2R) and MPO-ANCA.
Magnetic resonance imaging revealed hyperplastic bone marrow in the clivus and cervical
vertebra. Although T-cell receptor gene rearrangement was detected in the bone marrow
blood, bone marrow biopsy of the ilium showed no malignant findings. Then he experienced
bilateral auricular inflammation and painful erythema of the ankle. A leg skin biopsy
demonstrated neutrophilic infiltration into the dermis with no signs of vasculitis. His HLAtype was defined as Cw1. He was subsequently diagnosed with neuro-Sweet disease.
Intravenous administration of methylprednisolone (1,000 mg/day) for 5 days and subsequent
oral intake of prednisolone (60 mg/day) improved his symptoms. When the prednisolone dose
was reduced to 30 mg/day, his symptoms returned and a new lesion was detected in the
splenium of the corpus callosum. Upon additional treatment with cyclosporine, the
prednisolone dose could be reduced without symptom relapse; sIL-2R and MPO-ANCA
levels also decreased to normal. The present case suggested that the activity of neuro-Sweet
disease may be associated with myeloid hyperplasia, T-cell receptor gene rearrangement and
Humans and higher primates are unique in that they lack uricase, the enzyme capable of
oxidizing uric acid. As a consequence of this enzyme deficiency, humans have high serum
uric acid levels. In some people, uric acid levels rise above the solubility limit resulting in
crystallization in joints, acute inflammation in response to those crystals causes severe pain; a
condition known as gout. Treatment for severe gout includes injection of non-human uricase
to reduce serum uric acid levels. Krystexxa® is a hyper-PEGylated pig-baboon chimeric
uricase indicated for chronic refractory gout that induces an immunogenic response in 91% of
treated patients, including infusion reactions (26%) and anaphylaxis (6.5%). These properties
limit its use and effectiveness. An innovative approach has been used to develop a therapeutic
uricase with improved properties such as: soluble expression, neutral pH solubility, high E.
coli expression level, thermal stability, and excellent activity. More than 200 diverse uricase
sequences were aligned to guide protein engineering and reduce putative sequence liabilities.
A single uricase lead candidate was identified, which showed low potential for
immunogenicity in >200 human donor samples selected to represent diverse HLA haplotypes.
Cysteines were engineered into the lead sequence for site specific PEGylation and studies
demonstrated >95% PEGylation efficiency. PEGylated uricase retains enzymatic activity in
vitro at neutral pH, in human serum and in vivo (rats and canines) and has an extended halflife. In canines, an 85% reduction in serum uric acid levels was observed with a single
subcutaneous injection. This PEGylated, non-immunogenic uricase has the potential to
Ogasawara, N., et al. (2020). "Factors secreted from dental pulp stem cells show
multifaceted benefits for treating experimental temporomandibular joint
osteoarthritis." Osteoarthritis Cartilage 28(6): 831-841.
OBJECTIVE: Temporomandibular joint osteoarthritis (TMJOA) is a degenerative disease
characterized by progressive cartilage degeneration, abnormal bone remodeling, and chronic
pain. In this study, we aimed to investigate effective therapies to reverse or suppress TMJOA
progression. DESIGN: To this end, we performed intravenous administration of serum free
conditioned media from human exfoliated deciduous teeth stem cells (SHED-CM) into a
mechanical-stress induced murine TMJOA model. RESULTS: SHED-CM administration
markedly suppressed temporal muscle inflammation, and improved bone integrity and surface
smoothness of the destroyed condylar cartilage. Moreover, SHED-CM treatment decreased
the number of IL-1β, iNOS, and MMP-13 expressing chondrocytes, whereas it specifically
increased PCNA-positive cells in the multipotent polymorphic cell layer. Notably, the
numbers of TdT-mediated dUTP nick end labeling (TUNEL)-positive apoptotic chondrocytes
in the SHED-CM treated condyles were significantly lower than in those treated with
DMEM, whereas the proteoglycan positive area was restored to a level similar to that of the
sham treated group, demonstrating that SHED-CM treatment regenerated the mechanicalstress injured condylar cartilage and subchondral bone. Secretome analysis revealed that
SHED-CM contained multiple therapeutic factors that act in osteochondral regeneration.
CONCLUSIONS: Our data demonstrated that SHED-CM treatment promoted the
regeneration and repair of mechanical-stress induced mouse TMJOA. Our observations
suggest that SHED-CM has potential to be a potent tissue-regenerating therapeutic agent for
Ohn, J., et al. (2021). "Dissolving Candlelit Microneedle for Chronic Inflammatory
Skin Diseases." Adv Sci (Weinh) 8(14): 2004873.
Chronic inflammatory skin diseases (CISDs) negatively impact a large number of patients.
Injection of triamcinolone acetonide (TA), an anti-inflammatory steroid drug, directly into
the dermis of diseased skin using needle-syringe systems is a long-established procedure for
treating recalcitrant lichenified lesions of CISDs, referred to as TA intralesional injection
(TAILI). However, TAILI causes severe pain, causing patients to be stressed and reluctant to
undergo treatment. Furthermore, the practitioner dependency on the amount and depth of the
injected TA makes it difficult to predict the prognosis. Here, candle flame ("candlelit")shaped TA-loaded dissolving microneedles (Candlelit-DMN) are designed and fabricated out
of biocompatible and biodegradable molecules. Candlelit-DMN distributes TA evenly across
human skin tissue. Conjoined with the applicator, Candlelit-DMN is efficiently inserted into
human skin in a standardized manner, enabling TA to be delivered within the target layer. In
an in vivo skin inflammation mouse model, Candlelit-DMN inserted with the applicator
effectively alleviates inflammation by suppressing inflammatory cell infiltration and cytokine
gene expression, to the same extent as TAILI. This Candlelit-DMN with the applicator
arouses the interest of dermatologists, who prefer it to the current TAILI procedure.
Okamura, A., et al. (2023). "Preventive effect of metronidazole vaginal tablets on
vaginal bacteria-related postoperative complications with total laparoscopic
hysterectomy." J Med Case Rep 17(1): 47.
Okulicz-Kozaryn, I., et al. (2013). "Analgesic effects of tramadol in combination with
adjuvant drugs: an experimental study in rats." Pharmacology 91(1-2): 7-11.
BACKGROUND: The use of total laparoscopic hysterectomy is increasing. However, as with
conventional abdominal hysterectomy, vaginal bacteria-related postoperative complications
need to be managed in total laparoscopic hysterectomy. Therefore, we started to combine
metronidazole vaginal tablets with intravenous administration of cephem antibiotics
immediately before starting surgery to reduce complications. To evaluate the effect of this
combination, and to determine the risk factors for these complications, we retrospectively
collected medical records from our hospital and performed a multivariate analysis.
METHODS: We reviewed the medical records of 520 patients who underwent total
laparoscopic hysterectomy from 1 January 2015 to 31 December 2021. Among these cases,
we identified 16 cases as having vaginal bacteria-related postoperative complications, defined
as needing more than one additional day for treatment of postoperative complications, namely
postoperative infection (10 cases) and vaginal dehiscence (6 cases). First, we evaluate the
effect of metronidazole vaginal tablets by dividing the patients into two groups according to
whether metronidazole vaginal tablets were used, and comparing the vaginal bacteria-related
postoperative complication rates and other indices. Second, we performed a multivariate
logistic regression analysis to assess the influence of each of 17 representative factors,
including patient characteristics and symptoms, uterus and leiomyoma sizes, concomitant
procedures such as laparoscopic cystectomy and pelvic lymphadenectomy, and others.
RESULTS: In the multivariate analysis of the 520 cases, we confirmed that the use of
metronidazole vaginal tablets could reduce the vaginal bacteria-related postoperative
complications rate by more than half (odds ratio, 0.36). In addition to metronidazole vaginal
tablets use, concomitant laparoscopic cystectomy and blood transfusion were associated with
significant increases in the vaginal bacteria-related postoperative complication rate.
CONCLUSIONS: The effect of the addition of metronidazole vaginal tablets to pre- and
postsurgical treatment on the reduction of vaginal bacteria-related postoperative
complications was confirmed. This easy, safe, and low-cost method may improve the
Oladapo, O. T., et al. (2020). "Intravenous versus intramuscular prophylactic oxytocin
for the third stage of labour." Cochrane Database Syst Rev 11(11): Cd009332.
BACKGROUND: Tramadol is often coadministered subcutaneously with adjuvants to treat
pain, nausea/vomiting, dyspnea and delirium in cancer patients. The aim of the study was to
investigate analgesia of tramadol coadministered with adjuvants in rats. MATERIALS AND
METHODS: Male rats (Wistar race) received a single tramadol dose separately (0.45 mg/kg)
or tramadol with haloperidol (0.45 mg/kg), midazolam (0.3 mg/kg), levomepromazine (0.35
mg/kg), metoclopramide (1.0 mg/kg), hyoscine butylbromide (1.7 mg/kg) or ketamine (0.3
mg/kg) as a single subcutaneous injection. Analgesia was measured by a tail flick test after
15, 30, 60 and 90 min of drug administration. RESULTS: Tramadol analgesia was enhanced
with haloperidol (30, 60 and 90 min) and with midazolam (60 and 90 min). Tramadol with
levomepromazine (30, 60 and 90 min) and tramadol with metoclopramide (30 and 90 min)
attenuated tramadol analgesia. Tramadol with hyoscine butylbromide and tramadol with
ketamine did not change tramadol analgesia. CONCLUSIONS: Significant changes in
tramadol analgesia after the administration of different adjuvants could be demonstrated in
this experimental single-dose study. Future clinical trials have to further explore the benefits
of these drug combinations.
BACKGROUND: There is general agreement that oxytocin given either through the
intravenous or intramuscular route is effective in reducing postpartum blood loss. However, it
is unclear whether the subtle differences between the mode of action of these routes have any
effect on maternal and infant outcomes. This review was first published in 2012 and last
updated in 2018. OBJECTIVES: To determine the comparative effectiveness and safety of
oxytocin administered intravenously or intramuscularly for prophylactic management of the
third stage of labour after vaginal birth. SEARCH METHODS: We searched Cochrane
Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International
Clinical Trials Registry Platform (ICTRP) (19 December 2019), and reference lists of
retrieved studies. SELECTION CRITERIA: Eligible studies were randomised trials
comparing intravenous with intramuscular oxytocin for prophylactic management of the third
stage of labour after vaginal birth. We excluded quasi-randomised trials. DATA
COLLECTION AND ANALYSIS: Two review authors independently assessed studies for
inclusion and risk of bias, extracted data and checked them for accuracy. We assessed the
certainty of the evidence with the GRADE approach. MAIN RESULTS: Seven trials,
involving 7817 women, met the inclusion criteria for this review. The trials compared
intravenous versus intramuscular administration of oxytocin just after the birth of the anterior
shoulder or soon after the birth of the baby. All trials were conducted in hospital settings and
included women with term pregnancies, undergoing a vaginal birth. Overall, the included
studies were at moderate or low risk of bias, with two trials providing clear information on
allocation concealment and blinding. For GRADE outcomes, the certainty of the evidence
was generally moderate to high, except from two cases where the certainty of the evidence
was either low or very low. High-certainty evidence suggests that intravenous administration
of oxytocin in the third stage of labour compared with intramuscular administration carries a
lower risk for postpartum haemorrhage (PPH) ≥ 500 mL (average risk ratio (RR) 0.78, 95%
confidence interval (CI) 0.66 to 0.92; six trials; 7731 women) and blood transfusion (average
RR 0.44, 95% CI 0.26 to 0.77; four trials; 6684 women). Intravenous administration of
oxytocin probably reduces the risk of PPH ≥ 1000 mL, although the 95% CI crosses the line
Orhan, C. E., et al. (2013). "Antihyperalgesic and antiallodynic effect of sirolimus in
rat model of adjuvant arthritis." Eur J Pharmacol 705(1-3): 35-41.
Sirolimus is an immunosupressive drug that specifically inhibit the activation of Tlymphocytes. This study was undertaken to investigate whether treatment with sirolimus
exert analgesic effect in rat adjuvant-induced arthritis, an animal model of rheumatoid
arthritis. Arthritis was induced by a single subcutaneous injection of Freund's complete
adjuvant to male Wistar rats that were divided into four groups; control (saline), vehicle
(ethanol), sirolimus 0.75 and sirolimus 1.5. Sirolimus (0.75 and 1.5mg/kg/day) was
administered intraperitoneally using Monday-Wednesday-Friday dosing schedule for 29 days,
this dosing regimen revealed acceptable trough blood concentrations in arthritic rats.
Adjuvant inoculation resulted in paw inflammation, hyperalgesia and allodynia as assessed
by pletismometer, analgesymeter and dynamic plantar aesthesiometer respectively. Light
microscopic evaluation of the arthritic metacarpophalangeal joints revealed synovial
hypertrophy with inflammatory cellular infiltration, cartilage destruction and partial
subchondral bone resorption. ELISA tests of serum TNF-α, IL-1β or IL-6 did not show any
change in arthritic rats, while Western blotting analysis revealed a significant increase in
TNF-α (P<0.001), but not IL-1β or IL-6, protein expression in the lumbar spinal cord of
arthritic rats. Treatment with sirolimus significantly decreased the arthritic lesions (P<0.001)
and paw swelling (P<0.05), alleviated the histological features in the metacarpophalangeal
joint, resulted in antihyperalgesic and antiallodynic effects without affecting the locomotor
activity and prevented the increased spinal cord TNF-α level (P<0.05). It seems that
prevention of the increased TNF-α expression in the spinal cord may partially contribute to
the antihyperalgesic effect of sirolimus in adjuvant arthritic rats and sirolimus could be a
Ozeki, M., et al. (2019). "Efficacy and safety of sirolimus treatment for intractable
lymphatic anomalies: A study protocol for an open-label, single-arm, multicenter,
prospective study (SILA)." Regen Ther 10: 84-91.
INTRODUCTION: Lymphatic anomalies (LAs) refer to a group of diseases involving
systemic dysplasia of lymphatic vessels. These lesions are classified as cystic lymphatic
malformation (macrocystic, microcystic or mixed), generalized lymphatic anomaly, and
Gorham-Stout disease. LAs occur mainly in childhood, and present with various symptoms
including chronic airway problems, recurrent infection, and organ disorders. Individuals with
LAs often experience progressively worsening symptoms with a deteriorating quality of life.
Although limited treatment options are available, their efficacy has not been validated in
prospective clinical trials, and are usually based on case reports. Thus, there are no validated
standards of care for these patients because of the lack of prospective clinical trials.
METHODS: This open-label, single-arm, multicenter, prospective study will assess the
efficacy and safety of a mammalian target of the rapamycin inhibitor sirolimus in the
treatment of intractable LAs. Participants will receive oral sirolimus once a day for 52 weeks.
The dose is adjusted so that the nadir concentration remains within 5-15 ng/ml. The primary
endpoint is the response rate of radiological volumetric change of the target lesion confirmed
by central review at 52 weeks after treatment. The secondary endpoints are the response rates
at 12 and 24 weeks, respiratory function, pleural effusion, ascites, blood coagulation
parameters, bleeding, pain, quality of life, activities of daily living, adverse events, side
effects, laboratory examinations, vital signs, and pharmacokinetic data. RESULTS: This is
among the first multicenter studies to evaluate sirolimus treatment for intractable LAs, and
few studies to date have focused on the standard assessment of the efficacy for LAs
treatment. Our protocol uses novel, uncomplicated methods for radiological assessment, with
reference to the results of our previous retrospective survey and historical control data from
the literature. CONCLUSIONS: We propose a multicenter study to investigate the efficacy
and safety of sirolimus for intractable LAs (SILA study; trial registration UMIN000028905).
Our results will provide pivotal data to support the approval of sirolimus for the treatment of
Paisan, G. M., et al. (2017). "Lumbosacral Subdural Hematoma After Glioblastoma
Multiforme Resection: Possible Radiographic Evidence for the Downward Migration
of Intracranial Blood." World Neurosurg 108: 993.e913-993.e917.
BACKGROUND: Spinal subdural hematomas (SSDHs) are rare and usually associated with
bleeding diatheses, trauma, iatrogenic injury, spinal vascular malformations, or intraspinal
tumors. CASE DESCRIPTION: We report a case of a 75-year-old man who developed a
symptomatic lumbosacral SSDH after undergoing resection of a right temporal glioblastoma
multiforme. The patient subsequently recovered and was discharged home. Over the next 2
weeks, he developed progressively worsening symptoms of lower back pain, lower extremity
weakness, and urinary retention. Although the patient had no known risk factors for
developing a SSDH, magnetic resonance imaging on postoperative day 16 revealed an
extensive L2-sacrum SSDH. The patient underwent L2-L5 total laminectomies for evacuation
of the SSDH. His symptoms resolved after surgery. Literature review produced 26 other cases
of SSDHs after intracranial surgery in patients without obvious risk factors. In our case, the
lumbosacral SSDH may have originated from downward migration of intracranial blood in a
gravity-dependent fashion. Radiographic evidence of blood within the posterior thecal sac of
the patient's cervical spine supports this hypothesis. CONCLUSIONS: In most cases, SSDHs
after intracranial surgery resolve with conservative treatment; however, as shown in our case,
surgery may be required if there is progressive neurologic decline. Neurosurgeons should be
aware of this potential complication after intracranial surgery; a magnetic resonance imaging
Pan, S. A., et al. (2023). "Mechanisms of acupuncture for primary dysmenorrhea
based on PI3K/Akt/mTOR signaling pathway in rats." Zhen Ci Yan Jiu 48(12): 12581265.
OBJECTIVES: To observe the effect of electroacupuncture(EA) on phosphatidylinositol-3kinases(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR) signaling
pathway of uterus tissue in rats with primary dysmenorrhea(PDM), so as to investigate its
mechanisms underlying improvement of PDM. METHODS: Thirty healthy non-pregnant
female SD rats were randomly divided into blank, model and EA groups, with 10 rats in each
group. The PDM model was established by subcutaneous injection of estradiol diphenhydrate
combined with intraperitoneal injection of oxytocin. For rats of the EA group, EA(50 Hz, a
tolerable current intensity) was applied to "Guanyuan"(CV4) and bilateral "Sanyinjiao"(SP6)
for 20 min, once a day for 10 consecutive days. The number of writhing, wri-thing score, and
writhing latency were observed. The uterine histopathological changes were observed by
H.E. staining, and the ultrastructural changes of uterine tissue cells in each group were
observed by transmission electron microscopy. The contents of prostaglandin E2(PGE2),
prostaglandin F2α(PGF2α) and ratios of PGF2α/PGE2 in the serum and uterine tissue were
detected by ELISA. The relative expression levels of PI3K, Akt and mTOR and their
phosphorylation proteins in the uterine tissue were detected by Western blot and the ratios
were calculated. RESULTS: Compared with the blank group, the number and score of
writhing, latency of writhing, pathological injury score, contents of PGF2α and ratios of
PGF2α/PGE2 in the serum and uterine tissue, and the levels of p-PI3K/PI3K, p-Akt/Akt and
p-mTOR/mTOR in the uterine tissue were significantly increased in the model group(P<0.01,
P<0.05), while contents of PGE2 in the serum and uterine tissue were reduced(P<0.05). In
comparison with the model group, the number of writhing and writhing score, pathological
injury score, contents of PGF2α and ratios of PGF2α/PGE2 in both the serum and uterine
tissue, the levels of p-PI3K/PI3K, p-Akt/Akt and p-mTOR/mTOR were obviously
decreased(P<0.05, P<0.01), whereas the writhing latency was considerably prolonged in the
EA group(P<0.01), with elevated contents of PGE2 in the serum and uterine tissue(P<0.05).
H.E. staining showed slight dilation of uterine glandular cavity, and severe endometrial
edema with extensive cell shedding and a large number of vacuole-like degeneration,
apoptosis, pyknosis or fragmentation or disappearance of the nucleus, and neutrophil
Patil, S. A., A. C. Patil and P. A. Patil (2020). "Anesthetic efficacy of anterior middle
superior alveolar injection in single-visit endodontic therapy: an in vivo study." Clin
Oral Investig 24(5): 1701-1707.
OBJECTIVES: To evaluate and compare the anesthetic efficacy of anterior middle superior
alveolar (AMSA) injection in single-visit endodontic therapy, an in vivo study. MATERIALS
AND METHODS: Teeth in the maxillary anterior segment (N = 60) requiring single-visit
endodontic (SVE) therapy were selected. A conventional syringe with 26-guage needle
containing 1.5 ml lignocaine with 1:80,000 epinephrine was used for the AMSA injection.
The SVE therapy was performed using standard protocol. Profoundness of anesthesia during
therapy was evaluated at 15-, 30-, 60-, and 90-min intervals using pain rating score and
marked on visual analogue scale. In patients who reported pain/ineffectiveness of anesthesia
during the course of endodontic therapy, additional supplemental anesthesia (buccal/labial
infiltration) was administered. Depending on effectiveness of anesthesia with the AMSA
injection alone or the need for additional supplementary injections, patients were divided as:
group I-only AMSA and group II-AMSA with one or two supplemental anesthesia.
RESULTS: The AMSA injection was effective in 91.67% of the patients undergoing the SVE
therapy and the duration of anesthesia for the AMSA injection alone was adequate until the
completion of the SVE therapy. Supplementary injections were required in 8.33% of cases at
15-min interval to achieve profound anesthesia. CONCLUSION: The AMSA injection
technique could be used as an alternative to the conventional infiltration technique for
anesthetizing teeth in maxillary anterior segment during the SVE therapy. CLINICAL
RELEVANCE: The AMSA injection provides profound pulpal anesthesia of teeth in
Pena, E., L. Moroz and D. Singh (2016). "Lumbar Epidural Steroid Injections." JBJS
Essent Surg Tech 6(3): e25.
Lumbar radiculopathy is a common diagnosis for patients who present with low-back pain
and leg pain, typically along a particular dermatome. This pain is commonly associated with a
lumbar disc herniation. The prognosis is usually favorable, and the symptoms can resolve
spontaneously over time. In patients in whom leg and back symptoms are severe, lumbar
epidural (cortico)steroid injections are good options for the short to medium-term
management of pain. Currently, lumbar epidural steroid injections are performed with
radiographic guidance systems and fluoroscopy. This method is preferred because of the
increased accuracy in needle placement and the reduced risk of injury to nerves and vascular
structures. The procedure is performed with the following steps: (1) Following appropriate
patient selection through clinical evaluation and assessment of imaging studies such as
computed tomography or magnetic resonance imaging, the patient is prepared and draped
after providing written informed consent. (2) The level of neural compression to be injected
is identified with intermittent fluoroscopy and the use of a radiopaque marker. (3) The skin
and subcutaneous tissues are anesthetized. (4) A spinal needle (Quincke or Tuohy type) is
inserted after tissues are fully anesthetized. The needle is slowly advanced with the use of
intermittent fluoroscopy until the target is reached. In the case of an interlaminar approach,
this would be associated with a loss of syringe resistance and piercing of the ligamentum
flavum. In the case of a transforaminal approach, this would be associated with the 6 o'clock
position of the pedicle on the side in question. (5) Contrast material is then injected with the
use of live fluoroscopy to confirm appropriate placement and exclude intravascular and
intrathecal injection. (6) When adequate placement is confirmed, a solution of steroid and
anesthetic is administered. The needle is then removed. Most outcome reports after lumbar
epidural steroid injections are favorable for radicular symptoms. Associated back pain may
typically improve as well. Common complications include injection site pain or soreness,
Peng, X., et al. (2021). "Extracellular vesicles released from hiPSC-derived MSCs
attenuate chronic prostatitis/chronic pelvic pain syndrome in rats by
immunoregulation." Stem Cell Res Ther 12(1): 198.
BACKGROUND: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is an
intractable nonbacterial inflammatory disease. Mesenchymal stem cells (MSCs) derived from
human induced pluripotent stem cells (hiPSCs, iMSCs) have been well documented for the
management of inflammatory and autoimmune disorders because of their powerful
immunoregulatory and anti-inflammatory capacities. Recently, studies have indicated that
extracellular vesicles (EVs) released from iMSCs hold biological functions similar to their
parental cells. This study aimed to evaluate the therapeutic efficacy of EVs released from
iMSCs (iMSCs-EVs) on CP/CPPS and to explore the underlying mechanisms. METHODS:
An experimental autoimmune prostatitis (EAP) model was established in rats by
subcutaneous injection of prostate antigen with adjuvant. Then, iMSCs-EVs were injected
into EAP rats via the tail vein. Pain behavioral measurements, urodynamic tests, and
histopathological analyses were performed at 2, 4, and 6 weeks. The expression of
cyclooxygenase-2 (COX-2) was evaluated by immunofluorescence staining and Western blot.
The alterations of B cells, Th1 cells, Th2 cells, Th17 cells, and Treg cells in peripheral blood
and spleen were analyzed using flow cytometry. The levels of Th1-, Th2-, Th17-, and Tregrelated inflammatory mediators were determined by ELISA. RESULTS: After iMSCs-EVs
administration, rats had reduced pain as indicated by the recovery of nociceptive responses to
baseline. The voiding pressure was significantly reduced, and the intercontraction interval
was increased. The findings of histopathological analysis revealed that iMSCs-EVs could
significantly decrease inflammatory cell infiltration and promote basal lamina and glandular
epithelial tissue repair. Further studies demonstrated that the overexpression of COX-2 was
downregulated by iMSCs-EVs. Meanwhile, the increases in the percentages of Th1 and Th17
cells were dramatically reversed. Also, rats that received iMSCs-EVs showed markedly
increased percentages of Treg cells. The levels of those inflammatory mediators showed the
same changing tendency. CONCLUSIONS: iMSCs-EVs administration has the potential to
ameliorate chronic pelvic pain, improve voiding dysfunction, suppress inflammatory
reactions, and facilitate prostatic tissue repair. The functions are mediated by downregulating
Perasso, L., et al. (2010). "Systemic administration of mesenchymal stem cells
increases neuron survival after global cerebral ischemia in vivo (2VO)." Neural Plast
2010: 534925.
Although many studies have shown that administration of stem cells after focal cerebral
ischemia improves brain damage, very little data are available concerning the damage
induced by global cerebral ischemia. The latter causes neuronal death in selectively
vulnerable areas, including the hippocampal CA1 region. We tested the hypothesis that
intravenous infusion of bone marrowderived stromal cells (mesenchimal stem cells, MSC)
reduce brain damage after transient global ischemia. In adult male Sprague-Dawley rats
transient global ischemia was induced using bilateral common carotid artery occlusion for
20 min in addition to controlled hypotension. Five days after, the animals were anaesthetized
with urethane and the brain was fixed, sectioned and stained with hematoxylin-eosin to
investigate histological damage. MSC did not fully protect against ischemic damage, as the
number of viable neurons in this group was lower than in normal (sham-operated) rats.
However, in MSC-treated rats the number of viable CA1 pyramidal neurons was significally
higher than in rats that had been subjected to ischemia but not treated with MSC. We
conclude that intravenous administration of MSC after transient global ischemia reduces
Pi, C., et al. (2022). "Cortical pain induced by optogenetic cortical spreading
depression: from whole brain activity mapping." Mol Brain 15(1): 99.
BACKGROUND: Cortical spreading depression (CSD) is an electrophysiological event
underlying migraine aura. Traditional CSD models are invasive and often cause injuries. The
aim of the study was to establish a minimally invasive optogenetic CSD model and identify
the active networks after CSD using whole-brain activity mapping. METHODS: CSD was
induced in mice by light illumination, and their periorbital thresholds and behaviours in the
open field, elevated plus-maze and light-aversion were recorded. Using c-fos, we mapped the
brain activity after CSD. The whole brain was imaged, reconstructed and analyzed using the
Volumetric Imaging with Synchronized on-the-fly-scan and Readout technique. To ensure the
accuracy of the results, the immunofluorescence staining method was used to verify the
imaging results. RESULTS: The optogenetic CSD model showed significantly decreased
periorbital thresholds, increased facial grooming and freezing behaviours and prominent
light-aversion behaviours. Brain activity mapping revealed that the somatosensory, primary
sensory, olfactory, basal ganglia and default mode networks were activated. However, the
thalamus and trigeminal nucleus caudalis were not activated. CONCLUSIONS: Optogenetic
CSD model could mimic the behaviours of headache and photophobia. Moreover, the
optogenetic CSD could activate multiple sensory cortical regions without the thalamus or
Pitta, M., et al. (2016). "Intravenous administration of tranexamic acid effectively
reduces blood loss in primary total knee arthroplasty in a 610-patient consecutive case
series." Transfusion 56(2): 466-471.
Pusateri, A. E., et al. (2024). "Safety of Bioplasma FDP and Hemopure in rhesus
macaques after 30% hemorrhage." Trauma Surg Acute Care Open 9(Suppl 1):
e001147.
BACKGROUND: Tranexamic acid (TXA) has been reported to demonstrate efficacy in
reducing blood loss during arthroplasty procedures. STUDY DESIGN AND METHODS:
This study examines the effectiveness of TXA as a central element of a patient blood
management program (PBMP) by evaluating blood loss and transfusion of red blood cells in
three consecutive groups of patients undergoing routine total knee arthroplasty (TKA).
Approximately 200 patients were in each group as follows: Group 1 was a control without
TXA, Group 2 was intraarticular administration, and Group 3 was intravenous (IV)
administration. RESULTS: The IV group demonstrated a small but significant lower blood
loss compared to the two other groups measured by hemoglobin (Hb) drift and nadir Hb
levels. The routine use of TXA along with the other aspects of our PBMP provided
significant cost savings due to the reduction in transfusions as well as a decrease in length of
stay and has been an important element of our successful implementation of a PBMP.
CONCLUSION: This study demonstrates a significant benefit from the routine use of TXA
for total knee arthroplasty and is one of the first studies to demonstrate a small but significant
benefit for IV administration in comparison to intraarticular administration. The routine use
of TXA as a central element of a PBMP provides a cost savings and can help reduce the rate
OBJECTIVES: Prehospital transfusion can be life-saving when transport is delayed but
conventional plasma, red cells, and whole blood are often unavailable out of hospital. Shelfstable products are needed as a temporary bridge to in-hospital transfusion. Bioplasma FDP
(freeze-dried plasma) and Hemopure (hemoglobin-based oxygen carrier; HBOC) are products
with potential for prehospital use. In vivo use of these products together has not been
reported. This study assessed the safety of intravenous administration of HBOC+FDP,
relative to normal saline (NS), in rhesus macaques (RM). METHODS: After 30% blood
volume removal and 30 minutes in shock, animals were resuscitated with either NS or two
units (RM size adjusted) each of HBOC+FDP during 60 minutes. Sequential blood samples
were collected. After neurological assessment, animals were killed at 24 hours and tissues
collected for histopathology. RESULTS: Due to a shortage of RM during the COVID-19
pandemic, the study was stopped after nine animals (HBOC+FDP, seven; NS, two). All
animals displayed physiologic and tissue changes consistent with hemorrhagic shock and
recovered normally. There was no pattern of cardiovascular, blood gas, metabolic,
coagulation, histologic, or neurological changes suggestive of risk associated with
HBOC+FDP. CONCLUSION: There was no evidence of harm associated with the combined
use of Hemopure and Bioplasma FDP. No differences were noted between groups in safetyrelated cardiovascular, pulmonary, renal or other organ or metabolic parameters. Hemostasis
and thrombosis-related parameters were consistent with expected responses to hemorrhagic
shock and did not differ between groups. All animals survived normally with intact
Py, J. Y., et al. (2016). "Les effets indésirables retardés chez les donneurs de sang :
des données de l’hémovigilance aux études spécifiques." Transfusion Clinique et
Biologique 23(4): 233-239.
Résumé Objectifs Les effets indésirables retardés chez les donneurs de sang sont des
réactions qui se produisent après leur départ du lieu de prélèvement. Au-delà de leur gravité
intrinsèque, ils peuvent induire des complications sérieuses et amener le donneur à ne plus
revenir donner. L’établissement de transfusion sanguine ne connaîtra l’évènement que si le
donneur le lui signale. Cette incertitude crée une sous-appréciation du phénomène que nous
avons voulu explorer dans nos données et dans la littérature. Méthodes La déclaration
obligatoire des effets indésirables donneurs graves en hémovigilance fournit une première
vision des effets retardés, limitée à ceux qui sont spontanément remontés par les donneurs.
L’analyse des données enregistrées lors des prélèvements par l’établissement de transfusion
sanguine permet d’étendre cette vision aux effets indésirables non graves, mais toujours
limitée à ceux que le donneur signale. Une revue de la littérature a permis de retrouver des
études spécifiques sur les effets retardés, qui ont été comparées à nos données. Résultats
Notre base régionale d’effets indésirables donneurs graves comprend 1957 évènements
déclarés entre 2011 et 2015, dont 49 % surviennent pendant le prélèvement, 40 % après le
prélèvement mais avant le départ du donneur et 11 % après celui-ci. Le signalement des effets
indésirables donneurs en France métropolitaine sur le premier trimestre 2016 porte sur
16 050 évènements, dont 2,7 % sont retardés. La part des effets retardés augmente avec la
gravité de l’effet pour atteindre 27,6 % pour les plus graves. Elle varie de 2,2 à 2,7 % selon
que l’effet indésirable est un malaise vagal, un hématome ou une autre réaction à caractère
local. Elle atteint 16,2 % quand on isole les autres réactions à caractère général. Les données
de la littérature sont conformes aux nôtres dans le même contexte de remontée spontanée des
effets retardés par les donneurs. Mais quatre études publiées entre 2003 et 2013 ont
spécifiquement recherché les effets retardés auprès des donneurs. Leurs résultats convergent
pour conclure qu’au moins trois effets indésirables sur quatre échappent à notre connaissance
car ils vont survenir après que le donneur soit parti, sans compter un nombre encore plus
important de réactions mineures qui ne sont pas prises en compte par l’hémovigilance.
Conclusions La survenue d’un effet indésirable après que le donneur ait quitté le lieu de
prélèvement est donc un phénomène très largement sous-apprécié. Il reste à évaluer s’il pèse
Rahyussalim, A. J., et al. (2023). "Closed system paravertebral abscess evacuation on
spinal infection: A case series." Int J Surg Case Rep 104: 107941.
INTRODUCTION: Paravertebral abscess is a common complication of spondylitis
tuberculosis which has high prevalence in Indonesia. Surgical intervention such as open
surgery or endoscopic debridement is needed to remove and drainage the abscess in addition
to chemotherapy. However, this surgeries have several complications such as soft tissue
damage and abscess contamination to the healthy tissue. We reported closed system strategy
to evacuate the paravertebral abscess on spinal infection. METHODS: The technique is
performed by orthopaedic team under guidance of the C-Arm and ultrasound sonography
(USG) in March-June 202. The needle which connected to 20 cc syringe is inserted into the
lesion to aspirate the abscess. After evacuation of the abscess, 2-g broad spectrum antibiotic
is injected through the needle to eradicate the bacteria locally. RESULTS: We performed the
closed system paravertebral abscess evacuation in three patients, a 30-year-old male, 43-yearold male, and 22-year-old female. All the patients had back pain and limitation spine
movement due to pain and were diagnosed with spondylitis and paravertebral abscess based
on the plain radiography and magnetic resonance imaging (MRI). It reported that up to
2000 cc abscess can be evacuated with this micro invasive technique. CONCLUSION: The
closed system is a micro-invasive procedure result in minimal soft tissue injury and faster
recovery. It succesfully remove paravertebral abscess followed by direct antibiotic
Rath, W., P. Stelzl and S. Kehl (2021). "Outpatient Induction of Labor - Are Balloon
Catheters an Appropriate Method?" Geburtshilfe Frauenheilkd 81(1): 70-80.
As the number of labor inductions in high-income countries has steadily risen, hospital costs
and the additional burden on obstetric staff have also increased. Outpatient induction of labor
is therefore becoming increasingly important. It has been estimated that 20 - 50% of all
pregnant women requiring induction would be eligible for outpatient induction. The use of
balloon catheters in patients with an unripe cervix has been shown to be an effective and safe
method of cervical priming. Balloon catheters are as effective as the vaginal administration of
prostaglandin E (2) or oral misoprostol. The advantage of using a balloon catheter is that it
avoids uterine hyperstimulation and monitoring is less expensive. This makes balloon
catheters a suitable option for outpatient cervical ripening. Admittedly, intravenous
administration of oxytocin to induce or augment labor is required in approximately 75% of
cases. Balloon catheters are not associated with a higher risk of maternal and neonatal
infection compared to vaginal PGE (2) . Low-risk pregnancies (e.g., post-term pregnancies,
gestational diabetes) are suitable for outpatient cervical ripening with a balloon catheter. The
data for high-risk pregnancies are still insufficient. The following conditions are
recommended when considering an outpatient approach: strict selection of appropriate
patients (singleton pregnancy, cephalic presentation, intact membranes), CTG monitoring for
20 - 40 minutes after balloon placement, the patient must be given detailed instructions about
the indications for immediate readmission to hospital, and 24-hour phone access to the
hospital must be ensured. According to reviewed studies, the balloon catheter remained in
place between 12 hours ("overnight") and 24 hours. The most common reason for
readmission to hospital was expulsion of the balloon catheter. The advantages of outpatient
versus inpatient induction of cervical ripening with a balloon catheter were the significantly
shorter hospital stay, the lower costs, and higher patient satisfaction, with both procedures
having been shown to be equally effective. Complication rates (e.g., vaginal bleeding, severe
pain, uterine hyperstimulation syndrome) during the cervical ripening phase are low (0.3 1.5%); severe adverse outcomes (e.g., placental abruption) have not been reported. Compared
to inpatient induction of labor using vaginal PGE (2) , outpatient cervical ripening using a
balloon catheter had a lower rate of deliveries/24 hours and a significantly higher need for
Reining, M. and M. Kretzschmar (2023). "Loss of effectiveness with an implanted
drug delivery system for intrathecal pain therapy due to corrosion." Pain Pract 23(4):
459-462.
INTRODUCTION: Intrathecal drug delivery is an established invasive treatment option.
Most common complication is catheter malfunction, which can lead to overdose or
withdrawal. CASE PRESENTATION: A 61-year-old female patient underwent an elective
replacement of an intrathecal drug delivery pump. The patient complained about a loss of
effectiveness over the past 2 years. Intraoperatively, a white mass corresponding to morphine
precipitation in the pump pocket was found, which appeared to be due to corrosion at the
pump-catheter connection site. CONCLUSIONS: Recommendations on how to deal with the
decreasing effectiveness of intrathecal drug delivery and on intraoperative catheter handling
are provided.
Reis, P. and J. Mourão (2017). "Septo-optic dysplasia/de Morsier's syndrome." Saudi
J Anaesth 11(1): 106-107.
Riestenberg, R. A., et al. (2020). "Subarachnoid fat dissemination secondary to
intrathecal pump." J Clin Neurosci 78: 416-417.
Septo-optic dysplasia (SOD)/de Morsier's syndrome is characterized by optic nerve
hypoplasia, pituitary endocrine dysfunction, and midline brain abnormalities.
Hypopituitarism, hypothyroidism, hypogonadism, and adrenal insufficiency can lead to
severe hypoglycemia, adrenal crisis, seizures, and sudden death. Anesthetic management of
SOD was associated with high perioperative mortality. A 9-year-old male child proposed for
dental treatments/extractions. Medical history of SOD with hypopituitarism, hypothyroidism,
and delayed psychomotor development was observed. Anesthetic induction with sevoflurane
and intravenous administration of hydrocortisone plus dexamethasone were given. An
infusion of 5% glucose in sodium chloride 0.9% was started. Anesthesia with sevoflurane and
air, combined with local infiltration with 2% lidocaine, was maintained. During the
procedure, the patient was breathing spontaneously, hemodynamically stable, with normal
glucose levels measured every 30 min. The patient received 750 mg of paracetamol for
analgesia and was discharged from the hospital 24 h after the procedure without
complications. The mortality related to general anesthesia in such patients put us some
challenges. The procedure was imperative for improving the health and quality of life of the
patient, so we opted for inhalational anesthesia combined with local infiltration. We think
that combined anesthesia contributed to the abolition of pain and avoided adrenal suppression
Implantable intrathecal infusion pumps (ITPs) are an effective pain management modality for
patients who have failed non-operative options. We present the first report of asymptomatic
intracranial subarachnoid fat dissemination secondary to an ITP. A 39-year-old who
underwent implantation of an ITP for intractable pelvic pain developed altered mental status.
CT and MRI revealed subarachnoid fat deposition without evidence of a dermoid or
epidermoid cyst. She returned to her baseline mental status with her symptoms attributed to
delirium. The rare possibility of subarachnoid fat dissemination following transdural spinal
procedures should be considered as a potential complication of ITPs. Although fat may
persist in the subarachnoid space for years, asymptomatic patients can be safely managed
with observation alone.
Rusu, L. C., et al. (2021). "COVID-19 and Its Repercussions on Oral Health: A
Review." Medicina (Kaunas) 57(11).
In 2019, a new type of coronavirus, SARS-CoV-2, the causing agent of COVID-19, was first
detected in Wuhan, China. On 11 March 2020, the World Health Organization declared a
pandemic. The manifestations of COVID-19 are mostly age-dependent and potentially more
severe in cases with involved co-morbidities. The gravity of the symptoms depends on the
clinical stage of the infection. The most common symptoms include runny nose and nasal
congestion, anosmia, dysgeusia or hypogeusia, diarrhea, nausea/vomiting, respiratory
distress, fatigue, ocular symptoms, diarrhea, vomiting, and abdominal pain. These systemic
conditions are often accompanied by skin and mucosal lesions. Oral lesions reported in
patients with COVID-19 include: herpex simplex, candidiasis, geographic tongue, aphthouslike ulcers, hemorrhagic ulcerations, necrotic ulcerations, white hairy tongue, reddish
macules, erythematous surfaces, petechiae, and pustular enanthema. It is still unclear if these
manifestations are a direct result of the viral infection, a consequence of systemic
deterioration, or adverse reactions to treatments. Poor oral hygiene in hospitalized or
quarantined COVID-19 patients should also be considered as an aggravating condition. This
narrative review is focused on presenting the most relevant data from the literature regarding
oral manifestations related to SARS-CoV-2, as well as the challenges faced by the dental
system during this pandemic. A routine intraoral examination is recommended in COVID-19
patients, either suspected or confirmed, as, in certain cases, oral manifestations represent a
sign of severe infection or even of a life-threatening condition. It is our belief that extensive
knowledge of all possible manifestations, including oral lesions, in cases of COVID-19 is of
great importance in the present uncertain context, including new, currently emerging viral
Rusznák, K., et al. (2022). "Experimental Arthritis Inhibits Adult Hippocampal
Neurogenesis in Mice." Cells 11(5).
Sakai, H. and C. Leong (2019). "Prolonged functional life span of artificial red cells in
blood circulation by repeated methylene blue injections." Artif Cells Nanomed
Biotechnol 47(1): 3123-3128.
Background: Adult-born neurons of the hippocampal dentate gyrus play a role in specific
forms of learning, and disturbed neurogenesis seems to contribute to the development of
neuropsychiatric disorders, such as major depression. Neuroinflammation inhibits adult
neurogenesis, but the effect of peripheral inflammation on this form of neuroplasticity is
ambiguous. Objective: Our aim was to investigate the influence of acute and chronic
experimental arthritis on adult hippocampal neurogenesis and to elucidate putative regulatory
mechanisms. Methods: Arthritis was triggered by subcutaneous injection of complete
Freund's adjuvant (CFA) into the hind paws of adult male mice. The animals were killed
either seven days (acute inflammation) or 21 days (chronic inflammation) after the CFA
injection. Behavioral tests were used to demonstrate arthritis-related hypersensitivity to
painful stimuli. We used in vivo bioluminescence imaging to verify local inflammation. The
systemic inflammatory response was assessed by complete blood cell counts and by
measurement of the cytokine/chemokine concentrations of TNF-α, IL-1α, IL-4, IL-6, IL-10,
KC and MIP-2 in the inflamed hind limbs, peripheral blood and hippocampus to characterize
the inflammatory responses in the periphery and in the brain. In the hippocampal dentate
gyrus, the total number of newborn neurons was determined with quantitative
immunohistochemistry visualizing BrdU- and doublecortin-positive cells. Microglial
activation in the dentate gyrus was determined by quantifying the density of Iba1- and CD68positive cells. Results: Both acute and chronic arthritis resulted in paw edema, mechanical
and thermal hyperalgesia. We found phagocytic infiltration and increased levels of TNF-α,
IL-4, IL-6, KC and MIP-2 in the inflamed hind paws. Circulating neutrophil granulocytes and
IL-6 levels increased in the blood solely during the acute phase. In the dentate gyrus, chronic
arthritis reduced the number of doublecortin-positive cells, and we found increased density of
CD68-positive macrophages/microglia in both the acute and chronic phases. Cytokine levels,
however, were not altered in the hippocampus. Conclusions: Our data suggest that acute
peripheral inflammation initiates a cascade of molecular and cellular changes that eventually
leads to reduced adult hippocampal neurogenesis, which was detectable only in the chronic
Samson, A., et al. (2018). "Intravenous delivery of oncolytic reovirus to brain tumor
patients immunologically primes for subsequent checkpoint blockade." Sci Transl
Med 10(422).
Hemoglobin-vesicles (HbVs) are artificial oxygen carriers encapsulating purified and
concentrated hemoglobin solution in phospholipid vesicles (liposomes) and their safety and
efficacy as a transfusion alternative have been evaluated. Because of the absence of
enzymatic methemoglobin reduction system in HbV, the level of ferric methemoglobin
(metHb) increases gradually after intravenous administration. Our previous studies clarified
that the glycolytic electron energies, charged as NAD(P)H in red blood cells (RBC), are
donated to reduce metHb compartmentalized in HbV via a water-soluble electron mediator
such as methylene blue [MB; 3,7-bis(dimethylamino)phenothiazinium chloride], which freely
shuttle across both RBC biomembrane and HbV lipid membrane. Herein, we tried to test
repeated injections of MB after the massive HbV administration (28 mL/kg) to hemorrhagic
shocked Wistar rats (n = 3). MB was injected (3.1 mg/kg) at 7, 24 and 48 h after HbV
administration. Every MB injection showed rapid reduction of metHb and gradual reversal
increase. As a result, the functional life span of HbV was significantly extended over 60 h. It
is expected that further optimization of injection scheduling will decrease the total amount of
MB and prolong the functional life span of HbV.
Immune checkpoint inhibitors, including those targeting programmed cell death protein 1
(PD-1), are reshaping cancer therapeutic strategies. Evidence suggests, however, that tumor
response and patient survival are determined by tumor programmed death ligand 1 (PD-L1)
expression. We hypothesized that preconditioning of the tumor immune microenvironment
using targeted, virus-mediated interferon (IFN) stimulation would up-regulate tumor PD-L1
protein expression and increase cytotoxic T cell infiltration, improving the efficacy of
subsequent checkpoint blockade. Oncolytic viruses (OVs) represent a promising form of
cancer immunotherapy. For brain tumors, almost all studies to date have used direct
intralesional injection of OV, because of the largely untested belief that intravenous
administration will not deliver virus to this site. We show, in a window-of-opportunity
clinical study, that intravenous infusion of oncolytic human Orthoreovirus (referred to herein
as reovirus) leads to infection of tumor cells subsequently resected as part of standard clinical
care, both in high-grade glioma and in brain metastases, and increases cytotoxic T cell tumor
infiltration relative to patients not treated with virus. We further show that reovirus upregulates IFN-regulated gene expression, as well as the PD-1/PD-L1 axis in tumors, via an
IFN-mediated mechanism. Finally, we show that addition of PD-1 blockade to reovirus
enhances systemic therapy in a preclinical glioma model. These results support the
development of combined systemic immunovirotherapy strategies for the treatment of both
San Norberto García, E. M., et al. (2014). "Beneficial effects of intra-arterial and
intravenous prostaglandin E1 in intestinal ischaemia-reperfusion injury." Interact
Cardiovasc Thorac Surg 18(4): 466-474.
Sano, T., et al. (2012). "[Retrospective study on intravenous compound injection of
cancer pain patients with oxycodone and hydrocotarnine preparation in comparison
with subcutaneous administration]." Gan To Kagaku Ryoho 39(5): 769-775.
OBJECTIVES: Ischaemia-reperfusion (I/R) injury is encountered in conditions that diminish
intestinal blood flow. There is no clinically feasible technique available for mucosal
preservation. METHODS: One hundred Wistar rats were subjected to intestinal ischaemia for
15 and 60 min (I15', I60'), followed by 1 and 7 days of reperfusion (R1d, R7d). Rats were
subjected to ischaemia by clamping the superior mesenteric artery. Prostaglandin E1 (PGE1)
(2.500 ng/kg intra-arterial bolus or 20 ng/kg intravenous infusion) was administered
immediately prior to the commencement of the experimental period. Animals were divided
into 20 groups: sham (laparotomy alone), sacrificed at 1 or 7 days; saline administration, 15
or 60 min of ischaemia, 1 or 7 days of reperfusion; prostaglandin E1 administration, 15 or 60
min of ischaemia, 1 or 7 days of reperfusion, each one for intra-arterial or intravenous
administration. Ileal segments were excised and assessed for histopathological score,
polymorphonuclear (PMN) leucocytes encountered and myeloperoxidase (MPO) activity
measurement. RESULTS: I/R caused deterioration of histological characteristics.
Prophylactic administration of PGE1 resulted in a significant decrease in the histological
score compared with the respective saline group (analysis of variance, P < 0.005). In groups
treated with PGE1, PMN leucocyte infiltration was lower for the 60 min of ischaemia group
(I60'/R1d *P = 0.026; I60'/R7d P = 0.015). I15'/R7d did not lead to a significant reduction in
PMN infiltration (P = 0.061). Pretreatment with PGE1 attenuates MPO levels after intestinal
I/R injury (P < 0.05). No differences were encountered between types of administration.
CONCLUSIONS: Results of this study showed that administration of prostaglandin E1
prevents I/R injury by diminishing histological damage parameters, inhibiting PMN leucocyte
In Japan, although oral oxycodone is widely used for cancer pain treatment, there is no
injection preparation of oxycodone used as a single ingredient. Only the compound injection
of oxycodone and hydrocotarnine has received approval. Subcutaneous administration of the
drug is approved, but there are few efficacy and safety reports about its intravenous
administration. We compared 245 patients(187 intravenous administration patients and, 58
subcutaneous administration patients)to whom the compound injection of oxycodone and
hydrocotarnine was administered from April, 2008 to September, 2011, in order to investigate
the drug's efficacy and safety. The reasons for injection were the impossibility of oral
administration in 105 patients, a need for dose adjustment in 56 patients, and that other drugs
were not as effective in 37 patients, and side effect reduction in 33 patients. The average
change in the numeric rating scale(0-10)was 3. 7→1. 8 in intravenous administration, and 3.
4→1. 2 in subcutaneous administration. The incidence of main adverse events(intravenous
administration/subcutaneous administration)were constipation(37%/28%),
vomiting(31%/34%), and somnolence(52%/50%). There was no significant difference in
efficacy and safety. The conversion ratio differed in a case due to a change, and about 20 to
40% of addition was needed within four days after the start. It is considered that compound
Sato, Y., et al. (2014). "[Cardioversion for paroxysmal supraventricular tachycardia
during lung surgery in a patient with concealed Wolff-Parkinson-White syndrome]."
Masui 63(10): 1106-1110.
We report a case of paroxysmal supraventricular tachycardia (PSVT) that occurred during
video-assisted thoracoscopic (VATS) lobectomy in a patient with concealed WolffParkinson-White (WPW) syndrome. A 59-year-old man with lung cancer was scheduled for
VATS lobectomy under general anesthesia. After inserting a thoracic epidural catheter,
general anesthesia was induced with intravenous administration of propofol. Anesthesia was
maintained with inhalation of desfurane in an air/oxygen mixture and intravenous infusion of
remifentanil. Recurrent PSVT occurred three times, and the last episode of PSVT continued
for 50 minutes regardless of administration of antiarrhythmic drugs. Synchronized electric
shock via adhesive electrode pads on the patient's chest successfully converted PSVT back to
normal sinus rhythm. The remaining course and postoperative period were uneventful. An
electrophysiological study performed after hospital discharge detected concealed WPW
syndrome, which had contributed to the development of atrioventricular reciprocating
tachycardia. Concealed WPW syndrome is a rare, but critical complication that could
possibly cause lethal atrial tachyarrhythmias during the perioperative period. In the present
case, cardioversion using adhesive electrode pads briefly terminated PSVT in a patient with
Schmidt, B., et al. (2015). "Local pathology and systemic serum bupivacaine after
subcutaneous delivery of slow-releasing bupivacaine microspheres." Anesth Analg
120(1): 36-44.
Schultz, H., et al. (2023). "Multiple Retinal Emboli and Medial Canthal Swelling
Following Injection of Acellular Porcine Urinary Bladder Matrix for Hair
Restoration." Ophthalmic Plast Reconstr Surg 39(4): e126-e128.
BACKGROUND: Prolonged local anesthesia, particularly desirable to minimize acute and
chronic postoperative pain, has been provided by microspheres that slowly release
bupivacaine (MS-Bup). In this study, we report on the systemic drug concentrations and the
local dermatopathology that occur after subcutaneous injection of MS-Bup. METHODS: Rats
(approximately 300 g) were injected under the dorsolumbar skin with MS-Bup containing 40
mg of bupivacaine (base) or with 0.4 mL of 0.5% bupivacaine-HCl (BupHCl; 1.78 mg
bupivacaine). Blood was drawn, under sevoflurane anesthesia, at 10 minutes to 144 hours,
and the serum analyzed for total bupivacaine by liquid chromatography-tandem mass
spectrometry. In different animals, skin punch biopsies (4 mm) were taken at 1, 3, 7, 14, and
30 days after the same drug injections, sectioned at 5 μm, and stained with hematoxylineosin. Samples from skin injected with BupHCl, with MS-Bup suspended in carboxymethyl
cellulose (MS-Bup.CMC), or in methyl cellulose (MS-Bup.MC) were compared with their
respective drug-free controls (placebos). RESULTS: Serum bupivacaine reached a maximal
average value (n = 8) of 194.9 ng/mL at 8 hours after injection of MS-Bup (95% upper
prediction limit = 230.2 ng/mL), compared with the maximal average (n = 6) serum level of
374.9 ng/mL (95% prediction limit = 470.6 ng/mL) at 30 minutes after injection of BupHCl.
Serum bupivacaine decreased to undetectable levels (<3.23 ng/mL) at 8 hours after BupHCl
and was detectable at approximately 20% of the maximal value at 144 hours after MS-Bup
injection. BupHCl injection resulted in moderate lymphocytic infiltration of skeletal muscle
at 1 and 3 days. MS-Bup.CMC and placebo-CMC caused extensive infiltration of
macrophages, lymphocytes, and some neutrophils at 1 to 7 days, whereas MS-Bup.MC and
placebo-MC caused only mild inflammation. CONCLUSIONS: Subcutaneous administration
of microspheres releasing bupivacaine results in lower blood levels lasting for much longer
Acellular porcine urinary bladder matrix promotes wound healing and is also used to
stimulate hair growth. A 64-year-old female presented with acute-onset OD pain and
decreased visual acuity after subcutaneous injection of acellular porcine urinary bladder
matrix at the hairline. Fundus examination revealed multiple emboli at retinal arcade branch
points, and fluorescein angiography demonstrated corresponding areas of peripheral
nonperfusion. Two weeks later, external examination revealed new swelling of the right
medial canthus without erythema or fluctuance, which was felt to possibly represent
recruitment of vessels after occlusion in the facial vasculature. At 1-month follow up, visual
acuity of the OD improved with resolution of right medial canthal swelling. Fundus
examination was normal with no visible emboli. Herein, the authors present a case of retinal
occlusion and medial canthal swelling following injection of acellular porcine urinary bladder
matrix for hair restoration, which to the authors knowledge has not been previously reported.
Sharma, K. S., et al. (2022). "COVID-19: Consequences on pregnant women and
neonates." Health Sciences Review 4: 100044.
Sharma, P. K., et al. (2019). "A sensitive bioanalytical method for quantitative
determination of resiniferatoxin in rat plasma using ultra-high performance liquid
chromatography coupled to tandem mass spectrometry and its application in
pharmacokinetic study." J Pharm Biomed Anal 165: 284-291.
Introduction Human species is confronting with a gigantic global COVID-19 pandemic.
Initially, it was observed in Wuhan, China, and the COVID-19 cases spread across the globe
with lightning speed and resulted in the 21st century pandemic. If scientific reports are taken
care of, it is noteworthy that this virus possesses more specific characteristics due to its
structure. The distinctive structure has a higher binding affinity with angiotensin-converting
enzyme 2 (ACE2) protein, and this is used as an access point to gain access to hosts. Methods
A complete literature search was conducted using PubMed, Google Scholar, SciFinder, and
deep-diving Google Search using keywords such as "Pregnancy, COVID-19, Newborn, Fetus,
Coronavirus 2019, Neonate, Pregnant women, and vertical transmission". Result and
discussion The SARS-CoV-2 virus is unlike its former analogs: SARS-CoV, and MERS-CoV
in 2002 and 2012, respectively, or anything mankind has faced earlier concerning
viciousness, global spread, and gravity of a causative agent. The current review has delved
into articles published in various journals worldwide including the latest studies on the
impact of COVID-19 on pregnant women and neonates and has discussed complications and
challenges, psychological health, immunological response, vertical transmission, concurrent
disorders, vaccine debate, management recommendations, recent news of the approval of
Resiniferatoxin (RTX) is a daphnane diterpene isolated from the latex of Euphorbia resinifera
O. Berg, a potent activator of transient receptor potential vanilloid 1 (TrpV1), with a potency
10(3)-10(5) times greater than pure capsaicin. Intravenous administration of RTX at very low
concentration improves urodynamic parameters in patients with neurogenic detrusor
overactivity and also reduces bladder pain in patients. Herein, a simple, rapid, selective and
sensitive method for determination of RTX with silydianin as an internal standard was
developed using ultra-high performance liquid chromatography coupled to tandem mass
spectrometry with electrospray ionization source (UHPLC-ESI-MS/MS) in multiple reaction
monitoring mode. The mass spectrometer was operated in positive electrospray ionization
((+) ESI) mode. Multiple reaction monitoring (MRM) mode was performed with ion pairs of
m/z: 629.23→283.2 for RTX and 483.24→153.1 for IS. The limit of detection achieved in
this method for RTX was 0.05 ng/mL and had good linearity in calibration range of 0.250 ng/mL ( r(2) = 0.99). Precision and accuracy values were found to be < 15% (within
acceptable limit), extraction recovery (≥ 88.2%), matrix effect (≥ 89.7%) and stability were in
accordance with the bioanalytical guidelines. The sensitivity of this bio-analytical method
supported the successful pharmacokinetic evaluation of RTX on rat plasma (2.5 μg/kg dose;
i.v.) and has demonstrated pharmacokinetic parameters V(d) and AUC(0-∞) as
191.0 ± 71.31 mL/kg and 981.6 ± 137.40 min*ng/mL, respectively. The clearance was found
to be 2.6 ± 0.38 mL/min/kg and half-life was 53.6 ± 23.51 min. This efficient, rapid and
reliable method promises the quantification at low concentration of RTX, allowing
determination of the pharmacokinetic profile, which is essential in future drug delivery and
Shi, X., et al. (2018). "Radiotherapy for one rectal cancer patient with cirrhosis and
moderate to severe thrombocytopenia: a case report." Onco Targets Ther 11: 52035207.
When patients with cirrhosis and severe thrombocytopenia suffer malignant tumors, there is
usually no effective and feasible treatment method due to the high risk of hemorrhage.
Herein, we report a case in which radiotherapy was given to a patient with a strong desire for
the treatment. The patient was a 66-year-old man with a 13-year history of cirrhosis and a 10year history of thrombocytopenia, and was diagnosed with locally advanced rectal cancer
(LARC; T(4a)N(1)M(0), stage IIIB). The platelet count before radiotherapy was 32 ×
10(9)/L, and the blood coagulation was normal. The severity of thrombocytopenia increased
after 2 Gy × 7 fractions pelvic radiation, with platelet counts dropping to 16 × 10(9)/L.
Platelet counts failed to return to pre-therapy levels after supporting therapy including
recombinant human interleukin 11 subcutaneous injection and platelet transfusion. Although
radiotherapy was discontinued eventually, the data presented here represent a valuable
resource that can help inform treatment decisions for tumor patients with cirrhosis and
thrombocytopenia.
Shimizu, H., et al. (2011). "Pure red cell aplasia induced only by intravenous
administration of recombinant human erythropoietin." Acta Haematol 126(2): 114118.
Shin, T. H., et al. (2017). "Human adipose tissue-derived mesenchymal stem cells
alleviate atopic dermatitis via regulation of B lymphocyte maturation." Oncotarget
8(1): 512-522.
Antibody (Ab)-mediated pure red cell aplasia (PRCA) is a rare but important side effect in
patients with chronic kidney disease who receive recombinant human erythropoietin (rhEPO).
Ab-mediated PRCA was first reported in the 1990s, and the incidence subsequently increased
and reached a peak in 2001. After improvements in rhEPO products and the administration
route, the incidence was reduced by 90%, and now Ab-mediated PRCA only develops in a
limited number of patients who receive rhEPO subcutaneously for a long period. We describe
here the clinical course of one such rare patient with Ab-mediated PRCA. The patient was a
70-year-old man with chronic renal failure secondary to diabetic nephropathy. He had not
received rhEPO therapy before the initiation of hemodialysis. He started hemodialysis and
began to receive rhEPO therapy intravenously. Three months later, his hemoglobin level
started declining and he became transfusion dependent. A diagnosis of Ab-mediated PRCA
was made by bone marrow examination and detection of anti-EPO Abs. He was successfully
treated with cyclosporine and became independent of blood transfusions. This case is a
reminder that vigilance is required regarding the development of Ab-mediated PRCA upon
rhEPO therapy, regardless of the administration route.
Mesenchymal stem cell (MSC) has been applied for the therapy of allergic disorders due to
its beneficial immunomodulatory abilities. However, the underlying mechanisms for
therapeutic efficacy are reported to be diverse according to the source of cell isolation or the
route of administration. We sought to investigate the safety and the efficacy of human
adipose tissue-derived MSCs (hAT-MSCs) in mouse atopic dermatitis (AD) model and to
determine the distribution of cells after intravenous administration. Murine AD model was
established by multiple treatment of Dermatophagoides farinae. AD mice were intravenously
infused with hAT-MSCs and monitored for clinical symptoms. The administration of hATMSCs reduced the gross and histological signatures of AD, as well as serum IgE level. hATMSCs were mostly detected in lung and heart of mice within 3 days after administration and
were hardly detectable at 2 weeks. All of mice administered with hAT-MSCs survived until
sacrifice and did not demonstrate any adverse events. Co-culture experiments revealed that
hAT-MSCs significantly inhibited the proliferation and the maturation of B lymphocytes via
cyclooxygenase (COX)-2 signaling. Moreover, mast cell (MC) degranulation was suppressed
by hAT-MSC. In conclusion, the intravenous infusion of hAT-MSCs can alleviate AD
Sierra-Sánchez, Á., et al. (2021). "Current Advanced Therapies Based on Human
Mesenchymal Stem Cells for Skin Diseases." Front Cell Dev Biol 9: 643125.
Skin disease may be related with immunological disorders, external aggressions, or genetic
conditions. Injuries or cutaneous diseases such as wounds, burns, psoriasis, and scleroderma
among others are common pathologies in dermatology, and in some cases, conventional
treatments are ineffective. In recent years, advanced therapies using human mesenchymal
stem cells (hMSCs) from different sources has emerged as a promising strategy for the
treatment of many pathologies. Due to their properties; regenerative, immunomodulatory and
differentiation capacities, they could be applied for the treatment of cutaneous diseases. In
this review, a total of thirteen types of hMSCs used as advanced therapy have been analyzed,
considering the last 5 years (2015-2020). The most investigated types were those isolated
from umbilical cord blood (hUCB-MSCs), adipose tissue (hAT-MSCs) and bone marrow
(hBM-MSCs). The most studied diseases were wounds and ulcers, burns and psoriasis. At
preclinical level, in vivo studies with mice and rats were the main animal models used, and a
wide range of types of hMSCs were used. Clinical studies analyzed revealed that cell therapy
by intravenous administration was the advanced therapy preferred except in the case of
wounds and burns where tissue engineering was also reported. Although in most of the
clinical trials reviewed results have not been posted yet, safety was high and only local slight
adverse events (mild nausea or abdominal pain) were reported. In terms of effectiveness, it
was difficult to compare the results due to the different doses administered and variables
measured, but in general, percentage of wound's size reduction was higher than 80% in
wounds, Psoriasis Area and Severity Index and Severity Scoring for Atopic Dermatitis were
significantly reduced, for scleroderma, parameters such as Modified Rodnan skin score
(MRSC) or European Scleroderma Study Group activity index reported an improvement of
the disease and for hypertrophic scars, Vancouver Scar Scale (VSS) score was decreased
after applying these therapies. On balance, hMSCs used for the treatment of cutaneous
diseases is a promising strategy, however, the different experimental designs and endpoints
stablished in each study, makes necessary more research to find the best way to treat each
Singh, G., V. T. Cherian and B. P. Thomas (2010). "Low-concentration, continuous
brachial plexus block in the management of Purple Glove Syndrome: a case report." J
Med Case Rep 4: 48.
INTRODUCTION: Purple Glove Syndrome is a devastating complication of intravenous
phenytoin administration. Adequate analgesia and preservation of limb movement for
physiotherapy are the two essential components of management. CASE PRESENTATION: A
26-year-old Tamil woman from India developed Purple Glove Syndrome after intravenous
administration of phenytoin. She was managed conservatively by limb elevation,
physiotherapy and oral antibiotics. A 20G intravenous cannula was inserted into the sheath of
her brachial plexus and a continuous infusion of bupivacaine at a low concentration (0.1%)
with fentanyl (2 mug/ml) at a rate of 1 to 2 ml/hr was given. She had adequate analgesia with
preserved motor function which helped in physiotherapy and functional recovery of the hand
in a month. CONCLUSION: A continuous blockade of the brachial plexus with a low
concentration of bupivacaine and fentanyl helps to alleviate the vasospasm and the pain while
preserving the motor function for the patient to perform active movements of the finger and
hand.
Son, M. Y., et al. (2020). "[Gallbladder Perforation after Transarterial
Chemoembolization in a Patient with a Huge Hepatocellular Carcinoma]." Korean J
Gastroenterol 75(6): 351-355.
Souto, M. T. M. R., et al. (2020). "Ultrasound-guided continuous block of median and
ulnar nerves in horses: development of the technique." Veterinary Anaesthesia and
Analgesia 47(3): 405-413.
Transarterial chemoembolization (TACE) is a common treatment for unresectable
hepatocellular carcinoma (HCC). The most common complications after TACE are nonspecific symptoms called post-embolization syndrome, such as abdominal pain or fever. Rare
complications, such as liver failure, liver abscess, sepsis, pulmonary embolism, cholecystitis,
can also occur. On the other hand, gallbladder perforation is quite rare. This paper reports a
case of gallbladder perforation following TACE. A 76-year-old male with a single 9-cm-sized
HCC underwent TACE. Five days after TACE, he developed persistent right upper quadrant
pain and ileus. An abdomen CT scan confirmed gallbladder perforation with bile in the right
paracolic gutter and pelvic cavity. Percutaneous transhepatic gallbladder drainage was
performed with the intravenous administration of antibiotics. After 1 month, the patient
underwent right hemihepatectomy and cholecystectomy. Physicians should consider the
possibility of gallbladder perforation, which is a rare complication after TACE, when
unexplained abdominal pain persists.
Objective To develop a technique for ultrasound-guided continuous median and ulnar
peripheral nerve block in horses. Study design Anatomical and prospective experimental
study. Animals A total of 16 thoracic limbs from horse cadavers and 18 adult horses. Method
This study was conducted in three phases. Phase 1: Dissection of median and ulnar nerves in
the antebrachial region of two cadaver limbs to identify localizing landmarks. Description of
sonoanatomy in 14 cadaver limbs using ultrasound-guided perineural infiltration of a
combination of cellulose gel (5 mL), contrast medium (4 mL) and methylene blue (1 mL).
Catheters were inserted between the perineural sheath and epineurium in six limbs, followed
by computed tomography. Phase 2: Ultrasonographic images of the limbs of 18 healthy
horses of different breeds were used to define an acoustic window and optimize the approach
to nerves. Phase 3: Two case reports of horses with chronic pain of different etiologies.
Catheters were inserted between the epineurium and paraneural sheath of the median and/or
ulnar nerves guided by ultrasound, followed by continuous infusion of 0.4% ropivacaine.
Results Information from phase 1 was used to direct needle insertion, solution dispersion and
catheter implantation in phase 2, which resulted in 100% technique accuracy. In response to
the peripheral nerve block, pain reduction was apparent in the two clinical cases by increased
weight bearing in affected limbs and decreased requirement for systemic analgesic
medications. No local reactions were observed. Conclusions and clinical relevance The
ultrasound technique allowed real-time visualization of needle, catheter and drug dispersion
and resulted in a high success rate for nerve blocks. The horses administered a median and
ulnar nerve block exhibited no discomfort or signs of infection at the catheter insertion site.
Srebro, D., et al. (2017). "Magnesium in Pain Research: State of the Art." Curr Med
Chem 24(4): 424-434.
Magnesium has been shown to produce an antinociceptive effect on animal models of
neuropathic and inflammatory pain. It has also been shown to exert an analgesic effect on
humans in conditions presenting acute (postoperative pain) and chronic (neuropathic) pain.
As it is known that magnesium is a physiological antagonist of the N-methyl-Daspartate
(NMDA) receptor ion channel, and that the NMDA receptor plays a key role in central
sensitization, the primary mechanism through which magnesium produces its analgesic effect
is believed to be blockade of the NMDA receptor in the spinal cord. In addition, magnesium
blocks calcium channels and modulates potassium channels. The activation of the nitric oxide
(NO) pathway could have an important role in the antinociceptive effects of systemic
magnesium sulfate in the somatic, but not in the visceral model of inflammatory pain.
Although it is known for some time that intramuscular, intravenous and subcutaneous
injections of magnesium sulfate in humans, and intraperitoneal injection in rodents produce
local pain sensation, the mechanism of this action was elucidated only recently. It was
demonstrated that subcutaneous injection of an isotonic, pHadjusted (7.4) solution of
magnesium sulfate (6.2%) to rats produces local peripheral pain via activation of peripheral
TRPA1, TRPV1, TRPV4 and NMDA receptors and peripheral production of NO. In animal
models of pain, magnesium has been shown to exert both antinociceptive and pronociceptive
effects by acting on different ion channels and NO pathways, however, the precise
Sun, L., et al. (2021). "[Efficacy and safety of prophylactic intravenous administration
of tranexamic acid in abdominal aorta balloon-assisted pelvic tumor surgery]."
Zhonghua Yi Xue Za Zhi 101(12): 851-855.
Objective: To investigate the efficacy and safety of prophylactic intravenous (IV)
administration of tranexamic acid (TXA) in abdominal aorta balloon-assisted pelvic tumor
surgery. Methods: The data of patients who underwent abdominal aorta balloon-assisted
pelvic tumor surgery in Peking University People's Hospital from January 1, 2015 to
December 31, 2019 were retrospectively collected. According to whether receiving the
prophylactic use of TXA, the patients were divided into two groups: TXA group and control
group. After propensity score matching based on age, gender and surgeon, 51 patients in
TXA group and 51 patients in control group were allocated. The baseline, intraoperative and
postoperative clinical data of the two groups were compared to explore the efficacy and
safety of TXA. Results: A total of 525 cases undergoing abdominal aorta balloon-assisted
pelvic surgery were enrolled from 2015 to 2019, of which 51 cases received prophylactic use
of TXA, with a utilization rate of 9.7%. There were no significant differences in age
[(40.7±15.1) years vs (38.2±14.5) years, P=0.393], gender (male: 51.0% vs 49.0%, P=0.843),
body weight, body mass index (BMI), complications, American Society of Anesthesiologists
(ASA) classification, hemoglobin, hemocrit (Hct), platelet, coagulation function-related
indexes and tumor pathological types between the two groups (all P>0.05). Likewise, there
were no significant differences in operation time, anesthesia time, cumulative time of balloon
occlusion, intraoperative blood loss, intravenous fluid volume and blood transfusion volume
between the two groups (all P>0.05). Additionally, there were no significant differences in
postoperative ICU admission rate and length of hospital stay between the two groups (all
P>0.05), and no venous thromboembolism (VTE) or death was reported. Compared with the
control group, the rate of blood transfusion at 24 hours after operation in the TXA group was
lower (41.2% vs 70.6%, P=0.003). The level of fibrinogen degradation products was lower
[10.4 (6.1, 22.6) mg/L vs 13.2 (7.0, 24.7) mg/L], but the difference was not statistically
significant (P=0.326). Conclusions: Prophylactic IV use of TXA does not reduce
intraoperative bleeding in abdominal aorta balloon-assisted pelvic tumor surgery, but can
decrease the rate of postoperative blood transfusion. No increased risk of postoperative TXASur, B., et al. (2016). "Bee venom acupuncture alleviates trimellitic anhydrideinduced atopic dermatitis-like skin lesions in mice." BMC Complement Altern Med
BACKGROUND: Bee venom acupuncture (BVA), a novel type of acupuncture therapy in
which purified bee venom is injected into the specific acupuncture point on the diseased part
of the body, is used primarily for relieving pain and other musculoskeletal symptoms. In the
present study, therapeutic potential of BVA to improve atopic dermatitis, a representative
allergic dysfunction, was evaluated in the mouse model of trimellitic anhydride (TMA)induced skin impairment. METHODS: Mice were treated with 5% TMA on the dorsal flank
for sensitization and subsequently treated with 2% TMA on the dorsum of both ears for an
additional 12 days after a 3-day interval. From the 7(th) day of 2% TMA treatment, bilateral
subcutaneous injection of BV (BV, 0.3 mg/kg) was performed daily at BL40 acupuncture
points (located behind the knee) 1 h before 2% TMA treatment for 5 days. RESULTS: BVA
treatment markedly inhibited the expression levels of both T helper cell type 1 (Th1) and Th2
cytokines in ear skin and lymph nodes of TMA-treated mice. Clinical features of AD-like
symptoms such as ear skin symptom severity and thickness, inflammation, and lymph node
weight were significantly alleviated by BV treatment. BV treatment also inhibited the
proliferation and infiltration of T cells, the production of Th1 and Th2 cytokines, and the
synthesis of interleukin (IL)-4 and immunoglobulin E (IgE)-typical allergic Th2 responses in
blood. The inhibitory effect of BVA was more pronounced at BL40 acupoint than nonacupuncture point located at the base of the tail. CONCLUSIONS: These results indicate that
BV injection at specific acupuncture points effectively alleviates AD-like skin lesions by
inhibiting inflammatory and allergic responses in a TMA-induced contact hypersensitivity
Sveroni, D., et al. (2018). "Rifampicin: not always an innocent drug." BMJ Case Rep
11(1).
Rifampicin has been widely used due to its broad antibacterial spectrum. Acute haemolysis is
a rarely encountered complication of rifampicin. A 58-year-old woman was admitted to our
department because of high-grade fever with rigors, accompanied by abdominal and lumbar
pain and laboratory evidence of acute haemolysis. She had been treated for brucellosis
initially with doxycycline and streptomycin. Due to subsequent appearance of myositis,
ciprofloxacin and rifampicin were added for treatment of localised brucellosis. After
intravenous administration of rifampicin, the patient deteriorated significantly. After
exclusion of other causes of haemolysis, autoimmune haemolytic anaemia related to
rifampicin was established by strongly positive direct Coombs test. Drug withdrawal in
conjunction with intravenous immune globulin and prednisolone resulted in resolution of
haemolysis and no relapse in the ensuing 1-year period. Our case highlights the importance of
recognising commonly administrative drugs as cause of haemolytic anaemia, that can often be
life threatening.
Tabata, H., et al. (2021). "Possible role of intravenous administration of mesenchymal
stem cells to alleviate interstitial cystitis/bladder pain syndrome in a Toll-like
receptor-7 agonist-induced experimental animal model in rat." BMC Urol 21(1): 156.
Taguchi, T., et al. (2018). "Minimally invasive mitral valve repair via right minithoracotomy in patient with myelodysplastic syndrome." J Cardiothorac Surg 13(1):
45.
BACKGROUND: Interstitial cystitis/bladder pain syndrome (IC/BPS) categorized with and
without Hunner lesions is a condition that displays chronic pelvic pain related to the bladder
with no efficacious treatment options. There are strong associations suggested between
Hunner-type IC and autoimmune diseases. Recently, we established an animal model of
Hunner-type IC using a Toll-like receptor-7 (TLR7) agonist. Intravenous infusion of
mesenchymal stem cells (MSCs) can be used to treat injury via multimodal and orchestrated
therapeutic mechanisms including anti-inflammatory effects. Here, we investigated whether
infused MSCs elicit therapeutic efficacy associated with the TLR7-related anti-inflammatory
pathway in our Hunner-type IC model. METHODS: Voiding behaviors were monitored 24 h
prior to the Loxoribine (LX), which is a TLR7 agonist instillation in order to establish a
Hunner-type IC model (from - 24 to 0 h) in female Sprague-Dawley rats. LX was instilled
transurethrally into the bladder. At 0 h, the initial freezing behavior test confirmed that no
freezing behavior was observed in any of the animals. The LX-instilled animals were
randomized. Randomized LX-instilled rats were intravenously infused with MSCs or with
vehicle through the right external jugular vein. Sampling tissue for green fluorescent protein
(GFP)-positive MSCs were carried out at 48 h. Second voiding behavior tests were monitored
from 72 to 96 h. After the final evaluation of the freezing behavior test at 96 h after LX
instillation (72 h after MSC or vehicle infusion), histological evaluation with H&E staining
and quantitative real-time polymerase chain reaction (RT-PCR) to analyze the mRNA
expression levels of inflammatory cytokines were performed. RESULTS: Freezing behavior
was reduced in the MSC group, and voiding behavior in the MSC group did not deteriorate.
Hematoxylin-eosin staining showed that mucosal edema, leukocyte infiltration, and
hemorrhage were suppressed in the MSC group. The relative expression of interferon-β
mRNA in the bladder of the MSC group was inhibited. Numerous GFP-positive MSCs were
distributed mainly in the submucosal and mucosal layers of the inflammatory bladder wall.
CONCLUSION: Intravenous infusion of MSCs may have therapeutic efficacy in a LX-
BACKGROUND: Cardiac surgery for myelodysplastic syndrome (MDS) patients is
challenging because anemia and neutropenia develop as a result of the syndrome, leading to
infection and bleeding tendency during surgery. We report the case of minimally invasive
mitral valve repair via a right mini-thoracotomy and perioperative use of granulocyte colonystimulating factor (G-CSF) in a patient with MDS. CASE PRESENTATION: A 77-year-old
man with myelodysplastic syndrome (MDS) was referred for surgical treatment for mitral
valve regurgitation and underwent a minimally invasive mitral valve repair via a right minithoracotomy (MICS mitral procedure). On admission, laboratory results showed a leukocyte
count of 1500/μL and neutrophils at 190/μL. Prior to surgery, a subcutaneous injection of
granulocyte colony-stimulating factor (G-CSF) was given, based on a diagnosis of MDS by a
hematologist. The MICS-mitral procedure using artificial chordae and an annular ring
prosthesis was completed without requiring re-exploration for bleeding. Postoperatively, a GCSF injection was administered and transfusion was required. There was no infection
complication and the postoperative course was uneventful. CONCLUSION: A MICS-mitral
procedure may be an effective option for MR patients with MDS who require a mitral valve
Tamura, J., et al. (2021). "Comparison of the anesthetic effects between 5 mg/kg of
alfaxalone and 10 mg/kg of propofol administered intravenously in cats." J Vet Med
Sci 83(1): 73-77.
Tang, X. L., et al. (2022). "Effect of intravenous cell therapy in rats with old
myocardial infarction." Mol Cell Biochem 477(2): 431-444.
To compare the anesthetic effects after intravenous administration of alfaxalone or propofol
without premedication, either alfaxalone (5 mg/kg) or propofol (10 mg/kg) was administered
intravenously over 120 sec in 6 cats. Each cat received the alternate treatment at least a 7-day
interval. Anesthetic effects (tolerance of intubation, behavior changes and neurodepressive
score) and physiological parameters were evaluated. Both treatments produced a rapid loss of
consciousness, no apnea, and physiological parameters were maintained within clinically
acceptable ranges apart from transient hypoxemia. The degree of hypoxemia was greater after
the propofol treatment compared with the alfaxalone treatment. During the recovery period,
more adverse events (ataxia, muscular tremors) were observed after the alfaxalone treatment
compared with the propofol treatment.
Mounting evidence shows that cell therapy provides therapeutic benefits in experimental and
clinical settings of chronic heart failure. However, direct cardiac delivery of cells via
transendocardial injection is logistically complex, expensive, entails risks, and is not
amenable to multiple dosing. Intravenous administration would be a more convenient and
clinically applicable route for cell therapy. Thus, we determined whether intravenous infusion
of three widely used cell types improves left ventricular (LV) function and structure and
compared their efficacy. Rats with a 30-day-old myocardial infarction (MI) received
intravenous infusion of vehicle (PBS) or 1 of 3 types of cells: bone marrow mesenchymal
stromal cells (MSCs), cardiac mesenchymal cells (CMCs), and c-kit-positive cardiac cells
(CPCs), at a dose of 12 × 10(6) cells. Rats were followed for 35 days after treatment to
determine LV functional status by serial echocardiography and hemodynamic studies. Blood
samples were collected for Hemavet analysis to determine inflammatory cell profile. LV
ejection fraction (EF) dropped ≥ 20 points in all hearts at 30 days after MI and deteriorated
further at 35-day follow-up in the vehicle-treated group. In contrast, deterioration of EF was
halted in rats that received MSCs and attenuated in those that received CMCs or CPCs. None
of the 3 types of cells significantly altered scar size, myocardial content of collagen or CD45positive cells, or Hemavet profile. This study demonstrates that a single intravenous
administration of 3 types of cells in rats with chronic ischemic cardiomyopathy is effective in
attenuating the progressive deterioration in LV function. The extent of LV functional
Ten Hove, F. L., et al. (2024). "Needling and Lavage in Rotator Cuff Calcific
Tendinitis: Ultrasound-Guided Technique." JBJS Essent Surg Tech 14(1).
BACKGROUND: Rotator cuff calcific tendinitis (RCCT) is a commonly occurring disease,
with a prevalence of up to 42.5% in patients with shoulder pain(1,2). RCCT is characterized
by hydroxyapatite deposits in the tendons of the rotator cuff and is considered a self-limiting
disease that can be treated nonoperatively(3). However, in a substantial group of patients,
RCCT can have a very disabling and long-lasting course(1,4), requiring additional treatment.
Ultrasound-guided percutaneous needling and lavage (i.e., barbotage) is a safe and effective
treatment option for RCCT(5). In the present article, we focus on the 1-needle barbotage
technique utilized in combination with an injection of corticosteroids in the subacromial
bursa. DESCRIPTION: It must be emphasized that symptomatic RCCT should be confirmed
before barbotage is performed. Therefore, we recommend a diagnostic ultrasound and/or
physical examination prior to the barbotage. Barbotage is performed under ultrasound
guidance with the patient in the supine position. After sterile preparation and localization of
the calcified deposit(s), local anesthesia in the soft tissue (10 mL lidocaine 1%) is
administered. Next, the subacromial bursa is injected with 4 mL bupivacaine (5 mg/mL) and
1 mL methylprednisolone (40 mg/mL) with use of a 21G needle. The deposit(s) are then
punctured with use of an 18G needle. When the tip of the needle is in the center of the
deposit(s), they are flushed with a 0.9% saline solution and the dissolved calcium re-enters
the syringe passively. This process is repeated several times until no more calcium enters the
syringe. In the case of solid deposits, it may not be possible to aspirate calcium; if so, an
attempt to fragment the deposits by repeated perforations, and thus promote resorption, can
be made. Postoperatively, patients are instructed to take analgesics and to cool the shoulder.
ALTERNATIVES: RCTT can initially be treated nonoperatively with rest, nonsteroidal antiinflammatory drugs, and/or physiotherapy(3). If the initial nonoperative treatment fails,
extracorporeal shockwave therapy (ESWT), corticosteroid injections, and/or barbotage can be
considered(8). In severe chronic recalcitrant cases, arthroscopic debridement and/or removal
can be performed as a last resort. RATIONALE: Both barbotage and ESWT result in a
reduction of calcific deposits, as well as significant pain reduction and improvement of
function(8). No standard of care has been established until now; however, several prior metaTepper, J., et al. (2014). "A 26-Week Toxicity Assessment of AIR001 (Sodium
Nitrite) by Inhalation Exposure in Rats and by Intravenous Administration in Dogs."
Int J Toxicol 33(3): 162-174.
Historically, nitrogen oxides (NO(x)) in food, drinking water, as well as in the atmosphere
have been believed to be associated with adverse health consequences. More recently, NO(x)
have been implicated in normal homeostatic regulation, and exogenous administration has
been associated with health benefits. One such potential health benefit is the prospect that
inhaled nitrite will lower pulmonary blood pressure (BP) in patients with pulmonary arterial
hypertension (PAH), a disease with poor prognosis due to the lack of effective treatment. To
characterize potential chronic toxicity associated with inhaled AIR001 (sodium nitrite) for
use in the treatment of PAH, 26-week exposures to AIR001 were carried out by inhalation
administration in rats and by intravenous infusion in dogs. The studies revealed that
methemoglobinemia was the primary adverse effect in both species. Methemoglobin levels
less than 40% were well tolerated in both species, while levels greater than 50%
methemoglobin caused death in some rats. Additionally, a decrease in systemic BP was also
observed with inhaled AIR001 exposure in dogs. These acute secondary and exaggerated
pharmacological effects occurred daily throughout the 26-week treatment period. Chronic
exposure did not alter the magnitude of either methemoglobinemia or hypotension or result in
additional toxicity or compensatory responses. Based on the exposure levels that produced
these pharmacodynamic responses in animals, relative to those measured in early clinical
studies, it appears that an adequate margin of safety exists to support the continued clinical
Terada, K., et al. (2023). "Therapeutic efficacy of intravenous infusion of
mesenchymal stem cells in rat perinatal brain injury." Pediatr Res 94(6): 1921-1928.
BACKGROUND: Perinatal brain injury is multifactorial and primarily associated with brain
prematurity, inflammation, and hypoxia-ischemia. Although recent advances in perinatal
medicine have improved the survival rates of preterm infants, neurodevelopmental
disorders remain a significant complication. We tested whether the intravenous infusion of
mesenchymal stem cells (MSCs) had therapeutic efficacy against perinatal brain injury in
rats. METHODS: Pregnant rats at embryonic day (E) 18 received lipopolysaccharide and the
pups were born at E21. On postnatal day (PND) 7, the left common carotid artery of each pup
was ligated, and they were exposed to 8% oxygen for 2 h. They were randomized on PND10,
and MSCs or vehicle were intravenously infused. We performed behavioral assessments,
measured brain volume using MRI, and performed histological analyses on PND49.
RESULTS: Infused MSCs showed functional improvements in our model. In vivo MRI
revealed that MSC infusion increased non-ischemic brain volume compared to the vehicle
group. Histological analyses showed that cortical thickness, the number of NeuN(+) and
GAD67(+) cells, and synaptophysin density in the non-ischemic hemisphere in the MSC
group were greater than the vehicle group, but less than the control group. CONCLUSIONS:
Infused MSCs improve sensorimotor and cognitive functions in perinatal brain injury and
enhance neuronal growth. IMPACT: Intravenous infusion of MSCs improved neurological
function in rats with perinatal brain injury, including motor, sensorimotor, cognitive, spatial,
and learning memory. Infused MSCs increased residual (non-ischemic) tissue volume,
number of neuronal cells, GABAergic cells, and cortical synapses in the contralesional (right)
hemisphere. Intravenous administration of MSC might be suitable for the treatment of
Thanasa, E., et al. (2023). "Adnexal Torsion of a Mature Cystic Ovarian Teratoma
With Hemorrhagic Infarction Misdiagnosed As Pelvic Inflammatory Disease in a
Perimenopausal Patient: A Case Report." Cureus 15(5): e38680.
Mature cystic teratomas are common benign ovarian tumors. They usually occur in young
women, less than 40 years old. Our case report concerns a patient of perimenopausal age who
came to the hospital complaining about mild abdominal pain, fever below 37.8°C, and
diarrhea. The patient had an intrauterine contraceptive device inserted. Based on the clinical
findings and imaging, a possible diagnosis of pelvic inflammatory disease was set, and
intravenous administration of broad-spectrum antibiotics started immediately. The decision
for performing laparotomy was taken after the fact that the clinical condition and blood tests
of the patient had shown no improvement. Intraoperatively, the presence of a large twisted
ovarian mass with signs of total necrosis due to adnexal torsion was detected. A histological
examination of the surgical specimen confirmed the diagnosis of mature cystic teratoma in
the right ovary. The postoperative course was uneventful. The presentation of the case
follows a brief literature review of this rare medical condition regarding the diagnostic and
therapeutic approach of these patients.
Toutain, C. E., et al. (2017). "Safety evaluation of the interchangeable use of
robenacoxib (Onsior™) tablets and solution for injection in dogs." BMC Vet Res
13(1): 359.
BACKGROUND: Robenacoxib (Onsior™) is a non-steroidal anti-inflammatory drug
developed for canine and feline use for the control of pain and inflammation. It is available as
both tablets and solution for injection. The objective of this safety study was to investigate
the interchangeable use of two robenacoxib formulations in dogs using a novel study design
alternating between oral tablets and subcutaneous injections. Thirty-two naïve healthy 4month dogs were enrolled in this 88-day study and were randomized among four groups to be
untreated or to receive robenacoxib at the highest recommended or elevated dose rates. The
dogs were administered three 20-day treatment cycles each separated by a 14-day washout
period. Each 20-day cycle was comprised of 10 days of once daily oral administration, 3 days
of subcutaneous administration, followed by further 7 days of oral administration (Groups 2
to 4). The control group (Group 1) received oral empty gelatin capsules or subcutaneous
saline injections. Assessment of safety was based on general health observations, clinical
observations, physical and neurological examinations including ophthalmological
examinations, electrocardiographic examinations and clinical pathology evaluations, food and
water consumption, body weight, and macroscopic and microscopic examinations. Blood
samples were collected for pharmacokinetic evaluation. RESULTS: Blood concentrations of
robenacoxib confirmed systemic exposure of all treated dogs. All dogs were in good health
through study termination and there were no serious adverse events during the course of the
study. No changes in body weight, food consumption, ophthalmic, neurological examinations,
electrocardiograms, buccal mucosal blood times, clinical pathology or organ weight were
attributable to robenacoxib formulation administration. Primary treatment-related
abnormalities were of low incidence at all doses. They were confined to macroscopic and
microscopic changes observed locally at the subcutaneous injection sites and microscopic
findings within the gastrointestinal tract. These findings were as expected based on previous
studies with robenacoxib solution for injection alone and the known properties of this class of
compound and mode of administration. There were no adverse effects which could be
attributed specifically to the interchangeable use of oral and injectable robenacoxib.
CONCLUSIONS: Alternating regimens of robenacoxib tablets and solution for injection
Toya, R., et al. (2022). "Implementation of (99m)Tc-GSA SPECT Image-guided
Inverse Planning into Palliative Radiotherapy for Diffuse Liver Metastases: A Novel
Approach." In Vivo 36(3): 1523-1526.
BACKGROUND/AIM: This is a report of the first clinical implementation of (99m)Tclabeled diethylene triamine pentaacetate-galactosyl human serum albumin ((99m)Tc-GSA)
single-photon emission computed tomography (SPECT) image-guided inverse planning into
palliative radiotherapy (RT) for diffuse liver metastases. CASE REPORT: A 48-year-old man
developed chemo-refractory diffuse liver metastases from thymic carcinoma characterized by
abdominal pain and distension. Palliative RT was performed with a total dose of 20 Gy in
five fractions using double arc volumetric modulated arc therapy to reduce the dose to
functional liver defined by (99m)Tc-GSA SPECT images. His symptoms were immediately
relieved after RT and did not experience radiation-induced liver disease. Both Functional
Assessment of Cancer Therapy (FACT)-G and FACT-Hep total scores improved after 2
weeks of RT initiation and did not become worse than baseline scores. CONCLUSION: The
(99m)Tc-GSA SPECT image-guided palliative RT is an effective and safe treatment for
patients with diffuse liver metastases.
Trivedi, D., A. K. Denniston and P. I. Murray (2011). "Safety profile of anterior
chamber paracentesis performed at the slit lamp." Clin Exp Ophthalmol 39(8): 725728.
BACKGROUND: Anterior chamber paracentesis is a valuable diagnostic tool in the
management of uveitis, but may be underutilized because of concerns over its safety. We
evaluated the safety profile of anterior chamber paracentesis performed at the slit lamp as an
outpatient procedure. DESIGN: Retrospective, observational case series in a single tertiary
centre. PARTICIPANTS: Five hundred and sixty patients with uveitis undergoing anterior
chamber paracentesis. METHODS: All anterior chamber paracenteses performed at the slit
lamp for diagnostic or research purposes between January 1997 and June 2009 were analysed
with regard to adverse events and pipet/syringe used. Procedures were included whether
carried out on undilated or dilated pupils. MAIN OUTCOME MEASURES: Adverse events
and serious adverse events. RESULTS: Out of 560 paracenteses, 510 were performed with a
27-gauge fixed-needle tuberculin syringe, and 50 using an O'Rourke aqueous pipet. All
patients were prescribed a short course of topical antibiotic and examined post-procedure and
1-2 weeks later. Out of 560 procedures there were four complications (0.7%). Two patients
had inadvertent injection of sterile air into the anterior chamber but with spontaneous
resolution and no adverse outcome (O'Rourke pipet for both). One patient had anterior lens
capsule touch that was self-sealing and left a tiny localized opacity (tuberculin syringe). One
patient had an allergic reaction to povidone iodine. No patients reported pain, and there were
no cases of iris trauma, entry site leak, hypotony, hyphaema or endophthalmitis.
CONCLUSION: Anterior chamber paracentesis can be performed safely as an outpatient
Tsuge, M., et al. (2023). "Successful use of dupilumab for egg-induced eosinophilic
gastroenteritis with duodenal ulcer: a pediatric case report and review of literature."
Allergy Asthma Clin Immunol 19(1): 103.
Vaccarisi, S., et al. (2012). "Laparoscopic Placement of “Self-Locating Catheter”: Our
Experience and a Review of Literature." Transplantation Proceedings 44(7): 18731875.
BACKGROUND: Non-esophageal eosinophilic gastrointestinal disorder (non-EoE-EGID) is
a rare disease in which eosinophils infiltrate parts of the gastrointestinal tract other than the
esophagus; however, the number of patients with non-EoE-EGID has been increasing in
recent years. Owing to its chronic course with repeated relapses, it can lead to developmental
delays due to malnutrition, especially in pediatric patients. No established treatment exists for
non-EoE-EGID, necessitating long-term systemic corticosteroid administration. Although the
efficacy of dupilumab, an anti-IL-4/13 receptor monoclonal antibody, for eosinophilic
esophagitis, has been reported, only few reports have demonstrated its efficacy in non-EoE
EGIDs. CASE PRESENTATION: A 13-year-old boy developed non-EoE-EGID with
duodenal ulcers, with chicken eggs as the trigger. He was successfully treated with an eggfree diet, proton pump inhibitors, and leukotriene receptor antagonists. However, at age 15,
he developed worsening upper abdominal pain and difficulty eating. Blood analysis revealed
eosinophilia; elevated erythrocyte sedimentation rate; and elevated levels of C-reactive
protein, total immunoglobulin E, and thymic and activation-regulated chemokines. Upper
gastrointestinal endoscopy revealed a duodenal ulcer with marked mucosal eosinophilic
infiltration. Gastrointestinal symptoms persisted even after starting systemic steroids, making
it difficult to reduce the steroid dose. Subcutaneous injection of dupilumab was initiated
because of comorbid atopic dermatitis exacerbation. After 3 months, the gastrointestinal
symptoms disappeared, and after 5 months, the duodenal ulcer disappeared and the eosinophil
count decreased in the mucosa. Six months later, systemic steroids were discontinued, and the
duodenal ulcer remained recurrence-free. The egg challenge test result was negative;
therefore, the egg-free diet was discontinued. Blood eosinophil count and serum IL-5, IL-13,
and eotaxin-3 levels decreased after dupilumab treatment. The serum levels of IL-5 and
eotaxin-3 remained within normal ranges, although the blood eosinophil counts increased
again after discontinuation of oral prednisolone. CONCLUSIONS: Suppression of IL-4R/IL13R-mediated signaling by dupilumab may improve abdominal symptoms and endoscopic
and histologic findings in patients with non-EoE-EGID, leading to the discontinuation of
Among the available devices for peritoneal dialysis, the Di Paolo self-locating catheter (SLC)
represents a milestone using to its ability to ensure a permanent reliable means of access to
the peritoneum. Our experience included 20 laparoscopic peritoneal catheter placements from
2008 to 2011. We performed the laparoscopic surgical technique using 3 trocars: 2 10 mm
and 1 5 mm. The technique allows catheter introduction into the pouch of Douglas under
direct vision. Among 20 treated patients, 1 died due to causes unrelated to peritoneal dialysis;
1 underwent transplantation, and 1 was switched to hemodialysis because of ultrafiltration
failure. The complications included 2 catheter displacements, only 1 of them needing
repositioning by open laparotomy, and 1 case of peritonitis. No infection in the subcutaneous
tunnel or obstruction and malfunction occurred among our patients. The Di Paolo SLC is
similar to Tenckhoff catheter but includes a small tungsten cylinder at the tip that engenders
continuous gravity in the peritoneal cavity, producing a reduced risk of dislocation. In a large
series of cases, Di Paolo et al. reported a 0.8% dislocation rate after SLC placement
compared with 12% using Tenckhoff catheters. They also demonstrated a reduced risk of
other complications, such as peritonitis, infection, obstruction, and failure. These data have
been confirmed by other authors with smaller case series. Thus, introduction of the SLC and
van der Maaden, K., et al. (2018). "Hollow microneedle-mediated micro-injections of
a liposomal HPV E7(43-63) synthetic long peptide vaccine for efficient induction of
cytotoxic and T-helper responses." J Control Release 269: 347-354.
Recent studies have shown that intradermal vaccination has great potential for T cellmediated cancer immunotherapy. However, classical intradermal immunization with a
hypodermic needle and syringe has several drawbacks. Therefore, in the present study a
digitally controlled hollow microneedle injection system (DC-hMN-iSystem) with an ultralow dead volume was developed to perform micro-injections (0.25-10μL) into skin in an
automated manner. A synthetic long peptide derived from human papilloma virus formulated
in cationic liposomes, which was used as a therapeutic cancer vaccine, was administered
intradermally by using the DC-hMN-iSystem. Fused silica hollow microneedles with an inner
diameter of 50μm and a bevel length of 66±26μm were successfully fabricated via
hydrofluoric acid etching. Upon piercing these microneedles into the skin using a protrusion
length of 400μm, microneedles were inserted at a depth of 350±55μm. Micro-injections of 110μL had an accuracy between 97 and 113% with a relative standard deviation (RSD) of 9%,
and lower volumes (0.25 and 0.5μL) had an accuracy of 86-103% with a RSD of 29% in ex
vivo human skin. Intradermal administration of the therapeutic cancer vaccine via microinjections induced strong functional cytotoxic and T-helper responses in mice, while
requiring much lower volumes as compared to classical intradermal immunization. In
conclusion, by using the newly developed DC-hMN-iSystem, very low vaccine volumes can
be precisely injected into skin in an automated manner. Thereby, this system shows potential
Vargas, R. A. A., et al. (2023). "Durotomy- and Irrigation-Related Serious Adverse
Events During Spinal Endoscopy: Illustrative Case Series and International Surgeon
Survey." Int J Spine Surg 17(3): 387-398.
BACKGROUND: Durotomy during endoscopic spine surgery can cause a patient's
neurological or cardiovascular status to deteriorate unexpectedly intra- or postoperatively.
There is currently limited literature regarding appropriate fluid management strategies,
irrigation-related risk factors, and clinical consequences of incidental durotomy during spinal
endoscopy, and no validated irrigation protocol exists for endoscopic spine surgery. Thus, the
present article sought to (1) describe 3 cases of durotomy, (2) investigate standard epidural
pressure measurements, and (3) survey endoscopic spine surgeons on the incidence of
adverse effects believed to result from durotomy. MATERIALS AND METHODS: The
authors first reviewed clinical outcomes and analyzed complications in 3 patients with
intraoperatively recognized incidental durotomy. Second, the authors conducted a small case
series with intraoperative epidural pressure measurements during gravity-assisted irrigated
video endoscopy of the lumbar spine. Measurements were conducted on 12 patients with a
transducer assembly that was introduced through the endoscopic working channel of the
RIWOSpine Panoview Plus and Vertebris endoscope to the decompression site in the spine.
Third, the authors conducted a retrospective, multiple-choice survey of endoscopic spine
surgeons to better understand the frequency and seriousness of problems they attributed to
irrigation fluid escaping from the surgical decompression site into the spinal canal and neural
axis. Descriptive and correlative statistical analyses were performed on the surgeons'
responses. RESULTS: In the first part of this study, durotomy-related complications during
irrigated spinal endoscopy were observed in 3 patients. Postoperative head computed
tomographic (CT) images revealed massive blood in the intracranial subarachnoid space, the
basal cisterns, the III and IV ventricle, and the lateral ventricles characteristic of an arterial
fisher grade IV subarachnoid hemorrhage, and hydrocephalus without evidence of aneurysms
or angiomas. Two additional patients developed intraoperative seizures, cardiac arrhythmia,
and hypotension. The head CT image in 1 of these 2 patients had intracranial air
entrapment.In the second part, epidural pressure measurements in 12 patients who underwent
uneventful routine lumbar interlaminar decompression for L4-L5 and L5-S1 disc herniation
showed an average epidural pressure of 24.5 mm Hg.In the third part, the online survey was
Verma, P., P. Tordik and A. Nosrat (2018). "Hazards of Improper Dispensary:
Literature Review and Report of an Accidental Chloroform Injection." J Endod 44(6):
1042-1047.
Several clear, transparent solutions are used in endodontics. Inappropriate dispensing
methods can lead to accidental injection or accidental irrigation. These accidents can cause
permanent tissue damage including damage to the bone, periodontium, nerves, and
vasculature. This article reports on the consequences of an accidental chloroform injection.
Nonsurgical retreatment of tooth #8 was planned as part of a restorative treatment plan in a
69-year-old woman. The dentist accidentally injected chloroform instead of local anesthesia
because chloroform was loaded into the anesthetic syringe. The patient experienced severe
pain and swelling and soft tissue necrosis and suffered permanent sensory and motor nerve
damage. A review of the literature was performed on accidents caused by improper
dispensary, namely accidental injections and accidental irrigations. The data were extracted
and summarized. Sodium hypochlorite, chlorhexidine, formalin, formocresol, 1:1000
adrenaline, benzalkonium chloride, and lighter fuel were accidentally injected as an intraoral
nerve block or as infiltration injections. Bone and soft tissue necrosis, tooth loss, and sensory
nerve damage (anesthesia and paresthesia) were the most common consequences reported.
Such disastrous events can be prevented by appropriate labeling and separate dispensing
methods for each solution. There is a need for disseminating information on toxicity and
biocompatibility of materials/solutions used in endodontics. The authors recommend training
dental students and endodontic residents on immediate and long-term therapeutic
Vidal, C., et al. (2020). "Predictive risk factors for postoperative pneumonia after
heart transplantation." BMC Anesthesiol 20(1): 8.
BACKGROUND: Pneumonia is a frequent complication in patients undergoing heart
transplantation (HTx) that increases morbidity and mortality in this population. Nevertheless,
the risk factors for postoperative pneumonia (POP) are still unknown. The aim of this study
was to investigate the predictive risk factors for POP in HTx recipients. METHODS: In this
retrospective study, all patients undergoing HTx between January 2014 and December 2015
were included. All cases of POP occurring until hospital discharge were investigated. The
study aimed to determine risk factors using univariate and multivariate Cox regression
models. Data are expressed in Odds Ratio [95% CI]. P < 0.05 was necessary to reject the null
hypothesis. RESULTS: A total of 175 patients were included without any patients being lost
to follow-up, and 89 instances of POP were diagnosed in 59 (34%) patients.
Enterobacteriaceae and Pseudomonas aeruginosa were the most common pathogens. In the
multivariate analysis, the risk factors were preoperative mechanical ventilation (OR 1.42
[1.12-1.80], P < 0.01) and perioperative blood transfusion (OR 1.42 [95% CI: 1.20-1.70],
P < 0.01). POP significantly impacted mortality at 30 days (OR: 4 [1.3-12.4], P = 0.01) and
1 year (OR: 6.8 [2.5-8.4], P < 0.01) and was associated with a longer duration of mechanical
ventilation, time to weaning from venoarterial extracorporeal membrane oxygenation and
stay in an intensive care unit. Plasma exchanges and intravenous administration of
immunoglobulins did not increase the risk of POP. CONCLUSION: After HTx, preoperative
mechanical ventilation and blood transfusion were risk factors for POP and were associated
with increased mortality. Enterobacteriaceae and Pseudomonas aeruginosa are the most
Vilos, G. A., et al. (2020). "Venous Gas Embolism during Hysteroscopic Endometrial
Ablation: Report of 5 Cases and Review of the Literature." Journal of Minimally
Invasive Gynecology 27(3): 748-754.
ABSTRACT Study Objective To highlight the circumstances, presentation, and treatment of
venous gas embolism (VGE) and provide guidance and propose potential changes in surgical
practice and perioperative monitoring to minimize the adverse consequences and sequalae of
this potentially serious complication. Design A case series. Setting A university-affiliated
teaching hospital. Patients Five women developed VGE during hysteroscopic endometrial
ablation. Interventions From 1990 through 2014, the principle author (G.A.V.) performed
5249 primary and 458 repeat hysteroscopic endometrial ablations under general anesthesia
using a monopolar 26F (9-mm) resectoscope connected to a peristaltic pump-driven active
inflow and outflow irrigation and distension system (1.5% glycine) and an 8-mm monopolar
loop electrode at a 120-W continuous (cut) and/or a 3- to 5-mm rollerball interrupted
(coagulation) waveform or a combination of them. Measurements and Main Results Among
5707 procedures, we encountered 5 (0.09%, 1/1140) incidents of VGE during primary
ablations. All patients exhibited the same symptoms of ventilatory and hemodynamic
decompensation, beginning with a reduction in end-tidal carbon dioxide and arterial oxygen
desaturation. All patients recovered after immediate cessation of the surgery and resuscitation
including ventilatory support with 100% O2 and intravenous fluids. Conclusions Although
entrainment of some air/gas bubbles is common during hysteroscopy, life-threatening/fatal
VGE is rare (1/1140 cases). Situational awareness and strict adherence to certain principles
including understanding the conditions, prerequisites, and pathophysiology of VGE; attention
to surgical principles and operative technique; close communication with the
anesthesiologist; and early therapeutic intervention are of paramount importance to avoid this
Vinay, K., et al. (2015). "Intralesional Rituximab in the Treatment of Refractory Oral
Pemphigus Vulgaris." JAMA Dermatol 151(8): 878-882.
IMPORTANCE: Oral lesions of pemphigus vulgaris are usually recalcitrant and respond
slowly to treatments. Corticosteroid injection is considered to be the most effective local
treatment in oral pemphigus vulgaris. However, intralesional corticosteroids are not effective
in all remnant lesions. In 3 such patients with pemphigus vulgaris, we evaluated the utility of
2 injections (on days 1 and 15) of intralesional rituximab, 5 mg/cm², in terms of accelerated
healing, limitation of the use of systemic immunosuppressants, and reduction of their adverse
effects. OBSERVATIONS: Three patients (1 man and 2 women) received 2 doses of
intralesional rituximab in March and April 2013. All 3 patients responded to the treatment. In
patients 1 and 2, the objective severity score was reduced to 0 at the final visit from a
baseline score of 4 and 5, respectively (range, 0-11). The subject severity score in these
patients was reduced to 1.0 and 0 from a baseline score of 22.0 and 22.5, respectively. After
clinical remission was achieved, patient 3 developed a relapse of mucosal lesions. At the final
visit, all of the patients were satisfied with the treatment, with a mean satisfaction score of 8
(maximum score, 10). We found a marked decline in the CD19 cell count from a pretreatment
mean count of 287 cells/µL to 6 cells/µL on day 15 after a single intralesional rituximab
injection. Adverse events were limited to local pain in 1 patient. CONCLUSIONS AND
RELEVANCE: Intralesional rituximab administration lacks the adverse effects of intravenous
administration. This method reduces the amount of drug administered and therefore is less
expensive. Encouraging results from our study should prompt further evaluation of this novel
route of rituximab administration in patients with refractory oral pemphigus vulgaris.
Wang, Q., et al. (2023). "Intra-cervical lymphatic immunotherapy for dust miteinduced allergic rhinoconjunctivitis in children: a 3-year prospective randomized
controlled trial." Front Immunol 14: 1144813.
BACKGROUND: Pediatric allergic rhinoconjunctivitis has become a public concern with an
increasing incidence year by year. Conventional subcutaneous immunotherapy (SCIT) has
long treatment time, high cost and poor compliance. The novel immunotherapy significantly
shortens the course of treatment by directly injecting allergens into cervical lymph nodes,
which can perform faster clinical benefits to children. OBJECTIVE: By comparing with
SCIT, this study aimed to evaluate the long-term efficacy and safety of intra-cervical
lymphatic immunotherapy (ICLIT). METHODS: This is a prospective randomized controlled
study. A total of 50 allergic rhinoconjunctivitis children with dust mite allergy was randomly
divided into ICLIT group and SCIT group, receiving three cervical intralymphatic injections
of dust mite allergen or three years of subcutaneous injection, separately. Primary outcomes
included total nasal symptom scores (TNSS), total ocular symptom scores (TOSS), total
symptom scores (TSS), total medication scores (TMS), and total quality of life score.
Secondary outcomes included pain perception and adverse reactions during treatment. Other
secondary outcome was change in Dermatophagoides pteronyssinus (Derp) and
Dermatophagoides farina (Derf) -specific IgE level. RESULTS: Both groups had significantly
decreased TNSS, TOSS, TSS, TMS, and total quality of life score after 36 months of
treatment (p<0.0001). Compared with SCIT, ICLIT could rapidly improve allergic symptoms
(p<0.0001). The short-term efficacy was consistent between the two groups (p=0.07), while
the long-term efficacy was better in SCIT group (p<0.0001). The pain perception in ICLIT
group was lower than that in SCIT group (p<0.0001). ICLIT group was safer. Specifically,
the children had only 3 mild local adverse reactions without systemic adverse reactions. The
SCIT group had 14 systemic adverse reactions. At last, the serum Derp and Derf-specific IgE
levels in ICLIT and SCIT groups decreased 3 years later (p<0.0001). CONCLUSION: ICLIT
could ameliorate significantly the allergic symptoms in pediatric patients with an advantage
in effectiveness and safety, besides an improved life quality including shortened period of
treatment, frequency of drug use and pain perception. CLINICAL TRIAL REGISTRATION:
Wang, X., et al. (2015). "Histopathological classification criteria of rat model of
chronic prostatitis/chronic pelvic pain syndrome." Int Urol Nephrol 47(2): 307-316.
OBJECTIVE: A variety of murine models of experimental prostatitis that mimic the
phenotype of human chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) have been
developed. However, there is still a lack of explicit diagnosis criteria about those animal
model. Our study is to establish histopathological classification criteria, which will be
conducive to evaluate the animal models. METHODS: We firstly established a rat model of
experimental autoimmune prostatitis that is considered a valid model for CP/CPPS. For
modelling, male Sprague-Dawley rats were immunized with autologous prostate tissue
homogenate supernatant emulsified with complete Freund's adjuvant by subcutaneous
injection into abdominal flank and simultaneously immunized with pertussis-diphtheriatetanus vaccine by intraperitoneal injection. Three immunizations were administered
semimonthly. At the 45th day, animals were killed, and prostate tissues were examined for
morphology. RESULTS: Histologically, the prostate tissues were characterized by
lymphoproliferation, atrophy of acini, and chronic inflammatory cells infiltration in the
stromal connective tissue around the acini or ducts. Finally, we built histopathological
classification criteria incorporating inflammation locations (mesenchyme, glands,
periglandular tissues), ranges (focal, multifocal, diffuse), and grades (grade I-IV). To verify
the effectiveness and practicability of the histopathological classification criteria, we
conducted the treatment study with one of the alpha blockers, tamsulosin. CONCLUSION:
The histopathological classification criteria of rat model of CP/CPPS will serve for further
Watt, R. P., H. Khatri and A. R. G. Dibble (2019). "Injectability as a function of
viscosity and dosing materials for subcutaneous administration." Int J Pharm 554:
376-386.
Weeks, J. M., A. A. Motsinger-Reif and M. M. Reems (2021). "In vitro iatrogenic
hemolysis of canine packed red blood cells during various rapid transfusion
techniques." J Vet Emerg Crit Care (San Antonio) 31(1): 25-31.
Injectability is a term related to the ease of parenteral administration of a dosing solution, and
includes dose preparation, dose administration, ergonomics related to these procedures, pain
of injection, and other adverse events at the injection site. This article focuses on force
measurements related to injectability, namely: force to expel syringe contents (expulsion
force - a mimic for in vivo injection force), needle-penetration force, and needle-bending
force, and these results are supplemented by expulsion time measurements with 18
participants, as well as injections in a porcine model. Based on the expulsion time
measurements, where 80 N injection force was found to be difficult for most people, we
consider the maximum acceptable injection force to be 40 N, and recommend targeting no
more than 20 N, especially if the configuration may be used in an autoinjector or similar
device. The injectability of antisense oligonucleotide solutions was assessed to determine
optimal dosing materials (among those evaluated) for a variety of solution viscosities. Dosing
materials varied in syringe inner diameter, needle inner diameter, needle length, and needle
wall thickness: standard-wall vs. thin-wall. In general, short (6-8 mm) thin-wall needles are
recommended as a way to improve patient perception and comfort during subcutaneous dose
OBJECTIVE: To evaluate which rapid blood administration technique causes the least
iatrogenic hemolysis in canine packed red blood cells (pRBCs) as determined by plasma free
hemoglobin (fHb) and percent hemolysis (% hemolysis). DESIGN: Prospective in vitro
randomized study. SETTING: Private referral center. ANIMALS: None. INTERVENTIONS:
Thirteen units of canine pRBCs were divided equally into 5 aliquots, resulting in 65 trials.
The aliquots of each unit were subjected to the following administration techniques: gravitydriven (control), an infusion pump at maximal rate, application of a pressure bag, manual
compression, and syringe bolus. Plasma fHb and % hemolysis were recorded before and after
each trial. Rate of administration (mL/s) was calculated for each method. MEASUREMENTS
AND MAIN RESULTS: Compared to the control, there were no significant increases in %
hemolysis or plasma fHb noted among any of the trial methods. The manual compression and
syringe bolus methods resulted in the fastest transfusion rates, whereas the infusion pump
was not faster than the gravity-driven method. Despite a storage time of ≤14 days, 15% of
pRBC units had unsuitable (>0.8%) hemolysis before even being subjected to the trials.
CONCLUSIONS: Commonly used rapid infusion techniques in small animal transfusion
medicine do not cause significant iatrogenic hemolysis of canine pRBCs in vitro, although a
significant risk is present in stored blood. This suggests that if an expedited transfusion is
needed, any method described in this study could be considered, although stored pRBCs
Xie, S., et al. (2022). "Bacteria-propelled microtubular motors for efficient
penetration and targeting delivery of thrombolytic agents." Acta Biomater 142: 49-59.
Xu, C., et al. (2022). "Response to roxadustat in a patient undergoing long-term
dialysis and allergic to erythropoiesis-stimulating agents: A case report." World J Clin
Cases 10(35): 13122-13128.
Effective thrombolysis is critical to rapidly rebuild blood flow for thrombosis patients. Drug
delivery systems have been developed to address inadequate pharmacokinetics of
thrombolytic agents, but challenges still remain in the timely removal of blood clots regarding
the dense fibrin networks. Herein, rod-shaped tubular micromotors were developed to achieve
efficient penetration and thorough destruction of thrombi. By using electrospun fiber
fragments as the template, urokinase (uPA)-loaded polydopamine (PDA) microtubes with
surface decorated fucoidan ((Fu)PDA(uPA)) were prepared at the aspect ratio of around 2.
One E. coli Nissle 1917 (EcN) was assembled into one microtube to construct a
(Fu)PDA(uPA)@EcN hybrid micromotor through PDA adhesion and L-aspartate induction.
The pharmacokinetic analysis indicates that the encapsulation of uPA into micromotors
extends the half-life from 0.4 to 5.6 h and increases the bioavailability over 10 times. EcNpropelled motion elevates adsorption capacities of (Fu)PDA(uPA)@EcN for more than four
times compared with that of (Fu)PDA(uPA). The fucoidan-mediated targeting causes 2-fold
higher thrombolysis capacity in vitro and over 10-fold higher uPA accumulation in thrombi in
vivo. In the treatment of venous thrombi at mouse hindlimbs, intravenous administration of
(Fu)PDA(uPA)@EcN completely removed blood clots with almost full recovery of blood
flows and apparently alleviated tail bleeding. It should be noted that (Fu)PDA(uPA)@EcN
treatment at a reduced uPA dose caused no significant difference in the blood flow rate
compared with those of (Fu)PDA(uPA). The synergistic action of fucoidan-induced targeting
and EcN-driven motion provides a prerequisite for promoting thrombolytic efficacy and
reducing uPA dose and bleeding side effect. STATEMENT OF SIGNIFICANCE: The
standard treatment to thrombosis patient is intravenous infusion of thrombolytic agents, but
the associated bleeding complications and impairment of normal haemostasis greatly offset
the therapeutic benefits. Drug delivery systems have been developed to address the
limitations of inadequate pharmacokinetics of thrombolytic agents, but challenges still exist
in less efficient penetration into dense networks for thorough destruction of thrombi. Up to
now only few attempts have been made to construct nano-/micromotors for combating
thrombosis and there is no single case that antithrombosis is assisted by bacteria or cells-
BACKGROUND: Hypoxia-inducible factor prolyl hydroxylase inhibitor is a new class of
drugs for treating renal anemia. It is a second-generation hypoxia-inducible factor prolyl
hydroxylase-2 (PHD2) inhibitor. Roxadustat can effectively increase hemoglobin in patients
with dialysis-dependent chronic kidney disease, with an adverse events profile comparable to
that of epoetin alfa. We administered roxadustat to a maintenance hemodialysis patient who
was allergic to erythropoiesis-stimulating agents (ESAs) and depended on blood transfusion
for five years. After applying Roxadustat, the patient's anemia improved significantly. CASE
SUMMARY: A 77-year-old Chinese man had type 2 diabetes for 16 years, underwent
maintenance hemodialysis for five years, and had fatigue for five years. Laboratory tests
showed severe anemia (hemoglobin concentration of 42 g/L). The patient was administered a
subcutaneous injection of ESAs before dialysis. He suffered an allergic shock immediately
and fainted. His blood pressure dropped to undetectable levels. He was not administered
ESAs henceforth. The patient was prescribed iron supplements and received blood
transfusions occasionally for five years. His hemoglobin concentration ranged from 42-68
g/L. After taking six weeks of oral roxadustat three times weekly (100 mg TIW), the patient's
hemoglobin concentration increased significantly, and his symptoms decreased. We adjusted
the doses of roxadustat, and the hemoglobin concentration was maintained between 97 and
126 g/L. CONCLUSION: Oral roxadustat is effective in treating anemia in maintenance
Xu, D., et al. (2013). "Butyrate-induced colonic hypersensitivity is mediated by
mitogen-activated protein kinase activation in rat dorsal root ganglia." Gut 62(10):
1466-1474.
OBJECTIVE: Increased faecal butyrate levels have been reported in irritable bowel
syndrome. Rectal instillation of sodium butyrate (NaB) increases visceral sensitivity in rats
by an unknown mechanism. We seek to examine the signal transduction pathways responsible
for the enhanced neuronal excitability in the dorsal root ganglion (DRG) following NaB
enemas and demonstrate that this is responsible for the colonic hypersensitivity reported in
this animal model. DESIGN: Colorectal distention (CRD) studies were performed in rats
treated with NaB rectal instillation with/without intrathecal or intravenous administration of
mitogen-activated protein (MAP) kinase kinase inhibitor U0126. Western blot analysis and
immunocytochemistry studies elucidated intracellular signalling pathways that modulate IA.
Patch-clamp recordings were performed on isolated DRG neurons treated with NaB,
with/without U0126. RESULTS: Visceromotor responses (VMR) were markedly enhanced in
NaB-treated rats. Western blot analysis of DRG neurons from NaB-treated rats showed a 2.2fold increase in phosphorylated ERK1/2 (pEKR1/2) and 1.9-fold increase in phosphorylated
voltage-gated potassium channel subunit 4.2 (pKv4.2). Intrathecal or intravenous
administration of U0126 reduced VMR to CRD in NaB-treated rats and prevented increases
in pERK1/2 and pKv4.2. Patch-clamp recordings of isolated DRG neurons showed that NaB
caused a reduction in IA to 48.9%±1.4% of control and an increase in neuronal excitability,
accompanied by a twofold increase in pERK1/2 and pKv4.2. Concurrent U0126
administration prevented these changes. CONCLUSIONS: Visceral hypersensitivity induced
by colonic NaB treatment is mediated by activation of the MAP kinase-ERK1/2 pathway,
which phosphorylates Kv4.2. This results in a reduction in IA and an enhancement of DRG
Xue, X., et al. (2023). "[Effect of electroacupuncture intervention on relieving pain
and inflammation by suppressing TLR4/NF-κB signaling in rats with primary
dysmenorrhea]." Zhen Ci Yan Jiu 48(1): 63-70.
OBJECTIVE: To investigate the mechanism of electroacupuncture(EA) intervention in rats
with primary dysmenorrhea(PDM) based on the Toll-like receptor 4(TLR4)/nuclear
factor(NF)-κB signaling pathway. METHODS: Forty female SD rats were randomly divided
into blank control, model, EA and medication groups, with 10 rats in each group. PDM rat
model was established by subcutaneous injection of estradiol benzoate combined with
intraperitoneal injection of oxytocin. At the same time of model procedures, EA(50 Hz, dense
wave) was applied to "Guanyuan" (CV4) and bilateral "Sanyinjiao" (SP6) of rats in the EA
group, with needles retained for 20 min, for 10 consecutive days. Rats in the medication
group received ibuprofen(125 mg/100 mL, 0.8 mL) by gavage for 10 consecutive days. At the
11th day, writhing behavior of rats was assessed. Uterine morphology was observed by eyes
and uterine pathological changes were observed after HE staining. Content of prostaglandin
E2 (PGE2) and prostaglandin F2α (PGF2α) in serum and uterine tissues was detected by
ELISA; NF-κB p65 positive expression in nucleus was detected by immunofluorescence;
protein expression levels of TLR4, NF-κB p65, p-NF-κB p65 and inflammatory factors
interleukin (IL) -1β and IL-18 were detected by Western blot. RESULTS: After modeling,
uterus tissues were congested and edematous, with necrosis of luminal epithelium, severe
edema and extensive shedding of endometrium, nuclear pyknosis, fragmentation and
disappearance, neutrophils infiltration, and slight expansion of glandular cavity, which was
milder in the EA and the medication groups. Compared with the blank control group,
writhing times, scores and incubation period, HE pathological scores, PGF2α contents in
serum and uterine tissues, ratio of NF-κB p65 positive expression in nucleus, TLR4, NF-κB
p65, p-NF-κB p65, IL-1β and IL-18 protein expression levels in uterine tissues of rats in the
model group were all significantly increased(P<0.01), while PGE2 contents in serum and
uterine tissues were significantly decreased(P<0.01). Compared with the model group,
writhing times and scores, HE pathological scores, PGF2α contents in serum and uterine
tissues, ratio of NF-κB p65 positive expression in nucleus, TLR4, NF-κB p65, p-NF-κB p65,
IL-1β and IL-18 protein expression levels in uterine tissues of rats in the EA and medication
group were all significantly decreased(P<0.01), while writhing incubation period, PGE2
Yamada, C., et al. (2016). "A Case of Dermatomyositis and Anti-EJ Autoantibody
with Chronic Intestinal Pseudoobstruction Successfully Treated with Octreotide."
Case Rep Rheumatol 2016: 9510316.
Chronic intestinal pseudoobstruction (CIPO) is a serious complication in patients with
connective tissue disease (CTD) and is sometimes life-threatening or fatal despite intensive
medical treatment. Here, we report a patient with dermatomyositis (DM) and anti-EJ
autoantibody who developed CIPO that was improved by octreotide. Because her abdominal
pain and bloatedness were so severe and persistent, we introduced octreotide to relieve
symptoms. In this case, continuous intravenous administration as well as long-acting
subcutaneous injection of octreotide was effective for treating CIPO.
Yamashita, S., et al. (2023). "Polybacterial Iliopsoas Muscle Abscess as an Indication
for Early Diagnosis of Crohn's Disease." Am J Case Rep 24: e941399.
Yang, F., et al. (2023). "Cauda Equina Syndrome Caused by Intradural Bone Graft
Materials After Endoscopic Lumbar Fusion." Orthopedics 46(6): e384-e386.
BACKGROUND Crohn disease (CD) is a chronic, relapsing inflammatory bowel disease
characterized by penetrations or fistulae in the gastrointestinal tract and abscesses in the
surrounding tissues. Diagnosis of CD is difficult with an iliopsoas muscle abscess (IMA) as
an initial presentation. CASE REPORT A 22-year-old Japanese man had right hip pain 17
days prior to admission. Because of worsening pain, he was admitted to our hospital. Physical
examination revealed limitation of his right hip motion and a positive right psoas sign.
Abdominal contrast-enhanced computed tomography (CT) revealed a large right IMA.
Continuous drainage, which revealed polymicrobial pus, with intravenous administration of
antibiotics dramatically decreased the size of the IMA. The drainage tube was removed on
hospitalization day 9 because barium enema and contrast radiography of the abscess through
the drainage tube showed no fistula. However, on day 19 of hospitalization, the IMA was
redetected by abdominal CT. Continuous abscess drainage was resumed, and the third
contrast radiograph of the abscess revealed contrast medium flow into the small intestine.
Colonoscopy detected stenoses and circumferential ulceration of the terminal ileum.
Histopathological examination of the ileum biopsy showed histocyte aggregation with
lymphocyte or plasmacyte infiltration of the lamina propria, compatible with a CD diagnosis.
Laparoscopic ileocecal resection was performed on day 64 of hospitalization.
CONCLUSIONS Penetration of the intestinal tract caused by CD should be suspected in a
patient with a polymicrobial IMA. It is essential to identify the fistula and subsequently
Yazaki, K., et al. (2022). "Child Neurology: Pathologically Confirmed Thrombotic
Microangiopathy Caused by Onasemnogene Abeparvovec Treatment for SMA."
Neurology 98(19): 808-813.
A 53-year-old man presented to the emergency department with severe lower back pain,
saddle anesthesia, and urinary dysfunction. He had undergone endoscopic lumbar interbody
fusion for highly migrated lumbar disk herniation and lumbar instability 10 days ago.
Emergency computed tomography showed that the bone graft materials had migrated to the
sacral canal, and a mass with low intensity was seen located at the end of the dural cavity on
T2-weighted magnetic resonance imaging. It was suspected that the bone graft materials had
migrated into the dural cavity at the operative level and fallen into the end of the dural cavity
due to gravity, causing acute cauda equina syndrome (CES). After emergency durotomy, the
bone graft materials were completely removed. At the 18-month follow-up, the patient
recovered without further complications. This procedure resulted in a rare case of CES
caused by intradural bone graft after endoscopic lumbar interbody fusion. Spine surgeons
should be aware of this rare but potentially dangerous complication, especially in water-based
endoscopic lumbar interbody fusion. This case report shows that early recognition and
prompt treatment can significantly improve the symptoms of CES, including saddle numbness
and bladder dysfunction. [Orthopedics. 2023;46(6):e384-e386.].
Onasemnogene abeparvovec is an adeno-associated virus vector-based gene therapy for
spinal muscular atrophy (SMA). Although several cases of drug-induced thrombotic
microangiopathy due to onasemnogene abeparvovec have been reported, none has been
confirmed pathologically. Here, we present renal histopathologic findings of TMA due to
onasemnogene abeparvovec. On day 5 after receiving onasemnogene abeparvovec, a 23month-old girl with SMA type 1 developed thrombocytopenia, microangiopathic hemolytic
anemia, liver dysfunction, acute kidney injury, and hypertension. She was diagnosed with
TMA and received an increased dose of prednisolone, antihypertensives, diuretics, packed
red blood cell and platelet transfusion, a single dose of eculizumab, 4 cycles of
plasmapheresis, and intermittent and continuous hemodialysis. Her TMA resolved by day 30.
On day 49, renal biopsy was performed. Light microscopy revealed proliferation of
glomerular mesangial cells and matrix, with mesangiolysis, endothelial cell swelling, and
partial double contours of the glomerular basement membrane. Electron microscopy showed
endothelial injury, with edematous changes of the subendothelial spaces and neoformation of
the basement membrane, without electron-dense depositions. These findings are compatible
with the recovery phase of TMA. One year after drug administration, her motor function is
improved. She can hold her posture against gravity and has neither dysphagia nor respiratory
disturbance, but mild hypertension persists. Physicians should be vigilant regarding TMA as
a severe side effect of onasemnogene abeparvovec treatment, especially when
thrombocytopenia, hemolytic anemia, increased lactate dehydrogenase, or acute kidney injury
Ye, L., et al. (2013). "Antitumor effect and toxicity of Lipusu in rat ovarian cancer
xenografts." Food Chem Toxicol 52: 200-206.
Paclitaxel has yielded superior therapeutic effects in treating ovarian cancer after
intraperitoneal (i.p.) injection. However, the dose-limiting toxicity of Cremophor-based
paclitaxel was severe abdominal pain, likely caused by the excipients (Cremophor/ethanol).
Lipusu, a paclitaxel liposome, has been widely applied for the treatment of ovarian cancer by
intravenous administration in China. In order to find potential benefits of i.p. administration
of Lipusu, we suppose that Lipusu could modulate paclitaxel toxicity without affecting
antitumor activity compared with Cremophor-based paclitaxel (PTX). Antitumor effects,
bone marrow toxicity, cardiotoxicity and biodistributions in NuTu19 ovarian cancer-bearing
rats, as well as the abdominalpain in normal mice were evaluated. Lipusu exerted similar
antitumor effects similar to PTX, but much lower bone marrow toxicity and cardiotoxicity.
Furthermore, Lipusu exhibited similar plasma drug exposure, higher exposure in tumor and
pelvic lymph nodes and lower exposure in bone marrow and heart compared with PTX.
Additionally, Lipusu induced notably lighter abdominalpain than PTX. These data suggested
that Lipusu has similar antitumor effect and superior lymphatic targeting with reduced
toxicities compared with PTX via i.p. route, which could be related with altered
biodistributions. Therefore, Lipusu could be attractive for further evaluation of treating
Yi, K. M. and X. Li (2022). "Fatal noncardiogenic pulmonary edema related to
nonionic, iso-osmolar iodine contrast medium: one case report." BMC Pulm Med
22(1): 118.
BACKGROUND: Noncardiogenic pulmonary edema (NCPE) is a rare and life-threatening
allergy-like reaction to the intravascular injection of a nonionic radiographic agent. We first
describe a very rare case of fatal NCPE after the intravenous injection of nonionic, isoosmolar iodine contrast media. Case presentation A 55-year-old male patient was admitted to
the hospital with esophageal cancer. After the intravenous administration of 100 mL
iodixanol, the patient first exhibited digestive tract symptoms, including abdominal pain,
diarrhea, and vomiting, with no dyspnea, rash, itching, or throat edema. He received antiallergy treatment, but his symptoms did not improve; instead, he further developed
pulmonary edema. Arterial blood gas analysis results were as follows: pH, 7.08; PO(2),
70 mm Hg; PCO(2), 40 mm Hg; and SaO(2), 52%. Then, the patient received emergent
tracheal intubation and ventilation to assist breathing, and he was transferred to the intensive
care unit (ICU) for further treatment. In the ICU, the patient developed shock and respiratory
and circulatory failure; therefore, he received shock resuscitation, acidosis correction, muscle
relaxants to lower the work of breathing, and cardiotonic therapy. The patient eventually
died. During the ICU period, emergency bedside color ultrasound showed a diffuse B line in
both lungs, and the size of the cardiac cavity was normal, but the ventricular rate was
extremely fast. Chest radiography showed pulmonary edema with a normal cardiac silhouette,
and the brain natriuretic peptide (BNP) level was in the normal range. CONCLUSIONS:
NCPE is a rare and critical allergy-like reaction to the use of a nonionic iso-osmolar
radiocontrast contrast medium. Clinicians should pay very close attention to digestive tract
manifestations during the medical observation of patients, as gastrointestinal manifestations
Yonekura, K., et al. (2022). "Successful treatment of tumor stage mycosis fungoides
with total skin helical tomotherapy." J Dermatol 49(2): 289-293.
Total skin electron beam therapy (TSEBT) is a treatment option for mycosis fungoides (MF).
In Japan, it has been rarely performed because of the time required for each treatment,
physical burden on patients, and difficulties in providing uniform dosimetry. In recent years,
helical tomotherapy, an intensity-modulated radiation therapy that applies helical computed
tomography technology, has been used to treat cancer. Total skin helical tomotherapy
(TSHT) has been suggested as a promising alternative to TSEBT for patients with MF, but
there are few reports from Japan. We used TSHT to treat a 28-year-old Japanese woman with
tumor stage MF. She achieved complete remission with TSHT (12 Gy in six fractions over
6 days) and remained in remission for 32 months without additional treatment. Treatmentrelated grade 4 myelosuppression was observed, but resolved with blood transfusions and
subcutaneous injection of granulocyte colony stimulating factor. Other adverse events were
tolerable. Although careful attention should be paid to myelosuppression, TSHT might be a
useful treatment option for MF.
Zhan, L., et al. (2022). "The Diagnosis of Severe Fever with Thrombocytopenia
Syndrome Using Metagenomic Next-Generation Sequencing: Case Report and
Literature Review." Infect Drug Resist 15: 83-89.
Zhang, F., et al. (2019). "Microneedles combined with a sticky and heatable hydrogel
for local painless anesthesia." Biomater Sci 7(11): 4503-4507.
BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an infectious
disease caused by a bunyaviridae virus. Its main clinical manifestation is fever with
thrombocytopenia, which may be accompanied by other clinical symptoms. Here, we report a
patient diagnosed with SFTS using metagenomic next‑generation sequencing (mNGS). CASE
PRESENTATION: A 56-year-old female patient was hospitalized with intermittent diarrhea
and fever. She visited a local clinic for treatment, but instead of improving, the symptoms
progressed to unconsciousness. DIAGNOSIS: Using mNGS, we isolated the bunyaviridae
virus and several other pathogens from the patient's blood samples to confirm the diagnosis.
INTERVENTIONS: The patient was treated with symptomatic and supportive therapy,
including intravenous human γ-globulin (20 g/d), platelet transfusion, platelet elevation
(subcutaneous injection of recombinant human thrombopoietin, 15,000 IU), white blood cell
elevation (subcutaneous injection of recombinant human granulocyte colony-stimulating
factor, 200 ug, qd); and antibiotic (cefoperazone sodium and tazobactam sodium, 2 g, q8h),
antiviral (ganciclovir, 250 mg, q12h), and antifungal therapy (voriconazole for injection, 0.2
g, q12h). After ten days of treatment, the patient's condition gradually improved.
CONCLUSION: Compared to traditional detection methods, mNGS has many advantages. It
can quickly identify the pathogen when the patient's clinical manifestations are complex and
In view of the inherent defects of traditional syringe anesthesia (pain, inaccurate anesthesia
area, swelling after injection, slow recovery etc.), this article proposed a new anesthesia
system based on microneedles and a hydrogel. After loading with AuNPs, a sticky PDAPAM-AuNP hydrogel with near-infrared (NIR) light response properties was prepared here.
After using microneedles (to open the skin of the target anesthesia area), a hydrogel patch
embedded with a medical anesthetic soaked sponge was pasted to realize local painless
anesthesia. The effects of anesthesia can also be modulated by external NIR. Compared to
traditional syringe anesthesia, this hydrogel + microneedle method resulted in reduced pain,
higher anesthetic accuracy and faster recovery, making it a promising local anesthesia
alternative in clinical applications.
Zhang, F. F., et al. (2023). "[Heat-tonifying acupuncture relieves pain and synovial
inflammatory injury by regulating Keap1-Nrf2/ARE/ HO-1 signaling pathway in
rabbits with cold syndrome type rheumatoid arthritis]." Zhen Ci Yan Jiu 48(7): 650657.
Zhang, J., et al. (2020). "Synergistic effects of EMPs and PMPs on pulmonary
vascular leakage and lung injury after ischemia/reperfusion." Cell Commun Signal
18(1): 184.
OBJECTIVE: To observe the effect of heat-tonifying needling on Keap1-Nrf2/ARE/HO-1
signal transduction pathway in knee synovium in rabbits with cold syndrome type rheumatoid
arthritis (RA), so as to explore its mechanisms underl-ying improvement of RA. METHODS:
New Zealand rabbits were randomly divided into normal control, RA model, uniform
reinforcing-reducing acupuncture, twisting reinforcing acupuncture and heat-tonifying
acupuncture groups, with 6 rabbits in each group. The cold syndrome type RA model was
established by subcutaneous injection of mixture fluid of ovalbumin and Freund's complete
adjuvant at the shoulder-back as well as injection of mixture of ovalbumin and normal saline
into knee-joint cavity combined with ice-compress freezing. Acupuncture stimulation
(uniform reinforcing-reducing, or twisting reinforcing or heat-tonifying) was applied to
bilateral "Zusanli"(ST36) for 1 min with the needle retained for 30 min, once a day for 7
consecutive days. The general conditions of rabbits in each group were recorded, the thermal
pain threshold (TPT) and perimeter of knee joints was measured. Conditions of the synovium
in the knee cavity, hydrops, blood flow signal, articular surface, and related muscles were
observed by using a color Doppler ultrasonic diagnostic apparatus, and the blood flow signals
inside the synovium (image scores) were divided into 0 (no signals), I (1 or 2 dot-like signal),
II (less than half) ad III (more than half). After H.E. staining, the pathological changes (0-3
points) were assessed according to the state of inflammatory cell infiltration, and hyperplasia
of synovial matrix and coating cells. The expression levels of Keap1, Nrf2, HO-1 and GSHPX1 mRNAs in the knee synovium were detected by quantitative real-time PCR, and the
expression of knee synovial HO-1 protein was measured by Western blot. RESULTS: In
comparison with the normal control group, the model group had a significant increase in the
perimeter, pathological score, expression of Nrf2, HO-1 mRNAs and HO-1 protein (P<0.05),
and an obvious decrease in the TPT, expression levels of Keap1 and GSH-PX1 mRNAs
(P<0.05). Relevant to the model group, all the three acupuncture maneuvers reversed
modeling-induced increase of perimeter and pathological score (P<0.05), decrease of TPT
and expression of GSH-PX1 mRNA(P<0.05), further down-regulated expression of Keap1
mRNA (P<0.05), further up-regulated the expression of Nrf2, HO-1 mRNAs and HO-1
BACKGROUND: Vascular leakage is an important pathophysiological process of critical
conditions such as shock and ischemia-reperfusion (I/R)-induced lung injury. Microparticles
(MPs), including endothelial cell-derived microparticles (EMPs), platelet-derived
microparticles (PMPs) and leukocyte-derived microparticles (LMPs), have been shown to
participate in many diseases. Whether and which of these MPs take part in pulmonary
vascular leakage and lung injury after I/R and whether these MPs have synergistic effect and
the underlying mechanism are not known. METHODS: Using hemorrhage/transfusion
(Hemo/Trans) and aorta abdominalis occlusion-induced I/R rat models, the role of EMPs,
PMPs and LMPs and the mechanisms in pulmonary vascular leakage and lung injury were
observed. RESULTS: The concentrations of EMPs, PMPs and LMPs were significantly
increased after I/R. Intravenous administration of EMPs and PMPs but not LMPs induced
pulmonary vascular leakage and lung injury. Furthermore, EMPs induced pulmonary
sequestration of platelets and promoted more PMPs production, and played a synergistic
effect on pulmonary vascular leakage. MiR-1, miR-155 and miR-542 in EMPs, and miR-126
and miR-29 in PMPs, were significantly increased after hypoxia/reoxygenation (H/R). Of
which, inhibition of miR-155 in EMPs and miR-126 in PMPs alleviated the detrimental
effects of EMPs and PMPs on vascular barrier function and lung injury. Overexpression of
miR-155 in EMPs down-regulated the expression of tight junction related proteins such as
ZO-1 and claudin-5, while overexpression of miR-126 up-regulated the expression of
caveolin-1 (Cav-1), the trans-cellular transportation related protein such as caveolin-1 (Cav1). Inhibiting EMPs and PMPs production with blebbistatin (BLE) and amitriptyline (AMI)
alleviated I/R induced pulmonary vascular leakage and lung injury. CONCLUSIONS: EMPs
and PMPs contribute to the pulmonary vascular leakage and lung injury after I/R. EMPs
mediate pulmonary sequestration of platelets, producing more PMPs to play synergistic
effect. Mechanically, EMPs carrying miR-155 that down-regulates ZO-1 and claudin-5 and
PMPs carrying miR-126 that up-regulates Cav-1, synergistically mediate pulmonary vascular
Zhang, X. J., et al. (2023). "Analysis of Adverse Drug Reaction Reports from a Public
Hospital in Shanxi Province in 2022." Risk Manag Healthc Policy 16: 1391-1401.
OBJECTIVE: Through analyzing the characteristics and influencing factors of adverse drug
reactions/adverse events (ADR/ADE) in a hospital to promote rational drug use in the clinic.
METHODS: A total of 1221 ADR/ADE reports collected from a hospital in 2022 were
retrieved through the National Adverse Drug Reaction Monitoring Center. The effective
reports were screened according to the Guiding Principles for Collection and Reporting of
Individual Adverse Drug Reactions, and classified the standardized drugs. The
systems/organs and main clinical symptoms affected by ADR/ADE were classified according
to the WHO Glossary of Adverse Drug Reaction Terms. The severity, age and gender,
occupational distribution, drug category, route of administration, drug dosage form,
system/organ involved, and main clinical symptoms of ADR/ADE reports were analyzed.
RESULTS: Among 1221 ADR/ADE reports, 890 cases (75.27%) reported by doctors; 144
cases (11.79%) were serious; Precisely 49.22% of ADR/ADE occurred in patients aged 51 to
70 years old; The highest incidence of adverse reactions was 636 cases (52.09%) by
intravenous infusion, 406 cases (33.25%) by oral administration. The top categories of
reported cases were anti-infective drugs (29.40%) and anti-tumor drugs (27.52%);
Systems/organs involved in ADR/ADE were mainly the skin and its accessories (24.96%) and
blood system (21.35%). 166 cases were cured, 893 cases were symptomatic, 160 cases were
unknown, and 2 cases had sequelae. CONCLUSION: The occurrence of ADR/ADE is related
to many influencing factors such as age, drug categories, and route of administration.
Therefore, it is recommended that hospitals strengthen the monitoring of ADR/ADE,
Zhang, Y., et al. (2020). "Treatment of refractory gout with TNF-α antagonist
etanercept combined with febuxostat." Ann Palliat Med 9(6): 4332-4338.
Zheng, C. X., et al. (2020). "Orbital Cellulitis Following Uncomplicated Glaucoma
Drainage Device Surgery: Case Report and Review of Literature." J Ophthalmic Vis
Res 15(3): 412-418.
Zheng, M. X., et al. (2017). "[Role of mast cells in experimental autoimmune
prostatitis in rats]." Zhonghua Nan Ke Xue 23(5): 399-405.
A male patient, diagnosed as acute gouty arthritis with hypertension, gastrointestinal fungal
infection, gastric ulcer, and other diseases, received the following treatment: low purine diet,
alkalization of urine, omeprazole to inhibit gastric acid secretion, low-dose colchicine to
relieve joint pain, febuxostat to reduce uric acid synthesis, losartan potassium to reduce blood
pressure, atorvastatin calcium tablet to lower lipid, cefmendoxime proxetil to resist infection,
and TNF-α antagonist etanercept 25 mg subcutaneous injection two times a week (with 72
hours interval) for two weeks. As a result, the patient responded well to TNF antagonist
etanercept. The joint pain was significantly relieved one day after treatment and completely
relieved after five days. Two weeks later, the results of C-reaction protein (CRP) and blood
routine examination returned to normal. We drawed conclusions as follows: TNF antagonists
etanercept can alleviate the acute inflammatory response of gouty arthritis and ensure uric
acid-lowering therapy. However, the safety and effectiveness of the drug in the treatment of
acute, complex, and refractory gout still need to be confirmed by randomized, multi-center,
large sample clinical controlled study. This case report only supplies a new reference scheme
for the treatment of similar diseases.
PURPOSE: Orbital cellulitis (OC) is a rare postoperative complication of glaucoma drainage
device (GDD) implantation. To date, there have only been 10 reported cases of OC following
GDD implantation. CASE REPORT: Here, we report a case of OC in a 57-year-old man who
developed pain, proptosis, and limited extraocular motility two days after uneventful Ahmed
FP7 implantation in the right eye. Contrast-enhanced computed tomography of the orbits
demonstrated fat stranding and a small fluid collection, consistent with OC. He had minimal
improvement with intravenous antibiotics and ultimately underwent GDD explantation. A
systematic review of the literature showed that the development of OC following GDD
implantation can occur in the early or late postoperative period. Immediate hospitalization
with intravenous administration of broad-spectrum antibiotics is recommended. Explantation
of the infected GDD is often required for source control. CONCLUSION: OC is a rare
postoperative complication of GDD implantation. Prompt evaluation and treatment are
required, often combined with GDD explantation.
OBJECTIVE: To investigate the role of mast cells in chronic prostatitis / chronic pelvic pain
syndrome (CP/CPPS). METHODS: Forty-five male SD rats were equally randomized into a
control, an experimental autoimmune prostatitis (EAP) model, and an intervention group. The
EAP model was made in the latter two groups by subcutaneous injection of mixed suspension
of complete Freund's adjuvant and prostate tissue, while the controls were treated
subcutaneously with 0.9% sodium chloride. Tactile allodynia was quantified in the pelvic
region of the control and EAP animals using Von-Frey filaments at 5, 10, 20, 30 and 40 days.
After successful establishment of the EAP model, the rats of the intervention group were
injected intraperitonieally with cromolyn sodium for 10 days, and meanwhile tactile allodynia
was detected in the rats of the intervention and EAP model groups every other day. Then the
prostates of the rats were harvested for HE and toluidine blue staining and measurement of
the expression of mast cell tryptase by immunohistochemistry and Western blot. RESULTS:
Von-Frey assessment showed a more severe pelvic pain in the EAP model than in the control
rats, but milder in the intervention group than in the EAP models. HE staining revealed
infiltration of lymphocytes and neutrophils in the prostate and congestion surrounding the
gland in the EAP model rats, but none in the controls. However, both the infiltration and
congestion were significantly alleviated in the intervention group. Toluidine blue staining
shown that. Compared with the control group, the total count of mast cells and the number
degranulated mast cells were markedly increased in the EAP models (P <0.01) but decreased
in the intervention group (P <0.05). Both immunohistochemistry and Western blot manifested
that the expression of tryptase in the mast cells was remarkably upregulated in the EAP (both
P <0.01) but down-regulated in the intervention group (P <0.05 and P <0.01).
CONCLUSIONS: Both the total count of mast cells and the number of degranulated mast
cells are significantly increased in the prostate of EAP rats. Mast cells are one of the most
important mediators of type Ⅲ prostatitis-induced chronic pelvic pain, which can be used as a
Zhu, L. L., Y. H. Wang and Q. Zhou (2023). "Progress in Research on the
Mechanisms and Interventions of Phlebitis from the Perspective of Vascular
Endothelial Cell and Signaling Pathway." J Inflamm Res 16: 6469-6481.
BACKGROUND: Phlebitis is a common complication of intravenous administration and
greatly affects clinical outcomes, patient satisfaction, and health-care expenditure. Numerous
studies have revealed venous injuries only through visual and histopathological examination.
Although sporadic studies have explored the cellular and molecular biological mechanisms of
phlebitis and the outcomes of pharmacological interventions, an updated review over the last
decade is not available. METHODS: Progress in research on the mechanisms and
interventions of phlebitis was summarized from the perspective of endothelial cells and
signaling pathways by retrieving the PubMed, Web of Science Core Collection, MEDLINE,
Embase, and CNKI. RESULTS: Phlebitis involves multiple signaling pathways (eg, nuclear
factor kappa B, Wnt/β-catenin, focal adhesion kinase/protein kinase B, Toll-like receptor,
protein kinase C beta/NADPH oxidase, PI3K/AKT/TNF, and JAK2/STAT3), upregulation of
E-selectin, GBP5/NLRP3 inflammasome axis, cell apoptosis, intracellular ROS generation,
SOD reduction, stimulation of angiogenesis, and induction of autophagy-associated cell
death. Preventive and curative interventions included α-solanine, baicalein, escin, intermedin,
Y15, micro-ribonucleic acid-223, sotrastaurin, cimetidine, aescin, resveratrol, α-chaconine,
Chahuang ointment, QingLuoTongMai, Mailuo Shutong, and N-acetylcysteine. Laboratory
models included vascular endothelial cells, real-time cell-monitoring analysis, network
pharmacology analysis and experimental verification in vivo, animal models of phlebitis (rat,
rabbit, and mouse), rabbit models with peripherally inserted central catheters (PICC)
catheterization, models of PICC/central venous catheter indwelling with combined drugs in
human umbilical vein endothelial cells, and compatibility with endothelial cells. Factors
affecting vascular endothelial cell injury include difference in the same class of drugs,
concentration and exposure time of precipitant, and infusion strategy. CONCLUSION:
Phlebitis is accompanied by endothelial dysfunction and may involve multiple molecular and
cellular mechanisms. These findings improve our understanding of the molecular targets of
interventions and help identify effective candidates for the prophylaxis and treatment of
phlebitis. Vascular health and risk management should be considered when initiating
Excluded due to not related to safety, benefits and performances
(2011). "Analgesia for terminally ill adult patients. Preserve quality of life." Prescrire
Int 20(121): 268-273.
Adequate pain management is crucial in maintaining the best possible quality of life for terminally ill patients.
This article examines pain management in the palliative care setting, based on a review of the literature using
the standard Prescrire methodology. Accurate pain evaluation, preferably by the patient, is essential for
guiding treatment decisions. Some causes of pain are amenable to specific treatments. The expected benefits
and harms of the various treatment options and procedures must be weighed on a case by case basis. Quality
of life should always be the first priority. The World Health Organization has developed a "three-step
analgesic ladder", based on the use of increasingly potent analgesics: step I analgesics include paracetamol
and nonsteroidal anti-inflammatory drugs (NSAIDs); codeine is the standard step II analgesic; and morphine
is the standard step III analgesic. Fentanyl is an alternative to morphine. The daily morphine dose must be
determined for each patient. Morphine titration starts with oral doses given every 4 hours, but additional doses
can be taken every hour if necessary. Total consumption is then used to calculate the dose required the
following day. A sustained-release product can be used to reduce the number of doses required when a
consistently effective daily dose has been established. When patients are unable to take morphine orally, it can
be given by subcutaneous injection, and by subcutaneous or intravenous infusion. Pumps allow the patient to
self-administer morphine on demand. Fentanyl transdermal patches are another option for stable pain.
Immediate-release oral forms and injections are useful for preventing or treating breakthrough pain. If
morphine requirements increase during treatment, the most likely explanations are exacerbations of pain or an
excessively long interval between doses. Pharmacological tolerance and psychological dependence are rare
during palliative care. In case of renal failure, the morphine dose should be reduced, sustained-release
morphine should be replaced by immediate-release morphine, or morphine should be replaced by fentanyl, as
fentanyl metabolism is only slightly affected by renal function. The main adverse effects of morphine are
constipation, nausea and vomiting. Drowsiness is frequent at initiation of treatment. Respiratory depression is
rare when morphine is introduced gradually. Tricyclic antidepressants and carbamazepine have acceptable
harm-benefit balances in patients with neuropathic pain. Cannabinoids are another option but have not been
adequately assessed. Localised refractory pain may respond to local anaesthesia, chemical neurolysis or
surgical ablation. In practice, it is best to allow patients to control their own analgesic consumption, within
(2014). CADTH Common Drug Reviews. Golimumab (Simponi) (Subcutaneous
Injection): Adult Patients with Moderately to Severely Active Ulcerative Colitis Who
Have Had an Inadequate Response to, or Have Medical Contraindications for,
Conventional Therapies. Ottawa (ON), Canadian Agency for Drugs and Technologies
in Health
Copyright © CADTH 2014.
(2016). CADTH Common Drug Reviews. Canakinumab (Ilaris). Ottawa (ON),
Canadian Agency for Drugs and Technologies in Health
Copyright © CADTH 2016.
Ulcerative colitis (UC) is a form of inflammatory bowel disease (IBD) that leads to severe gastrointestinal
symptoms, including diarrhea, pain, and bloody stools. The inflammation can eventually lead to significant
mucosal damage and to life-threatening complications such as bowel perforation and sepsis. Patients with UC
are also at higher risk of malignancy, most notably colon cancer. UC is a relatively common disease in
Canada, with a prevalence of 104,000 patients and an incidence of 4,500 per year. There are a number of
management options for UC, including aminosalicylic acid, immunomodulators, corticosteroids, and most
recently, tumour necrosis factor (TNF) inhibitors. TNF is a key inflammatory mediator; thus, these inhibitors,
all monoclonal antibodies, are anti-inflammatory. The objective of this review is to perform a systematic
review of the beneficial and harmful effects of golimumab (Simponi) through subcutaneous injection at
recommended doses for the treatment of adult patients with moderately to severely active UC who have had
an inadequate response to, or have medical contraindications for, conventional therapy.
Juvenile idiopathic arthritis (JIA) is a relatively common, chronic childhood disorder, with clinical
manifestations mainly related to joint inflammation and including joint effusion, joint line tenderness and
warmth, restricted range of movement, and limitation of movement secondary to pain. Systemic onset JIA
(sJIA) is a subtype of the disease accounting for approximately 4% to 15% of patients, and is defined as
arthritis in one or more joints for at least 6 weeks in a child younger than 16 years with or preceded by fever
of at least 2 weeks that is documented to be daily for at least 3 days and accompanied by one or more of the
following: evanescent erythematous rash, generalized lymphadenopathy, hepatomegaly or splenomegaly, and
serositis. Patients with sJIA experience an intense inflammatory state leading to a particularly refractory
course and persistent disease. As a result, these patients are at high risk for serious complications such as joint
damage and growth impairment, as well as macrophage activation syndrome (MAS), a life-threatening
complication developing in 10% to 15% of children with sJIA and associated with a mortality rate that may
reach 20%. Canakinumab is a fully human monoclonal antibody that selectively binds and neutralizes
interleukin-1 beta, which plays a key role in the inflammatory process of sJIA. Canakinumab has a Health
Canada indication for the management of active sJIA in patients 2 years and older. The manufacturer has
requested that canakinumab be evaluated for reimbursement for the management of active sJIA in patients 2
years and older who are contraindicated to, or have discontinued, any biologic therapy for lack of efficacy or
intolerance. The objective of this report was to perform a systematic review of the beneficial and harmful
(2023). NICE Evidence Reviews Collection. Evidence reviews for position of the baby
during cord clamping: Intrapartum care: Evidence review N. London, National
Institute for Health and Care Excellence (NICE)
Copyright © NICE 2023.
Abdallah, A. A., et al. (2021). "Topical Tranexamic Acid in Total Knee Arthroplasty:
Does It Augment the Effect of the Intravenous Administration in Patients with
Moderate-to-High Risk of Bleeding? A Randomized Clinical Trial." J Knee Surg
34(14): 1570-1578.
After birth, the umbilical cord connecting the baby to the placenta is cut. Until recently the cord was clamped
and cut immediately after birth. However, in the last twenty years the benefits of delayed cord clamping for
term babies (usually waiting for at least 1 minute after birth) has been recognised, and delayed cord clamping
has become normal practice. This delay allows for blood to pass from the placenta to the baby (known as
placental transfusion) and aids cardiovascular transition from fetal to postnatal life. Based on the belief that
gravity may affect the volume of placental transfusion, babies may be held at or below vaginal level until the
cord is clamped. However, this can be difficult as many women wish to have skin-to-skin contact with their
baby as soon as it is born to facilitate bonding which may result in low compliance with delayed cord
clamping. It is not known if raising the baby to the level of the mother’s abdomen or chest prior to cord
clamping reduces the volume of placental transfusion leading to adverse outcomes for the baby. The aim of
this review is to assess whether there is a difference in outcomes for babies held at or below vaginal level or at
the mother’s abdominal or chest level during delayed cord clamping.
This study aimed to compare the superimposed clinical value of topical tranexamic acid (TXA) application
when it is simultaneously combined with intravenous (IV) administration versus the use of either IV TXA
alone or IA TXA alone during primary total knee arthroplasty (TKA) in patients with moderate-to-high risk of
bleeding. We hypothesized that the combined administration approach will result in a more adequate
reduction in the perioperative blood loss and blood transfusion rate. Ninety-four patients undergoing primary
TKA were randomly allocated into intra-articular (IA) alone, IV alone, and combined group. We used 2 g of
IV TXA in the IV TXA alone and combined groups 10 minutes before tourniquet deflation. However, we
applied 1.5 g TXA in 100 mL isotonic saline half topically before arthrotomy closure and half retrogradely
after wound closure through the drain. Follow-up period was 6 weeks. The primary outcome measures
included the drainage blood volume, total blood loss, hidden blood loss, intraoperative blood loss, and the
allogenic transfusion rate. Secondary outcomes included postoperative hemoglobin drop, amount of transfused
blood units, thromboembolism, and wound complications. Combined administration of TXA provided
significantly better results in terms of blood volume collected by the drain, total blood loss, and hidden blood
loss (p < 0.01). Contrarily, the intraoperative blood loss, the allogeneic transfusion rate, and the number of
transfused units were similar in all groups (p > 0.05). The subgroup analysis revealed that a combined IA and
IV TXA administration significantly reduced the total blood loss in patients with either moderate or high risk
of bleeding. Moreover, the degree of hemoglobin drop was significantly lesser with the combined approach.
No thromboembolic complications or wound infection occurred. In conclusion, the combined use of topical
and IV tranexamic acid resulted in a significant reduction in postoperative blood loss and hemoglobin level
following TKA but did not influence the rate of allogeneic blood transfusion. This is a Level I, therapeutic
Abdulla, S., W. Abdulla and R. Eckhardt (2011). "Caudal normal saline injections for
the treatment of post-dural puncture headache." Pain Physician 14(3): 271-279.
BACKGROUND: Post-dural puncture headache (PDPH) is the most common complication of procedures in
which the dura mater is penetrated. OBJECTIVES: To evaluate the effectiveness of caudal saline injections as
a therapeutic approach for handling post-dural puncture headache. STUDY DESIGN: Prospective
observational study between 1995 and 2010. SETTING: Associated teaching hospital. METHODS: A 5-cm
20-gauge short-beveled needle, connected by extension tube to a 20-mL syringe filled with normal saline was
used for injection. During injection in increments (limited by patient discomfort), the patients were asked
continually to quantify their pain experience on a visual analog scale (VAS) and on a 0-3 verbal categorical
rating scale (VRS) after 50, 80 and 100 mL of infusion over a 20 minute period. LIMITATIONS: This study
is limited by its sample size, observational design, and lack of long-term outcomes. RESULTS: PDPH
occurred in 60 of 1,716 patients undergoing dural puncture (3.5%). It was significantly more common in
women and occurred more often in young adults. The rate was highest in the spinal catheter group (13%) and
lowest in the Sprotte needle group (0.98%). Fifty-six patients underwent caudal saline injections which were
repeated in sessions of 1-2 times a day for 1-2 days. Most patients (n = 48) needed 3 or 4 (n=18) sessions.
Mean volumes during the 4 sessions were 120.0 mL, 114.9 mL, 106.5 mL, and 97.8 mL. Four patients were
finally treated with a blood patch. CONCLUSIONS: The use of fine gauge pencil-point needles may reduce
the incidence of PDPH. The technique of repeated caudal saline injections is easy, rapid, and effective in
providing the patient with almost immediate headache relief. In cases where this treatment fails, a blood patch
should be considered. Observations from this study suggest that randomized, controlled, double-blind studies
Abe, H., et al. (2013). "Safety assessment of intravenous administration of
trastuzumab in 100ml saline for the treatment of HER2- positive breast cancer
patients." Asian Pac J Cancer Prev 14(8): 4843-4846.
Abiodun, A. K., et al. (2023). "Disease severity and renal function among sickle cell
anaemia patients in a tertiary hospital, South-south, Nigeria: a cross sectional study."
Malawi Med J 35(1): 9-14.
BACKGROUND: The infusion rate is considered to affect incidence and severity of infusion reactions (IRs)
caused by protein formulations. Trastuzumab (TRS) is approved for 90-minute infusion as the initial dose
followed by 30-minute infusion with 250 ml saline. In the study, we evaluated the safety of TRS intravenously
administered over 30 minutes with 100 ml saline to reduce burden of patients, safety of infusion with 250 ml
saline already being established. MATERIALS AND METHODS: Women with HER2 positive breast cancer,
≥18 years and ≥55% left ventricular ejection fraction (LVEF), were registered in the study. Patients received
8mg/kg of TRS 250 ml over 90 minutes followed by 6mg/kg of TRS 100ml over 30 minutes in a three-week
cycle. RESULTS: A total of 31 patients were recruited, 24 for adjuvant therapy and seven with metastases.
The median age was 59 years (range 39 to 82). The total number of TRS doses ranged from 5 to 17 with the
median of 15. Mild IR occurred in two patients at the first dose. However, no IR was observed after reducing
to 100 ml saline. No decrease of LVEF, increase of serum brain natriuretic peptide or any other adverse events
were reported. CONCLUSIONS: Intravenous infusion of TRS with 100 ml saline over 30 minutes in breast
cancer patients can be considered safe based on results from the study. It can be given on an outpatient basis
as with the currently recommended dilution in 250 ml saline.
BACKGROUND: Renal disease is a recognized complication of sickle cell anaemia (SCA), especially from
the third decade of life and is linked to disease severity. This study assessed the association between disease
severity and renal function among SCA patients using routine and newer markers of renal function.
METHODS: This cross-sectional study recruited 85 SCA patients. Disease severity was assessed using
modified Adegoke criteria which include the frequency of transfusion, painful crises, packed cell volume, and
history of complications such as hypertension and chronic leg ulcers. Renal function was assessed using urea,
creatinine, and beta-2-microglobulin (β2-M). Association was determined between renal function and disease
severity using Pearson's correlation. P-value < 0.05 was taken as significant. RESULTS: The mean age of
participants was 27.2 ± 7.6 years with 41(48.2%) males and 44 (51.8%) females. The mean packed cell
volume, serum creatinine, serum urea, and β2-M were 24.0± 4.1%,17.6±7.5 mg/dL, 0.7±0.3mg/dL,
3.4±1.2mg/l respectively. A majority (54.1%) of them had a mild disease while 35.3% and 10.6% had
moderate and severe diseases, respectively. Forty of the SCA patients had urine specific gravity below 1.010.
The mean values of systolic blood pressure (p=0.001) diastolic blood pressure (p=0.001), serum creatinine
(p=0.028) and β2M (p=0.019) significantly increased with disease severity. There was a significant positive
correlation between SCA disease severity and serum urea (r=0.229; p=0.035), and serum β2-microglobulin
(r=0.270; p=0.012). CONCLUSION: Sickle cell anaemia severity is associated with a decline in renal function
using both traditional and novel renal markers. Serum β2-M may serve as a useful marker of renal function
Abu-Halaweh, S. A., et al. (2013). "Comparison of three methods of preventing
rocuronium induced pain on injection using venous occlusion technique: a randomized
prospective double blind controlled study." Middle East J Anaesthesiol 22(1): 87-92.
BACKGROUND: Intravenous administration of rocuronium bromide causes pain at the site of injection in
most patients. The mechanism that leads to this side effect is still unknown and multiple drugs' pretreatments
were used to prevent its occurrence with varying success rates. PURPOSE: The study aimed to evaluate the
effects of the pretreatment with lidocaine, fentanyl, and remifentanil using a venous occlusion technique in
preventing pain caused by intravenous injection of rocuronium during induction of general anesthesia.
METHOD: Two hundred patients, ASA I-II, requiring various types of surgical procedures under general
anesthesia with muscle relaxation and mechanical ventilation, were enrolled. Patients were pre-educated to
report pain severity on rocuronium injection on a 4-point severity scale. Patients were allocated randomly
using sealed envelopes method into one of four pretreatment groups: (Xylocaine group, 50), Remifentanyl
group 50), (Fentanyl group, 50), and (Normal saline group, 50). After venous occlusion, study drugs were
injected and the venous occlusion was maintained for one minute. Rocuronium was then administered and
patients were asked to report their pain RESULTS: Compared to control group, all pretreatment drugs were
effective in reducing pain on rocuronium injection. Xylocaine was the most effective (Mean difference-1.42,
P <0.001), followed by Remifentanil (Mean difference-1.32, P <0.001) and Fentanyl (Mean difference-0.50, P
<0.001) in reducing pain on rocuronium injection. Remifentanil was statistically comparable to Xylocaine (P
= 0.820) and both drugs were superior to Fentanyl in reducing pain on rocuronium injection. CONCLUSION:
Remifentanyl is a better choice of opioid in preventing pain on rocuronium injection using venous occlusion
Ackerman, L. L., A. A. Snider and J. Ye (2023). "Use of Subcutaneous Injection of
Epinephrine and Triamcinolone with Tranexamic Acid Reduces Blood Loss,
Transfusion Rates, and Length of Stay in Open Sagittal Craniosynostosis Repair." J
Craniofac Surg 34(7): 2107-2111.
Adatto, M. (2023). "Clinical evaluation of the efficacy of fractional radiofrequency for
the treatment and reduction of stretch marks: A prospective study." J Cosmet
Dermatol 22(1): 214-221.
OBJECTIVE: In 2017, we adopted the use of triamcinolone/epinephrine (TAC/Epi) scalp injection and later
added tranexamic acid (TXA) in open sagittal synostosis surgery. We believe that this reduced blood loss and
transfusion rates. METHODS: A total of 107 consecutive patients operated for sagittal synostosis aged <4
months from 2007 to 2019 were retrospectively reviewed. We collected demographics [age, sex, weight at
surgery, and length of stay (LOS)], intraoperative information [estimated blood loss (EBL)], administration of
packed red blood cell, transfusion of plasmalyte/albumen, operating time, baseline hemoglobin (Hb) and
hematocrit (Hct), type of local anesthetic (1/4% bupivacaine vs. TAC/Epi), and use/volume of TXA. Hb, Hct,
coagulation studies, and platelets at 2 hours postoperatively and postoperative day (POD) 1 were recorded.
RESULTS: There were 3 groups: 1/4% bupivacaine/epinephrine (N=64), TAC/Epi (N=13), and TAC/Epi
with TXA bolus/infusion intraoperatively (N=30). Groups receiving TAC/Epi or TAC/Epi with TXA had
lower mean EBL ( P <0.0001), lower rate/amount of packed red blood cell transfusion ( P <0.0001), lower
prothrombin time/international normalized ratio on POD 1 ( P <0.0001), higher platelets ( P <0.001), and
shorter operative time ( P <0.0001). LOS was shortest for TAC/Epi with TXA ( P <0.0001). No significant
differences between groups were noted on POD 1 Hb, Hct, or partial prothrombin time. Post hoc testing
revealed an advantage of TAC/Epi with TXA over TAC/Epi alone for 2-hour postoperative international
normalized ratio ( P =0.0249), Operating Room time ( P =0.0179), and LOS ( P =0.0049). CONCLUSIONS:
Use of TAC/Epi alone reduced EBL, LOS, Operating Room time, and improved laboratory values
postoperatively in open sagittal synostosis surgery. Addition of TXA further improved operative time and
BACKGROUND/OBJECTIVES: Skin resurfacing with fractional radiofrequency results in reepithelization,
collagen shrinkage, fibroblast stimulation, and neocollagenesis which may be beneficial for the improvement
of various skin lesions. This clinical study was conducted to evaluate the safety and efficacy of fractional
radiofrequency device (FRF) for the treatment of striae. METHODS: Seventeen subjects, totaling 67
treatment zones were evaluated. Subjects had 4 FRF treatment sessions to the striae areas, at 4-weeks interval.
3D-standardized photographs of the treatment area with a 3D camera were used to evaluate striae volumetric
improvement from baseline to follow up (FU) visits at 12 and 16 weeks post-final treatment. A satisfaction
questionnaire was completed by subjects at each of the follow-up visits. Additionally, the mean scores of the
live investigator assessments of Global Aesthetic Improvement Scale (GAIS), Subject Satisfaction Scale, Pain
Visual Analog Scale and Tolerability Score were calculated. RESULTS: A total of 15 subjects completed the
study (Fitzpatrick skin type I-III, average age 36.2 years) received 4 FRF treatments on multiple different body
zones with multiple passes over stretch marks on the abdomen, inner arms, lower buttocks, inner thighs,
and/or flanks. Analysis of 3D photographs of the striae affected zones at 16-week FU revealed an average
reduction in the striae volume of 19.1%, a reduction of redness of 14.3%, a reduction of pigmentation of
11.2%, and a reduction of striae color of 8.82%. The GAIS improved by 1.7-points when compared to
baseline. Treatments were well tolerated with subjects reporting a mean score of 3.8 out of 10 for pain and 3.1
out of 4 for tolerability (indicating the treatment was "tolerable"), with no occurrences of serious adverse
events. The average subject satisfaction at 16-week follow-up was 3.1, out of a total of 4, which signified
subjects were "satisfied" with their treatment. CONCLUSION: 3D Image analysis of the treated zones
presented overall reductions in the color and texture of striae after four treatments with FRF. A combination
of ablation and coagulation introduced by FRF treatment resulted in improvement to the appearance of the
Agostoni, M., et al. (2011). "Adverse events during monitored anesthesia care for GI
endoscopy: an 8-year experience." Gastrointestinal Endoscopy 74(2): 266-275.
Background The importance of sedation during endoscopy is well established. There is no consensus about
the best techniques for sedation, which specialist should perform it, and in which location. Objective To
provide data on the epidemiology of adverse events during sedation for endoscopy. Design Retrospective
analysis of a prospective database. Setting Endoscopy unit of a university hospital. Procedures A total of
17,999 procedures performed over 8 years. Interventions Sedation for GI endoscopy. Main Outcome
Measurements We recorded the following information: sex, age, body mass index, smoking habits, American
Society of Anesthesiologists and Mallampati scores, duration of the procedure, type of sedative drug
administered, whether the procedure was performed emergently, and endoscopic interventions during the
maneuver. Adverse events were defined as occurrences that warranted intervention and were classified as
hypotension, desaturation, bradycardia, hypertension, arrhythmia, aspiration, respiratory depression, vomiting,
cardiac arrest, respiratory arrest, angina, hypoglycemia, and/or allergic reaction. Results Deep sedation with
intravenous propofol target controlled infusion pump was the most frequently used means of administering
sedation. Adverse events were rare in both the adult (4.5%) and pediatric (2.6%) populations. Six
complications occurred in more than 0.1% of adult cases: arterial hypotension, desaturation, bradycardia,
arterial hypertension, arrhythmia, and aspiration. Only bradycardia (2.1%) and hypotension (0.44%) occurred
in children. Three adult patients (0.017%) died, and no pediatric patients died. Some predictive models for the
occurrence of complications are proposed. Limitations Retrospective analysis, single-center data collection.
Conclusions Deep sedation during endoscopic procedures is safe in both adults and children. Our data may be
Agrawal, A., et al. (2020). "The efficacy of intralesional dexamethasone versus
intravenous dexamethasone in surgery for impacted third molars: A randomized
controlled trial." Natl J Maxillofac Surg 11(1): 94-97.
OBJECTIVES: A randomized prospective double-blind study was conducted to determine the efficacy of submucosal local infiltration vs. intravenous dexamethasone in reducing postoperative pain, swelling and trismus
after surgical removal of impacted mandibular third molars. MATERIALS AND METHODS: Forty five
patients were included in the study and were randomly divided into three groups. Each group consisted of 15
patients for which the first and second groups were given 8 mg of dexamethasone intrlesionally &
intravenously respectively, at 30 minutes prior to surgery; the third group served as control. Duration of facial
swelling was evaluated subjectively by the patients themselves. Severity of postoperative pain was quantified
by counting the number of analgesics taken by the patients during and after surgery (six subsequent days).
Postoperative trismus was determined by measuring the maximum incisal opening before surgery and on the
seventh day. RESULTS: Results showed that duration of postoperative edema was almost the same in the
three test groups. During surgery, the intravenous dexamethasone group showed a significantly lesser pain
than the other two groups; the intralesional dexamethasone group showed less marked pain than the control
group. Additionally, patients who had taken steroids had a marked increase in the incisal opening
postoperatively over the control group. Trismus was significantly reduced in the methylprednisolone group as
compared to the dexamethasone group. CONCLUSION: It is concluded that both preoperative local
infiltration and intravenous administration of dexamethasone significantly reduced postoperative pain and
trismus after surgical removal of mandibular third molars. An intravenous dexamethasone is more effective in
Ahmad, S., et al. (2013). "The effect of intravenous dexamethasone and lidocaine on
propofol-induced vascular pain: a randomized double-blinded placebo-controlled
trial." Pain Res Treat 2013: 734531.
Ahn, J., J. S. Chang and J. W. Kim (2022). "Postoperative Pneumonia and Aspiration
Pneumonia Following Elderly Hip Fractures." The Journal of nutrition, health and
aging 26(7): 732-738.
Background. The mechanism for pain associated with intravenous administration of propofol is believed to be
related to the release of nitric oxide. We hypothesized that pain following propofol injection would be reduced
by pretreatment with dexamethasone. Methods. One hundred fourteen female subjects received 5 mL of
preservative-free saline, 0.5 mg · kg(-1) of lignocaine hydrochloride 10 mg · mL(-1) or 0.25 mg · kg(-1) of
dexamethasone, intravenously, following exsanguination and occlusion of the veins of the arm. This was
followed by a 0.5 mg · kg(-1) injection of propofol. Pain scores, facial grimacing, arm withdrawal, and
vocalization were recorded prior to and at 15 and 30 seconds following the injection of propofol. Results. The
incidence of moderate to severe pain following the injection of propofol was significantly decreased with both
lidocaine and dexamethasone. Hand withdrawal was also significantly decreased in comparison to saline.
Conclusion. Low dose dexamethasone is commonly used as an antiemetic, and, in larger doses, it has been
demonstrated to provide prolonged postoperative analgesia. At higher analgesic doses, dexamethasone may
also reduce pain associated with the injection of propofol. This effect is probably related to the effect of the
steroid on nitric oxide production associated with intravenous propofol injection.
Objectives The present study aimed to investigate the incidence of and risk factors for postoperative
pneumonia and aspiration pneumonia after hip fracture surgery. Design Retrospective cohort study from 2005
to 2021. Setting Asan Medical Center in Seoul, Republic of Korea. Participants A total 1,208 patients aged ≥
65 years who underwent hip fracture surgery. Measurements Postoperative pneumonia was defined as cases
with new infiltration on chest x-ray or chest computed tomography (CT) after surgery or confirmed by a
pulmonologist's consultation and diagnosis. Aspiration pneumonia was defined as: 1) radiologic findings of
hospital-acquired pneumonia on chest radiographs or CT, medical record of aspiration pneumonia confirmed
by a pulmonologist's consultation, and history of vomiting or aspiration, or 2) gravity-dependent opacity on
chest CT when the history of vomiting or aspiration is ambiguous. Patient demographics, past medical history,
pre-injury Koval score, Charlson Comorbidity Index (CCI), blood test results, length of hospital stay, and inhospital mortality were evaluated. A comparison analysis and binary logistic regression were performed to
identify the incidence and risk factors for postoperative pneumonia and aspiration pneumonia. Results
Postoperative pneumonia was diagnosed in 47 patients (3.9%), including 20 with aspiration pneumonia
(1.7%). In the multivariate analysis, postoperative delirium (odds ratio [OR], 3.42; P < 0.001), American
Society of Anesthesiologists (ASA) scores ≥ 3 (OR, 2.11; P = 0.021), and CCI (OR, 1.21; P = 0.013) were
significant risk factors for postoperative pneumonia. Male sex (OR, 3.01; P = 0.017), postoperative delirium
(OR, 3.16; P = 0.014), and preoperative serum albumin levels < 3.5 g/dL (OR, 7.00; P = 0.010) were
significant risk factors for aspiration pneumonia. Conclusion ASA classification ≥ 3, higher CCI, and
postoperative delirium were the risk factors for postoperative pneumonia. Male sex, postoperative delirium,
and lower preoperative serum albumin level were the risk factors for aspiration pneumonia. Thus, physicians
Alam, A., et al. (2013). "The prevention of transfusion-associated circulatory
overload." Transfus Med Rev 27(2): 105-112.
Ali, A., et al. (2015). "Doubtful effect of continuous intraarticular analgesia after total
knee arthroplasty: a randomized double-blind study of 200 patients." Acta Orthop
86(3): 373-377.
Transfusion-associated circulatory overload (TACO) is an important and potentially injurious complication of
transfusion that is underappreciated by clinicians. Risk factors for TACO include being at an extreme of age,
having preexisting cardiac and/or (potentially) renal dysfunction, acute myocardial infarction, and individuals
receiving plasma. Keys to preventing TACO, aside from identifying high-risk individuals, should be
multifaceted. We advocate for the widespread use of pretransfusion checklists and implementation of
nonemergent transfusion protocols. We suggest the regular use of pretransfusion diuretics in high-risk
individuals. When a transfusion is required, we believe that "critical" nursing supervision and leadership are
instrumental in the coordination of slow transfusion rates on computerized infusion pumps and ensuring
patients are appropriately monitored. We believe that using these methodologies on a global scale will prevent
many TACO events and minimize the severity when it does occur.
BACKGROUND AND PURPOSE: Local infiltration analgesia (LIA) is well established for effective
postoperative pain relief in total knee arthroplasty (TKA). To prolong the effect of LIA, infusion pumps with
local intraarticular analgesia can be used. We evaluated the effect of such an infusion pump for the first 48 h
postoperatively regarding pain, knee function, length of stay (LOS) in hospital, and complications.
PATIENTS AND METHODS: 200 patients received peroperative LIA and a continuous intraarticular
elastomeric infusion pump set at 2 mL/h. The patients were randomized either to ropivacaine (7.5 mg/mL) or
to NaCl (9 mg/mL) in the pump. Visual analog scale (VAS) pain (0-100 mm), analgesic consumption, side
effects of medicine, range of motion (ROM), leg-raising ability, LOS, and complications during the first 3
months were recorded. RESULTS: On the first postoperative day, the ropivacaine group had lower VAS pain
(33 vs. 40 at 12 noon and 36 vs. 43 at 8 p.m.; p = 0.02 and 0.03, respectively), but after that all recorded
variables were similar between the groups. During the first 3 months, the ropivacaine group had a greater
number of superficial and deep surgical wound infections (11 patients vs. 2 patients, p = 0.02). There were no
other statistically significant differences between the groups. INTERPRETATION: Continuous intraarticular
analgesia (CIAA) with ropivacaine after TKA has no relevant clinical effect on VAS pain and does not affect
LOS, analgesic consumption, ROM, or leg-raising ability. There may, however, be a higher risk of woundAlijla, S. S. and F. A. Binti Amran (2022). "Comparison of the Analgesic Effect of
Subcutaneous Bupivacaine Infiltration and Intravenous Diclofenac vs. Intravenous
Diclofenac Monotherapy After Inguinal Hernioplasty: A Retrospective Study." Cureus
14(8): e28312.
Background Postoperative pain is a significant problem encountered by patients after a surgical intervention,
and there is a crucial need for effective postoperative pain control. The studies have shown that multimodal
analgesia and wound infiltration are effective ways to reduce this pain and have a substantial role in the
reduction of postoperative medications requirement. This study aimed to evaluate the effect of subcutaneous
infiltration of bupivacaine hydrochloride and intravenous (IV) diclofenac as postoperative pain relief in adults
undergoing inguinal hernia repair. Methods A single-center retrospective study included 104 patients aged 1865 undergoing unilateral inguinal herniorrhaphy at the selected hospital. The patients were in two groups of
52 each. Group A received a 75 mg dose of IV diclofenac plus a subcutaneous injection of 10 mL of
bupivacaine hydrochloride (HCl) 0.5% while Group B only received the IV diclofenac without the
bupivacaine injection. The postoperative pain was assessed at one, two, three, six, and 12 hrs after the
operation using the visual analog scale (VAS), which exhibited a range of pain from zero (no pain) to 10
(extreme pain). Results Of a total of 104 patients, 92% of patients were male. The patients' mean age was 36 ±
11 years, and the mean body mass index (BMI) was 22 ±3 kg/m(2). American Society of Anesthesiologists
physical class I was similar in both groups (90.4% versus 84.6%). Patients in Group A had significantly lower
VAS pain scores at one, two, three, six, and 12 hrs after the operation and a longer emergence time than
Group B (all p-values were < 0.001). Subcutaneous bupivacaine infiltration and IV diclofenac were also found
to be an effective analgesic technique in open hernia repair with mesh (p-value < 0.001 for all). Conclusion
Subcutaneous injection of bupivacaine combined with IV diclofenac provides superior analgesia to
Almasi, M., et al. (2016). "Does Intravenous Administration of Recombinant Tissue
Plasminogen Activator for Ischemic Stroke can Cause Inferior Myocardial
Infarction?" Neurol Int 8(2): 6617.
Al-Naggar, M. R., et al. (2019). "Intralesional bleomycin injection vs microneedlingassisted topical bleomycin spraying in treatment of plantar warts." J Cosmet Dermatol
18(1): 124-128.
Al-Qurain, A. A., et al. (2021). "Simultaneous LC-MS/MS quantification of
oxycodone, tramadol and fentanyl and their metabolites (noroxycodone,
oxymorphone, O- desmethyltramadol, N- desmethyltramadol, and norfentanyl) in
human plasma and whole blood collected via venepuncture and volumetric absorptive
micro sampling." J Pharm Biomed Anal 203: 114171.
Recombinant tissue plasminogen activator (rTPA) is one of the main portions of acute ischemic stroke
management, but unfortunately has some complications. Myocardial infarction (MI) is a hazardous
complication of administration of intravenous rTPA that has been reported recently. A 78-year-old lady was
admitted for elective coronary artery bypass graft surgery. On the second day of admission, she developed
acute left hemiparesis and intravenous rTPA was administered within 120 minutes. Three hours later, she has
had chest pain. Rescue percutaneous coronary intervention was performed on right coronary artery due to
diagnosis of inferior MI, and the symptoms were resolved.
BACKGROUND: Warts, or verrucae, are benign epithelial profilerations of skin and mucosa caused by
infection with HPV and poses a challenge to treat. OBJECTIVE: To compare between single and
microneedling-assisted multipuncture techniques of intralesional application in treatment of plantar warts.
METHODS: The study included 60 Patients who were divided into two groups (A&B). Each group consisted
of (30) patients. Group (A) subjects received intralesional bleomycin with a single injection using syringe
needle. For Group (B) subjects, we combined microneedling with topical spraying of bleomycin (MN + Bleo)
and followed by occlusion for 2 hours. RESULTS: The results revealed complete clearance of warts in 21
patients in group (A) (70%) whom were treated by intralesional (IL) bleomycin vs 25 patients (83.3%) in
group (B) whom were treated by spraying of bleomycin following microneedling. Side effects other than pain,
erythema, and transient induration were relatively infrequent, and no nail changes or Raynaud's phenomenon
was observed in both groups. CONCLUSION: We established a good safety and efficacy profile for
bleomycin in plantar wart treatment and we demonstrated that microneedling followed by bleomycin spraying
had a higher clearance and proved less painful as opposed to bleomycin injection.
INTRODUCTION: A range of opioids are commonly prescribed to manage chronic pain, but individual
patient responses vary greatly, especially in older populations. One source of that variability are differences in
absorption, metabolism and excretion, i.e. pharmacokinetics. Blood, plasma and serum concentrations of
opioids allow that variability to be quantified and may be used to optimise opioid dosing. As an aid to that
process, there is an unmet need to rapidly quantify several opioids and their metabolites in a single analytical
method. AIMS: To develop a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for
simultaneous quantification of tramadol, oxycodone, fentanyl and their major metabolites in various human
matrices. METHODS: Sample preparation involved adding three deuterated internal standards followed by
protein precipitation with 100 % acetonitrile, evaporation and reconstitution. Separation of analytes via LC
was achieved on a reversed phase column via binary gradient elution using 0.005 % formic acid in water and
100 % acetonitrile as mobile phases. Analytes were detected via MS/MS with multiple reaction monitoring
(MRM). RESULTS: The method was accurate with the inter-day and intra-day accuracy of quality control
samples (QCs) below 15 %. It was also precise with inter-day and intra-day coefficient of variation below 15
%. The lower limit of quantification (LLOQ) was 0.2 ng/mL for all analytes except tramadol and its
metabolites, where the LLOQ was 10 ng/mL. Recovery was greater than 88 % for all analytes, except for Odesmethyltramadol (81 %). Analytes were stable over four freeze-thaw cycles, for 24 h on the bench top and
for 24 h post-preparation. The inter- and intra-day variability of concentrations determined in blood and
plasma were within 84-124%, whereas the inter- and intra-day variability for blood samples prepared using
volumetric absorptive micro-sampling (VAMS) compared to those prepared from whole blood ranged
between 83-122%. CONCLUSION: A LC-MS/MS method is described that is able to accurately and precisely
quantify a number of commonly prescribed opioids and their major metabolites in plasma and whole blood,
Alsousou, J., S. M. McDonnell and J. Elo (2010). "A simple cost effective technique
for soft tissue protection during intramedullary nailing of the tibia." Acta Orthop Belg
76(6): 827-829.
Alswaitti, M., M. K. Ishak and N. A. M. Isa (2018). "Optimized gravitational-based
data clustering algorithm." Engineering Applications of Artificial Intelligence 73: 126148.
Intramedullary nailing has revolutionized the management of tibial diaphyseal fractures. However, anterior
knee pain remains a common complication. Although knee pain causes are still largely unknown, there is
evidence to suggest that adhesions resulting from soft tissue damage may contribute to it. We describe a
simple cost-effective technique that utilises a syringe to protect the patellar ligament and Hoffa's fat pad
during intramedullary nailing of the tibia.
Gravitational clustering is a nature-inspired and heuristic-based technique. The performance of nature-inspired
algorithms relies on the balance achieved between exploitation and exploration. A modification over a data
clustering algorithm based on the universal gravity rule is proposed in this paper. Although gravitational
clustering algorithm has a high exploration ability, it lacks a proper exploitation mechanism because of the
impulsive velocity of agents that search the solution space, which leads to the huge step size of agent positions
through iterations. This study proposes the following solutions to impose a balance between exploitation and
exploration: (i) the dependence of the agent on velocity history is removed to avoid high velocity caused by
accumulating previous velocities, and (ii) an initialization step of centroid positions is added using the
variance and median initialization method with a predefined number of clusters. The initialization step
eliminates the effects of random initialization and subrogates the exploration process. Experiments are
conducted using 13 benchmark datasets from the UCI machine learning repository. In addition, the proposed
algorithm is tested on two case studies using the electrical hotspots and cervical cell datasets. The
performance of the proposed clustering algorithm is compared qualitatively and quantitatively with several
state-of-the-art clustering algorithms. The obtained results indicate that the proposed clustering algorithm
outperforms conventional techniques. Furthermore, the clusters obtained using the proposed algorithm are
more homogeneous than those obtained using conventional techniques. The proposed algorithm quantitatively
Altomare, M., et al. (2019). "Acute appendicitis. Update of clinical scores." Ann Ital
Chir 90: 231-237.
OBJECTIVES: Evaluate Alvarado Score's (AS) accuracy related with C-reactive protein (CRP). Evaluate the
accuracy rate of ultrasonography (US). MATERIALS AND METHODS: We analyzed data on 290 patients
admitted to Emergency Department (ED) of Sant'Andrea Hospital (Rome - Italy) presenting abdominal pain in
lower quadrants between Jan2009-Apr2015. AS, laboratory tests, images and report from CT-scan and US
were collected. Histological examination is considered as Gold Standard. We calculated Specificity(Sp),
Sensitivity(Se), Accuracy(Ac), positive predictive value(PPV), and negative predictive value(NPV). We use
Exact Fisher Test (EFT) for samples less than 50 units, and Chi square test (χ2). CRP were assessed as
possible laboratory marker to be added to AS. RESULTS: Two hundred and forty patients (82%) were
enrolled following the inclusion criteria. The variations obtained from the AS with C-reactive protein show no
difference. CT-scan vs US results show a higher Sp for US despite CT (p= 0.0509 χ2=3.803. Se and NPV are
higher in CT compared to the US (Se: p=0.000315 χ2= 12.88 NVP: p=0.015. We evaluated Ac of US and CT
within the individual groups (low(L), Intermediate(I), High(H): L; 37 patients show no statistically significant
difference (EFT=1; p>0.05). I: show superiority of CT-scan in Se and NPV (FE:0.0162 p<0.05; FE:0.0432
p<0.05). Regarding H only Se show an acceptable p-value (p<0.0021). CONCLUSION: Alvarado score (AS)
can be used as the first diagnostic approach in the diagnosis of acute appendicitis (AA). Ultrasound must be
considered the first level instrumental examination; necessary and sufficient in low risk patients (0-3 pt) to
exclude, with a high reliability rate, the diagnosis of acute appendicitis. KEY WORDS: Acute Appendicitis,
Álvaro-Gracia, J. M., et al. (2017). "Intravenous administration of expanded
allogeneic adipose-derived mesenchymal stem cells in refractory rheumatoid arthritis
(Cx611): results of a multicentre, dose escalation, randomised, single-blind, placebocontrolled phase Ib/IIa clinical trial." Ann Rheum Dis 76(1): 196-202.
Aly, A. K., et al. (2023). "Stent Graft Placement for the Treatment of Hepatic Artery
Injury in Patients with Cancer: Primary Patency and Clinical Outcomes." Journal of
Vascular and Interventional Radiology 34(1): 79-85.e71.
OBJECTIVES: To evaluate the safety and tolerability of the intravenous administration of Cx611, a
preparation of allogeneic expanded adipose-derived stem cells (eASCs), in patients with refractory rheumatoid
arthritis (RA), as well as to obtain preliminary clinical efficacy data in this population. METHODS: It is a
multicentre, dose escalation, randomised, single-blind (double-blind for efficacy), placebo-controlled, phase
Ib/IIa clinical trial. Patients with active refractory RA (failure to at least two biologicals) were randomised to
receive three intravenous infusions of Cx611: 1 million/kg (cohort A), 2 million/kg (cohort B), 4 million/kg
(cohort C) or placebo, on days 1, 8 and 15, and they were followed for therapy assessment for 24 weeks.
RESULTS: Fifty-three patients were treated (20 in cohort A, 20 in cohort B, 6 in cohort C and 7 in placebo
group). A total of 141 adverse events (AEs) were reported. Seventeen patients from the group A (85%), 15
from the group B (75%), 6 from the group C (100%) and 4 from the placebo group (57%) experienced at least
one AE.Eight AEs from 6 patients were grade 3 in intensity (severe), 5 in cohort A (lacunar infarction,
diarrhoea, tendon rupture, rheumatoid nodule and arthritis), 2 in cohort B (sciatica and RA) and 1 in the
placebo group (asthenia). Only one of the grade 3 AEs was serious (the lacunar infarction). American College
of Rheumatology 20 responses for cohorts A, B, C and placebo were 45%, 20%, 33% and 29%, respectively,
at month 1, and 25%, 15%, 17% and 0%, respectively, at month 3. CONCLUSIONS: The intravenous
infusion of Cx611 was in general well tolerated, without evidence of dose-related toxicity at the dose range
and time period studied. In addition, a trend for clinical efficacy was observed. These data, in our opinion,
justify further investigation of this innovative therapy in patients with RA. TRIAL REGISTRATION
Purpose To evaluate the safety, primary patency, and clinical outcomes of hepatic artery stent graft (SG)
placement for vascular injuries. Materials and Methods Patients treated with hepatic arterial SG placement for
vascular injuries between September 2018 and September 2021 were reviewed. Data on demographic
characteristics, indication, stent graft characteristics, antiplatelet/anticoagulant use, clinical success rate,
complications, and type of follow-up imaging were collected. Follow-up images were reviewed by 2
independent reviewers to assess primary patency. A time-to-event analysis was performed. The median
duration of stent graft patency was estimated using Kaplan-Meier curves. A Cox proportional hazard model
was used to evaluate factors related to stent graft patency. Results Thirty-five patients were treated with
hepatic arterial SG placement, 11 for postoperative bleeds and 24 for hepatic artery infusion pump
catheter–related complications. Clinical success was achieved in 32 (91%) patients (95% CI, 77–98). The
median primary patency was 87 days (95% CI, 73–293). Stent grafts of ≥6-mm diameter retained patency for a
longer duration than that with stent grafts of smaller diameters (6 mm vs 5 mm; hazard ratio, 0.35; 95% CI,
0.14–0.88; P = .026; and 7+ mm vs 5 mm; hazard ratio, 0.27; 95% CI, 0.09–0.83; P = .023).
Anticoagulation/antiplatelet regimen was not associated with increased stent graft patency duration (P > .05).
Only minor complications were reported in 2 (5.7%) patients. Conclusions Stent grafts can be used safely and
effectively to treat injuries of the hepatic artery. Stent graft diameters of ≥6 mm seem to provide more durable
Alzubi, J. A. (2021). "Blockchain-based Lamport Merkle Digital Signature:
Authentication tool in IoT healthcare." Computer Communications 170: 200-208.
Internet of Things (IoT) includes medical devices, servers, and applications linked using computer networks to
collect and share data. Recently there is a massive surge in IoT-enabled applications, especially in the medical
field. Medical devices, like intravenous pumps, Magnetic Resonance Imaging (MRI) machines, infusion
pumps, and ventilators, are connected with the hospital networks to enhance the quality and efficiency of
delivering medical care. Integrated with the cloud server, IoT improves patients’ lifestyles and minimizes the
time and cost by efficiently managing the medical resources. However, due to the presence of malicious users,
sensitive patient data is often compromised. Motivated and driven by these factors, this work proposes a
blockchain-assisted highly secure system for medical IoT devices using Lamport Merkle Digital Signature
(LMDS). Initially, the Lamport Merkle Digital Signature Generation (LMDSG) model performs the task of
authenticating IoT devices by constructing a tree in which the leaves symbolize sensitive patient medical
data’s hash function. Further, a Centralized Healthcare Controller (CHC) performs the task of determining the
root of the LMDSG by using Lamport Merkle Digital Signature Verification (LMDSV). In this verification
process, when the hash of the public key ‘pbkey′ is equal to leaf ‘Pgn’, then it is the root of the tree, and the
signature is valid. In this way, the proposed LMDS technique efficiently identifies malicious user behavior
with minimum Computational Overhead (CO) and Computational Time (CT). The proposed LMDS
technique’s performance is analyzed in terms of CO, CT, and authentication accuracy. The experimental
analysis proves that the proposed LMDS technique ensures higher security and minimum CT and CO in
Anderst, W. J. (2015). "Bootstrap prediction bands for cervical spine intervertebral
kinematics during in vivo three-dimensional head movements." J Biomech 48(7):
1270-1276.
Anderst, W. J., et al. (2014). "In vivo cervical facet joint capsule deformation during
flexion-extension." Spine (Phila Pa 1976) 39(8): E514-520.
There is substantial inter-subject variability in intervertebral range of motion (ROM) in the cervical spine.
This makes it difficult to define "normal" ROM, and to assess the effects of age, injury, and surgical
procedures on spine kinematics. The objective of this study was to define normal intervertebral kinematics in
the cervical spine during dynamic functional loading. Twenty-nine participants performed dynamic
flexion\extension, axial rotation, and lateral bending while biplane radiographs were collected at 30 images/s.
Vertebral motion was tracked with sub-millimeter accuracy using a validated volumetric model-based tracking
process that matched subject-specific CT-based bone models to the radiographs. Gaussian point-by-point and
bootstrap techniques were used to determine 90% prediction bands for the intervertebral kinematic curves at
1% intervals of each movement cycle. Cross validation was performed to estimate the true achieved coverage
for each method. For a targeted coverage of 90%, the estimated true coverage using bootstrap prediction bands
averaged 86±5%, while the estimated true coverage using Gaussian point-by-point intervals averaged 56±10%
over all movements and all motion segments. Bootstrap prediction bands are recommended as the standard for
evaluating full ROM cervical spine kinematic curves. The data presented here can be used to identify
abnormal motion in patients presenting with neck pain, to drive computational models, and to assess the
biofidelity of in vitro loading paradigms.
STUDY DESIGN: Nonrandomized controlled cohort. OBJECTIVE: To characterize subaxial cervical facet
joint kinematics and facet joint capsule (FJC) deformation during in vivo, dynamic flexion-extension. To
assess the effect of single-level anterior arthrodesis on adjacent segment FJC deformation. SUMMARY OF
BACKGROUND DATA: The cervical facet joint has been identified as the most common source of neck
pain, and it is thought to play a role in chronic neck pain related to whiplash injury. Our current knowledge of
cervical facet joint kinematics is based on cadaveric mechanical testing. METHODS: Fourteen asymptomatic
controls and 9 C5-C6 arthrodesis patients performed full range of motion flexion-extension while biplane
radiographs were collected at 30 Hz. A volumetric model-based tracking process determined 3-dimensional
vertebral position with submillimeter accuracy. FJC fibers were modeled and grouped into anterior, lateral,
posterior-lateral, posterior, and posterior-medial regions. FJC fiber deformations (total, shear, and
compression-distraction) relative to the static position were determined for each cervical motion segment (C2C3 through C6-C7) during flexion-extension. RESULTS: No significant differences in the rate of fiber
deformation in flexion were identified among motion segments (P = 0.159); however, significant differences
were observed among fiber regions (P < 0.001). Significant differences in the rate of fiber deformation in
extension were identified among motion segments (P < 0.001) and among fiber regions (P = 0.001). The rate
of FJC deformation in extension adjacent to the arthrodesis was 45% less than that in corresponding motion
segments in control subjects (P = 0.001). CONCLUSION: In control subjects, FJC deformations are
significantly different among vertebral levels and capsule regions when vertebrae are in an extended
orientation. In a flexed orientation, FJC deformations are different only among capsule regions. Single-level
anterior arthrodesis is associated with significantly less FJC deformation adjacent to the arthrodesis when the
Anderst, W. J., et al. (2018). "Intervertebral kinematics of the cervical spine before,
during, and after high-velocity low-amplitude manipulation." Spine J 18(12): 23332342.
BACKGROUND CONTEXT: Neck pain is one of the most commonly reported symptoms in primary care
settings, and a major contributor to health-care costs. Cervical manipulation is a common and clinically
effective intervention for neck pain. However, the in vivo biomechanics of manipulation are unknown due to
previous challenges with accurately measuring intervertebral kinematics in vivo during the manipulation.
PURPOSE: The objectives were to characterize manual forces and facet joint gapping during cervical spine
manipulation and to assess changes in clinical and functional outcomes after manipulation. It was
hypothesized that patient-reported pain would decrease and intervertebral range of motion (ROM) would
increase after manipulation. STUDY DESIGN/SETTING: Laboratory-based prospective observational study.
PATIENT SAMPLE: 12 patients with acute mechanical neck pain (4 men and 8 women; average age 40 ± 15
years). OUTCOME MEASURES: Amount and rate of cervical facet joint gapping during manipulation,
amount and rate of force applied during manipulation, change in active intervertebral ROM from before to
after manipulation, and numeric pain rating scale (NPRS) to measure change in pain after manipulation.
METHODS: Initially, all participants completed a NPRS (0-10). Participants then performed full ROM
flexion-extension, rotation, and lateral bending while seated within a custom biplane radiography system.
Synchronized biplane radiographs were collected at 30 images/s for 3 seconds during each movement trial.
Next, synchronized, 2.0-milliseconds duration pulsed biplane radiographs were collected at 160 images/s for
0.8 seconds during the manipulation. The manipulation was performed by a licensed chiropractor using an
articular pillar push technique. For the final five participants, two pressure sensors placed on the thumb of the
chiropractor (Novel pliance system) recorded pressure at 160 Hz. After manipulation, all participants repeated
the full ROM movement testing and once again completed the NPRS. A validated volumetric model-based
tracking process that matched subject-specific bone models (from computed tomography) to the biplane
radiographs was used to track bone motion with submillimeter accuracy. Facet joint gapping was calculated as
the average distance between adjacent articular facet surfaces. Pre- to postmanipulation changes were assessed
using the Wilcoxon signed-rank test. RESULTS: The facet gap increased 0.9 ± 0.40 mm during manipulation.
The average rate of facet gapping was 6.2 ± 3.9 mm/s. The peak force and rate of force application during
manipulation were 65 ± 4 N and 440 ± 58 N/s. Pain score improved from 3.7 ± 1.2 before manipulation to 2.0
± 1.4 after manipulation (p <. 001). Intervertebral ROM increased after manipulation by 1.2° (p = .006), 2.1°
(p = .01), and 3.9° (p = .003) at the C4/C5, C5/C6, and C6/C7 motion segments, respectively, during flexionAnger, K. E., et al. (2014). "Safety of compounded calcium chloride admixtures for
peripheral intravenous administration in the setting of a calcium gluconate shortage." J
Pharm Pract 27(5): 474-477.
Calcium gluconate is preferred over calcium chloride for intravenous (IV) repletion of calcium deficiencies in
the inpatient setting. In the setting of a national shortage of IV calcium gluconate, our institution implemented
a compounded calcium chloride admixture for IV administration. The objective of this analysis is to evaluate
the peripheral infusion site safety of compounded IV calcium chloride admixtures in adult inpatients. A total
of 222 patients, encompassing 224 inpatient admissions, from April to June 2011 were retrospectively
reviewed. Sterile preparations of calcium chloride in 5% dextrose (600 mg/250 mL and 300 mg/100 mL) were
used during the study time period. Adverse infusion site reactions were assessed using an institutional
infiltration and phlebitis grading system. A total of 333 doses were administered peripherally. In all, 4 (1.8%)
patients experienced a moderate to severe infusion site reaction, with 3 due to phlebitis and 1 due to
infiltration. Naranjo Nomogram for Adverse Drug Reaction Assessment classified all 4 reactions to have a
possible link to calcium chloride administration. Peripheral administration of compounded calcium chloride
admixtures in 5% dextrose is associated with a low incidence of IV infusion site reactions and can be
considered as an alternative in the event of a calcium gluconate shortage.
Aoki, Y., et al. (2022). "Effects of fentanyl administration in mechanically ventilated
patients in the intensive care unit: a systematic review and meta-analysis." BMC
Anesthesiol 22(1): 323.
BACKGROUND: Fentanyl is selected to manage pain in critical care patients on mechanical ventilation in the
intensive care unit (ICU). However, the usefulness of fentanyl compared with other opioids is unknown. This
study examined the evidence for using fentanyl to improve the clinical outcomes of ICU patients, using the
Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. METHODS: We
searched the MEDLINE, Cochrane Central Register of Controlled Trials, and Igaku Chuo Zasshi databases in
June 2021. Two independent assessors reviewed studies to identify randomized, controlled trials (RCTs) that
compared the intravenous administration of fentanyl and other opioids in mechanically ventilated patients in
the ICU. The study quality was assessed using the GRADE system and Cochrane methodology. The primary
outcome was mortality. The secondary outcomes were the duration of mechanical ventilation, duration of the
ICU stay, incidence of severe adverse events, and incidence of delirium. We integrated outcome data using a
random-effects model and showed absolute values and certainty of evidence in the GRADE evidence profile.
RESULTS: Seven RCTs met the study inclusion criteria with 534 patients (251 were treated with fentanyl and
283 with other opioids, including 242 with remifentanil and 41 with morphine). Among 191 participants from
2 RCTs, fentanyl was not associated with mortality (risk ratio [RR], 0.79; 95% confidence interval [CI], 0.24
to 2.60; low-quality evidence). Regarding the secondary outcomes, fentanyl did not shorten the duration of
mechanical ventilation (mean difference, 0.49 h; 95% CI, - 0.90 to 1.88; moderate-quality evidence) or the
duration of the ICU stay (mean difference, 7.04 h; 95% CI, - 3.27 to 17.35; moderate-quality evidence)
compared with other opioids. Fentanyl did not increase the incidence of severe adverse events (RR, 0.98; 95%
CI, 0.50 to 1.90; low-quality evidence) or delirium (RR, 1.27; 95% CI, 0.79 to 2.04; low-quality evidence).
CONCLUSIONS: Although fentanyl is a frequently administered opioid in the ICU, patients' outcomes are not
different between fentanyl use and use of other opioids. However, the GRADE evaluation provides little
certainty to support the results of this systematic review. Therefore, further large RCTs are required to
confirm our conclusions. TRIAL REGISTRATION: PROSPERO, CRD42019130648 (
Ardila, C. M., G. A. Jiménez-Arbeláez and A. M. Vivares-Builes (2023).
"Perioperative analgesic efficacy and adverse events of fentanyl in dentistry: A
systematic review." Oral Dis.
Arthur, J. R., et al. (2020). "Intraosseous Regional Administration of Antibiotic
Prophylaxis in Total Knee Arthroplasty." JBJS Essent Surg Tech 10(4).
OBJECTIVES: To assess the efficacy and adverse events linked to the utilization of fentanyl for perioperative
pain management in dentistry. METHODS: This systematic review of randomized clinical trials (RCTs)
adhered to the PRISMA guidelines and incorporated various databases. RESULTS: Eleven RCTs studying
674 patients were analyzed. Perioperative pain was predominantly evaluated in patients undergoing surgery
for impacted molars, although some studies also included patients with other conditions such as oral
submucous fibrosis, maxillary cancer, bony temporomandibular joint ankylosis, irreversible pulpitis, among
others. Combined with dexmedetomidine, fentanyl produced enhanced analgesic effects. It demonstrated
comparable efficacy when compared to nefopam and nalbuphine. Both intranasal and intravenous
administration routes proved equally effective. In four RCTs, the transdermal fentanyl patch outperformed the
control group, except in the clinical trial where it was compared to ropivacaine. The main adverse events
associated with the use of fentanyl included nausea, vomiting, drowsiness, delirium, and respiratory
depression; however, they were like those reported in the comparison groups. CONCLUSIONS: While
fentanyl demonstrated satisfactory perioperative analgesic efficacy, there were other alternatives that
displayed better or comparable outcomes. Due to the risks and potential for misuse of fentanyl, these
alternatives must be considered although adverse events were also reported.
BACKGROUND: Periprosthetic joint infection (PJI) is a devastating complication following total knee
arthroplasty (TKA), and perioperative antibiotics are commonly administered to try to mitigate the chance of
infection. Intraosseous regional administration (IORA) of prophylactic antibiotics during TKA is a method of
antibiotic delivery that has been shown to achieve markedly higher tissue concentrations at much lower doses.
Other advantages include ease of administration, ability to time the antibiotic delivery with the surgical start
time for maximal effectiveness, and less systemic side effects. The concept is similar to a Bier block, except
that IORA involves the use of antibiotics instead of local anesthetic to perfuse the limb and is given via
intraosseous rather than intravenous access. DESCRIPTION: After standard patient preparation and draping,
the tourniquet is inflated and an intraosseous needle is inserted into the proximal medial face of the tibia, just
medial and slightly above the level of the tubercle. A large syringe containing the desired antibiotic (typically
500 mg vancomycin suspended in normal saline solution) is connected to the needle and the solution is
administered over 1 to 2 minutes. The intraosseous needle can then be removed and the surgical procedure
proceeds as it normally would per surgeon preference and technique. ALTERNATIVES: Systemic
administration of intravenous antibiotics, vancomycin powder, and antibiotic-impregnated cement are
alternative options that can be utilized during TKA. RATIONALE: IORA has several distinct advantages over
other methods of antibiotic delivery, including the ability to (1) deliver antibiotic directly to the surgical bed
and avoid systemic delivery, (2) precisely time and quickly administer antibiotics to achieve highest
concentrations at the start of and throughout the surgical procedure, and (3) avoid several common and
potentially serious side effects, especially those associated with antibiotics such as vancomycin. EXPECTED
OUTCOMES: This technique for antibiotic delivery achieves markedly higher tissue concentrations compared
with systemic administration, without prolonged preoperative infusion times. Intraosseous delivery optimizes
timing and reduces the risk of systemic side effects while simultaneously providing equal or enhanced
antibiotic prophylaxis in TKA. This delivery mechanism is especially useful in patients who are at high risk
for infection and in the revision TKA setting. Further, there is little to no additional risk and the use of this
method does not substantially prolong operative time. IMPORTANT TIPS: The proximal aspect of the tibia is
the optimal injection site because the cortex is thinner in this region, making needle insertion easier.
Additionally, the metaphyseal bone allows faster flow rates for the infusion. We have found that insertions
made slightly more proximally are easier and have faster flow rates. Of note, although the antibiotic is infused
Arun-Kumar, V. and J. Naresh-Babu (2021). "Is There a Role for Preoperative Local
Infiltration of Tranexamic Acid in Elective Spine Surgery? A Prospective Randomized
Controlled Trial Analyzing the Efficacy of Intravenous, Local Infiltration, and Topical
Administration of Tranexamic Acid." Global Spine J 11(1): 21-27.
STUDY DESIGN: Randomized control trial. OBJECTIVE: The purpose of the study is to evaluate the safety
and efficacy of tranexamic acid in reducing blood loss when administered through various routes in
instrumented spine surgeries. METHODS: A total of 104 patients undergoing instrumented spine surgery
were randomly assigned to 4 groups (n = 26 in each group). Groups included (1) ivTXA-intravenous
administration of tranexamic acid (TXA) 1 hour prior to surgery, (2) loTXA-local infiltration of TXA
bilaterally into the paraspinal musculature prior to incision, (3) tTXA-topical application of TXA just before
wound closure, and (4) control group. Outcome measures included intraoperative blood loss, postoperative
blood loss, need for blood transfusion, length of hospital stay, and hematological parameters. RESULTS: All
the 3 different modes of TXA administration were found to be effective in reducing blood loss in the treated
groups compared with the control group. Intraoperative blood loss was significantly reduced in ivTXA (223.6
± 40.1 mL, P < .0001) and loTXA (256.07 ± 119 mL, P = .0039) groups when compared with controls (344 ±
88.5 mL).The postoperative blood loss was least in tTXA followed by ivTXA, loTXA, and controls. There
was 67% reduction in need for blood transfusion in tTXA group, 55.5% reduction in ivTXA group, and 33%
reduction in loTXA group when compared with the control group. CONCLUSION: In instrumented spine
surgery, ivTXA and loTXA were found to be equally effective in reducing the intraoperative blood loss. The
tTXA has better postoperative blood conserving effects. This is the first study to detail about safety and
efficacy on local infiltration of TXA in spine surgery, which is an effective and safe method for reducing
Asadov, C., et al. (2018). "β-Thalassemia intermedia: a comprehensive overview and
novel approaches." Int J Hematol 108(1): 5-21.
Attia, S., et al. (2022). "Pain perception following computer-controlled versus
conventional dental anesthesia: randomized controlled trial." BMC Oral Health 22(1):
425.
β-Thalassemia intermedia is a clinical condition of intermediate gravity between β-thalassemia minor, the
asymptomatic carrier, and β-thalassemia major, the transfusion-dependent severe anemia. It is characterized
by a significant clinical polymorphism, which is attributable to its genetic heterogeneity. Ineffective
erythropoiesis, chronic anemia, and iron overload contribute to the clinical complications of thalassemia
intermedia through stepwise pathophysiological mechanisms. These complications, including splenomegaly,
extramedullary erythropoiesis, iron accumulation, leg ulcers, thrombophilia, and bone abnormalities can be
managed via fetal hemoglobin induction, occasional transfusions, chelation, and in some cases, stem cell
transplantation. Given its clinical diversity, thalassemia intermedia patients require tailored approaches to
therapy. Here we present an overview and novel approaches to the genetic basis, pathophysiological
mechanisms, clinical complications, and optimal management of thalassemia intermedia.
BACKGROUND: The administration of local anesthesia (LA) in dental practice requires an injection which is
the leading cause of patients' fear and anxiety. Computer-controlled local anesthetic injector, designed to
reduce the pain of performing local anesthesia by controlling the speed of injection. This single-blind
randomised control trial aimed to compare the pain perception after computer-controlled local anesthesia
(CCLA) and conventional LA. METHODS: Dental students were both test and operator group versus an
experienced dentist as additional operator of the LA. Data were collected regarding gender, age, medical
condition, smoking habits. Additionally, operator feedback about the handling, pain at insertion and during
infiltration, excitement (Dental Anxiety Scale), and complications were assessed. RESULTS: Out of the 60
included participants, the majority were females (n = 41; 68.3%), medically healthy (n = 54; 90%), and did not
receive medications (n = 54; 90%). While the participating students administered 62 (51.7%) injections, the
experienced dentist administered 58 (48.3%) injections. The difference in pain perception on puncture
between CCLA and conventional injections was not statistically significant (Sig. = 0.285); however, pain
perception during injection was significantly different (Sig. = 0.029) between CCLA (1.65 ± 1.93) and
conventional injections (2.49 ± 2.31). CONCLUSION: The professional experience influenced the pain
perception while applying the LA. CCLA did not reduce pain on puncture significantly; however, pain
perception during the injection was significantly reduced in the case of using CCLA devices compared to the
Aubrun, F., et al. (2018). "Opioid-related genetic polymorphisms do not influence
postoperative opioid requirement: A prospective observational study." Eur J
Anaesthesiol 35(7): 496-504.
BACKGROUND: Among the various factors that may influence the pharmacological response to opioids,
genetic polymorphisms [single nucleotide polymorphisms (SNP)] have generated some interest.
OBJECTIVES: To examine the influence on morphine dose requirements and adverse events in the
postoperative period of four SNP [opioid receptor mu1 (OPRM1), ATP-binding cassette subfamily B, member
1 (ABCB1) ex-21 and ex-26, catechol-o-methyltransferase (COMT)] in candidate genes involved in morphine
pharmacodynamics and pharmacokinetics. DESIGN: A single centre prospective study. SETTING: University
Hospital, Paris, France, from 2 January 2007 to 15 November 2011. PATIENTS: A total of 438 white adults
scheduled for major orthopaedic surgery (spine, hip and knee) under general anaesthesia. The main exclusion
criteria were receiving opioids for chronic pain, nonopioid drugs within 2 days prior to surgery, pregnancy,
renal insufficiency, sleep apnoea obstruction syndrome, morbid obesity, severe hepatic impairment, cognitive
dysfunction. INTERVENTIONS: Assays of plasma concentrations of morphine and metabolites (morphine 3glucuronide and morphine 6-glucuronide) were performed and common polymorphisms in four candidate
genes [OPRM1 A118G rs1799971; P-glycoprotein (ABCB1) T3435C (rs1045642) and G2677T/A
(rs2032582); COMT Val 158 Met (rs4680)] were analysed.Morphine was titrated by staff in the
postanaesthesia care unit (PACU) and in the ward patient-controlled intravenous analgesia was used for 24 h.
MAIN OUTCOME MEASURES: The dose of morphine required to achieve pain relief and the influence of
SNP in genes involved in morphine pharmacodynamics and kinetics on morphine dose requirements.
Secondary endpoints were the concentrations of morphine, morphine 6-glucuronide and morphine 3gluguronide, the proportion of patients requiring a rescue analgesic and the proportion of morphine-related
adverse events. RESULTS: A total of 404 patients completed the study to final analysis. The mean ± SD
morphine dose to achieve pain relief was 15.8 ± 8.8 mg in the PACU and 22.7 ± 18.6 mg during patientcontrolled intravenous administration. Morphine-related adverse events were observed in 37%. There was no
relationship between any genetic polymorphisms and morphine dose, morphine 3-gluguronide and morphine
6-glucuronide concentration, morphine-related adverse events or pain level. In the PACU only, P-glycoprotein
polymorphisms (ex-21; ex-26) were significantly associated with morphine concentration but the prediction of
the model was poor (R = 0.04) CONCLUSION: No major relationship has been demonstrated between SNP of
OPRM1, ABCB1, COMT and morphine requirement, pain level or adverse effects in the postoperative period.
Avery, L. M., et al. (2019). "Assessment of the Physical Compatibility of Eravacycline
and Common Parenteral Drugs During Simulated Y-site Administration." Clin Ther
41(10): 2162-2170.
PURPOSE: Eravacycline is a broad-spectrum, intravenous fluorocycline antibiotic approved for the treatment
of complicated intra-abdominal infections in adults. A 60-minute infusion is recommended for each infused
dose. Compatibility data that may allow convenient Y-site administration of eravacycline with other parenteral
medications are unavailable. We aimed to determine the physical compatibility of eravacycline with other
intravenous medications by simulated Y-site administration. METHODS: Eravacycline was reconstituted
according to published prescribing information and diluted with 0.9% sodium chloride to a concentration of
0.6 mg/mL. Simulated Y-site administration was performed by mixing 5 mL of eravacycline with an equal
volume of 51 other intravenous medications, including crystalloid and carbohydrate hydration fluids and 20
antimicrobials. Secondary medications were assessed at the upper range of concentrations considered standard
for intravenous infusion. Mixtures underwent visual inspection and turbidity measurement immediately on
mixture and at 3 subsequent time points (30, 60, and 120 minutes after admixture), and pH was measured at
60 minutes for comparison with the baseline value of the secondary medication. FINDINGS: Eravacycline
was physically compatible with 41 parenteral drugs (80%) by simulated Y-site administration. Incompatibility
was observed with albumin, amiodarone hydrochloride, ceftaroline fosamil, colistimethate sodium,
furosemide, meropenem, meropenem/vaborbactam, micafungin sodium, propofol, and sodium bicarbonate.
IMPLICATIONS: Eravacycline for injection was physically compatible with most parenteral medications
assessed. Pharmacists and nurses should be knowledgeable of the observed incompatibilities with
Babu, K. G., et al. (2019). "Modified Epirubicin, cisplatin, and 5-FU regimen as firstline chemotherapy in metastatic gastric or gastroesophageal junction adenocarcinoma:
A Phase II study." South Asian J Cancer 8(2): 85-87.
BACKGROUND: Epirubicin, cisplatin, and 5-FU (ECF) is one of the most commonly used first-line
chemotherapy regimens in metastatic gastric cancer. However, due to protracted infusion schedule, need for
special infusion pumps, and catheter-related complications, the practical utility and acceptability of standard
ECF regimen are limited, particularly in resource-constrained settings including India. MATERIALS AND
METHODS: In the present study, we have used a more convenient modification of the standard ECF protocol
(using 5 days intravenous infusion of 5-FU at a dose of 750 mg/m(2)/day, given over 6 h through a peripheral
venous line), in Indian patients with metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma.
The primary endpoint was overall survival (OS). The secondary endpoints were overall response rate (ORR),
progression-free survival (PFS), and toxicity profile. RESULTS: Between January 2014 and December 2017,
107 patients were assigned and treated with this modified ECF regimen. The median age was 52 years (range,
34-62); 66.3% were males and 36.5% of the patients had ≥ 3 metastatic disease site involvement at baseline.
Dose reductions due to toxicity were required in 14.9% of the patients. The ORR was 32.7%; median PFS and
OS were 5.9 months (95% confidence interval [CI]: 4.7-6.9) and 10.4 months (95% CI: 8.4-11.8),
respectively. Both the hematological and nonhematological toxicities were manageable, and there was no
toxicity-related death. The most frequent Grade 3-4 adverse events were neutropenia (18.7%), febrile
neutropenia (13.1%), mucositis (5.6%), and diarrhea (5.6%). CONCLUSIONS: In the present study, the
modified ECF regimen demonstrated significant efficacy with an acceptable toxicity profile in Indian patients
with metastatic gastric and GEJ adenocarcinoma. The survival outcomes of this modified schedule were
comparable with those of the standard ECF regimen, as reported earlier. Clearly, this modified and more
convenient ECF protocol should be explored and validated through large prospective randomized trials.
Bagher, S. M., et al. (2023). "The Effect of Using a Camouflaged Dental Syringe on
Children's Anxiety and Behavioral Pain." Cureus 15(12): e50023.
BACKGROUND: Seeing a dental syringe can be terrifying, especially for young children, and hiding it during
local anesthesia (LA) administration can sometimes be challenging for the pediatric dentist. OBJECTIVE: To
assess the effect of a camouflaged dental syringe on children's anxiety and behavioral pain in comparison to
the traditional dental syringe during local anesthesia administration in pediatric patients. MATERIALS AND
METHODS: This randomized clinical trial included cooperative and healthy 6- to 10-year-old children
scheduled for non-urgent dental treatment that required buccal infiltration anesthesia (BIA) in the maxillary
arch. The subjects were randomized into either the test or the control groups. In the test group, subjects
received BIA using the camouflaged dental syringe. Subjects in the control group received the BIA using a
traditional dental syringe. A single-trained dentist administered all the anesthesia. Heart rate (HR) was
monitored at three different time points (before, during, and after) the BIA administration. Subjects' anxiety
and behavioral pain were measured using Venham's Anxiety Rating Scale (VARS) and the Face, Leg,
Activity, Cry, and Consolability (FLACC) scale, respectively, by two trained and calibrated investigators.
RESULTS: A total of 60 subjects with a mean age of 8.3 ±1.3 years were included. The scores of the VARS
in the subjects in the camouflaged group were somewhat lower than the subjects in the traditional group, but
the observed difference did not reach statistical significance (P=0.113). However, subjects in the camouflaged
group showed significantly lower FLACC scores compared to the traditional group (P=0.034).
CONCLUSION: The utilization of a camouflaged dental syringe is effective in improving children's behavior
Bajwa, S. J. S., et al. (2023). "Recent advancements in total intravenous anaesthesia
and anaesthetic pharmacology." Indian J Anaesth 67(1): 56-62.
Baker, E. K., et al. (2021). "A protocol for cell therapy infusion in neonates." Stem
Cells Transl Med 10(5): 773-780.
Target-controlled infusion pumps and depth of anaesthesia monitors have made total intravenous anaesthesia
(TIVA) easy, safe, and precise. The merits of TIVA were highlighted during the coronavirus disease 2019
(COVID-19) pandemic, confirming its potential further in the post-COVID clinical practice as well. Ciprofol
and remimazolam are newer drugs that are being tried with a hope to upgrade the practice of TIVA. While
research on safe and effective drugs continues, TIVA is being practised with a combination of drugs and
adjuncts to overcome the disadvantages of each and to provide complete and balanced anaesthesia with
additional benefits in recovery and pain relief postoperatively. Modulation of TIVA for the special population
groups is still under process. Advancement in digital technology with mobile apps has increased the scope of
TIVA in day-to-day use. The formulation and update of guidelines can establish a safe and efficient practice
of TIVA.
Baker, J. F., et al. (2023). "Corticosteroid Injections for Symptomatic Treatment of
Osteoarthritis of the Knee: A Pilot Blinded Randomized Trial." ACR Open Rheumatol
5(10): 529-535.
Balogh, O., et al. (2017). "The use of semi-quantitative tests at Cesarean section
delivery for the differentiation of canine fetal fluids from maternal urine on the basis
of biochemical characteristics." Theriogenology 88: 174-182.
Cell therapies for neonatal morbidities are progressing to early phase clinical trials. However, protocols for
intravenous (IV) delivery of cell therapies to infants have not been evaluated. It has been assumed the cell
dose prescribed is the dose delivered. Early in our clinical trial of human amnion epithelial cells (hAECs), we
observed cells settling in the syringe and IV tubing used to deliver the suspension. The effect on dose delivery
was unknown. We aimed to quantify this observation and determine an optimal protocol for IV delivery of
hAECs to extremely preterm infants. A standard pediatric infusion protocol was modeled in the laboratory. A
syringe pump delivered the hAEC suspension over 60 minutes via a pediatric blood transfusion set (200-μm
filter and 2.2 mL IV line). The infusion protocol was varied by agitation methods, IV-line volumes (0.2-2.2
mL), albumin concentrations (2% vs 4%), and syringe orientations (horizontal vs vertical) to assess whether
these variables influenced the dose delivered. The influence of flow rate (3-15 mL/h) was assessed after other
variables were optimized. The standard infusion protocol delivered 17.6% ± 9% of the intended hAEC dose.
Increasing albumin concentration to 4%, positioning the syringe and IV line vertically, and decreasing IV-line
volume to 0.6 mL delivered 99.7% ± 13% of the intended hAEC dose. Flow rate did not affect dose delivery.
Cell therapy infusion protocols must be considered. We describe the refinement of a cell infusion protocol that
delivers intended cell doses and could form the basis of future neonatal cell delivery protocols.
OBJECTIVE: To quantify the effect of corticosteroids compared to lidocaine-only injections over 12 weeks
among patients with knee osteoarthritis (KOA). METHODS: Participants with KOA were randomized to
receive a knee injection of methylprednisolone acetate 1 mL (40 mg) plus 2 mL lidocaine (1%) or 1 mL saline
and 2 mL lidocaine. Participants and providers were blinded to treatment allocation using an opacified
syringe. The outcome was the average change from baseline of the total Knee Injury and Osteoarthritis
Outcome Score (KOOS) (range 0-100) assessed at 2-week intervals over 12 weeks. Participants received
KOOS questionnaires on their smartphones through a web-based platform. We used linear mixed-effects
regressions with robust variance estimators to evaluate the association between the intervention and change in
KOOS total and subscales (ClinicalTrials.gov identifier NCT03835910; registered 2019-02-11). RESULTS:
Of the 33 randomized participants, 31 were included in the final analysis. The predicted mean (SE) change in
total KOOS over the 12-week follow-up was 9.4 (3.2) in the corticosteroids arm versus -1.3 (1.4) in the
control arm (P = 0.003). Of participants, 47% achieved change as large as the minimal clinically important
difference (16 units) in the intervention arm compared to 6% of participants in the lidocaine arm. Further,
there were greater improvements in the intervention arm for KOOS subscales and for Patient Reported
Outcomes Measurement Information System (PROMIS) assessments of pain intensity, behavior, and
interference. CONCLUSION: Corticosteroid injections demonstrated clinically meaningful improvements in
KOA symptoms over 12 weeks of follow-up. These data support larger studies to better quantify short-term
In dogs, there is no diagnostic test to identify and differentiate fetal fluids from maternal urine in the event
that a clear–yellowish vulvar discharge is observed pre-whelping. The objective of this study was to find a test
that could easily and accurately identify rupture of the fetal membranes preceding parturition. Maternal urine,
and amniotic fluid (AMF) and allantoic fluid (ALF) from only one fetus per bitch, were collected
intraoperatively during Cesarean section. Specific gravity (SG) was analyzed with a refractometer, whereas
the presence of leukocytes, protein, glucose, ketones, bilirubin, urobilinogen, nitrite, erythrocyte/hemoglobin
(Hb), and the pH were assessed using a urine dipstick (Combur-Test®). Combined calcium and magnesium
(Ca/Mg) content were evaluated with the Total Hardness Test. The AmniSure test, which detects rupture of
fetal membranes in women on the basis of the presence of human placental alpha microglobulin-1, was also
performed on canine AMF, ALF, and urine. Data were analyzed using the Fisher's exact test, Wilcoxon
signed-rank test, and Pearson's correlation. Sensitivity, specificity, and positive and negative likelihood ratios
(LR) were calculated for parameters with significant difference between urine and both fetal fluids. Maternal
urine had higher SG and lower leukocyte, protein, Hb, and Ca/Mg content than AMF and ALF. Glucose was
more often present in AMF (n = 17) and ALF (n = 12) than in urine (n = 1), whereas ketone bodies were
rarely detected in ALF compared with urine. Bilirubin content was higher in urine and ALF than in AMF.
AMF pH was less variable and higher than the pH of ALF or urine. The AmniSure was negative in all samples
tested. Sensitivity and specificity for SG and for the detection of leukocytes, protein, glucose, Hb, Ca/Mg, and
glucose without ketones in urine and fetal fluids were between 42% to 100% and 65% to 100%, respectively.
Best positive LR was achieved for the detection of glucose without ketones and best negative LR for SG of
1.022 or less. In conclusion, the AmniSure test, which is used in humans with high diagnostic accuracy,
cannot identify AMF and ALF in dogs. On the basis of our results in 26 dogs undergoing Cesarean section,
the presence or absence of fetal fluids could be best determined by a positive glucose test without ketone
bodies or by SG higher than 1.022, respectively. These tests may serve as additional tools to recognize
parturition if clear–yellowish vulvar discharge is present in a term pregnant bitch, but their accuracy and
Balwani, M., et al. (2020). "Phase 3 Trial of RNAi Therapeutic Givosiran for Acute
Intermittent Porphyria." N Engl J Med 382(24): 2289-2301.
BACKGROUND: Up-regulation of hepatic delta-aminolevulinic acid synthase 1 (ALAS1), with resultant
accumulation of delta-aminolevulinic acid (ALA) and porphobilinogen, is central to the pathogenesis of acute
attacks and chronic symptoms in acute hepatic porphyria. Givosiran, an RNA interference therapy, inhibits
ALAS1 expression. METHODS: In this double-blind, placebo-controlled, phase 3 trial, we randomly assigned
symptomatic patients with acute hepatic porphyria to receive either subcutaneous givosiran (2.5 mg per
kilogram of body weight) or placebo monthly for 6 months. The primary end point was the annualized rate of
composite porphyria attacks among patients with acute intermittent porphyria, the most common subtype of
acute hepatic porphyria. (Composite porphyria attacks resulted in hospitalization, an urgent health care visit,
or intravenous administration of hemin at home.) Key secondary end points were levels of ALA and
porphobilinogen and the annualized attack rate among patients with acute hepatic porphyria, along with hemin
use and daily worst pain scores in patients with acute intermittent porphyria. RESULTS: A total of 94 patients
underwent randomization (48 in the givosiran group and 46 in the placebo group). Among the 89 patients with
acute intermittent porphyria, the mean annualized attack rate was 3.2 in the givosiran group and 12.5 in the
placebo group, representing a 74% lower rate in the givosiran group (P<0.001); the results were similar
among the 94 patients with acute hepatic porphyria. Among the patients with acute intermittent porphyria,
givosiran led to lower levels of urinary ALA and porphobilinogen, fewer days of hemin use, and better daily
scores for pain than placebo. Key adverse events that were observed more frequently in the givosiran group
were elevations in serum aminotransferase levels, changes in serum creatinine levels and the estimated
glomerular filtration rate, and injection-site reactions. CONCLUSIONS: Among patients with acute
intermittent porphyria, those who received givosiran had a significantly lower rate of porphyria attacks and
better results for multiple other disease manifestations than those who received placebo. The increased
efficacy was accompanied by a higher frequency of hepatic and renal adverse events. (Funded by Alnylam
Banerjee, S. and S. McCormack (2019). CADTH Rapid Response Reports.
Intravenous Iron Preparations for Patients Undergoing Elective Surgery: A Review of
Clinical Effectiveness, Cost-Effectiveness, and Guidelines. Ottawa (ON), Canadian
Agency for Drugs and Technologies in Health
Copyright © 2019 Canadian Agency for Drugs and Technologies in Health.
Preoperative anemia, which is often associated with iron deficiency, is a risk factor for poor outcome in
patients undergoing surgery. According to the World Health Organization, anemia is defined as a circulating
hemoglobin concentration of less than 130 g/L for men and less than 120 g/L for women. Iron deficiency is
categorized as either absolute (iron deficiency anemia) or functional (anemia of inflammation, and also
referred to as anemia of chronic disease). Several factors may contribute to iron deficiency anemia such as
inadequate iron absorption, and bleeding due to an underlying disease condition. Iron is needed as a substrate
for the bone marrow to produce erythrocytes. The prevalence of preoperative anemia varies between 5% and
76% depending on the age of the patient, the nature of the condition and the type of surgery planned; the
prevalence being 26% for major orthopedic surgery, and 50% for cardiac surgery. Treatment options for iron
deficiency anemia include blood transfusion, oral iron, and intravenous iron. Traditionally, the focus was on
the use of blood transfusion to manage anemia in the preoperative phase. However, blood transfusion is
associated with risks such as infection, transfusion reaction, postoperative complications, and extended
hospital stay.(,)(,) Furthermore, blood transfusion may have substantial cost implications. Oral iron is
inexpensive and easy to administer but is associated with gastrointestinal side effects such as abdominal pain,
diarrhea, constipation and dyspepsia which negatively impact compliance. Iron dextran formulations were
developed both for intramuscular and intravenous administration, however due to the associated adverse
effects, they were phased out. Since then, various formulations of intravenous iron (such as iron sucrose, ferric
gluconate, ferrumoxytol, ferric carboxymaltose, iron isomaltiside) have been developed. These newer
formulations have shown promise in treating anemia in a number of disease conditions (such as inflammatory
bowel disease, chronic heart failure and chronic kidney disease. There is some suggestion that intravenous
iron may be a useful treatment option for iron deficient anemia in patients undergoing surgery. The purpose of
this report is to review the clinical effectiveness and cost-effectiveness of intravenous iron preparations
administered preoperatively, for iron deficient adult patients undergoing elective surgery. Additionally, this
report aims to review the evidence-based guidelines regarding the use of intravenous iron preparations
administered preoperatively, for iron deficient adult patients undergoing elective surgery (i.e., any surgery
Bangs, M. E., et al. (2020). "Safety and tolerability of monthly galcanezumab
injections in patients with migraine: integrated results from migraine clinical studies."
BMC Neurol 20(1): 25.
BACKGROUND: Galcanezumab, a humanized monoclonal antibody that selectively binds to calcitonin generelated peptide, has demonstrated a significant reduction in monthly migraine headache days in phase 2 and 3
trials. In these analyses, we aimed to evaluate the safety and tolerability of galcanezumab compared with
placebo for prevention of episodic or chronic migraine. METHODS: Data were integrated from three doubleblind clinical studies for the up to 6-month galcanezumab exposure group (N = 1435), and from five clinical
studies for the up to 1-year all-galcanezumab exposure group (N = 2276). Patients received a monthly 120 mg
subcutaneous injection of galcanezumab (with a 240 mg loading dose in month 1), 240 mg galcanezumab, or
placebo. Outcomes measured were treatment-emergent adverse events (TEAEs), serious AEs (SAEs), and
discontinuation due to AEs (DCAEs). Laboratory results, vital signs, electrocardiogram (ECG), suicidal
ideation and behavior results were evaluated. RESULTS: TEAEs that occurred more frequently in
galcanezumab-treated patients included injection site pain, injection site reactions excluding pain,
constipation, vertigo, and pruritus. The proportion of DCAEs among galcanezumab-treated patients ranged
between 1.8 and 3.0%, and differed from placebo group for galcanezumab 240 mg (P < 0.05). Fewer than
2.0% of patients in either galcanezumab dose-group compared with 1.0% of placebo-treated patients reported
a SAE. There were no clinically meaningful differences between galcanezumab and placebo in laboratory
measures, vital signs including blood pressure, ECGs, cardiovascular-related AEs, or suicidal ideation and
behavior. CONCLUSIONS: Galcanezumab demonstrated a favorable safety and tolerability profile for up to
1 year of treatment for the prevention of migraine. TRIAL REGISTRATION: Clinical Trials
CGAB = NCT02163993, EVOLVE-1 = NCT02614183, EVOLVE-2 = NCT02614196,
REGAIN = NCT02614261, and CGAJ = NCT02614287. All were first posted on 25 November 2015, except
Barriga-Martín, A., et al. (2023). "[Translated article] Relation between the volume of
injected cement and the vertebral volume in the clinical outcome and in the
appearance of leakage after a percutaneous vertebroplasty." Rev Esp Cir Ortop
Traumatol 67(3): T181-t187.
OBJECTIVES: To assess the connection between the volume of injected cement and the vertebral volume
measured through a volumetric analysis with a computed tomography (CT scan) in relation to the clinical
result and the appearance of a leakage in patients who underwent a percutaneous vertebroplasty after an
osteoporotic fracture. MATERIALS AND METHODS: A prospective study of 27 patients (18 female-9 male)
with an average age of 69 years old (50-81), and with a one-year follow-up. The study group presented 41
vertebrae with osteoporotic fractures that were treated with a percutaneous vertebroplasty with a bilateral
transpedicular approach. The volume of injected cement was registered in each procedure and it was assessed
together with the spinal volume measured through a volumetric analysis with CT scans. The percentage of the
spinal filler was calculated. The appearance of cement leakage was proved by means of a simple radiography
and a postoperative CT scan in all the cases. The leaks were classified according to the location in relation to
the vertebral body (posterior, lateral, anterior and in the disc), and the significance (minor: smaller than the
largest diameter of the pedicle; moderate: larger than the pedicle but smaller than the height of the vertebra;
major: larger than the height of the vertebra). RESULTS: The average vertebra volume was 26.1cm(3), the
average volume of the injected cement was 2.0cm(3) and the percentage of the average filler was 9%. A total
of 15 leaks in 41 vertebrae appeared (37%). The leaks were posterior in 2 vertebrae, vascular in 8 and into the
disc in 5 vertebrae. They were deemed as minor in 12 cases, moderate in 1 and major in 2 cases. The
preoperative assessment of the pain was as it follows: VAS (8) and Oswestry (67%). The cessation of pain
was immediate after a year with the following postoperative results: VAS (1.7) and Oswestry (19%). The only
complication was the temporary neuritis with a spontaneous resolution. CONCLUSIONS: The injection of
small amounts of cement, lower than the ones referred to by literary sources, obtains clinical results similar to
the ones obtained by injecting higher amounts and it reduces the number of cement leaks and further
Baskın, S. B., et al. (2014). "The comparison of heparinized insulin syringes and
safety-engineered blood gas syringes used in arterial blood gas sampling in the ED
setting (randomized controlled study)." Am J Emerg Med 32(5): 432-437.
INTRODUCTION: The arterial blood gas measurement process is a painful and invasive procedure, often
uncomfortable for both the patient and the physician. Because the patient-related factors that determine the
difficulty of the process cannot be controlled, the physician-related factors and blood gas measurement
techniques are a modifiable area of improvement that ought to be considered. Many hospitals use insulin
syringes or syringes washed with heparin for the purpose of blood gas measurement because they do not have
blood gas-specific syringes. In this prospective cross-sectional study, we aimed to compare safety-engineered
blood gas syringes and conventional heparinized syringes used during the arterial blood gas extraction process
in terms of ease of operation, the physician-patient satisfaction, laboratory appropriateness, and complications.
METHODS: Our study included patients whose arterial blood gas needed to be measured in the emergency
department and who agreed to participate in the study. Patients were randomly divided into 2 groups. The
arterial blood gas of the patients from the first group was measured by using conventional heparinized
syringes, whereas safety-engineered blood gas syringes were used to measure the arterial blood gas of the
patients from the second group. The groups were compared in terms of demographic data, the number of
attempts, the physician and patient satisfaction, early and late-term complications, and laboratory
appropriateness of the taken sample. RESULTS: A total of 550 patients were included in our study in a 2month study period. There were no significant differences between patients in terms of sex, age, weight,
height, body mass index, and wrist circumference. In addition, the number of attempts (P=.489), patients' pain
level during the procedure (P=.145), and the degree of difficulty of the procedure according to the patient
(P=.109) and physician (P=.554) were not significantly different between the groups. After arterial blood gas
extraction procedure, 115 patients (20.9%) developed complications. In the conventional heparinized syringe
group, the complication rate (n=69; 25.1%) was significantly higher compared with the group that used safetyengineered blood gas syringes (n=46; 16%; P=.0211). Localized pain, which is one of the most common early
complications, was more frequent in the conventional heparinized syringe group (19.3%). Complications in
women (P=.003) and local pain (P=.01) developed lesser in the second group that used safety-engineered
blood gas syringes, and the patient-physician satisfaction was higher in that group, as well. In the evaluation
48 hours after the procedure, the ratios of infection and local hematoma were higher in the conventional
heparinized syringe group (P=.0213 and P < .0001). CONCLUSION: In this study, we did not find any
significant differences between the conventional heparinized syringes and safety-engineered blood gas
Batista, E., et al. (2020). "New EMPIR project – Metrology for Drug Delivery." Flow
Measurement and Instrumentation 72: 101716.
This document presents the scientific and technical objectives, state of the art and expected progress beyond
it, and most importantly the expected impact on metrology, science, standards, and society of the new joint
research project - MeDD II, Metrology for Drug Delivery (follow up of project MeDD I). It was selected for
funding through the EURAMET EMPIR program of the European Commission and the participating
countries. The project started in June 2019 and will last for three years. It involves 15 partners from National
and Designated Metrology Institutes, companies, and academia. The main objective is to enable traceable
measurements of volume, flow and pressure of existing drug delivery devices (like infusion pumps and
analysers) and inline sensors that work at flow rates lower than 100 nL/min, in order to prevent inaccurate
measurement results. This project will also investigate fast changing flow rates, liquid mixing behaviour and
occlusion phenomena in multi-infusion systems with the purpose of improving dosing accuracy in each
infusion line.
Batista, E., et al. (2020). "Experimental testing for metrological traceability and
accuracy of liquid microflows and microfluidics." Flow Measurement and
Instrumentation 71: 101691.
Baù, M., et al. (2020). "Risk and Protective Factors for Gastrointestinal Symptoms
associated with Antibiotic Treatment in Children: A Population Study." Pediatr
Gastroenterol Hepatol Nutr 23(1): 35-48.
Micro-flows are growing more important and useful for a wide variety of scientific and engineering fields
such as bioanalysis, drug development and administration, Organ-on-a-Chip, etc, but accurate and reliable
measurements traceable to the International System of Units can be challenging in micro-to-femto flow
operating ranges. In this paper a gravimetric method has been used to quantify the measurement error of the
volumetric flow rate of water from 1000 μL/h to 1 μL/h delivered by a syringe pump in different experimental
conditions that replicate the current microfluidics setups. Several sources of error have been determined such
as the mass measurement, the fluid evaporation dependent on the gravimetric methodology implemented and
the repeatability, believed to be closely related to the operating mode of the stepper motor and drive screw
pitch of the syringe pump. The elastic deformability of the medical grade 1 mL polypropylene syringes
commonly used in micro-flows has greatly affected the volumetric flow rate, unlike the glass syringes tested.
Finally, testing the gravimetric method while adding PDMS microfluidic channels to the flow circuit served to
demonstrate that material, dimensions and shape of the microchannels did not show significant influence on
the volumetric flow rate error for the flow rates imposed, important to establish well defined methodologies
for microfluidics.
PURPOSE: Gastrointestinal symptoms are often related to antibiotic treatment. Their incidence, risk and
protective conditions in children are not well defined and represent the aims of this study. METHODS: We
prospectively enrolled inpatient children submitted to antibiotic treatment. Indication, type, dose and duration
of treatment, probiotic supplementation and gastrointestinal symptoms were recorded at recruitment, after two
and four weeks. Antibiotic-associated diarrhea (AAD) was defined as the presence of at least 3 loose/liquid
stools within 14 days from antibiotic onset. RESULTS: AAD occurred in 59/289 (20.4%) of patients, with
increased risk in children younger than 3 years (relative risk [RR]=4.25), in lower respiratory (RR=2.11) and
urinary infections (RR=3.67), intravenous administration (RR=1.81) and previous AAD episodes (RR=1.87).
Abdominal pain occurred in 27/289 (9.3%), particularly in children >6 years (RR=4.15), with previous
abdominal pain (RR=7.2) or constipation (RR=4.06). Constipation was recorded in 23/289 (8.0%), with
increased risk in children having surgery (RR=2.56) or previous constipation (RR=7.38). Probiotic
supplementation significantly reduced AAD (RR=0.30) and abdominal pain (RR=0.36). Lactobacillus
rhamnosus GG (LGG) and L. reuteri significantly reduced AAD (RR=0.37 and 0.35) and abdominal pain
(RR=0.37 and 0.24). CONCLUSION: AAD occurred in 20.4% of children, with increased risk at younger age,
lower respiratory and urinary tract infections, intravenous treatment and previous AAD. LGG and L. reuteri
Bayraktaroğlu, S., et al. (2011). "The relationship between the myocardial T2* value
and left ventricular volumetric and functional parameters in thalassemia major
patients." Diagn Interv Radiol 17(4): 346-351.
PURPOSE: Cardiac involvement in thalassemia major (TM) is mainly characterized by left ventricular
dysfunction caused by iron overload. Cardiovascular magnetic resonance imaging (MRI) including myocardial
T2* measurement is becoming increasingly popular for quantitatively evaluating myocardial iron overload.
The aim of this study was to evaluate the relationship between the myocardial T2* value and left ventricular
functional parameters and to examine the associations between the degree of cardiac iron load and various
clinical parameters. MATERIALS AND METHODS: A retrospective analysis of 47 patients (25 males and 22
females; mean age, 23.0±5.4 years) with TM was performed. Myocardial iron load was assessed by T2*
measurements, and volumetric functions were analyzed using the steady state free precession sequence.
RESULTS In patients with myocardial iron deposition (T2* < 20 ms), the mean left ventricular ejection
fraction (LVEF) was 64.73±4.94%. The LVEF of patients with myocardial siderosis was significantly lower
than that of patients without myocardial siderosis (r=0.35, P = 0.014). Inverse and significant correlations
between both the left ventricular (LV) end-systolic volume index and the LV end-diastolic volume index and
the myocardial T2* value (r=-0.32, P = 0.027 and r=-0.29, P = 0.046, respectively) were observed. There was
an inverse correlation between the myocardial T2* value and the liver iron concentration (r=-0.31, P = 0.037).
Cardiac T2* was not associated with serum ferritin levels, pre-transfusion hemoglobin levels or the annual red
cell consumption rate. CONCLUSION: Myocardial iron load assessed by cardiac MRI (T2*) is associated
with deterioration in left ventricular function. Thalassemia major patients with myocardial siderosis may have
Belardo, C., et al. (2023). "Biphasic Hormetic-like Effect of Lebecetin, a C-type
Lectin of Snake Venom, on Formalin-induced Inflammation in Mice." Curr
Neuropharmacol.
Berger, M. N., et al. (2023). "Immunogenicity, safety, usability and acceptability of
microarray patches for vaccination: a systematic review and meta-analysis." BMJ
Glob Health 8(10).
BACKGROUND: Integrins, important extracellular matrix (ECM) receptor proteins, are affected by
inflammation and can participate in the maintenance of many painful conditions. Although they are ubiquitous
and changeable across all cell types, the roles of these cell adhesion molecules in pathological pain have not
been fully explored. OBJECTIVE: We evaluated the effects of the subcutaneous injection of lebecetin, a Ctype lectin isolated from Macrovipera lebetina snake venom, previously reported to inhibit α5β1 and αv
integrin activity, on different components of inflammation induced by the formalin administration in the hind
paw of mice. METHODS: The formalin-induced nocifensive behavior, edema, and histopathological changes
in the hind paw associated with cytokine, iNOS, and COX2 expression, nociceptive-specific neuron activity,
and microglial activation analysis in the spinal cord were evaluated in mice receiving vehicle or lebecetin
pretreatment. RESULTS: Lebecetin inhibited the nocifensive responses in the formalin test, related edema,
and cell infiltration in the injected paw in a biphasic, hormetic-like, and dose-dependent way. According to
that hormetic trend, a reduction in pro-inflammatory cytokines IL-6, IL-8, and TNF-alpha and upregulation of
the anti-inflammatory cytokine IL-10 in the spinal cord were found with the lowest doses of lebecetin.
Moreover, COX2 and iNOS expression in serum and spinal cord followed the same biphasic pattern of
cytokines. Finally, nociceptive neurons sensitization and activated microglia were normalized in the dorsal
horn of the spinal cord by lebecetin. CONCLUSION: These findings implicate specific roles of integrins in
BACKGROUND: Microarray patches (MAPs) deliver vaccines to the epidermis and the upper dermis, where
abundant immune cells reside. There are several potential benefits to using MAPs, including reduced sharps
risk, thermostability, no need for reconstitution, tolerability and self-administration. We aimed to explore and
evaluate the immunogenicity, safety, usability and acceptability of MAPs for vaccination. METHODS: We
searched CINAHL, Cochrane Library, Ovid Embase, Ovid MEDLINE and Web of Science from inception to
January 2023. Eligibility criteria included all research studies in any language, which examined microarrays
or microneedles intended or used for vaccination and explored immunogenicity, safety, usability or
acceptability in their findings. Two reviewers conducted title and abstract screening, full-text reviewing and
data extraction. RESULTS: Twenty-two studies were included (quantitative=15, qualitative=2 and mixed
methods=5). The risk of bias was mostly low, with two studies at high risk of bias. Four clinical trials were
included, three using influenza antigens and one with Japanese encephalitis delivered by MAP. A metaanalysis indicated similar or higher immunogenicity in influenza MAPs compared with needle and syringe
(N&S) (standardised mean difference=10.80, 95% CI: 3.51 to 18.08, p<0.00001). There were no significant
differences in immune cell function between MAPs and N&S. No serious adverse events were reported in
MAPs. Erythema was more common after MAP application than N&S but was brief and well tolerated. Lower
pain scores were usually reported after MAP application than N&S. Most studies found MAPs easy to use and
highly acceptable among healthcare professionals, laypeople and parents. CONCLUSION: MAPs for
vaccination were safe and well tolerated and evoked similar or enhanced immunogenicity than N&S, but
further research is needed. Vaccine uptake may be increased using MAPs due to less pain, enhanced
thermostability, layperson and self-administration. MAPs could benefit at-risk groups and low and middleBerliner, C., et al. (2022). "Anterior Pituitary Volume in Patients with Transfusion
Dependent Anemias: Volumetric Approaches and Relation to Pituitary MRI‑R2." Clin
Neuroradiol 32(1): 259-267.
PURPOSE: Anterior pituitary iron overload and volume shrinkage is common in patients with transfusiondependent anemia and associated with growth retardation and hypogonadotropic hypogonadism. We
investigated the accuracy of different MRI-based pituitary volumetric approaches and the relationship
between pituitary volume and MRI-R2, particularly with respect to growth and hypogonadism. METHODS:
In 43 patients with transfusion-dependent anemia (12-38 years) and 32 healthy controls (12-72 years), anterior
pituitary volume was measured by a sagittal T1 GRE 3D sequence at 1.5T and analyzed by 3D semiautomated threshold volumetry (3D-volumetry). This reference method was compared with planimetric 2Dvolumetry, approximate volume calculations, and pituitary height. Using a multiple SE sequence, pituitary
iron as MRI-R2 was assessed by fitting proton signal intensities to echo times. Growth and hypogonadism
were obtained from height percentile tables and patients' medical charts. From body surface area and age
adjusted anterior pituitary volumes of controls, Z‑scores were calculated for all subjects. Separation of
controls and patients with respect to Z and pituitary R2 was performed by bivariate linear discriminant
analysis. RESULTS: Tuned 2D volumes showed highest agreement with reference 3D-volumes (bias -4.8%;
95% CI:-8.8%|-0.7%). A linear discriminant equation of Z = -17.8 + 1.45 · R2 revealed optimum threshold
sensitivity and specificity of 65% and 100% for discrimination of patients from controls, respectively. Of
correctly classified patients 71% and 75% showed hypogonadism and growth retardation, respectively.
CONCLUSION: Accurate assessment of anterior pituitary size requires 3D or precise 2D volumetry, with
shorter analysis time for the latter. Anterior pituitary volume Z‑scores and R2 allow for the identification of
Berteau, C., et al. (2010). "Evaluation of performance, safety, subject acceptance, and
compliance of a disposable autoinjector for subcutaneous injections in healthy
volunteers." Patient Prefer Adherence 4: 379-388.
OBJECTIVE: A disposable autoinjector was developed for subcutaneous (SC) self-injection by patients with
chronic diseases. To verify its performance and evaluate its acceptance, a clinical study was conducted in
healthy volunteers, comparing SC injections performed by subjects using the autoinjector with SC injections
performed by nurses using a syringe. METHODS: This was a randomized, single-center, crossover study
comparing SC self-injection using an autoinjector with SC nurse-administered injection using a syringe. Two
volumes (0.2 mL and 1 mL) were injected into healthy volunteers. Study objectives included assessment of
the accuracy and consistency of the volume injected by the injection systems, and skin reaction and pain
associated with the injection. The fluid depot in the SC tissue layer was evaluated by ultrasound. Subject
acceptance was evaluated using questionnaires on attitudes and emotions towards the injection technique, and
challenged by seeking the subjects' preferred system for a final study injection or future treatment. RESULTS:
A total of 960 injections (480 with autoinjector, 480 with syringe) were performed in 40 subjects. There were
no significant differences in mean fluid leakage and injected volumes between the systems. Pain associated
with the injection was significantly lower with the auto-injector than with the syringe. Local skin reaction at
the injection site was overall satisfactory. Injections were appropriately performed by all subjects. At study
end, all 40 subjects preferred the autoinjector for a final study injection and for future treatment.
CONCLUSION: This study indicated that the autoinjector used by the subject was similar to a syringe used by
a nurse in terms of performance and safety in administering the injections, and better in terms of pain, overall
Bertholet-Thomas, A., et al. (2018). "Teenagers and young adults with nephropathic
cystinosis display significant bone disease and cortical impairment." Pediatr Nephrol
33(7): 1165-1172.
Beyar-Katz, O., et al. (2022). "Thrombopoietin receptor agonist for treating bone
marrow aplasia following anti-CD19 CAR-T cells-single-center experience." Ann
Hematol 101(8): 1769-1776.
BACKGROUND: Bone impairment appears to be a novel complication of nephropathic cystinosis despite
cysteamine therapy. Its exact underlying pathophysiology is nevertheless unclear. The objective of this study
was to evaluate bone status among patients included in the French Crystobs study. METHODS: In addition to
clinical data, bone status was evaluated using biomarkers (ALP, PTH, 25-D, 1-25D, FGF23), DXA (spine and
total body), and high-resolution peripheral quantitative computed tomography (HR-pQCT) at the tibia and
radius. Results were compared to age- and gender-matched healthy controls (1:2 basis) from the local
reference cohorts. RESULTS: At a median age of 22.5 (10.2-34.6) years, 10 patients with nephropathic
cystinosis were included (2 receiving conservative therapies, 2 undergoing hemodialysis, 6 with a past of renal
transplantation); 7 out of 10 patients complained of a bone symptom (past of fracture, bone deformations,
and/or bone pain). Biochemicals and spine DXA did not show any significant abnormalities. Using HRpQCT, significant decreases in cortical parameters (e.g., cortical thickness 850 (520-1100) versus 1225 (4801680) μm; p < 0.05) and total volumetric bone mineral density (290 (233-360) versus 323 (232-406)
mg/cm(3); p < 0.05) were observed in cystinotic patients in comparison to controls at the tibia. There were no
differences for trabecular parameters. Similar results were observed at the radius. CONCLUSIONS: In this
pilot study, bone impairment (rather cortical than trabecular) is a significant clinical problem in nephropathic
cystinosis; 70% of patients displayed significant bone symptoms, during teenage or young adulthood. This
Anti CD-19 chimeric antigen receptor T (CAR-T) cells demonstrate effective early anti-tumor response;
however, impaired hematopoietic recovery is observed in about 30% of patients with prolonged cytopenia
appearing as an unmet need for optimal treatment. All adult patients given commercially available anti CD-19
CAR-T for diffuse large B cell lymphoma (DLBCL) were screened at 21-28 days after CAR-T infusion for
cytopenia. In case of severe persistent cytopenia, patients were given TPO receptor agonists. Initial dose of
eltrombopag was 50 mg/day and gradually increased to a maximal dose of 150 mg/day. Romiplostim was
given as subcutaneous injection once a week for 2 doses (125 mcg). Response was defined as transfusion
independency along with resolution of severe neutropenia (ANC > 500 /microL) and/or
platelets > 20,000/microL for three consecutive values on different days. TPO receptor agonists were tapered
down when response was met. From May 2019 to December 2021, 93 patients were eligible (74%,
tisagenlecleucel and 26%, axicabtagene ciloleucel). The median age was 69 (range, 19-85) years. Six patients
(6.5%) (tisagenlecleucel, n = 4 or axicabtagene ciloleucel, n = 2) demonstrated prolonged severe cytopenia and
were treated with TPO receptor agonists (eltrombopag, n = 4; romiplastim, n = 1, both drugs, n = 1). Median
time from CAR-T infusion to initiation of TPO receptor agonist was 43 (range, 21-55) days. All patients were
transfusion-dependent and were given daily GCSF prior to TPO receptor agonist administration. Response to
TPO receptor agonists was seen in all 6 patients. Median time from TPO receptor agonist initiation to
resolution of cytopenia was 22 (range, 8-124) days for Hb, 27 (range, 6-38) days for platelets, and 29 (range,
7-61) days for neutrophils. A complete resolution of all blood counts (ANC > 500 /microL and
platelets > 20,000/microL and hemoglobin > 8 gr/dL) was seen in 5/6 patients. No toxicity was observed
during the therapy course. This paper supports further investigation of TPO receptor agonists in the treatment
Bi, Y., et al. (2021). "The Effect of Ketamine on Acute and Chronic Wound Pain in
Patients Undergoing Breast Surgery: A Meta-Analysis and Systematic Review." Pain
Pract 21(3): 316-332.
INTRODUCTION: Perioperative use of ketamine has been discussed widely in many kinds of surgery. The
aim of our study was to evaluate the short-term and long-term benefits and safety of ketamine after breast
surgery. METHOD: We performed a quantitative systematic review. We included randomized controlled
trials that compared intravenous administration of ketamine to a placebo control group, or compared
bupivacaine in combination with ketamine to bupivacaine alone in thoracic paravertebral blocks or pectoral
blocks among patients undergoing breast surgery. The primary outcome was postoperative pain intensity.
Secondary outcomes included cumulative opioid consumption during the 0- to 24-hour postoperative period,
the effect on postmastectomy pain syndrome, the effect on postoperative depression, and the adverse events
associated with the use of ketamine. RESULTS: Thirteen randomized controlled trials with 1,182 patients
were included for analysis. Compared with placebo, intravenous ketamine was effective in reducing wound
pain intensity during the first 6 hours after surgery (weighted mean difference [WMD] -0.83; 95% confidence
interval [CI] -1.65, -0.01; P = 0.048) and during the first 24 hours after surgery (WMD -0.65; 95% CI -0.95, 0.35; P < 0.001), and in decreasing opioid consumption (WMD -4.14; 95% CI -8.00, -0.29; P = 0.035) during
the first 24 hours after surgery, without increasing the risks for gastrointestinal and central nervous system
adverse events. Adding ketamine to bupivacaine in thoracic paravertebral blocks was also effective in
reducing postoperative wound pain during the first 6 hours after surgery (WMD -0.59; 95% CI, -1.06, -0.12;
P = 0.014) and during the first 24 hours after surgery (WMD -0.90; 95% CI -1.27, -0.53; P < 0.001), and in
decreasing opioid consumption (WMD - 4.59; 95% CI -5.76, -3.42; P < 0.001) during the first 24 hours after
surgery. Perioperative use of ketamine was associated with improved postoperative depression symptoms
(standardized mean difference -0.80; 95% CI - 1.34, -0.27; P = 0.003) and less incidence of postmastectomy
pain syndrome (relative risk 0.79; 95% CI 0.63, 0.99; P = 0.043). CONCLUSION: Ketamine is an effective
and safe multimodal analgesic in patients undergoing breast surgery, administered both intravenously and
when added to bupivacaine in paravertebral blocks. In addition, ketamine showed a long-term benefit for
Bigal, M. E., et al. (2015). "Safety, tolerability, and efficacy of TEV-48125 for
preventive treatment of chronic migraine: a multicentre, randomised, double-blind,
placebo-controlled, phase 2b study." Lancet Neurol 14(11): 1091-1100.
BACKGROUND: Benefits of calcitonin-gene related peptide (CGRP) inhibition have not been established in
chronic migraine. Here we assess the safety, tolerability, and efficacy of two doses of TEV-48125, a
monoclonal anti-CGRP antibody, in the preventive treatment of chronic migraine. METHODS: In this
multicentre, randomised, double-blind, double-dummy, placebo-controlled, parallel-group phase 2b study, we
enrolled men and women (aged 18-65 years) from 62 sites in the USA who had chronic migraine. Using a
randomisation list generated by a central computerised system and an interactive web response system, we
randomly assigned patients (1:1:1, stratified by sex and use of concomitant preventive drugs) to three 28-day
treatment cycles of subcutaneous TEV-48125 675/225 mg (675 mg in the first treatment cycle and 225 mg in
the second and third treatment cycles), TEV-48125 900 mg (900 mg in all three treatment cycles), or placebo.
Investigators, patients, and the funder were blinded to treatment allocation. Daily headache information was
captured using an electronic diary. Primary endpoints were change from baseline in the number of headachehours during the third treatment cycle (weeks 9-12) and safety and tolerability during the study. Secondary
endpoint was change in the number of moderate or severe headache-days in weeks 9-12 relative to baseline.
Efficacy endpoints were analysed for the intention-to-treat population. Safety and tolerability were analysed
using descriptive statistics. This trial is registered with ClinicalTrials.gov, number, NCT02021773.
FINDINGS: Between Jan 8, 2014, and Aug 27, 2014, we enrolled 264 participants: 89 were randomly
assigned to receive placebo, 88 to receive 675/225 mg TEV-48125, and 87 to receive 900 mg TEV-48125.
The mean change from baseline in number of headache-hours during weeks 9-12 was -59.84 h (SD 80.38) in
the 675/225 mg group and -67.51 h (79.37) in the 900 mg group, compared with -37.10 h (79.44) in the
placebo group. The least square mean difference in the reduction of headache-hours between the placebo and
675/225 mg dose groups was -22.74 h (95% CI -44.28 to -1.21; p=0.0386), whereas the difference between
placebo and 900 mg dose groups was -30.41 h (-51.88 to -8.95; p=0.0057). Adverse events were reported by
36 (40%) patients in the placebo group, 47 (53%) patients in the 675/225 mg dose group, and 41 (47%)
patients in the 900 mg dose group, whereas treatment-related adverse events were recorded in 15 (17%)
patients, 25 (29%) patients, and 28 (32%) patients, respectively. The most common adverse events were mild
injection-site pain and pruritus. Four (1%) patients had serious non-treatment-related adverse events (one
patient in the placebo group, one patient in the 675/225 mg group, and two patients in the 900 mg group); no
treatment-related adverse events were serious and there were no relevant changes in blood pressure or other
Bigdelian, H., et al. (2023). "Topical and Intravenous Tranexamic Acid in Acyanotic
Children Undergoing Congenital Heart Surgery: A Randomized Clinical Trial." J Surg
Res 288: 64-70.
INTRODUCTION: Postoperative bleeding is a common complication in congenital heart surgery. We aimed
to evaluate effects of topical and intravenous tranexamic acid (TXA) administration on postoperative
hemoglobin and bleeding in children with acyanotic congenital heart disease (CHD). METHODS: In this
randomized clinical trial, 50 acyanotic CHD children were allocated into two groups of topical (n = 25) and
infusion (n = 25). Children in the infusion group were given intravenous TXA 50 mg/kg(-1) after sternotomy.
Children in topical group were given 50 mg/kg(-1) TXA added to 20 mL of saline intrapericardially before
sternal closure. Primary endpoint of study was comparison of postoperative hemoglobin and bleeding between
topical and infusion groups. A linear mixed model (LMM) was used to estimate longitudinal changes in
postoperative endpoints. RESULTS: We did not observe significant differences in children's characteristics
between two groups. Also, intraoperative and postoperative outcomes did not differ between two groups but
children with intravenous TXA experienced significantly longer intubation time than topical children
(P = 0.047). LMM analysis revealed that postoperative bleeding in topical group was lower compared to
infusion group (P = 0.036). Also, age of children had a significant effect on mean changes of hemoglobin
during postoperative care (β = -0.27, P = 0.030). No children died and none had serious postoperative
complications such as seizures and reoperation. CONCLUSIONS: We found that topical TXA is not superior
to intravenous administration in management of blood loss. Also, no additional effect was found about topical
TXA in further reducing transfusion rates and postoperative complications in acyanotic CHD children
Biko, D. M., et al. (2018). "Magnetic Resonance Myocardial Perfusion Imaging:
Safety and Indications in Pediatrics and Young Adults." Pediatr Cardiol 39(2): 275282.
The purpose of this study was to assess the safety and indications for cardiac magnetic resonance (CMR) with
myocardial perfusion imaging (MPI) in a cohort of children and young adults. A retrospective review of 178
children and young adults who underwent CMR with MPI was performed. Studies were categorized based on
study protocols as MPI with resting perfusion only, adenosine stress MPI, exercise-induced stress MPI, and
MPI for cardiac mass diagnosis. Relevant clinical history, exam indications, and adverse reactions following
gadolinium-based contrast agent and adenosine administration were recorded. Studies were reviewed for the
presence of myocardial perfusion defects, wall motion abnormalities, and delayed myocardial enhancement.
The most common indications from MPI were congenital heart disease (CHD), Kawasaki disease, anomalous
coronary artery, or myocardial mass characterization. Of these, 51% were protocoled with adenosine stress,
23% without stress, 6% with exercise stress, and 20% for cardiac mass evaluation. Excluding patients for
myocardial mass evaluation, MPI defects were present in 16% (14 with adenosine stress, 1 with exercise
stress, 8 on resting studies only). For cardiac mass evaluation, a mass was confirmed in 58%. No adverse
reactions occurred with intravenous administration of a gadolinium-based contrast agent. Three self-limited
adverse reactions, 2 patients with chest pain, and 1 patient with bradycardia, occurred following adenosine
administration. MPI is a safe modality for the evaluation of pediatric and young adults with minimal adverse
events. The most common indications for MPI were for the evaluation of CHD, Kawasaki disease, anomalous
Bjerkvig, C. K., et al. (2018). "Emergency sternal intraosseous access for warm fresh
whole blood transfusion in damage control resuscitation." J Trauma Acute Care Surg
84(6S Suppl 1): S120-s124.
Bonde, A., et al. (2024). "Imaging of the hepatic arterial infusion pump: Primer for
radiologists." Clinical Imaging 105: 110022.
Bonutti, P. M., J. W. Mesko and R. Ramakrishnan (2018). "Long-term Wear Data
From a Prospective Multicenter Study of Second-Generation Highly Cross-linked
Polyethylene Inserts in Total Hip Arthroplasty." Orthopedics 41(4): e529-e533.
BACKGROUND: Intraosseous (IO) vascular access is increasingly used as an emergency tool for achieving
access to the systemic circulation in critically ill patients. The role of IO transfusion of blood in damage
control resuscitation is however questionable due to possible inadequate flow rate and hemolysis. Some
experts claim that IO transfusion is contraindicated. In this study, we have challenged this statement by
looking at flow rates of autologous fresh whole blood reinfusion and hemolysis using two of the commonly
used Food and Drug Administration-approved and Conformité Européenne (CE)-marked sternal needles.
Additionally, the success rate of sternal access between the two devices is evaluated. METHODS: Volunteer
professional military personnel, were enrolled prospectively in a nonrandomized observational study design.
We collected 450 mL of autologous whole blood from each participant. Participants were divided into the
following three groups of 10: Tactically Advanced Lifesaving IO Needle (T.A.L.O.N.) IO, FAST1 IO, and
intravenous group. The reinfusion was done by gravity only. Blood sampling was performed before blood
collection and 30 minutes after reinfusion. Investigation of hemolysis was performed by measurements of
haptoglobin and lactate dehydrogenase. Success rate was evaluated by correct aspiration of bone marrow.
RESULTS: Median reinfusion rate was 46.2 mL/min in the FAST1 group, 32.4 mL/min in the T.A.L.O.N.
group, and 74.1 mL/min in the intravenous group. Blood samples from all participants were within normal
ranges. There was no statistically significant difference in haptoglobin and lactate dehydrogenase between the
groups. In the FAST1 group, 1 (9%) of 11 procedures failed. In the T.A.L.O.N. group, 4 (29%) of 14
procedures failed. CONCLUSION: Although preferable, achieving peripheral venous access in the bleeding
patient is a major problem. Our findings suggest that fresh whole-blood transfusion through the IO route is
safe, reliable, and provide sufficient flow for resuscitation. LEVEL OF EVIDENCE: Therapeutic/Care
Hepatic arterial infusion (HAI) pumps are used to deliver liver-directed therapy by allowing the administration
of selective chemotherapy to the liver via a catheter implanted most commonly into the gastroduodenal artery
connected to a subcutaneous pump. This selective administration helps maximize the chemotherapeutic effect
within the hepatic tumors while minimizing systemic toxicity. While HAI therapy has primarily been used to
treat liver-only metastatic colorectal cancer, the indications have expanded to other malignancies, including
intrahepatic cholangiocarcinoma. Radiologists play an important role in pre-operative planning, assessment of
treatment response, and evaluation for potential complications using various imaging studies, including
computed tomography angiography, magnetic resonance imaging, and perfusion scintigraphy. This article
describes the radiologist's role as part of a multi-disciplinary oncology team to help maximize the success of
HAI therapy and also helps radiologists familiarize themselves with various aspects of HAI pumps.
In a prospective multicenter trial on highly cross-linked polyethylene inserts in patients undergoing total hip
arthroplasty, 118 patients consented to 10-year follow-up. Medium-term follow-up results showed low wear at
5 and 7 years after surgery. The current study focuses on long-term data at 10 years. Patients were followed up
by either phone or office visit to collect long-term clinical data including Harris hip score and adverse events.
There were 2 deaths and 2 revisions, 1 at 6.5 years for pelvic cyst and severe pain and another at 8.0 years for
recurrent dislocation. For wear analysis, suitable radiographic images for 48 patients (52 hips) at minimum
10-year follow-up were available. Mean age of the cohort was 62.5 years (62% female). Femoral head
penetration was measured using Martell's method from the radiographic images between the 6-week and the
subsequent follow-ups. Polyethylene wear rate was calculated from the penetration data. Descriptive statistics
were performed. There was no evidence of significant oxidation or locking mechanism failure. Mean Harris
hip score of the group was 94.3. No osteolysis was noted by an independent radiographic reviewer. The slope
of the bestfit regression line to the femoral head penetration data, which represents the overall linear wear rate
of the polyethylene, was 0.014 mm/y. The wear rate was significantly below the 0.100 mm/y critical threshold
for development of osteolysis. Volumetric wear rate was calculated to be 11.6 mm(3)/y. The secondgeneration highly cross-linked polyethylene acetabular inserts had low wear in the long term (10.3 years) with
no incidence of osteolysis. [Orthopedics. 2018; 41(4):e529-e533.].
Borrini, L., et al. (2014). "Occurrence of Adverse Events in Long-Term Intrathecal
Baclofen Infusion: A 1-Year Follow-Up Study of 158 Adults." Archives of Physical
Medicine and Rehabilitation 95(6): 1032-1038.
Objective To assess the frequency and types of adverse events (AEs) related to intrathecal baclofen (ITB)
therapy in adults, and associated risk factors. Design A prospective, observational cohort study of adults
followed up from January 1 to December 31, 2010. Setting A neurologic rehabilitation department in a
university hospital. Participants All consecutive adult subjects (N=158) receiving ITB via a pump, either
implanted or followed up during the study period. Intervention Not applicable. Main Outcome Measures
Frequency and type of AEs. Results In 2010, 158 subjects were followed up for ITB therapy, of whom 128
were implanted before 2010 (nonsurgical subjects), and 30 underwent implantation in 2010 (surgical
subjects). Of these 30 subjects, 20 were “newly implanted” and 10 were “replacements.” The most frequent
pathologic disorders were spinal cord injury (42%) and multiple sclerosis (28%). Twenty-eight subjects (18%)
experienced a total of 38 AEs. The rate of AEs was .023 per month of ITB treatment. AEs were related to the
surgical procedure in 53% of cases, to the device in 29% (predominantly catheter dysfunctions), and to
adverse effects of baclofen in 18%. AEs related to the surgical incision (scar complications and collections)
were more frequent in replacement than newly implanted subjects (P=.009). No significant association
between occurrence of an AE and subject characteristics (age, gait capacity, spinal vs cerebral spasticity,
duration of ITB therapy follow-up) was found. Nearly half of the AEs were serious, extending admission time
by a mean of 16 days. No AE induced long-term morbidity or death. Conclusions The AE rate was relatively
low in this cohort. This has to be balanced against the clinical, functional, and quality-of-life improvements,
Boudaoud, A. W., et al. (2023). "Traceability of the primary Nano-flow measurement
System: Measuring the local inner diameter of a glass capillary." Measurement 218:
113141.
Bourget, P., et al. (2014). "Comparison of Raman spectroscopy vs. high performance
liquid chromatography for quality control of complex therapeutic objects: Model of
elastomeric portable pumps filled with a fluorouracil solution." Journal of
Pharmaceutical and Biomedical Analysis 91: 176-184.
As part of the Metrology for Drug Delivery (“MeDD II”) European joint research project, a primary method
for the measurement of liquid flow rates at the nanolitre per minute scale has been developed. This primary
standard allows the calibration of flow meters and flow generators such as infusion pumps, pressure
controllers and syringe pumps, for flow rates ranging from 10 nl/min to 1500 nl/min with relative expanded
uncertainties (k=2) of 12 % and 0.15 %, respectively. The system is based on the measurement of the
displacements over time of a liquid/air interface moving inside a cylindrical glass capillary tube. The flow rate
is obtained by multiplying the resulting flow velocity by the cross-sectional area of the tube which depends on
the square of the capillary’s inner radius. In order to ensure the traceability of flow rate measurements to
International System of Units, camera and frame rate calibration procedures have been established. However,
the measured flow rates depend on the local value of the inner diameter which must also be traceable. In this
paper, we present a method to measure the inner diameter of cylindrical thin-walled capillaries by confocal
microscopy. The method allows visualizing the inside of a tube by filling it with a fluorescent solution and
acquiring z-stacked images along its full height. The mean inner diameter is deduced from the widths of the
fluorescent signal in the obtained images which are measured by image processing. The method was applied
on capillaries with different inner diameters and the results were compared with the values given by
manufacturers. The relative expanded uncertainties (k=2) were estimated to a maximum of 4 %, which is two
This study compares the performance of a reference method of HPLC to Raman spectroscopy (RS) for the
analytical quality control (AQC) of complex therapeutic objects. We assessed a model consisting of a widely
used anticancer drug, i.e., 5-fluorouracil, which was compounded in a complex medical device, i.e., an
elastomeric portable infusion pump. In view of the main objective, the two methods provided excellent results
for the analytical validation key criteria, i.e., trueness, precision and accuracy, ranging from 7.5 to 50mg/mL
and in either isotonic sodium or 5% dextrose. The Spearman and Kendall correlation tests (p-value<1×10−15)
and the statistical studies performed on the graphs confirm a strong correlation in the results between RS and
the standard HPLC under the experimental conditions. The selection of a spectral interval between 700 and
1400cm−1 for both the characterization and quantification by RS was the result of a gradual process
optimization, combining matrix and packaging responses. In this new application, we demonstrate at least
eight benefits of RS: (a) operator safety, (b) elimination of disposables, (c) elimination of analysis waste,
which contributes to the protection of the environment, (d) a fast analytical response of less than 2min, (e) the
ability to identify the solubilizing phase, (f) reduction of the risk of errors because no intrusion or dilution are
needed, (g) negligible maintenance costs and (h) a reduction in the budget dedicated to technician training.
Overall, we indicate the potential of non-intrusive AQC performed by RS, especially when the analysis is not
Bourne, C., et al. (2012). "[Massive transfusion: analysis of practices according to
available medical devices]." Ann Fr Anesth Reanim 31(6): 537-542.
Bracken, H., et al. (2021). "Oral Misoprostol alone versus oral misoprostol followed
by oxytocin for labour induction in women with hypertension in pregnancy (MOLI):
protocol for a randomised controlled trial." BMC Pregnancy Childbirth 21(1): 537.
INTRODUCTION: An assessment of practices and available medical devices during the treatment of a
massive haemorrhage has been realised in the shock unit of our hospital. MATERIAL AND METHODS:
Parameters influencing transfusion flow rate have been identified. Medical devices and equipment to
accelerate the flow rate were analyzed on the basis of manufacturers' data and users opinion in relation with
their practices. RESULTS: The system, from blood bags to venous access, influences flow rate: red blood cell
viscosity, catheter and pressure gradient. Three types of acceleration systems are available: accelerated
transfusion set, pressure cuff with a gravity blood IV set and fast-flow fluid warmers. Their benefits and
disadvantages are presented and discussed. DISCUSSION: Maximum flow rates noted by manufacturers are
not the real values because some parameters such as venous catheter diameter (limitative factor) and the red
blood cell viscosity (diluted or not) are not considered. The choice of an infusion system is mainly based on
the technical capacities (flow rate fluctuations, pressure gradient on blood bags, warming, air purging),
practical modalities of use (medical devices and assembly) and cost. The pressure cuff with transfusion
gravity set should be limited to non-critical situations or during the assembly of the fast flow fluid warmers
(but no warming fluids, no air embolism prevention). The accelerated transfusion set is not the best option for
a shock unit because it needs an operator permanently. The fast-flow fluid warmers are recommended for all
BACKGROUND: Every year approximately 30,000 women die from hypertensive disease in pregnancy.
Magnesium sulphate and anti-hypertensives reduce morbidity, but delivery is the only cure. Low dose oral
misoprostol, a prostaglandin E1 analogue, is a highly effective method for labour induction. Usually, once
active labour has commenced, the misoprostol is replaced with an intravenous oxytocin infusion if ongoing
stimulation is required. However, some studies have shown that oral misoprostol can be continued into active
labour, a simpler and potentially more acceptable protocol for women. To date, these two protocols have
never been directly compared. METHODS: This pragmatic, open-label, randomised trial will compare a
misoprostol alone labour induction protocol with the standard misoprostol plus oxytocin protocol in three
Indian hospitals. The study will recruit 520 pregnant women being induced for hypertensive disease in
pregnancy and requiring augmentation after membrane rupture. Participants will be randomised to receive
either further oral misoprostol 25mcg every 2 h, or titrated intravenous oxytocin. The primary outcome will be
caesarean birth. Secondary outcomes will assess the efficacy of the induction process, maternal and
fetal/neonatal complications and patient acceptability. This protocol (version 1.04) adheres to the SPIRIT
checklist. A cost-effectiveness analysis, situational analysis and formal qualitative assessment of women's
experience are also planned. DISCUSSION: Avoiding oxytocin and continuing low dose misoprostol into
active labour may have a number of benefits for both women and the health care system. Misoprostol is heat
stable, oral medication and thus easy to store, transport and administer; qualities particularly desirable in low
resource settings. An oral medication protocol requires less equipment (e.g. electronic infusion pumps) and
may free up health care providers to assist with other aspects of the woman's care. The simplicity of the
protocol may also help to reduce human errors associated with the delivery of intravenous infusions. Finally,
women may prefer to be mobile during labour and not restricted by an intravenous infusion. There is a need,
therefore, to assess whether augmentation using oral misoprostol is superior clinically and economically to the
standard protocol of intravenous oxytocin. TRIAL REGISTRATION: Clinical Trials.gov, NCT03749902 ,
Brown, S., A. Yao and P. J. Taub (2018). "Antifibrinolytic Agents in Plastic Surgery:
Current Practices and Future Directions." Plast Reconstr Surg 141(6): 937e-949e.
BACKGROUND: Prevention of blood loss is a chief consideration in plastic and reconstructive surgery. The
antifibrinolytic drugs tranexamic acid and ε-aminocaproic acid have emerged as promising agents to reduce
both perioperative blood loss and transfusion requirements. However, published reports in the plastic surgery
literature are lacking. The authors sought to summarize the current knowledge of the use of antifibrinolytics in
plastic surgery by reviewing the existing literature for clinical outcomes and recommendations. METHODS:
A systematic review of the PubMed, Cochrane, and Google Scholar databases was conducted for publications
examining the use of antifibrinolytics in plastic surgery. Studies were abstracted for procedure type,
antifibrinolytic dose, time and mode of administration, blood loss, transfusion requirements, and
complications. RESULTS: Thirty-three studies were deemed eligible for inclusion, comprising a total of 1823
patients undergoing plastic surgical procedures with tranexamic acid (n = 1328) and/or ε-aminocaproic acid (n
= 495). CONCLUSIONS: Tranexamic acid and ε-aminocaproic acid are widely used to reduce blood loss and
transfusion requirements in craniofacial and orthognathic surgery, without an increased risk of adverse events.
Intravenous administration is most commonly used, although topical formulations show similar efficacy with
a reduced systemic distribution. Tranexamic acid has also emerged as a promising agent in aesthetic surgery
and burn care, due to its favorable safety profile and role in reducing blood loss, achieving an improved
surgical field, and reducing edema and ecchymosis. Further investigation of these agents in the fields of burn
Bryant, B. J., et al. (2010). "Gravity sedimentation of granulocytapheresis
concentrates with hydroxyethyl starch efficiently removes red blood cells and retains
neutrophils." Transfusion 50(6): 1203-1209.
BACKGROUND: Transfusion of granulocytapheresis concentrates can be limited by the volume of
incompatible donor red blood cells (RBCs) in the component. Efficient reduction of RBCs in granulocyte
units would result in safe transfusion of RBC-incompatible units. STUDY DESIGN AND METHODS:
Granulocyte concentrates were collected by continuous-flow apheresis from granulocyte-colony-stimulating
factor (G-CSF) and dexamethasone-stimulated volunteer donors, with 6% hydroxyethyl starch (HES) added
continuously during apheresis as a RBC sedimenting agent to enhance granulocyte collection efficiency. After
collection, the component was placed in a plasma extractor for 4 hours. A sharp line of demarcation between
the starch-sedimented RBCs and the granulocyte-rich supernatant developed, and the supernatant was
transferred to a sterilely docked transfer pack. RBC reduction and white blood cell recovery were determined.
RESULTS: Gravity sedimentation was performed on 165 granulocyte concentrates. Mean sedimentation time
was 267 minutes (range, 150-440 min). RBC depletion was 92% (range, 71%-99%) with mean residual RBC
content of 3.2 +/- 1.4 mL. Twelve percent of components contained less than 2 mL of RBCs. Mean
granulocyte and platelet (PLT) recoveries were 80 and 81%, respectively. There were no transfusion reactions
or signs of hemolysis after transfusion of 66 RBC-incompatible granulocyte concentrates (RBC volume, 1.68.2 mL). The remaining concentrates were used for topical or intrapleural applications. CONCLUSIONS:
RBCs were significantly reduced and granulocytes and PLTs effectively retained in G-CSF/steroid-mobilized
granulocyte components collected with HES and processed by gravity sedimentation. This procedure allows
safe transfusion of RBC-incompatible sedimented granulocyte units and may be used to expand the pool of
Buchko, J. Z., T. Gurney-Dunlop and J. J. Shin (2015). "Knee chondrolysis by
infusion of bupivacaine with epinephrine through an intra-articular pain pump catheter
after arthroscopic ACL reconstruction." Am J Sports Med 43(2): 337-344.
Bugbee, W. D., et al. (2016). "Use of an Anti-Gravity Treadmill for Early
Postoperative Rehabilitation After Total Knee Replacement: A Pilot Study to
Determine Safety and Feasibility." Am J Orthop (Belle Mead NJ) 45(4): E167-173.
BACKGROUND: Postoperative knee chondrolysis caused by continuous intra-articular pain pumps infusing
bupivacaine with epinephrine is a rare but serious complication. PURPOSE: To determine the association
between postoperative intra-articular infusion of bupivacaine with epinephrine and the development of knee
chondrolysis in patients who have undergone arthroscopic anterior cruciate ligament reconstruction (ACLR).
The authors hypothesized that the development of knee chondrolysis after ACLR is associated with
postoperative high-dose intra-articular bupivacaine with epinephrine infusion. STUDY DESIGN: Cohort
study; Level of evidence, 3. METHODS: In this retrospective cohort study, the charts of all patients treated
with arthroscopic ACLR by a single surgeon between January 1, 2004, and December 31, 2006, were
reviewed. Patients with severe articular cartilage damage at the time of the index procedure, with known knee
joint infection, inflammatory arthritis, multiligament knee injury, bilateral knee injury, or any previous knee
surgery, were excluded. Patients were grouped into 2 cohorts: the exposure group (those who had
postoperative infusion of bupivacaine with epinephrine via an intra-articular pain pump [IAPP]) and the
nonexposure group (those without postoperative infusion). RESULTS: A total of 105 patients met the
inclusion and exclusion criteria. There were 57 male and 48 female patients with a mean age at surgery of
25.5 ± 8.6 years (range, 13-52 years). The exposure group consisted of 46 patients and the control group of 59
patients. Thirteen of 46 patients (28.3%) who received an IAPP developed chondrolysis. There were no cases
of chondrolysis in the control group. Of those in the exposure group, 32 patients were exposed to 0.5%
bupivacaine with epinephrine and 12 developed chondrolysis (37.5%), while 14 patients were exposed to
0.25% bupivacaine with epinephrine and 1 developed chondrolysis (7.1%). Patients exposed to 0.5%
bupivacaine with epinephrine had a significantly higher incidence of chondrolysis compared with those
exposed to 0.25% (P = .03). Patients with chondrolysis had severe pain and limitations in daily activity.
CONCLUSION: The development of knee chondrolysis was associated with the intra-articular infusion of
bupivacaine with epinephrine postoperatively. Furthermore, the presented evidence suggests that this occurs
in a dose-dependent manner. The risk of knee chondrolysis might be reduced by avoidance of intra-articular
infusion of bupivacaine with epinephrine. We recommend against continuous intra-articular infusion of local
The objective was to determine the safety, feasibility, and effects of anti-gravity gait training on functional
outcomes (Knee Injury and Osteoarthritis Outcome Score [KOOS], the Timed Up and Go test [TUG],
Numerical Rating Scale [NRS] for pain) with the AlterG® Anti-Gravity Treadmill® device for total knee
arthroplasty (TKA) rehabilitation. Subjects (N = 30) were randomized to land-based vs anti-gravity gait
training over 4 weeks of physical therapy after TKA. Adverse events, complications, and therapist satisfaction
were recorded. All patients completed rehabilitation protocols without adverse events. KOOS, TUG, and NRS
scores improved in both groups with no significant differences between groups. For the AlterG group,
Sports/Recreation and Quality of Life subscales of the KOOS had the most improvement. At the end of
physical therapy, TUG and NRS pain scores improved from 14 seconds to 8 seconds and from 2.8 to 1.1,
respectively. Subjectively, therapists reported 100% satisfaction with the AlterG. This initial pilot study
demonstrated that the AlterG Anti-Gravity Treadmill device was safe and feasible. While functional outcomes
improved over time with use of the anti-gravity gait training, further studies are needed to define the role of
this device as an alternative or adjunct to established rehabilitation protocols.
Burke, H. M., et al. (2014). "Observational study of the acceptability of Sayana®
Press among intramuscular DMPA users in Uganda and Senegal." Contraception
89(5): 361-367.
Butterfield, J. (2015). "Assessing the Montevideo interpretation of quantum
mechanics." Studies in History and Philosophy of Science Part B: Studies in History
and Philosophy of Modern Physics 52: 75-85.
BACKGROUND: Sayana® Press (SP), a subcutaneous formulation of depot medroxyprogesterone acetate
(DMPA) in Uniject™, has potential to be a valuable innovation in family planning (FP) because it may
overcome logistic and safety challenges in delivering intramuscular DMPA (DMPA IM). However, SP's
acceptability is unknown. We measured acceptability of SP among DMPA IM users. STUDY DESIGN: This
open-label observational study was conducted in clinics in three districts in Senegal and community-based
distribution services in two districts in Uganda. Experienced DMPA IM users were offered SP by community
health workers (CHWs) or clinic-based providers. SP decliners were asked to discuss their reasons. Those
who received SP were interviewed pre- and postinjection and 3 months later, when they were asked if they
would select SP over DMPA IM if it were available. RESULTS: One hundred twenty women in Uganda and
242 in Senegal received SP (117 and 240 were followed up, respectively). Nine Ugandan and seven
Senegalese SP decliners were interviewed. Three months after receiving SP, 84% [95% confidence interval
(CI)=75%-93%] of Ugandan participants and 80% (95% CI=74%-87%) of Senegalese participants said they
would select SP over DMPA IM. Main reasons for selecting SP were fewer side effects, liking the method,
fast administration, less pain and method effectiveness. Thirty-four adverse events were reported but were not
serious. No pregnancies were reported. CONCLUSION: Current DMPA IM users in Senegal and Uganda
accepted SP, and most preferred SP over DMPA IM. SP can be safely introduced into FP programs and
administered by trained CHWs, with expectation of client uptake. IMPLICATIONS: We found SP acceptable
and safe in diverse settings among current intramuscular DMPA users, including those who received SP from
CHWs. This provides evidence that SP would be used and could therefore reduce unmet family planning
This paper gives a philosophical assessment of the Montevideo interpretation of quantum theory, advocated
by Gambini, Pullin and co-authors. This interpretation has the merit of linking its proposal about how to solve
the measurement problem to the search for quantum gravity: namely by suggesting that quantum gravity
makes for fundamental limitations on the accuracy of clocks, which imply a type of decoherence that
‘collapses the wave-packet’. I begin (Section 2) by sketching the topics of decoherence, and quantum clocks,
on which the interpretation depends. Then I expound the interpretation, from a philosopher‫׳‬s perspective (3
Evolution with respect to a real clock, 4 The meanings and roles of a mixture, 5 Throwing away the ladder).
Finally, in Section 6, I argue that the interpretation, at least as developed so far, is best seen as a form of the
Everett interpretation: namely with an effective or approximate branching, that is induced by environmental
decoherence of the familiar kind, and by the Montevideans’ ‘temporal decoherence’.
Cabello González, C. and P. C. Trandafir (2018). "Estudio de calidad de vida con la
PDQ39 en pacientes con enfermedad de Parkinson tratados con terapias avanzadas."
Revista Científica de la Sociedad Española de Enfermería Neurológica 48: 9-14.
Resumen La enfermedad de Parkinson es una enfermedad neurodegenerativa que puede llevar
progresivamente a la pérdida de calidad de vida y a la discapacidad. El tratamiento convencional es efectivo
en los primeros años de evolución de la enfermedad, pero cuando aparecen complicaciones motoras y no
motoras que repercuten claramente en su calidad de vida, es momento de plantearse otros tipos de terapias. En
la actualidad disponemos de tres terapias avanzadas que han demostrado ser beneficiosas para este tipo de
pacientes: la estimulación cerebral profunda, la terapia con bomba de apomorfina subcutánea y la terapia con
bomba de Duodopa® a través del duodeno. Objetivos Conocer el impacto de las terapias avanzadas en la
calidad de vida de los pacientes con EP, medida con la escala PDQ39. Método Estudio observacional,
prospectivo, no aleatorizado. Se realizaron tres mediciones (n=20) con la PDQ39 en diferentes momentos: 1.ª
previa al inicio de la TAV, 2.ª a los 3-5 meses y 3.ª a los 6-10 meses. Resultados Los hombres que se tratan
con terapias avanzadas son menores y con menos años de evolución de la enfermedad que las mujeres. Existen
diferencias significativas entre las tres medidas para el bienestar emocional, el estigma, el estado cognitivo y
la valoración total de la PDQ39. Asimismo, hay diferencias significativas, por parejas, a largo plazo para los
mismos. El apoyo social empeora al someterse a estas terapias. Conclusiones Se refleja la mejoría, de manera
global (PDQ39 total), en la calidad de vida medida con la escala PDQ39 en los pacientes sometidos a TAV en
el Complejo Hospitalario de Navarra en un periodo de 10 meses. Parkinson's disease is a neurological chronic
degenerative disorder which can lead to a progressive loss of quality of life and to incapacitation.
Conventional treatment is effective in the first years of the disease, but other kinds of therapy should be
considered upon the onset of motor and non-motor complications that are clearly impacting quality of life. At
present we have three advanced therapies which have proven beneficial for these types of patients, namely:
deep cerebral stimulation, subcutaneous apomorphine infusion pumps, and continuous intestinal levodopa
infusion to the duodenum (Duodopa®). Objectives To assess the impact of advanced therapies on the quality
of life of patients with Parkinson's disease, measured using the PDQ39 scale. Methods Observational,
prospective, non-randomized study. Three measurements (n=20) using the PDQ39 scale were taken: the first
before initiating advanced therapy, the second at 3-5 months, and the third at 6-10 months. Results Men who
receive treatment with advanced therapies are younger and have fewer years of progression of the disease than
women. There were significant differences between the three measurements in terms of emotional well-being,
stigmatization, cognitive state and overall assessment of PDQ39. Similarly, significant differences were found
Cabello González, C. and P. C. Trandafir (2018). "The study of health-related quality
of life using PDQ39 in patients with Parkinson's disease treated with advanced
therapies." Revista Científica de la Sociedad de Enfermería Neurológica (English ed.)
48: 9-14.
Parkinson's disease is a neurological chronic degenerative disorder which can lead to a progressive loss of
quality of life and to incapacitation. Conventional treatment is effective in the first years of the disease, but
other kinds of therapy should be considered upon the onset of motor and non-motor complications that are
clearly impacting quality of life. At present we have three advanced therapies which have proven beneficial
for these types of patients, namely: deep cerebral stimulation, subcutaneous apomorphine infusion pumps, and
continuous intestinal levodopa infusion to the duodenum (Duodopa®). Objectives To assess the impact of
advanced therapies on the quality of life of patients with Parkinson's disease, measured using the PDQ39
scale. Methods Observational, prospective, non-randomized study. Three measurements (n=20) using the
PDQ39 scale were taken: the first before initiating advanced therapy, the second at 3–5 months, and the third
at 6–10 months. Results Men who receive treatment with advanced therapies are younger and have fewer
years of progression of the disease than women. There were significant differences between the three
measurements in terms of emotional well-being, stigmatisation, cognitive state and overall assessment of
PDQ39. Similarly, significant differences were found in pairs in the long term in these parameters. Social
support deteriorated after entering advanced therapy. Conclusions Significant global improvements were
observed in quality of life, measured using the PDQ39 scale, of patients with Parkinson's disease, treated with
advanced therapy in the Hospital of Navarre for 10 months. Resumen La enfermedad de Parkinson es una
enfermedad neurodegenerativa que puede llevar progresivamente a la pérdida de calidad de vida y a la
discapacidad. El tratamiento convencional es efectivo en los primeros años de evolución de la enfermedad,
pero cuando aparecen complicaciones motoras y no motoras que repercuten claramente en su calidad de vida,
es momento de plantearse otros tipos de terapias. En la actualidad disponemos de tres terapias avanzadas que
han demostrado ser beneficiosas para este tipo de pacientes: la estimulación cerebral profunda, la terapia con
bomba de apomorfina subcutánea y la terapia con bomba de Duodopa® a través del duodeno. Objetivos
Conocer el impacto de las terapias avanzadas en la calidad de vida de los pacientes con EP, medida con la
escala PDQ39. Método Estudio observacional, prospectivo, no aleatorizado. Se realizaron tres mediciones
(n=20) con la PDQ39 en diferentes momentos: 1.ª previa al inicio de la TAV, 2.ª a los 3–5 meses y 3.ª a los
6–10 meses. Resultados Los hombres que se tratan con terapias avanzadas son menores y con menos años de
evolución de la enfermedad que las mujeres. Existen diferencias significativas entre las tres medidas para el
bienestar emocional, el estigma, el estado cognitivo y la valoración total de la PDQ39. Asimismo, hay
Cahn, A., et al. (2013). "Safety, tolerability, pharmacokinetics and pharmacodynamics
of GSK2239633, a CC-chemokine receptor 4 antagonist, in healthy male subjects:
results from an open-label and from a randomised study." BMC Pharmacol Toxicol
14: 14.
BACKGROUND: The CC-chemokine receptor 4 (CCR4) is thought potentially to play a critical role in
asthma pathogenesis due to its ability to recruit type 2 T-helper lymphocytes to the inflamed airways.
Therefore, CCR4 provides an excellent target for anti-inflammatory therapy. METHODS: The safety,
tolerability, pharmacokinetics and pharmacodynamics of the CCR4 antagonist GSK2239633, N-(3-((3-(5chlorothiophene-2-sulfonamido)-4-methoxy-1H-indazol-1-yl)methyl)benzyl)-2-hydroxy-2methylpropanamide, were examined in healthy males. Two studies were performed: 1) an open-label, study in
which six subjects received a single intravenous infusion of [14C]-GSK2239633 100 μg (10 kBq)
(NCT01086462), and 2) a randomised, double-blind, placebo-controlled, cross-over, ascending dose study in
which 24 subjects received single oral doses of GSK2239633 150-1500 mg (NCT01371812). RESULTS:
Following intravenous dosing, plasma GSK2239633 displayed rapid, bi-phasic distribution and slow terminal
elimination (t½: 13.5 hours), suggesting that GSK2239633 was a low to moderate clearance drug. Following
oral dosing, blood levels of GSK2239633 reached Cmax rapidly (median tmax: 1.0-1.5 hours). Estimated
GSK2239633 bioavailability was low with a maximum value determined of only 16%. Food increased
GSK2239633 systemic exposure (as assessed by AUC and Cmax). Increases in AUC and Cmax were less than
dose proportional. Adverse events were reported by three subjects (50%) following intravenous
administration, and by 19 subjects (79%) following oral administration; most (46/47; 98%) events were
mild/moderate in intensity. GSK2239633 1500 mg inhibited thymus- and activation-regulated chemokineinduced (TARC) actin polymerisation reaching a mean CCR4 occupancy of 74%. CONCLUSION: In
Calleja, J. L., et al. (2016). "Ferric carboxymaltose reduces transfusions and hospital
stay in patients with colon cancer and anemia." Int J Colorectal Dis 31(3): 543-551.
PURPOSE: The purpose of the study was to evaluate the efficacy of preoperative intravenous (IV) ferric
carboxymaltose (FCM) administration vs. no-IV iron in colon cancer (CC) anemic patients undergoing
elective surgery with curative intention. METHODS: This was a multicenter, observational study including
two cohorts of consecutive CC anemic patients: the no-IV iron treatment group was obtained retrospectively
while FCM-treated patients were recorded prospectively. RESULTS: A total of 266 patients were included:
111 received FCM (median dose 1000 mg) and 155 were no-IV iron subjects. Both groups were similar in
terms of demographic characteristics, tumor location, surgical approach, and intra-operative bleeding severity.
The FCM group showed a significant lower need for red blood cell (RBC) transfusion during the study (9.9
vs. 38.7%; OR: 5.9, p < 0.001). In spite of lower hemoglobin levels at baseline diagnosis and lower
transfusion rates in the FCM group, the proportion of responders was significantly higher with respect to the
no-IV group both at hospital admission (48.1 vs. 20.0%, p < 0.0001) and at 30 days post-surgery (80.0 vs.
48.9%, p < 0.0001). The percentage of patients with normalized hemoglobin levels was also higher in the
FCM group (40.0 vs. 26.7% at 30 days, p < 0.05). A lower number of reinterventions and post-surgery
complications were seen in the FCM group (20.7 vs. 26.5%; p = 0.311). The FCM group presented a
significant shorter hospital stay (8.4 ± 6.8 vs. 10.9 ± 12.4 days to discharge; p < 0.001). CONCLUSIONS:
Preoperative ferric carboxymaltose treatment in patients with CC and iron deficiency anemia significantly
reduced RBC transfusion requirements and hospital length of stay, reaching higher response rates and
Cappellini, M. D., et al. (2019). "Sotatercept, a novel transforming growth factor β
ligand trap, improves anemia in β-thalassemia: a phase II, open-label, dose-finding
study." Haematologica 104(3): 477-484.
Cavalli, F. S., et al. (2023). "Intravenous Use of Tranexamic Acid in Total Knee
Arthroplasty with no Tourniquet." Rev Bras Ortop (Sao Paulo) 58(4): e599-e603.
β-thalassemia, a hereditary blood disorder caused by defective synthesis of hemoglobin β globin chains, leads
to ineffective erythropoiesis and chronic anemia that may require blood transfusions. Sotatercept (ACE-011)
acts as a ligand trap to inhibit negative regulators of late-stage erythropoiesis in the transforming growth
factor β superfamily, correcting ineffective erythropoiesis. In this phase II, open-label, dose-finding study, 16
patients with transfusion-dependent β -thalassemia and 30 patients with non-transfusion-dependent βthalassemia were enrolled at seven centers in four countries between November 2012 and November 2014.
Patients were treated with sotatercept at doses of 0.1, 0.3, 0.5, 0.75, or 1.0 mg/kg to determine a safe and
effective dose. Doses were administered by subcutaneous injection every 3 weeks. Patients were treated for ≤
22 months. Response was assessed as a ≥20% reduction in transfusion burden sustained for 24 weeks in
transfusion-dependent β-thalassemia patients, and an increase in hemoglobin level of ≥1.0 g/dL sustained for
12 weeks in non-transfusion-dependent β-thalassemia patients. Sotatercept was well tolerated. After a median
treatment duration of 14.4 months (range 0.6-35.9), no severe life-threatening adverse events were observed.
Thirteen percent of patients reported serious but manageable adverse events. The active dose of sotatercept
was ≥0.3 mg/kg for patients with non-transfusion-dependent β-thalassemia and ≥0.5 mg/kg for those with
transfusion-dependent β-thalassemia. Of 30 non-transfusion-dependent β-thalassemia patients treated with ≥
0.1 mg/kg sotatercept, 18 (60%) achieved a mean hemoglobin increase ≥1.0 g/dL, and 11 (37%) an increase ≥
1.5 g/dL, sustained for ≥12 weeks. Four (100%) transfusion-dependent β-thalassemia patients treated with 1.0
mg/kg sotatercept achieved a transfusion-burden reduction of ≥20%. Sotatercept was effective and well
tolerated in patients with β-thalassemia. Most patients with non-transfusion-dependent β-thalassemia treated
with higher doses achieved sustained increases in hemoglobin level. Transfusion-dependent β-thalassemia
patients treated with higher doses of sotatercept achieved notable reductions in transfusion requirements. This
Objective: To identify blood transfusion requirements and postoperative complications in patients
undergoing total knee arthroplasty (TKA) with no tourniquet and intraoperative intravenous administration of
tranexamic acid. Methods: This retrospective observational study analyzed 49 preopeative and
postoperative medical records of patients undergoing TKA. A paired t-test compared changes in hemoglobin
(HB) and packed cell volume (PCV), and an independent t-test with Welch correction compared HB and PCV
changes between genders. A Spearman correlation test determined associations between age and days of
postoperative hospitalization with HB and PCV changes. The significance level adopted was p < 0.05. Results:
The patients' mean age was 71.9 ± 6.7 years; most subjects were women (73.5%). The right side (59.2%)
was the most affected. Only one participant required a blood transfusion, while three subjects had
complications during the postoperative follow-up. No patient had a thromboembolic event. The median length
of postoperative hospital stay was 2 days (interquartile range [IQR] = 1.0). There were reductions in HB and
PCV levels between the pre-operative and postoperative period, and female patients had a higher HB
reduction. Conclusion: TKA with tranexamic acid and no tourniquet did not cause significant postoperative
complications or require blood transfusions.
Cavallini, A., D. Marcer and S. Ferrari Ruffino (2014). "Endovenous ablation of
incompetent saphenous veins with a new 1,540-nanometer diode laser and ball-tipped
fiber." Ann Vasc Surg 28(3): 686-694.
Čečka, F., et al. (2018). "Results of a randomized controlled trial comparing closedsuction drains versus passive gravity drains after pancreatic resection." Surgery
164(5): 1057-1063.
BACKGROUND: Endovenous laser ablation (EVLA) is an efficient method to treat incompetent saphenous
veins with high occlusion rates. The major side effects are postoperative pain and bruising. Laser systems with
higher wavelengths, associated with new energy delivery devices, have recently shown excellent short-term
results, while reducing the previously reported side effects. The aim of this study is to show the first outcome
after EVLA of incompetent saphenous veins with a newly developed ball-tipped fiber and a new wavelength
1,540-nm diode laser. METHODS: Forty-five incompetent saphenous veins in 35 patients (27 women) were
treated: 33 great saphenous veins, 6 short saphenous veins, and 6 anterior saphenous veins. The gravity of
chronic venous disease was determined according to the clinical-etiology-anatomy-pathophysiology (CEAP)
classification, and the severity of symptoms was scored according to the revised Venous Clinical Severity
Score. Patient satisfaction was assessed on a 0-3 scale. RESULTS: The average linear endovenous energy
density was 63.5 J/cm of vein length. Patients returned to daily activities after a mean of 1.7 days (SD: 2) after
treatment. The modified CEAP clinical severity score improved drastically from a preintervention mean of 4.9
(SD: 2.6) to 0.17 (SD: 0.38) at day 30. During the follow-up period (mean: 168 days [range: 90-240 days]), all
the veins were occluded. All patients except 1 were satisfied or very satisfied with the method. No severe
complications occurred. Two patients (5%) developed mild paresthesia in the treated area, which
spontaneously resolved after 3 months. Postoperative ecchymoses are frequent (83%). Sixteen patients (43%)
experienced pain, but only 5 patients (14%) described it as quite intense and required analgesic therapy.
CONCLUSION: EVLA of saphenous veins with a 1,540-nm diode laser using a ball-tipped fiber is a safe and
Background This dual-center, randomized controlled trial aimed to compare 2 types of intra-abdominal drains
after pancreatic resection and their effect on the development of pancreatic fistulae and postoperative
complications. Methods Patients undergoing pancreatic resection were randomized to receive either a closedsuction drain or a closed, passive gravity drain. The primary endpoint was the rate of postoperative pancreatic
fistula. A secondary endpoint was postoperative morbidity during follow-up of 3 months. The planned sample
size was 223 patients. Results A total of 294 patients were assessed for eligibility, 223 of whom were
randomly allocated. One patient was lost during follow-up, and 111 patients in each group were analyzed. The
rate of postoperative pancreatic fistula (closed-suction 43.2%, passive 36.9%, P = .47) and overall morbidity
(closed-suction 51.4%, passive 40.5%, P = .43) were not different between the groups. We did not find any
differences between the groups in reoperation rate (P = .45), readmission rate (P = .27), hospital stay (P = .68),
or postoperative hemorrhage (P = .11). We found a significantly lesser amount of drain fluid in the passive
gravity drains between the second and fifth postoperative days and also on the day of drain removal compared
with closed-suction drains. Conclusion The type of drain (passive versus closed suction) had no influence on
the rate of postoperative pancreatic fistulae. The closed-suction drains did not increase the rate of
postoperative complications. We found that the passive gravity drains are more at risk for obstruction,
Cerveri, P., et al. (2016). "Patient-specific modeling of the trochlear morphologic
anomalies by means of hyperbolic paraboloids." Comput Assist Surg (Abingdon)
21(1): 29-38.
Diagnostic and therapeutic purposes are issuing pressing demands to improve the evaluation of the dysplasia
condition of the femoral trochlea. The traditional clinical assessment of the dysplasia, based on Dejour
classification, recognized 4 increasing (A, B, C, D) levels of severity. It has been extensively questioned in the
literature that this classification methodology can be defective suggesting that quantitative measures can
ensure more reliable criteria for the dysplasia severity assessment. This study reports on a novel technique to
model the trochlear surface (TS), digitally reconstructed by 3D volumetric imaging, using three hyperbolic
paraboloids (HP), one to describe the global trochlear aspect, two to represent the local aspects of the medial
and lateral compartments, respectively. Results on a cohort of 43 patients, affected by aspecific anterior knee
pain, demonstrate the consistency of the estimated model parameters with the morphologic aspect of the TS.
The obtained small fitting error (on average lower than 0.80 mm) demonstrated that the ventral aspect of the
trochlear morphology can be modeled with high accuracy by HPs. We also showed that HP modeling provides
a continuous representation of morphologic variations in shape parameter space while we found that similar
morphologic anomalies of the trochlear aspect are actually attributed to different severity grades in the Dejour
classification. This finding is in agreement with recent works in the literature reporting that morphometric
parameters can only optimistically be used to discriminate between the Grade A and the remaining three
grades. In conclusion, we can assert that the proposed methodology is a further step toward modeling of
anatomical surfaces that can be used to quantify deviations to normality on a patient-specific basis.
Chalmers, B. P., et al. (2021). "Is There a Synergistic Effect of Topical Plus
Intravenous Tranexamic Acid Versus Intravenous Administration Alone on Blood
Loss and Transfusions in Primary Total Hip and Knee Arthroplasties?" Arthroplast
Today 7: 194-199.
Chan, A. K. Y., et al. (2022). "Effectiveness of 38% Silver Diamine Fluoride in
Reducing Dentine Hypersensitivity on Exposed Root Surface in Older Chinese Adults:
Study Protocol for a Randomised Double-Blind Study." Dent J (Basel) 10(10).
BACKGROUND: The optimal route and dosing regimen of tranexamic acid (TXA) in primary total hip
arthroplasty (THA) and total knee arthroplasty (TKA) remain unclear. As such, we sought to analyze if there
was a synergistic effect of intravenous (IV) and topical TXA on blood loss and transfusions. METHODS: We
retrospectively analyzed 6720 primary TKAs and 6559 THAs performed from February 1, 2016 to December
31, 2019 at a single institution in patients who received a double IV dose (6159 TKAs and 6276 THAs)
compared with a combined single IV and topical dose (561 TKAs and 283 THAs) of TXA. Multivariate
logistic regression models, adjusting for age, body mass index, American Society of Anesthesiologists class,
preoperative hemoglobin, and TXA administration, were performed for significant variables from a univariate
analysis. RESULTS: In the TKA cohort, the mean total blood loss was statistically similar for double IV (305
mL, 95% confidence interval [CI] = 301-310 mL) TXA compared with combined TXA (310 mL, 95% CI =
299-321 mL) (P = .43). Furthermore, there was no difference in the rate of transfusion (odds ratio = 1.23, 95%
CI = 0.57-2.67, P = .598). In the THA cohort, there was statistically higher blood loss with double IV (328
mL, 95% CI = 323-333 mL) TXA than in the combined group (295 mL, 95% CI = 280-310 mL) (P < .001).
The rate of transfusion was statistically similar at ~2% (P = .970). CONCLUSIONS: A double IV TXA dose
and a combined single IV and topical TXA dose were equally effective in minimizing blood transfusions
(~2%) at primary TKA and THA. We did not find a synergistic effect when combining a systemic IV TXA
BACKGROUND: Dentine hypersensitivity on an exposed root surface induces pain, affects daily oral hygiene
practice, limits dietary choices and negatively affects quality of life. Silver diamine fluoride is marketed in the
United States as a desensitising agent, but well-designed clinical trials are limited. This study evaluates the
anti-hypersensitivity effect of silver diamine fluoride on hypersensitive teeth due to an exposed root surface in
older Chinese adults. METHODS/DESIGN: We will conduct a randomised double-blind clinical trial with a
sample size of at least 148 Chinese older adults aged 65 or above who have dentine hypersensitivity due to an
exposed root surface. We will collect written consent before the study. A trained examiner will examine the
participants' teeth with a blast of compressed air from a 3-in-1 syringe. Those adults who report a selfperceived sensitivity score (SS) (0 to 10) of 8 or more on at least one tooth with an exposed root surface will
be recruited. The recruited older adults will be randomly allocated into two groups using a block
randomisation of six. Group 1 participants will receive the application of 38% silver diamine fluoride solution
every 4 weeks. Group 2 participants will receive the application of 5% potassium nitrate solution every 4
weeks. Dietary advice, oral hygiene instruction and fluoride toothpaste at 1450 ppm will be provided to
participants in both groups. The same trained examiner will perform follow-up examinations for the
participants and determine the dentine hypersensitivity in SS of the most hypersensitive tooth (with the
highest pre-treatment SS) immediately after the intervention and at 4-week and 8-week intervals.
DISCUSSION: There is no consensus on the standard of care for a professionally applied desensitising agent
in older adults. This trial will provide evidence for clinicians to devise an effective dental care plan for older
Chan, A. K. Y., et al. (2023). "Treating hypersensitivity in older adults with silver
diamine fluoride: A randomised clinical trial." J Dent 136: 104616.
OBJECTIVE: This study aimed to evaluate the desensitizing effect of topically applied 38% silver diamine
fluoride (SDF) solution on the exposed root surface of hypersensitive teeth in older adults. METHOD: This
double-blind randomised clinical trial recruited healthy older adults with dentine hypersensitivity. A trained
examiner tested the most hypersensitive tooth root surface with a blast of compressed cold air from a three-inone syringe. The participants gave a sensitivity score (SS) in visual analogue scale from 0 (no pain) to 10
(agonizing) at the baseline visit. Then, they received 38% SDF or 5% potassium nitrate solution (control) as
intervention on the root surface. After the intervention, they received a compressed cold air test and reported
the SS again. The compressed cold air test followed by intervention was repeated at 4- and 8-week follow ups.
The primary outcome was the reduction in SS at 8-week follow-up with reference to the SS at baseline before
intervention. Shapiro-Wilk and Mann-Whitney U tests were performed for data analysis following a normality
test of SS. RESULTS: This trial recruited 148 participants, and 139 (94%) participants completed the trial.
The median percentage reductions in SS in the SDF and potassium nitrate groups were 60% and 50%,
respectively (p < 0.001). CONCLUSION: According to the results, 38% SDF solution reduced
hypersensitivity on the exposed root surface of older adults. In addition, 38% SDF was more effective than
5% potassium nitrate solution to reduce hypersensitivity on the exposed root surface of older adults.
CLINICAL SIGNIFICANCE: Dentin hypersensitivity is common amongst older adults and negatively affects
their quality of life. To date, there is no gold standard professionally applied desensitizing therapy in treating
hypersensitivity. Evidence from this clinical trial could aid clinical practice and improve oral health in older
Chan, M., et al. (2017). "Magnetic Resonance-Guided High-Intensity-Focused
Ultrasound for Palliation of Painful Skeletal Metastases: A Pilot Study." Technol
Cancer Res Treat 16(5): 570-576.
Chavez-Chiang, C. E., et al. (2011). "The highly accurate anteriolateral portal for
injecting the knee." Sports Med Arthrosc Rehabil Ther Technol 3(1): 6.
BACKGROUND: Bone is one of the most common sites of metastases, with bone metastases-related pain
representing a significant source of morbidity among patients with cancer. Magnetic resonance-guided
focused ultrasound is a noninvasive, outpatient modality with the potential for treating painful bone
metastases. The aim of this study is to report our initial experience with magnetic resonance-guided focused
ultrasound in the treatment of bone metastases and our preliminary analysis of urinary cytokine levels after
therapy. METHODS: This was a single-center pilot study of 10 patients with metastatic cancer to investigate
the feasibility of magnetic resonance-guided focused ultrasound for primary pain control in device-accessible
skeletal metastases. Treatments were performed on a clinical magnetic resonance-guided focused ultrasound
system using a volumetric ablation technique. Primary efficacy was assessed using Brief Pain Inventory scores
and morphine equivalent daily dose intake at 3 time points: before, day 14, and day 30 after the magnetic
resonance-guided focused ultrasound treatment. Urine cytokines were measured 3 days before treatment and 2
days after the treatment. RESULTS: Of the 10 patients, 8 were followed up 14 days and 6 were followed up
30 days after the treatment. At day 14, 3 patients (37.5%) exhibited partial pain response and 4 patients (50%)
exhibited an indeterminate response, and at day 30 after the treatment, 5 patients (83%) exhibited partial pain
response. No treatment-related adverse events were recorded. Of the urine cytokines measured, only
Transforming growth factor alpha (TGFα) demonstrated an overall decrease, with a trend toward statistical
significance ( P = .078). CONCLUSION: Our study corroborates magnetic resonance-guided focused
ultrasound as a feasible and safe modality as a primary, palliative treatment for painful bone metastases and
contributes to the limited body of literature using magnetic resonance-guided focused ultrasound for this
BACKGROUND: The extended knee lateral midpatellar portal for intraarticular injection of the knee is
accurate but is not practical for all patients. We hypothesized that a modified anteriolateral portal where the
synovial membrane of the medial femoral condyle is the target would be highly accurate and effective for
intraarticular injection of the knee. METHODS: 83 subjects with non-effusive osteoarthritis of the knee were
randomized to intraarticular injection using the modified anteriolateral bent knee versus the standard lateral
midpatellar portal. After hydrodissection of the synovial membrane with lidocaine using a mechanical syringe
(reciprocating procedure device), 80 mg of triamcinolone acetonide were injected into the knee with a 2.0-in
(5.1-cm) 21-gauge needle. Baseline pain, procedural pain, and pain at outcome (2 weeks and 6 months) were
determined with the 10 cm Visual Analogue Pain Score (VAS). The accuracy of needle placement was
determined by sonographic imaging. RESULTS: The lateral midpatellar and anteriolateral portals resulted in
equivalent clinical outcomes including procedural pain (VAS midpatellar: 4.6 ± 3.1 cm; anteriolateral: 4.8 ±
3.2 cm; p = 0.77), pain at outcome (VAS midpatellar: 2.6 ± 2.8 cm; anteriolateral: 1.7 ± 2.3 cm; p = 0.11),
responders (midpatellar: 45%; anteriolateral: 56%; p = 0.33), duration of therapeutic effect (midpatellar: 3.9 ±
2.4 months; anteriolateral: 4.1 ± 2.2 months; p = 0.69), and time to next procedure (midpatellar: 7.3 ± 3.3
months; anteriolateral: 7.7 ± 3.7 months; p = 0.71). The anteriolateral portal was 97% accurate by real-time
ultrasound imaging. CONCLUSION: The modified anteriolateral bent knee portal is an effective, accurate,
and equivalent alternative to the standard lateral midpatellar portal for intraarticular injection of the knee.
Chen, C.-Y., et al. (2020). "Clinical spectrum of intra-abdominal abscesses in children
admitted to the pediatric emergency department." Journal of Microbiology,
Immunology and Infection 53(2): 283-291.
Background To analyze clinical spectrum of intra-abdominal abscesses in children and find helpful clinical
parameters could aid physicians in earlier detection and differential diagnosis. Methods From 2004 to 2011,
we retrospectively analyzed 66 pediatric patients, aged 18 years or younger with intra-abdominal abscesses.
The data were obtained and studied: demographics, clinical presentations, etiologies, laboratory tests,
microbiology, imaging studies, treatment modalities, complications and long-term outcomes. Results There
were 66 patients (mean age, 9.27 ± 4.16 years) diagnosed as intra-abdominal abscesses. The two most
common presented symptoms were fever and abdominal pain (90.9%; 78.8%, respectively). Most patients
presented with leukocytosis (81.8%) and elevated C-reactive protein (CRP) levels (95.5%). In patients with
abscesses in solid organs, urine white blood cell counts, nitrate and leukocyte esterase were all significant
parameters (all P < 0.05), and urine pH and specific gravity were both lower than those in non-solid organs
(P = 0.026; P = 0.043, respectively). Escherichia coli (E. coli) was the most common organism cultured from
renal abscess. Streptococcus viridans was the most common organism cultured from liver abscess. Moreover,
the two most predominant bacteria in periappendical and intraperitoneal abscesses were E. coli and
Bacteroides fragilis. Conclusions We suggest that primary physicians should keep this disease in mind when
children present with predisposing risk factors, fever, abdominal pain, leukocytosis and elevated CRP level.
Besides, we recommend the urinary analysis or ultrasonography (US) is valuable in patients with fever and
Chen, D. W., et al. (2010). "Continuous intra-articular infusion of bupivacaine for
post-operative pain relief after total hip arthroplasty: a randomized, placebocontrolled, double-blind study." Eur J Pain 14(5): 529-534.
Chen, H., M. C. Schall and N. Fethke (2018). "Accuracy of angular displacements and
velocities from inertial-based inclinometers." Applied Ergonomics 67: 151-161.
Chen, M., et al. (2022). "Envafolimab - first PD-1/PD-L1 antibody to be administered
by subcutaneous injection for microsatellite instability-high or deficient mismatch
repair advanced solid tumors." Expert Opin Biol Ther 22(10): 1227-1232.
BACKGROUND: Instillation of local anesthetics into a surgical site has been gaining popularity in postoperative pain management. AIM: To determine whether continuous intra-articular infusion of bupivacaine
via pain-control infusion pumps (PCIP) enhances and sustains analgesia after total hip arthroplasty (THA).
METHODS: Ninety-two patients undergoing THA were randomized to receive continuous intra-articular
infusion of either 0.5% bupivacaine or 0.9% normal saline at a flow rate of 2 mL/h via a PCIP for 48 h. The
primary outcome measure was pain intensity on Visual Analogue Scale (VAS) scores in the first 72 h. Other
measures included time to first rescue dose of narcotics, amount of narcotic use, presence of adverse events,
length of hospital stay, and hip function evaluated with the Western Ontario and McMaster Universities
Osteoarthritis (WOMAC) index. RESULTS: Despite a longer time to first narcotic rescue (56 versus 21 min,
p<0.0001) in patients receiving bupivacaine, the two groups did not differ significantly in overall pain relief
(p=0.54). A lower VAS score was found only at time 0 and 2 h; no difference in VAS score was noted at any
other time point. Additionally, no difference was found in terms of amount of narcotic use, incidence of
adverse events, hospitalization days, and the WOMAC score. CONCLUSION: Continuous intra-articular
infusion of 0.5% bupivacaine at 2 mL/h via a PCIP does not provide sustained post-operative pain relief in
patients undergoing THA.
The objective of this study was to evaluate the accuracy of various sensor fusion algorithms for measuring
upper arm elevation relative to gravity (i.e., angular displacement and velocity summary measures) across
different motion speeds. Thirteen participants completed a cyclic, short duration, arm-intensive work task that
involved transfering wooden dowels at three work rates (slow, medium, fast). Angular displacement and
velocity measurements of upper arm elevation were simultaneously measured using an inertial measurement
unit (IMU) and an optical motion capture (OMC) system. Results indicated that IMU-based inclinometer
solutions can reduce root-mean-square errors in comparison to accelerometer-based inclination estimates by as
much as 87%, depending on the work rate and sensor fusion approach applied. The findings suggest that IMUbased inclinometers can substantially improve inclinometer accuracy in comparison to traditional
accelerometer-based inclinometers. Ergonomists may use the non-proprietary sensor fusion algorithms
provided here to more accurately estimate upper arm elevation.
INTRODUCTION: Programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors mobilize and
activate the anti-tumor activity of the immune system by blocking the inhibitory effects of the PD-1/PD-L1
signaling pathway in T cells. Several anti-PD-1 or -PD-L1 monoclonal antibodies have been approved for the
treatment of advanced solid tumors. However, most of immune checkpoint inhibitors (ICIs) are administered
via intravenous infusion, which is inconvenient and leads to unsatisfactory patient compliance in the treatment
process. Therefore, subcutaneous envafolimab is a potential treatment modality for advanced solid tumors.
AREA COVERED: A phase I clinical trial showed that the safety and pharmacokinetic profiles of
envafolimab were similar to those of other traditional antibodies. Additionally, clinical findings from a phase
II trial revealed that envafolimab monotherapy exhibited satisfactory clinical therapeutic effects and no
significant adverse events in patients with microsatellite instability-high/deficient mismatch Repair (MSIH/dMMR) solid tumors who failed at least one line of prior systemic therapy. EXPERT OPINION:
Subcutaneous envafolimab may serve as a more convenient and acceptable treatment modality than those
approved PD-1/PD-L1 inhibitors for patients with an advanced solid tumor, which may revolutionize the
Chen, Q., et al. (2021). "[Study on the safety and effectiveness of low-dose tranexamic
acid in operation of multi-level continuous thoracic ossification of ligament flavum]."
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 35(7): 873-877.
OBJECTIVE: To investigate the safety and effectiveness of low-dose tranexamic acid (TXA) in operation of
multi-level continuous thoracic ossification of ligament flavum (TOLF). METHODS: A clinical data of 26
patients who underwent operation for multi-level continuous TOLF and met the selection criteria between
July 2015 and January 2019 was retrospectively analyzed. Among them, 13 cases (group A) were received
intravenous infusion of TXA (10 mg/kg) at 15 minutes before operation, and maintained the infusion at 1
mg/(kg·h) until the end of the operation; 13 cases (group B) were received the same dose of normal saline
before and during operation. There was no significant difference in gender, age, body mass index, diseased
segment, and preoperative hemoglobin, platelet count, activated partial thromboplastin time, prothrombin
time, international normalized ratio (INR) between the two groups ( P>0.05). The hemoglobin, platelet count,
activated partial thromboplastin time, prothrombin time, INR, the number of deep vein thrombosis of the
lower extremities, operation time, intraoperative blood loss, postoperative drainage volume, total blood loss,
and the time of drainage tube extubation in the two groups were recorded and compared. RESULTS: All
operations in the two groups were successfully completed. Compared with group B, the operation time and
time of drainage tube extubation in group A were shortened, and the intraoperative blood loss, postoperative
drainage volume, and total blood loss were reduced. The differences between the two groups were significant
( P<0.05). None of the two groups received blood transfusion, and the hemoglobin level of group A at 24
hours after operation was significantly higher than that of group B ( t=5.062, P=0.000). The incisions in both
groups healed and sutures were removed within 2 weeks after operation, and no complications occurred.
There was no significant difference between the two groups in activated partial thromboplastin time,
prothrombin time, INR, and platelet count at 24 hours after operation ( P>0.05). CONCLUSION: In multilevel continuous TOLF operation, intravenous administration of low-dose TXA can effectively reduce blood
Chen, T. P., et al. (2017). "Comparison of the effectiveness and safety of topical
versus intravenous tranexamic acid in primary total knee arthroplasty: a meta-analysis
of randomized controlled trials." J Orthop Surg Res 12(1): 11.
Chen, X., et al. (2023). "Video-Based versus On-Site Neonatal Pain Assessment in
Neonatal Intensive Care Units: The Impact of Video-Based Neonatal Pain Assessment
in Real-World Scenario on Pain Diagnosis and Its Artificial Intelligence Application."
Diagnostics (Basel) 13(16).
BACKGROUND: This study aims to compare the effectiveness and safety of topical versus intravenous
tranexamic acid (TXA) in reducing blood loss in primary total knee arthroplasty (TKA). METHODS:
PubMed, Embase, the Cochrane Library, Web of Science, Chinese Biomedicine Literature (CBM), Wanfang
Database and China National Knowledge Infrastructure (CNKI), and Google Scholar were searched for
randomized controlled studies (RCTs) that compared topical versus intravenous TXA in terms of reducing
blood loss during TKA from their inception to September 2015. This systematic review and meta-analysis was
performed according to PRISMA criteria. RESULTS: Twelve studies reporting 12 RCTs comprising 1130
patients were included. Compared with the intravenous administration of TXA, the topical administration of
TXA showed no significant differences in total blood loss (MD 2.08, 95% CI -68.43 to 72.60, P = 0.95), blood
loss in drainage (MD 18.49, 95% CI -40.01 to 76.98, P = 0.54), hidden blood loss (MD 4.75, 95% CI -337.94
to 347.44, P = 0.99), need for transfusion (RR = 0.92, 95% CI 0.67~1.25, P = 0.58), hemoglobin (Hb) decline
(MD -0.42, 95% CI -0.89 to 0.05, P = 0.08), and DVT occurrence (RR = 1.17, 95% CI 0.55~2.50, P = 0.68).
CONCLUSIONS: Compared with intravenous administration TXA, topical administration TXA exhibits
comparable effectiveness and safety in terms of reducing blood loss during TKA. Due to the poor quality of
the included studies, more high-quality RCTs are needed to identify the optimal method and dose of TXA
BACKGROUND: Neonatal pain assessment (NPA) represents a huge global problem of essential importance,
as a timely and accurate assessment of neonatal pain is indispensable for implementing pain management.
PURPOSE: To investigate the consistency of pain scores derived through video-based NPA (VB-NPA) and
on-site NPA (OS-NPA), providing the scientific foundation and feasibility of adopting VB-NPA results in a
real-world scenario as the gold standard for neonatal pain in clinical studies and labels for artificial
intelligence (AI)-based NPA (AI-NPA) applications. SETTING: A total of 598 neonates were recruited from a
pediatric hospital in China. METHODS: This observational study recorded 598 neonates who underwent one
of 10 painful procedures, including arterial blood sampling, heel blood sampling, fingertip blood sampling,
intravenous injection, subcutaneous injection, peripheral intravenous cannulation, nasopharyngeal suctioning,
retention enema, adhesive removal, and wound dressing. Two experienced nurses performed OS-NPA and
VB-NPA at a 10-day interval through double-blind scoring using the Neonatal Infant Pain Scale to evaluate
the pain level of the neonates. Intra-rater and inter-rater reliability were calculated and analyzed, and a paired
samples t-test was used to explore the bias and consistency of the assessors' pain scores derived through OSNPA and VB-NPA. The impact of different label sources was evaluated using three state-of-the-art AI
methods trained with labels given by OS-NPA and VB-NPA, respectively. RESULTS: The intra-rater
reliability of the same assessor was 0.976-0.983 across different times, as measured by the intraclass
correlation coefficient. The inter-rater reliability was 0.983 for single measures and 0.992 for average
measures. No significant differences were observed between the OS-NPA scores and the assessment of an
independent VB-NPA assessor. The different label sources only caused a limited accuracy loss of 0.022-0.044
for the three AI methods. CONCLUSION: VB-NPA in a real-world scenario is an effective way to assess
neonatal pain due to its high intra-rater and inter-rater reliability compared to OS-NPA and could be used for
Chen, Y., et al. (2020). "Dexamethasone on postoperative gastrointestinal motility: A
placebo-controlled, double-blinded, randomized controlled trial." J Gastroenterol
Hepatol 35(9): 1549-1554.
BACKGROUND AND AIM: Following abdominal surgery, patients usually experience a transient episode of
impaired gastrointestinal motility. This study aimed to determine whether a single preoperative dose of
dexamethasone can promote the recovery of gastrointestinal function in patients following elective
gastrointestinal surgery. METHODS: In this single-center, two-arm, parallel, randomized controlled trial, we
studied 126 patients (aged 18-80 years) who underwent elective open or laparoscopic bowel surgery for
malignant or benign pathology. At the induction of anesthesia, a treatment group (n = 64) received a single
dose of 8-mg intravenous dexamethasone, and a control group (n = 62) received normal saline. RESULTS:
Intravenous administration of 8-mg dexamethasone significantly decreased the time to return of flatus by an
average of approximately 8 h (P < 0.05). Abdominal distension was significantly reduced on the third day
after surgery in the dexamethasone group (P < 0.05), and the time to tolerance of a liquid diet was shorter in
the dexamethasone group (P < 0.01). There were no significant differences in other secondary outcomes,
including postoperative pain, complication rates, length of hospital stay, or time to first defecation, between
the two groups. CONCLUSIONS: A single intravenous dose of 8-mg dexamethasone at induction of
anesthesia significantly decreases the time to return of flatus, improves abdominal distension at 72 h, and
promotes tolerance of a liquid diet. Although further studies are required to confirm our results, we
Chen, Y., et al. (2021). "A spasticity assessment method for voluntary movement
using data fusion and machine learning." Biomedical Signal Processing and Control
65: 102353.
Chidambaran, V., A. Costandi and A. D'Mello (2015). "Propofol: a review of its role
in pediatric anesthesia and sedation." CNS Drugs 29(7): 543-563.
The assessment of spasticity under voluntary movement is helpful for the therapist to comprehensively assess
the patient's dyskinesia. However, current researches focus on spasticity evaluation based on passive motion.
We propose a new method for evaluating spasticity under active motion. Our method is based on the
following three steps: (i) Empirical Mode Decomposition (EMD) is used to reduce involuntary movement
noise in patients' active movement; (ii) Extract voluntary movement segments of each muscle for feature
extract and fusion; (iii) Use machine learning methods to evaluate the degree of spasm in patients. To
investigates the feasibility of the method proposed in this paper, An experiment of elbow flexion and
extension against gravity is designed, and the electromyographic signal of brachioradialis (BR), biceps
brachialis (BB), triceps brachialis (TB) and elbow motion data of 13 subjects were collected. We compared
the classification effect of filter method, window length and classifier type. Moreover, we analyze the
improvement of classification effect by data fusion. The results showed that the random forest with a window
length of 256 ms had the best effect (F1-score = 0.952). Compared with the electromyographic signal (F1score = 0.756) or motion signal only (F1-score = 0.7053), the method presented in this paper had better
classification accuracy. Result demonstrated the feasibility of our method. This study can assist doctors to
evaluate patients' spasmodic state under active movement, and has the application potential of wearable
Propofol is an intravenous agent used commonly for the induction and maintenance of anesthesia, procedural,
and critical care sedation in children. The mechanisms of action on the central nervous system involve
interactions at various neurotransmitter receptors, especially the gamma-aminobutyric acid A receptor.
Approved for use in the USA by the Food and Drug Administration in 1989, its use for induction of anesthesia
in children less than 3 years of age still remains off-label. Despite its wide use in pediatric anesthesia, there is
conflicting literature about its safety and serious adverse effects in particular subsets of children. Particularly
as children are not "little adults", in this review, we emphasize the maturational aspects of propofol
pharmacokinetics. Despite the myriad of propofol pharmacokinetic-pharmacodynamic studies and the ability
to use allometrical scaling to smooth out differences due to size and age, there is no optimal model that can be
used in target controlled infusion pumps for providing closed loop total intravenous anesthesia in children. As
the commercial formulation of propofol is a nutrient-rich emulsion, the risk for bacterial contamination exists
despite the Food and Drug Administration mandating addition of antimicrobial preservative, calling for
manufacturers' directions to discard open vials after 6 h. While propofol has advantages over inhalation
anesthesia such as less postoperative nausea and emergence delirium in children, pain on injection remains a
problem even with newer formulations. Propofol is known to depress mitochondrial function by its action as
an uncoupling agent in oxidative phosphorylation. This has implications for children with mitochondrial
diseases and the occurrence of propofol-related infusion syndrome, a rare but seriously life-threatening
complication of propofol. At the time of this review, there is no direct evidence in humans for propofolinduced neurotoxicity to the infant brain; however, current concerns of neuroapoptosis in developing brains
Choi, S., M. Lee and B. Kwon (2014). "A study on difference and importance of
sacral slope and pelvic sacral angle that affect lumbar curvature." Technol Health Care
22(3): 467-472.
Individual pelvic sacral angle was measured, compared and analyzed for the 6 male and female adults who
were diagnosed with lumbar spinal stenosis, foraminal stenosis and mild spondylolisthesis in accordance with
spinal parameters, pelvic parameters and occlusion state of sacroiliac joint presented by the author of this
thesis based on the fact that the degree of lumbar excessive lordosis that was one of the causes for lumbar pain
was determined by sacral slope. The measured values were compared with the standard values of the average
normal range from 20 s to 40 s of normal Koreans stated in the study on the change in lumbar lordosis angle,
lumbosacral angle and sacral slope in accordance with the age by Oh et al. [5] and sacral slope and pelvic
sacral slope of each individual of the subjects for measurement were compared. Comparing the difference
between the two tilt angles possessed by an individual is a comparison to determine how much the sacroiliac
joint connecting pelvis and sacral vertebrae compensated and corrected the sacral vertebrae slope by pelvic tilt
under the condition of synarthrodial joint.Under the condition that the location conforming to the line in
which the sagittal line of gravity connects with pelvic ASIS and pubic pubic tuberele is the neutral location of
pelvic tilt, sacral slope being greater than pelvic sacral slope means pelvic anterior tilting, whereas sacral
slope being smaller than pelvic sacral slope means pelvic posterior tilting. On that account, male B, female A
and female C had a pelvic posterior tilting of 16 degrees, 1 degree and 5 degrees respectively, whereas male
A, male C and female B had a pelvic anterior tilting of 3 degrees, 9 degrees and 4 degrees respectively. In
addition, the 6 patients the values of lumbar lordosis angle, lumbosacral angle and sacral slope that were
almost twice as much as the normal standard values of Koreans. It is believed that this is because the pelvic
sacral slope maintaining an angle that is slightly greater than the normal range by being located in the lowest
end of spine considering that the compensation for pelvic tilt, in other words, pelvic limb is not much causes
an excess of lumbar lordosis angle. The meaning of this study based on these results is to prove that PSA is
one of the important factors that fundamentally determine lumbar curvature. And this is because it is definitely
required to have a study on the guideline for appropriate posture and life habit to the maintenance and
management of ideal PSA before the end of growth phase and also the exercise therapy and adjustment for the
Chou, B., et al. (2022). "Volumetric de-escalation and improved acute toxicity with
proton craniospinal irradiation using a vertebral body-sparing technique." Pediatr
Blood Cancer 69(5): e29489.
PURPOSE: In growing children, craniospinal irradiation (CSI) has historically treated the entire vertebral
body (VB) to avoid potential long-term spinal abnormalities. Vertebral body-sparing proton craniospinal
irradiation (VBSpCSI) is a technique that spares the majority of the VB from significant irradiation, and longterm safety outcomes have been reported previously. This retrospective study reviews the acute toxicity
profile of children treated with VBSpCSI in a cohort comparison with photon-based craniospinal radiotherapy
(3DCRT). METHODS: Thirty-eight pediatric CSI patients treated between 2008 and 2018 were
retrospectively evaluated for treatment-related toxicity. Acute toxicity outcomes and acute hematologic
profiles were compared according to treatment modality, either VBSpCSI or 3DCRT. Statistical analysis was
performed using Fisher's exact test for toxicity. RESULTS: Twenty-five patients received VBSpCSI and 13
patients received photon CSI. Mean patient age at treatment was 7.5 years (range 2-16). The cohorts were well
matched with respect to gender, age, and CSI dose. Patients receiving VBSpCSI had lower rates of grade 2+
gastrointestinal (GI) toxicity (24% vs. 76.5%, p = .005), grade 2+ nausea (24% vs. 61.5%, p = .035), and anygrade esophagitis (0% vs. 38%, p = .0026). Patients treated with VBSpCSI had lower red blood cell
transfusion rates (21.7% vs. 60%, p = .049) and grade 4+ lymphopenia (33.3% vs. 77.8%, p = .046).
CONCLUSIONS: VBSpCSI in children is a volumetric de-escalation from traditional volumes, which
irradiate the entire VB to full or intermediate doses. In our study, VBSpCSI was associated with lower rates of
acute GI and hematologic toxicities. Long-term growth outcomes and disease control outcomes are needed for
Chou, Y. H., et al. (2019). "Safety of Perfluorobutane (Sonazoid) in Characterizing
Focal Liver Lesions." J Med Ultrasound 27(2): 81-85.
Choudhury, M. Z. B., A. I. Tsirikos and P. A. Millner (2017). "Neuromuscular
scoliosis: clinical presentation, types of deformity, assessment and principles of
treatment." Orthopaedics and Trauma 31(6): 350-356.
BACKGROUND: The purpose of this study was to report the safety of perfluorobutane (Sonazoid) as a
vascular-phase imaging agent in characterizing focal liver lesions (FLLs). MATERIALS AND METHODS:
From May 2014 to April 2015, a total of 54 individuals who received Sonazoid contrast-enhanced ultrasound
(CEUS) were enrolled at 5 hospitals of 4 medical centers. All individuals were included in safety evaluation.
A prospective study to evaluate the adverse effect (AE) incidences after intravenous administration of
Sonazoid. RESULTS: Sonazoid was well tolerated. Treatment-emergent adverse events (TEAEs) representing
AE were recorded for 13 (24.1%) patients. The most common AE was abdominal pain (9.3%), followed by
heart rate irregularity (5.6%). The majority of these patients (69.2%) experienced TEAEs that were mild in
intensity. Sonazoid causes no significant AEs after intravenous injection. The only noteworthy AEs are related
to tolerable myalgia (3.7%), abdominal pain (1.9%), and headache (1.9%). None of the 54 patients showed
serious adverse effects. CONCLUSION: Sonazoid shows good safety and tolerance of intravenous use during
CEUS of the liver for evaluation of FLLs.
Scoliosis affects very commonly children with neurological or myopathic conditions. It can be associated with
increased kyphosis or lordosis. The coronal curve extends to the sacrum producing pelvic obliquity. The
deformity develops due to poor muscle control and spasticity as the spine cannot resist forces against gravity.
It can produce severe problems including spino-pelvic imbalance causing back pain, costo-pelvic impingement
pain on the concave side of the curve which can both affect sitting ability and posture, as well as respiratory
complications and difficulties in provision of patient care. There is no conservative measure that can stop
deformity progression. Surgical intervention is indicated in the presence of a progressive and symptomatic
deformity which affects the patient's quality of life. The degree of neurological disability and associated comorbidities must be taken into account during decision-making as these are directly correlated with the risk of
perioperative complications. Thorough preoperative assessment should be undertaken by a multidisciplinary
medical, surgical and allied health professional team in a centre with experience in the global management of
such patients. This will reduce the risk of complications and improve patient outcomes. This review gives an
overview of neuromuscular spinal deformity focussing on assessment and treatment.
Chromy, A. and L. Zalud (2020). "The RoScan Thermal 3D Body Scanning System:
Medical Applicability and Benefits for Unobtrusive Sensing and Objective
Diagnosis." Sensors (Basel) 20(22).
Chu, C. H. and E. C. Lo (2014). "Immediate post-application effect of professional
prophylaxis with 8% arginine-calcium carbonate desensitizing paste on hypersensitive
teeth. A practitioner-based clinical trial." Am J Dent 27(1): 7-11.
The RoScan is a novel, high-accuracy multispectral surface scanning system producing colored 3D models
that include a thermal layer. (1) Background: at present, medicine still exhibits a lack of objective diagnostic
methods. As many diseases involve thermal changes, thermography may appear to be a convenient technique
for the given purpose; however, there are three limiting problems: exact localization, resolution vs. range, and
impossibility of quantification. (2) Methods: the basic principles and benefits of the system are described. The
procedures rely on a robotic manipulator with multiple sensors to create a multispectral 3D model.
Importantly, the structure is robust, scene-independent, and features quantifiable measurement uncertainty;
thus, all of the above problems of medical thermography are resolved. (3) Results: the benefits were
demonstrated by several pilot case studies: medicament efficacy assessment in dermatology, objective
recovery progress assessment in traumatology, applied force quantification in forensic sciences, exact
localization of the cause of pain in physiotherapy, objective assessment of atopic dermatitis, and soft tissue
volumetric measurements. (4) Conclusion: the RoScan addresses medical quantification, which embodies a
frequent problem in several medical sectors, and can deliver new, objective information to improve the quality
of healthcare and to eliminate false diagnoses.
Chu, Y., et al. (2022). "Physicochemical Characterization and Pharmacological
Evaluation of Novel Propofol Micelles with Low-Lipid and Low-Free Propofol."
Pharmaceutics 14(2).
Chung, H., et al. (2021). "Safety, Tolerability, Pharmacokinetics, and
Pharmacodynamics of Cholic Acid (MT921) after a Subcutaneous Injection in the
Submental Area to Humans." Pharmaceuticals (Basel) 14(8).
PURPOSE: This practitioner-based clinical trial compared the pain reduction achieved by professional
prophylaxis with 8% arginine calcium carbonate (CaCO3) desensitizing paste versus 5% potassium nitrate
(KNO3) toothpaste on adult patients with tooth hypersensitivity. METHODS: All dentists in Hong Kong were
invited to join the study. Each participating dentist identified six adult patients with hypersensitive teeth after
scaling in the clinic. For each patient, the most hypersensitive tooth was selected. Each hypersensitive tooth
was isolated and tested with a blast of compressed cold air delivered from a three-in-one syringe. The patient
was then asked to indicate a sensitivity score (SS) from 0 to 10. Three patients received professional
prophylaxis with 8% arginine CaCO3 desensitizing paste (Group 1), and the other three received prophylaxis
with desensitizing toothpaste containing 5% KNO3 and 1,450 ppm fluoride (Group 2). The teeth were tested
for a second time with compressed cold air, and the patients were asked to report the SS again. A nonparametric test was used to analyze the results following a normality test of the SS. RESULTS: A total of 303
patients were recruited by 65 participating dentists. The mean age of the patients was 40.1, and 59% were
female. The median pre-treatment SS of Groups 1 and 2 were both 7, whereas the post-treatment SS were 3
and 4, respectively (P < 0.001). The median percentage reductions in sensitivity scores of Groups 1 and 2
were 57.14% and 38.75%, respectively (P < 0.001).
We developed safe and stable mixed polymeric micelles with low lipids and free propofol for intravenous
administration, to overcome the biological barrier of the reticuloendothelial system (RES), reduce pain upon
injection, and complications of marketed propofol formulation. The propofol-mixed micelles were composed
of distearoyl-phosphatidylethanolamine -methoxy-poly (ethylene glycol 2000) (DSPE mPEG2k) and Solutol
HS 15 and were optimized using Box Behnken design (BBD). The optimized formulation was evaluated for
globule size, zeta potential, loading content, encapsulation efficiency, pain on injection, histological
evaluation, hemolysis test, in vivo anesthetic action, and pharmacokinetics, in comparison to the
commercialized emulsion Diprivan. The optimized micelle formulation displayed homogenous particle sizes,
and the free drug concentration in the micelles was 60.9% lower than that of Diprivan. The paw-lick study
demonstrated that propofol-mixed micelles significantly reduced pain symptoms. The anesthetic action of the
mixed micelles were similar with the Diprivan. Therefore, we conclude that the novel propofol-mixed micelle
reduces injection-site pain and the risk of hyperlipidemia due to the low content of free propofol and low-lipid
constituent. It may be a more promising clinical alternative for anesthetic.
This study aimed to explore pharmacokinetics, pharmacodynamics, and safety/tolerability of MT921, an
injectable cholic acid, after a single subcutaneous administration to healthy volunteers. A randomized, doubleblinded, placebo-controlled, single dose-ascending phase 1 study enrolled 24 subjects who were assigned to
three groups (60 mg, 120 mg, and 150 mg) of MT921. Blood samples were obtained for a 24-h period before
and after injecting MT921 to the submental fat area. Plasma concentrations of cholic acid and deoxycholic
acid were determined for pharmacokinetic analysis. Levels of free fatty acid, triglyceride, and total cholesterol
were measured for pharmacodynamic analysis. Safety and tolerability were assessed until 21 days post-dose.
While systemic exposure to cholic acid tended to increase as the MT921 dose increased, pharmacokinetic
profiles of deoxycholic acid were similar among dose groups without showing significant changes.
Pharmacodynamic profiles were comparable when measured at baseline and post-dose. The most frequent
adverse events were injection site pain and edema. All adverse drug reactions resolved without treatment.
MT921 appeared to be well-tolerated after an injection to the submental area at a dose up to 150 mg. Systemic
exposure to cholic acid increased as the dose increased. Blood lipid profiles and deoxycholic acid levels were
not affected by MT921 treatment.
Clarke, D. K., et al. (2020). "Safety and immunogenicity of a highly attenuated
rVSVN4CT1-EBOVGP1 Ebola virus vaccine: a randomised, double-blind, placebocontrolled, phase 1 clinical trial." Lancet Infect Dis 20(4): 455-466.
BACKGROUND: The safety and immunogenicity of a highly attenuated recombinant vesicular stomatitis
virus (rVSV) expressing HIV-1 gag (rVSVN4CT1-HIV-1gag1) was shown in previous phase 1 clinical
studies. An rVSV vector expressing Ebola virus glycoprotein (EBOV-GP) in place of HIV-1 gag
(rVSVN4CT1-EBOVGP1) showed single-dose protection from lethal challenge with low passage Ebola virus
in non-human primates. We aimed to evaluate the safety and immunogenicity of the rVSVN4CT1-EBOVGP1
vaccine in healthy adults. METHODS: We did a randomised double-blind, placebo-controlled, phase 1 doseescalation study at a single clinical site (Optimal Research) in Melbourne, FL, USA. Eligible participants were
healthy men and non-pregnant women aged 18-60 years, with a body-mass index (BMI) of less than 40
kg/m(2), no history of filovirus infection, VSV infection, or receipt of rVSV in previous studies, and who had
not visited regions where Ebola virus outbreaks have occurred. Three cohorts were enrolled to assess a low
(2·5 × 10(4) plaque forming units [PFU]), intermediate (2 × 10(5) PFU), or high dose (1·8 × 10(6) PFU) of
the vaccine. Participants within each cohort were randomly allocated (10:3) to receive vaccine or placebo by
intramuscular injection in a homologous prime and boost regimen, with 4 weeks between doses. All syringes
were masked with syringe sleeves; participants and study site staff were not blinded to dose level but were
blinded to active vaccine and placebo. The primary outcomes were safety and tolerability; immunogenicity,
assessed as GP-specific humoral immune response (at 2 weeks after each dose) and cellular immune response
(at 1 and 2 weeks after each dose), was a secondary outcome. All randomised participants were included in
primary and safety analyses. This trial is registered with ClinicalTrials.gov, NCT02718469. FINDINGS:
Between Dec 22, 2015, and Sept 15, 2016, 39 individuals (18 [46%] men and 21 [54%] women, mean age 51
years [SD 10]) were enrolled, with ten participants receiving the vaccine and three participants receiving
placebo in each of three cohorts. One participant in the intermediate dose cohort was withdrawn from the
study because of a diagnosis of invasive ductal breast carcinoma 24 days after the first vaccination, which was
considered unrelated to the vaccine. No severe adverse events were observed. Solicited local adverse events
occurred in ten (26%) of 39 participants after the first dose and nine (24%) of 38 participants after the second
dose; the events lasted 3 days or less, were predominantly injection site tenderness (17 events) and injection
site pain (ten events), and were either mild (19 events) or moderate (ten events) in intensity. Systemic adverse
events occurred in 13 (33%) of 39 participants after the first dose and eight (21%) of 38 participants after the
second dose; the events were mild (45 events) or moderate (11 events) in severity, and the most common
Clavijo, L. C., et al. (2023). "The addition of evolocumab to maximal tolerated statin
therapy improves walking performance in patients with peripheral arterial disease and
intermittent claudication (Evol-PAD study)." Cardiovasc Revasc Med 55: 1-5.
OBJECTIVE: To test the hypothesis that in patients with peripheral arterial disease (PAD) and claudication,
treated with maximal tolerated statin therapy, the addition of a monthly subcutaneous injection of evolocumab
for 6 months improves treadmill walking performance. BACKGROUND: Lipid lowering therapy improves
walking parameters in patients with PAD and claudication. Evolocumab decreases cardiac and limb adverse
events in patients with PAD; however, the effect of evolocumab on walking performance is not known.
METHODS: We performed a double-blind, randomized, placebo-controlled study to compare maximal
walking time (MWT) and pain free walking time (PFWT) in patients with PAD and claudication treated with
monthly subcutaneous injections of evolocumab 420 mg (n = 35) or placebo (n = 35). We also performed
measurements of lower limb perfusion, brachial flow mediated dilatation (FMD), carotid intima media
thickness (IMT), and serum biomarkers of PAD disease severity. RESULTS: After six-months of treatment
with evolocumab MWT increased by 37.7 % (87.5 ± 24 s) compared to 1.4 % (-21.7 ± 22.9 s) in the placebo
group, p = 0.01. PFWT increased by 55.3 % (67.3 ± 21.2 s) in the evolocumab group compared to 20.3 %
(8.5 ± 20.3 s) in the placebo group, p = 0.051. There was no difference in lower extremity arterial perfusion
measurements. FMD increased by 42.0 ± 73.9 % (1.01 ± 0.7 %) in the evolocumab group and decreased by
16.29 ± 20.06 % (0.99 ± 0.68 %) in the placebo group (p < 0.001). IMT decreased by 7.16 ± 4.6 %
(0.06 ± 0.04 mm) in the evolocumab group and increased by 6.68 ± 4.9 % (0.05 ± 0.03 mm) in the placebo
group, (p < 0.001). CONCLUSIONS: The addition of evolocumab to maximal tolerated statin therapy
improves maximal walking time in patients with PAD and claudication, increases FMD, and decreases IMT.
CONDENSED ABSTRACT: Peripheral arterial disease (PAD) impairs quality of life by causing lower
extremity intermittent claudication, rest pain, or amputation. Evolocumab is a monthly injectable monoclonal
antibody medication that reduces cholesterol. In this study, we randomly treated patients with PAD and
claudication, and on background statin therapy, with evolocumab or placebo, and found that evolocumab
improves walking performance on a treadmill test by increasing maximal walking time. We also found that
Cohen, S., et al. (2019). "Decreased Injection Site Pain Associated with PhosphateFree Etanercept Formulation in Rheumatoid Arthritis or Psoriatic Arthritis Patients: A
Randomized Controlled Trial." Rheumatol Ther 6(2): 245-254.
INTRODUCTION: Etanercept, a tumor necrosis factor inhibitor, is used to treat rheumatoid arthritis (RA) and
psoriatic arthritis (PsA), and is administered via subcutaneous injection. Injection site pain (ISP) associated
with subcutaneous administration may affect compliance or hinder initiation of prescribed medications. To
improve the patient experience, a new phosphate-free formulation of etanercept was evaluated for reduced ISP
associated with administration. METHODS: This phase 3b, multicenter, randomized, double-blind, cross-over
study compared the prior formulation of etanercept to a phosphate-free formulation. Etanercept-naïve adults
with RA or PsA indicated for treatment with etanercept were eligible. Patients were randomized (1:1) to
receive both etanercept formulations (50 mg) in one of two crossover sequences: prior formulation followed
by phosphate-free formulation (sequence AB) or phosphate-free formulation followed by prior formulation
(sequence BA) at visits 1 week apart. Patients self-reported ISP using a fit-for-purpose 100-mm visual analog
scale within 30 s after injection. Safety outcomes included incidence of treatment-emergent adverse events.
Mixed-effects analysis of variance model was used to assess ISP, with treatment, study period, sequence, and
disease indication as fixed-effect covariates and patient-within-sequence as random effect. RESULTS: A total
of 111 patients enrolled (56 sequence AB; 55 sequence BA). Mean ISP score for prior formulation was
23.1 mm and for phosphate-free formulation was 19.1 mm (mean difference - 4 mm; 95% confidence interval:
- 8.0, 0.0; P = 0.048). Patients with the highest ISP scores from the prior formulation (by quartile cut points)
had the largest reduction in pain with phosphate-free formulation. Injection site reactions were few in number
and similar between formulations; no new safety signals were observed. CONCLUSIONS: The new
phosphate-free formulation of etanercept had statistically significantly lower mean pain scores than the prior
formulation, with largest pain reductions observed among patients who reported highest pain with the prior
formulation. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02986139. FUNDING: Amgen Inc,
Colas, A.-E. (2017). "Lésions de postures cutanées, ophtalmiques et nerveuses en
pédiatrie : comment les éviter ?" Anesthésie & Réanimation 3(6): 525-530.
Résumé Les complications posturales sont rares mais parfois responsables de séquelles fonctionnelles
majeures. L’imputabilité de la posture opératoire est le plus souvent intriquée avec celles du terrain et de
l’anesthésie. La physiopathologie des lésions de posture est directement liée à l’action de la pesanteur et des
forces de cisaillement qui en découlent. La prévention des lésions cutanéomuqueuses et musculaires repose
sur le maintien de l’hémodynamique, la prévention de l’hypothermie, la limitation de la durée de l’installation
dans une position à risque et l’utilisation de gels de protection viscoélastiques. La prévention des lésions
nerveuses passe par l’évaluation préopératoire des comorbidités et par la limitation de la durée des positions à
risque. La prévention des lésions oculaires liées à une compression ou un traumatisme direct repose sur une
vérification itérative pendant l’intervention de l’occlusion palpébrale et de l’absence de contrainte sur le globe
oculaire. Lors des interventions en décubitus ventral, l’installation de la tête en position neutre et au-dessus du
niveau du cœur est recommandée, ainsi que le maintien d’une normotension et d’une normovolémie au cours
de l’intervention. Summary Positional injuries are rare but sometimes responsible for major functional
sequelae. The imputability of positioning is often entangled with patient's comorbidities and anaesthesia. The
pathophysiology of these injuries is directly in relation to the action of gravity and the resulting shear forces.
The prevention of mucosal, cutaneous and muscular lesions relies on the maintenance of stable
hemodynamics, the prevention of hypothermia, the limitation of the time spent in a risky position and the use
of visco-elastic padding gels. The prevention of nerve damage involves the preoperative assessment of
comorbidities and the limitation of the duration of positions at risk. The prevention of ocular lesions caused
either by compression or direct trauma is based on repeated verification of palpebral occlusion and avoidance
of any direct stress to the eyeball during the procedure. Positioning the head in the neutral position, verifying
that the head remains above the heart level is recommended in these circumstances, as well as maintenance of
Comella, K., et al. (2017). "Autologous Stromal Vascular Fraction in the Intravenous
Treatment of End-Stage Chronic Obstructive Pulmonary Disease: A Phase I Trial of
Safety and Tolerability." J Clin Med Res 9(8): 701-708.
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a consistently progressive, ultimately
fatal disease for which no treatment exists capable of either reversing or even interrupting its course. It afflicts
more than 5% of the population in many countries, and it accordingly represents the third most frequent cause
of death in the US, where it accounts for more than 600 billion in health care costs, morbidity, and mortality.
Adipose tissue contains within its stromal compartment a high abundance of adipose stem/stromal cells
(ASCs), which can be readily separated from the adipocyte population by methods which require less than 2 h
of processing time and yield a concentrated cellular preparation termed the stromal vascular fraction (SVF).
The SVF contains all cellular elements of fat, excluding adipocytes. Recent clinical studies have begun to
explore the feasibility and safety of the local injection or intravascular delivery of SVF or more purified
populations of ASCs derived by culture protocols. Several pre-clinical studies have demonstrated a
remarkable ability of ASC to nearly fully ameliorate the progress of emphysema due to cigarette smoke
exposure as well as other causes. However, no prior clinical studies have evaluated the safety of
administration of either ASC or SVF in subjects with COPD. We hypothesized that harvest, isolation, and
immediate intravenous infusion of autologous SVF would be feasible and safe in subjects with COPD; and
that such an approach, if ultimately determined to be efficacious as well as safe, would provide a highly
practical method for treatment of COPD. METHODS: In this study, an initial phase I trial evaluating the early
and delayed safety of SVF infusion was performed. Twelve subjects were enrolled in the study, in which
adipose tissue was harvested using standard liposuction techniques, followed by SVF isolation and
intravenous infusion of 150 - 300 million cells. Standardized questionnaires were administered to study
feasibility as well as immediate and delayed outcomes and adverse events as primary endpoints. Secondary
endpoints included subjective wellness and attitudes towards the procedure, as well as willingness to undergo
the procedure a second time. The follow-up time ranged from 3 to 12 months, averaging 12 months.
RESULTS: Of the 12 subjects, only one experienced an immediate adverse event, related to bruising from the
liposuction. No observed pulmonary or cardiac issues were observed as related to the procedure. There were
no deaths over the 12-month study period, and none identified in the subsequent telephonic follow-up.
Attitudes toward the procedure were predominantly positive, and 92% of the study subjects expressed a desire
to undergo the procedure a second time. CONCLUSIONS: This study is the first to demonstrate safety of SVF
infusion in humans with serious pulmonary disease. Specifically, the use of intravenous infusion as a route to
Cortes, J. E., et al. (2019). "Quizartinib versus salvage chemotherapy in relapsed or
refractory FLT3-ITD acute myeloid leukaemia (QuANTUM-R): a multicentre,
randomised, controlled, open-label, phase 3 trial." Lancet Oncol 20(7): 984-997.
BACKGROUND: Patients with relapsed or refractory FLT3 internal tandem duplication (FLT3-ITD)-positive
acute myeloid leukaemia have a poor prognosis, including high frequency of relapse, poorer response to
salvage therapy, and shorter overall survival than those with FLT3 wild-type disease. We aimed to assess
whether single-agent quizartinib, an oral, highly potent and selective type II FLT3 inhibitor, improves overall
survival versus salvage chemotherapy. METHODS: QuANTUM-R is a randomised, controlled, phase 3 trial
done at 152 hospitals and cancer centres in 19 countries. Eligible patients aged 18 years or older with ECOG
performance status 0-2 with relapsed or refractory (duration of first composite complete remission ≤6 months)
FLT3-ITD acute myeloid leukaemia after standard therapy with or without allogeneic haemopoietic stem-cell
transplantation were randomly assigned (2:1; permuted block size of 6; stratified by response to previous
therapy and choice of chemotherapy via a phone-based and web-based interactive response system) to
quizartinib (60 mg [30 mg lead-in] orally once daily) or investigator's choice of preselected chemotherapy:
subcutaneous low-dose cytarabine (subcutaneous injection of cytarabine 20 mg twice daily on days 1-10 of
28-day cycles); intravenous infusions of mitoxantrone (8 mg/m(2) per day), etoposide (100 mg/m(2) per day),
and cytarabine (1000 mg/m(2) per day on days 1-5 of up to two 28-day cycles); or intravenous granulocyte
colony-stimulating factor (300 μg/m(2) per day or 5 μg/kg per day subcutaneously on days 1-5), fludarabine
(intravenous infusion 30 mg/m(2) per day on days 2-6), cytarabine (intravenous infusion 2000 mg/m(2) per
day on days 2-6), and idarubicin (intravenous infusion 10 mg/m(2) per day on days 2-4 in up to two 28-day
cycles). Patients proceeding to haemopoietic stem-cell transplantation after quizartinib could resume
quizartinib after haemopoietic stem-cell transplantation. The primary endpoint was overall survival in the
intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT02039726, and
follow-up is ongoing. FINDINGS: Between May 7, 2014, and Sept 13, 2017, 367 patients were enrolled, of
whom 245 were randomly allocated to quizartinib and 122 to chemotherapy. Four patients in the quizartinib
group and 28 in the chemotherapy group were not treated. Median follow-up was 23·5 months (IQR 15·432·3). Overall survival was longer for quizartinib than for chemotherapy (hazard ratio 0·76 [95% CI 0·580·98; p=0·02]). Median overall survival was 6·2 months (5·3-7·2) in the quizartinib group and 4·7 months
(4·0-5·5) in the chemotherapy group. The most common non-haematological grade 3-5 treatment-emergent
adverse events (within ≤30 days of last dose or >30 days if suspected to be a treatment-related event) for
quizartinib (241 patients) and chemotherapy (94 patients) were sepsis or septic shock (46 patients [19%] for
Coulombe, J. C., et al. (2023). "Changes in Vertebral Bone Density and Paraspinal
Muscle Morphology Following Spaceflight and 1 Year Readaptation on Earth." JBMR
Plus 7(12): e10810.
Astronauts have an increased risk of back pain and disc herniation upon returning to Earth. Thus, it is
imperative to understand the effects of spaceflight and readaptation to gravity on the musculoskeletal tissues
of the spine. Here we investigated whether ~6 months of spaceflight led to regional differences in bone loss
within the vertebral body. Additionally, we evaluated the relationships between vertebral bone density and
paraspinal muscle morphology before flight, after flight, and after readaptation on Earth. We measured
vertebral trabecular bone mineral density (Tb.BMD), paraspinal muscle cross-sectional area (CSA), and
muscle density in 17 astronauts using computed tomography (CT) images of the lumbar spine obtained before
flight (before flight, n = 17), after flight (spaceflight, n = 17), and ~12 months of readaptation to gravitational
loading on Earth (follow-up, n = 15). Spaceflight-induced declines in Tb.BMD were greater in the superior
region of the vertebral body (-6.7%) than the inferior (-3.1%, p = 0.052 versus superior region) and transverse
regions (-4.3%, p = 0.057 versus superior region). After a year of readaptation to Earth's gravity, Tb.BMD in
the transverse region remained significantly below preflight levels (-4.66%, p = 0.0094). Paraspinal muscle
CSA and muscle density declined -1.0% (p = 0.005) and -0.83% (p = 0.001) per month of spaceflight,
respectively. Ultimately, bone loss in the superior vertebral body, along with fatty infiltration of paraspinal
muscles and incomplete recovery even after a year of readaptation on Earth, may contribute to spinal
pathology in long-duration astronauts. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC
Cox, D. S., et al. (2021). "Randomized, Open-Label, Single-Dose, Parallel-Group
Pharmacokinetic Study of PF-06410293 (adalimumab-afzb), an Adalimumab
Biosimilar, by Subcutaneous Dosing Using a Prefilled Syringe or a Prefilled Pen in
Healthy Subjects." Clin Pharmacol Drug Dev 10(10): 1166-1173.
Cronin, J., et al. (2019). "The non-drug costs associated with the administration of an
intravenous biologic treatment in the hospital setting." Ir J Med Sci 188(3): 821-834.
This open-label, single-dose, randomized, parallel-group, 2-arm phase 1 bioequivalence (BE) study assessed
the pharmacokinetics (PK), safety, and tolerability of PF-06410293 (ADL-PF), an adalimumab (ADL)
biosimilar, following administration by prefilled pen (PFP) or prefilled syringe (PFS). A total of 164 healthy
adult subjects were randomized (1:1) to receive ADL-PF (40 mg subcutaneously) in the lower abdomen or
upper anterior thigh by PFS or PFP; 163 subjects were included in the primary PK analysis. The
concentration-time profiles of the ADL-PF PFS and PFP treatment arms were similar. The 90% confidence
intervals for the test/reference ratios of the primary end points (area under the serum concentration-time
profile from time 0 to 2 weeks after dosing and maximum observed serum concentration) fell within the
80.00%-125.00% prespecified margin for BE. Comparable numbers of subjects experienced adverse events
(AEs) between treatment groups, and injection-site pain was similar at all times and for the 2 injection-site
locations. This study demonstrated the BE of ADL-PF following subcutaneous administration using either a
PFS or PFP device. ADL-PF by PFS or PFP injection was well tolerated, with the distribution of AEs,
including injection-site reactions, being similar between treatment arms.
BACKGROUND: In Ireland, over 20,000 people are affected by inflammatory bowel disease (IBD). The
licenced biologic therapies to treat moderate to severe IBD are reported to have similar effectiveness levels
but differ in their methods of delivery. Certain therapies are administered by intravenous (IV) infusion in the
hospital setting, others are delivered by subcutaneous injection in the community. AIM: To determine the nondrug costs involved in administering an IV biologic infusion in the hospital setting. METHODS: This timeand-motion study was conducted at an Infusion Day Unit (IDU) in an Irish teaching hospital. The sequence
and duration of each patient's use of resources was recorded and costed. Bootstrap methods were applied to
ensure that robust estimates of the accuracy of the non-parametric population statistics were reliably
estimated. RESULTS: The mean time the patient spent at the IDU was 143.78 mins with a mean treatment
time of 129.81 min. The main driver of patient time was the drug infusion time (39%), followed by the
monitoring period (25%). The mean cost was €224.54 per treatment. Nurse time was the main expenditure
driver (37%), followed by laboratory costs (27%) and other healthcare professional's costs (14%).
CONCLUSIONS: The study confirms that the non-drug costs associated with the delivery of an IV biologic in
the hospital setting are non-trivial. Given the current budgetary climate of health systems, the compounding
prevalence of IBD and the expected increase in patient numbers, it is imperative that physicians also consider
Cruickshank, A., et al. (2019). "Eutectic mixture of lidocaine and prilocaine versus 1%
lidocaine injection for lumbar punctures in pediatric oncology patients." Pediatr Blood
Cancer 66(11): e27957.
Crystal, D. T., et al. (2021). "Opioid-sparing Strategies in Alloplastic Breast
Reconstruction: A Systematic Review." Plast Reconstr Surg Glob Open 9(11): e3932.
BACKGROUND: The role of local analgesics for lumbar punctures (LPs) in pediatric oncology patients has
not been specifically studied. AIM: To compare the efficacy of eutectic mixture of local anesthetics (EMLA)
cream to 1% lidocaine injection for LPs. METHOD: This was a retrospective observational study of all
patients receiving either EMLA cream (EMLA group) or 1% lidocaine subcutaneous injection (lidocaine
group) in addition to fentanyl and propofol for LPs over 18 months. Demographics, vital parameters,
procedural and recovery times, propofol and fentanyl doses, and adverse events were studied. RESULTS:
Two hundred ninety LPs in 49 children were studied: 148 in the EMLA group and 142 in the lidocaine group.
There was no difference in demographics or preprocedural parameters between the two groups. LPs in the
EMLA group were completed in a shorter time (7.5 minutes [CI 7.0-8.1] vs 9.4 minutes [CI 8.9-9.9]) with a
faster recovery time (38.7 minutes [CI 36.9-40.9] vs 43.9 minutes. [CI 41.9-45.9]) as compared with the
lidocaine group (P < 0.001). The EMLA group required less maintenance doses (0.54 mg/kg [CI 0.47-0.62] vs
1.14 mg/kg [CI 1.06-1.21]) and total doses (2.58 mg/kg [CI 2.42-2.75] vs 3.12 mg/kg [CI 2.95-3.29]) of
propofol as compared with the lidocaine group (P < 0.0001). Adverse events in the EMLA group were less
(19% vs 41%) as compared with the lidocaine group (P < 0.0001). CONCLUSION: The addition of EMLA
cream for procedural sedation for LPs in pediatric oncology patients significantly improves pain management
INTRODUCTION: Pain and discomfort are frequently experienced following mastectomy with concomitant
breast implant- or tissue expander-based alloplastic breast reconstruction (AlBR). Unfortunately,
postoperative opioids have decreased efficacy in AlBR, short-term complication profiles, and are fraught by
long-term dependence. This systematic review aims to identify opioid-sparing pain management strategies in
AlBR. METHODS: A systematic literature search of MEDLINE, Embase, Web of Science, and Cochrane
Central Register was performed in September 2018. PRISMA guidelines were followed, and the review was
prospectively registered in PROSPERO (CRD42018107911). The search identified 1184 articles. Inclusion
criteria were defined as patients 18 years or older undergoing AlBR. RESULTS: Fourteen articles were
identified assessing opioid-sparing strategies in AlBR. This literature included articles evaluating enhanced
recovery protocols (two), intercostal blocks (two), paravertebral blocks (four), liposomal bupivacaine (three),
diclofenac (one), and local anesthesia infusion pumps (two). The literature included five randomized trials and
nine cohort studies. Study characteristics, bias (low to high risk), and reporting outcomes were extensively
heterogeneous between articles. Qualitative analysis suggests reduced opioid utilization in enhanced recovery
after surgery (ERAS) pathways, paravertebral blocks, and use of liposomal bupivacaine. CONCLUSIONS: A
variety of opioid-sparing strategies are described for pain management in AlBR. Multimodal analgesia should
be provided via ERAS pathways as they appear to reduce pain and spare opioid use. Targeted paravertebral
blocks and liposomal bupivacaine field blocks appear to be beneficial in sparing opioids and should be
considered as essential components of ERAS protocols. Additional prospective, randomized trials are
Cuthbertson, J., et al. (2011). "Addition of metformin to exogenous glucagon-like
peptide-1 results in increased serum glucagon-like peptide-1 concentrations and
greater glucose lowering in type 2 diabetes mellitus." Metabolism 60(1): 52-56.
Glucagon-like peptide-1 (GLP-1) is an incretin hormone that lowers blood glucose after meals in type 2
diabetes mellitus. The therapeutic potential of GLP-1 in diabetes is limited by rapid inactivation by the
enzyme dipeptidylpeptidase-4 (DPP-4). Metformin has been reported to inhibit DPP-4. Here we investigated
the acute effects of metformin and GLP-1 alone or in combination on plasma DPP-4 activity, active GLP-1
concentrations, and glucose lowering in type 2 diabetes mellitus. Ten subjects with type 2 diabetes mellitus (8
male and 2 female; age, 68.7 ± 2.6 years [mean ± SEM]; body mass index, 29.6 ± 1.7 kg/m²; hemoglobin
A(1c), 7.0% ± 0.1%) received 1 of 3 combinations after an overnight fast in a randomized crossover design:
metformin 1 g orally plus subcutaneous injection saline (Metformin), GLP-1 (1.5 nmol/kg body weight
subcutaneously) plus placebo tablet (GLP-1), or metformin 1 g plus GLP-1(Metformin + GLP-1). At 15
minutes, glucose was raised to 15 mmol/L by rapid intravenous infusion of glucose; and responses were
assessed over the next 3 hours. This stimulus does not activate the enteroinsular axis and secretion of
endogenous GLP-1, enabling the effect of exogenously administered GLP-1 to be examined. Mean area under
curve (AUC) (0-180 minutes) plasma glucose responses were lowest after Metformin + GLP-1 (mean ± SEM,
1629 ± 90 mmol/[L min]) compared with GLP-1 (1885 ± 86 mmol/[L min], P < .002) and Metformin (2045 ±
115 mmol/[L min], P < .001). Mean AUC serum insulin responses were similar after either Metformin + GLP1 (5426 ± 498 mU/[L min]) or GLP-1 (5655 ± 854 mU/[L min]) treatment, and both were higher than
Metformin (3521 ± 410 mU/[L min]; P < .001 and P < .05, respectively). Mean AUC for plasma DPP-4
activity was lower after Metformin + GLP-1 (1505 ± 2 μmol/[mL min], P < .001) and Metformin (1508 ± 2 μ
mol/[mL min], P < .002) compared with GLP-1 (1587 ± 3 μmol/[mL min]). Mean AUC measures for plasma
active GLP-1 concentrations were higher after Metformin + GLP-1 (820 x 10⁴ ± 51 x 10⁴ pmol/[L min])
compared with GLP-1 (484 x 10⁴ ± 31 x 10⁴ pmol/[L min], P < .001) and Metformin (419 × 10⁴ ± 34 x 10⁴
pmol/[L min], P < .001), respectively. In patients with type 2 diabetes mellitus, metformin inhibits DPP-4
activity and thus increases active GLP-1 concentrations after subcutaneous injection. In combination with
GLP-1, metformin significantly lowers plasma glucose concentrations in type 2 diabetes mellitus subjects
compared with GLP-1 alone, whereas insulin responses were similar. Metformin enhances serum
concentrations of injected active GLP-1(7-36)amide, and the combination results in added glucose-lowering
da Silva, P. S., et al. (2011). "Use of ketofol for procedural sedation and analgesia in
children with hematological diseases." Pediatr Int 53(1): 62-67.
BACKGROUND: The aim of this study was to evaluate the effectiveness and safety of intravenous ketaminepropofol admixture ("ketofol") in the same syringe for procedural sedation and analgesia in children
undergoing bone marrow aspiration. METHODS: This was a prospective, observational pilot study. Patients
aged between 4 and 12 years requiring sedation for bone marrow aspiration were included. Ketofol (1:1
mixture of ketamine 10 mg/mL and propofol 10 mg/mL) was given intravenously in 0.5 mg/kg aliquots each
with a 1-min interval and titrated to reach sedation levels of 3 or 4 (Ramsay score). The primary outcome was
patient satisfaction with the degree of sedation. Secondary outcomes included injection pain, total sedation
time, recovery time, hemodynamic and respiratory parameters, and adverse events. RESULTS: A total of 20
patients were enrolled in the study. The median total dose of ketofol administered was 1.25 mg/kg each of
propofol and ketamine (95%CI 0.77-2 mg/kg). The median score on the visual analog scale was 0 (extremely
comfortable) (0-1.5; 95%CI 0.2-2.2). Median recovery time was 23 min (20.5-28 min; 95%CI 17.1-51.2). The
incidence of injection pain was 2/20. Two patients had transient diplopia and one child reported dreams. No
patients had hypotension, vomiting or required airway intervention. CONCLUSION: Ketofol provided
effective sedation, which was reflected in the high degree of satisfaction recorded by children requiring
procedural sedation and analgesia for bone marrow aspiration. We also observed rapid recovery and no
clinically significant complications. A large number of patients is required to evaluate and validate these
Danese, S., et al. (2019). "Randomised trial and open-label extension study of an antiinterleukin-6 antibody in Crohn's disease (ANDANTE I and II)." Gut 68(1): 40-48.
OBJECTIVE: Neutralising pro-inflammatory interleukin-6 (IL-6) may effectively treat Crohn's disease (CD).
Effects of PF-04236921, an anti-IL-6 antibody, in adults with CD are reported. DESIGN: Parallel-group, doseranging, double-blind trial with 4-week screening and 12-week treatment periods. After induction, patients
entered 28-week follow-up or 48-week open-label extension (OLE) with 28-week follow-up. Adults with
confirmed CD and inadequate response to anti-tumour necrosis factor (TNF) therapy were included. Induction
study: 249 patients randomised 1:1:1:1 to placebo, PF-04236921 10, 50 or 200 mg by subcutaneous injection
on days 1 and 28. OLE study: PF-04236921 50 mg every 8 weeks up to six doses followed by 28-week followup. RESULTS: 247 patients were randomised and received treatment in the induction study. The 200 mg dose
was discontinued due to safety findings in another study (NCT01405196) and was not included in the primary
efficacy analysis. Crohn's Disease Activity Index (CDAI)-70 response rates with PF-04236921 50 mg were
significantly greater than placebo at weeks 8 (49.3% vs 30.6%, P<0.05) and 12 (47.4% vs 28.6%, P<0.05) and
met the primary end point. Week 12 CDAI remission rates with PF-04236921 50 mg and placebo were 27.4%
and 10.9%, respectively (16.5% difference; P<0.05). 191 subjects received treatment in the OLE. Common
treatment-emergent and serious adverse events in both studies included worsening CD, abdominal pain and
nasopharyngitis. CONCLUSIONS: PF-04236921 50 mg induced clinical response and remission in refractory
patients with moderate-to-severe CD following failure of anti-TNF therapy. GI abscess and perforation were
observed, a specific focus of attention during future clinical development. TRIAL REGISTRATION
Danski, M. T., et al. (2016). "[Incidence of local complications and risk factors
associated with peripheral intravenous catheter in neonates]." Rev Esc Enferm USP
50(1): 22-28.
das Neves, J. F. N. P., et al. (2010). "Phenylephrine for Blood Pressure Control in
Elective Cesarean Section: Therapeutic versus Prophylactic Doses." Brazilian Journal
of Anesthesiology 60(4): 391-398.
OBJECTIVE: To evaluate the incidence of complications related to the use of peripheral intravenous catheter
in neonates and identify the associated risk factors. METHOD: Prospective cohort study conducted in a
Neonatal Intensive Care Unit. Participants were the hospitalized neonates undergoing peripheral intravenous
puncture in the period from February to June 2013. RESULTS: The incidence of complications was 63.15%,
being infiltration/extravasation (69.89%), phlebitis (17.84%) and obstruction (12.27%). The risk factors were
the presence of infection (p = 0.0192) and weight at the puncture day (p = 0.0093), type of intermittent
infusion associated with continuous infusion (p <0.0001), endotracheal intubation (p = 0.0008), infusion of
basic plan (p = 0.0027), total parenteral nutrition (P = 0.0002), blood transfusion associated with other
infusions (p = 0.0003) and other drugs (p = 0.0004). Higher risk of developing complications in the first 48
hours after puncture. CONCLUSION: A high rate of complications related to the use of peripheral
intravenous catheter, and risk factors associated with infection, weight, drugs and infused solutions, and type
of infusion.
Summary Background and objectives Spinal block is commonly used in cesarean sections and, if some
prophylactic measures are not taken, the incidence of hypotension is higher than 80%. The objective of this
study was to compare the efficacy of the administration of therapeutic or prophylactic doses of phenylephrine
to maintain blood pressure in patients undergoing spinal block for elective cesarean section. Methods One
hundred and twenty gravidas undergoing elective cesarean sections under spinal block, randomly divided in
three equal groups according to the regimen of phenylephrine administered, were included in this study. In
Group 1, continuous infusion of phenylephrine, using an infusion pump at 0.15 μg.kg-1.min-1 was
administered after the spinal block. In Group 2, a single dose of prophylactic phenylephrine 50 μg was
administered after the spinal block, and Group 3 received a single dose of phenylephrine 50 μg in case of
hypotension, which was defined as a drop in SBP and/or DBP of up to 20% of baseline levels. The incidence
of hypotension, nausea, and vomiting as well as the Apgar score were evaluated. Results The incidence of
hypotension was significantly greater in Group 3, affecting 85% of the gravidas. In Groups 1 and 2
hypotension was seen in 17.5% and 32.5% of the cases respectively (p < 0.001). The incidence of nausea was
much higher in Group 3 affecting 40% of the patients while in Groups 1 and 2 it was 10% and 15%
respectively which was statistically significant. Conclusions According to the methodology used, this study
showed that prophylactic continuous infusion of phenylephrine initiated immediately after the spinal block for
cesarean section is more effective in reducing the incidence of hypotension and maternal and fetal side effects.
Resumo Justificativa e objetivos A anestesia raquídea é utilizada com fre quên cia em casos de cesariana e se
algumas medidas profiláticas não forem adotadas a incidência de hipotensão arterial é superior a 80%. O
objetivo deste estudo foi comparar a eficácia da fenilefrina quando administrada terapêutica ou
profilaticamente para a manutenção da pressão arterial em pacientes submetidas à anestesia raquídea para
cesarianas eletivas. Método Foram estudadas 120 gestantes submetidas a cesarianas eletivas sob anestesia
raquídea, alocadas aleatoriamente em três grupos iguais, conforme o regime de administração de fenilefrina.
No Grupo 1, administrou-se fenilefrina em infusão contínua, em bomba de infusão, na dose de 0,15 μg.Kg1.min-1 após a anestesia raquídea. No Grupo 2, foi administrada fenilefrina em dose única, de forma
profilática, na dose de 50 μg após a anestesia raquídea e, no Grupo 3, fenilefrina em dose única de 50 μg em
caso de hipotensão arterial definida como queda da PAS e/ou PAD de até 20% em relação à média dos valores
basais. Avaliou-se a incidência de hipotensão arterial, náuseas, vômitos e do índice de Apgar. Resultados A
Dasci, M. F., et al. (2024). "A secure blood-saving protocol for Jehovah's Witnesses in
primary total hip replacement." Jt Dis Relat Surg 35(1): 12-19.
OBJECTIVES: The study aimed to analyze the efficacy of the blood management protocol developed by our
team for patients who are Jehovah's Witnesses (JW) presenting for primary total hip replacement (THR).
PATIENTS AND METHODS: Thirty JW patients (6 males, 24 females; mean age: 70.1±9.8 years; range, 65
to 81 years) and 30 age- and sex-matched controls (6 males, 24 females; mean age: 68.7±9.1 years; range, 62
to 79 years) who underwent primary THR at our institution between January 2018 and June 2020 were
retrospectively evaluated. While the surgical technique of THR was not different among the groups, blood
loss management differed between the groups. Patients in the control group were given 1 g of intravenous
tranexamic acid (TXA) 15 min before the surgical incision. In addition to the same TXA protocol,
intraoperative cell salvage with a continuous autologous transfusion system was used for JW patients. The
estimated blood loss (EBL) was determined using Meunier's formula. Hemoglobin (Hgb) decline, EBL on the
first and third postoperative days, allogenic blood transfusion (ABT) requirement, and complications were
analyzed between groups. RESULTS: There were no significant differences between groups regarding
demographic and clinical characteristics (p>0.05), ABT requirement (p>0.999), and Hgb decline in the first
and third postoperative days (p=0.540 and p=0.836, respectively). Furthermore, both groups did not
significantly differ between EBL in the first and third postoperative days (p=0.396 and p=0.616, respectively)
and the length of hospital stay (p=0.547). Similar complication rates were noted for both groups. Hemoglobin
level assessments revealed that values on the first and third postoperative days were significantly lower than
the baseline Hgb value in both cohorts (p<0.001). CONCLUSION: A combination of intravenous
administration of 1 g of TXA, meticulous hemostasis, and intraoperative use of cell saver constitutes a
reasonable strategy for achieving the goal of transfusion-free primary THR with predictable levels of blood
Dawe, E. J. C., et al. (2015). "The effect of different methods of stability assessment
on fixation rate and complications in supination external rotation (SER) 2/4 ankle
fractures." Foot and Ankle Surgery 21(2): 86-90.
De Andres, J., et al. (2021). "Predictive Clinical Decision Support System Using
Machine Learning and Imaging Biomarkers in Patients With Neurostimulation
Therapy: A Pilot Study." Pain Physician 24(8): E1279-e1290.
Background Distinguishing stable supination-external rotation (SER) 2 from unstable SER 4 ankle fractures,
using standard radiographs, is controversial. Examination under anaesthesia (EUA), gravity-stress (GS) and
weight-bearing (WB) radiographs can aid surgical decision-making. We evaluated the effect of three methods
of fracture stability assessment. Methods Radiographs and case-notes of 312 consecutive patients with SER
2/4 fractures were reviewed. We recorded ankle stability assessment (plain film (PF) and EUA vs. GS vs. WB
radiographs), management (conservative vs. operative), unplanned surgery and complications. Results Forty
five percent assessed with GS underwent surgery (6% for PF/EUA, 4% for WB; P=0.0001). Amongst GS
patients, 11% underwent additional surgery (0.1% PF/EUA, 0% WB; P=0.0001). Complications occurred in
2% of the WB group (8% for PF/EUA, 22% for GS; P=0.007). Conclusion This study associates GS
assessment with higher rates of surgery and complications. Subsequent studies may determine the longer term
effect stability assessments have on post-traumatic arthritis.
BACKGROUND: Chronic pain is correlated with alterations in brain structure and function. The selection
process for the ideal candidate for spinal cord stimulation (SCS) therapy is based on functional variables
analysis and pain evaluation scores. In addition to the difficulties involved in the initial selection of patients
and the predictive analysis of the trial phase, the large rate of explants is one of the most important concerns
in the analysis of the suitability of implanted candidates. OBJECTIVE: To investigate the usefulness of
imaging biomarkers, functional connectivity (FC) and volumetry of the whole brain in patients with Failed
back surgery syndrome (FBSS) and to create a clinical patient-based decision support system (CDSS)
combining neuroimaging and clinical data for predicting the effectiveness of neurostimulation therapy after a
trial phase. STUDY DESIGN: A prospective, consecutive, observational, single center study. SETTING: The
Multidisciplinary Pain Management Department of the General University Hospital in Valencia, Spain.
METHODS: A prospective, consecutive, and observational single-center study. Using Resting-state functional
magnetic resonance imaging (rs-fMRI) and Region of interest (ROI) to ROI analysis, we compared the
functional connectivity between regions to detect differences in FC and volume changes. Basal magnetic
resonance images were obtained in a 1.5T system and clinical variables were collected twice, at the basal
condition and at 6-months post-SCS implant. We also conducted a seed-to-voxel analysis with 9 items as
seed-areas characterizing the functional connectivity networks. A decreased in 10 units in the Pain Detect
Questionnaire (PD-Q) score was established to define the subgroup of Responders Group (R-G) to
neurostimulation therapy. The clinical variables collected and the imaging biomarkers obtained (FC and
volumes) were tested on a set of 6 machine learning approaches in an effort to find the best classifier system
for predicting the effectiveness of the neurostimulator. RESULTS: Twenty-four patients were analyzed and
only seven were classified in the R-G. Volumetric differences were found in the left putamen, F = 34.06, P =
0.02. Four pairwise brain areas showed statistical differences in the rs-fMRI including the right insular cortex.
Linear Discriminant Analysis showed the best performance for building the CDSS combining clinical
variables and significant imaging biomarkers, the prediction increased diagnostic accuracy in the R-G patients
from 29% in current practice to 96% of long-term success. CONCLUSION: These findings confirm a major
role of the left putamen and the four pairs of brain regions in FBBS patients and suggest that a CDSS would
de Graaf, F. R., et al. (2010). "Diagnostic accuracy of 320-row multidetector
computed tomography coronary angiography to noninvasively assess in-stent
restenosis." Invest Radiol 45(6): 331-340.
OBJECTIVES: Percutaneous coronary intervention with stent implantation is routinely performed to treat
patients with obstructive coronary artery disease. However, thus far, noninvasive assessment of in-stent
restenosis has been challenging. Recently, 320-row multidetector computed tomography coronary
angiography (CTA) was introduced, allowing volumetric image acquisition of the heart in a single heart beat
or gantry rotation. The aim of this study was to evaluate the diagnostic performance of 320-row CTA in the
evaluation of significant in-stent restenosis. Invasive coronary angiography (ICA) served as the standard of
reference, using a quantitative approach. MATERIALS AND METHODS: The population consisted of
patients with previous coronary stent implantation who were clinically referred for cardiac evaluation because
of recurrent chest pain and who underwent both CTA and ICA. CTA studies were performed using a 320-row
CTA scanner with 320 detector-rows, each 0.5 mm wide, and a gantry rotation time of 350 milliseconds. Tube
voltage and current were adapted to body mass index and thoracic anatomy. The entire heart was imaged in a
single heart beat, with a maximum of 16-cm craniocaudal coverage. During the scan, the ECG was registered
simultaneously for prospective triggering of the data. First, CTA stent image quality was assessed using a 3point grading scale: (1) good image quality, (2) moderate image quality, and (3) poor image quality.
Subsequently, the presence of in-stent restenosis was determined on a stent and patient basis by a blinded
observer. Significant in-stent restenosis was defined as >or=50% luminal narrowing in the stent lumen or the
presence of significant stent edge stenosis. Overlapping stents were considered to represent a single stent.
Results were compared with ICA using quantitative coronary angiography. In addition, CTA stent image
quality and diagnostic accuracy were related to stent characteristics and heart rate during CTA image
acquisition. RESULTS: The population consisted of 53 patients (37 men, mean age: 65 +/- 13 years) with a
total of 89 stents available for evaluation. ICA identified 12 stents (13%) with significant in-stent restenosis.
A total of 7 stents (8%) were of nondiagnostic CTA stent image quality, and were considered positive.
Sensitivity, specificity, positive, and negative predictive values were 92%, 83%, 46%, and 98%, respectively
on a stent basis. Five CTA studies (9%) were of nondiagnostic quality for the evaluation of in-stent restenosis
and were considered positive. Sensitivity, specificity, positive, and negative predictive values were 100%,
81%, 58%, and 100%, respectively on a patient level. Stent diameter <3 mm as well as stent strut thickness
>or=140 mum were associated with decreased CTA stent image quality and diagnostic accuracy. Heart rate
during CTA acquisition and stent overlap were not associated with image degradation. CONCLUSIONS: The
de Jonge, T. (2012). "[Pharmacological reduction of bleeding during hip
endoprosthetic replacement]." Orv Hetil 153(41): 1607-1612.
INTRODUCTION: Endoprosthetic replacement of the large joints is accompanied by major bleeding. During
the last few years several authors reported the perioperative administration of tranexamic acid and its
beneficial effect on reducing the blood loss. OBJECTIVES: In the present study, the author studied the effect
of intravenously administered tranexamic acid in patients undergoing primary total hip arthroplasty in order to
examine whether this treatment could reduce postoperative blood loss, the amount of transfused packed red
cells, and the cost of the blood saving and/or transfusion. METHODS: The author compared retrospectively
the data of 104 patients undergoing primary total hip arthroplasty between April, 2010 and December, 2011.
54 patients were administered tranexamic acid (Group 1) and 50 patients were treated without tranexamic acid
(Group 2). The amount of postoperative bleeding, haemoglobin, hematocrit, red blood cell count, and the
number of units of the transfused packed red cells were recorded. Cost effectiveness of treatment with
tranexamic acid was calculated. RESULTS: Postoperative blood loss in Group 1 was 732 ml (210-1280 ml),
and in Group 2 1092 ml (420-2640 ml). Ten of the 54 patients in Group 1 had to be transfused, and the allover need was 20 units of packed red cells. 49 of the 50 patients in Group 2 received 98 units of allogenic
blood. Thromboembolic complication was not observed in connection with the use of tranexamic acid. The
reduction of blood loss with the application of tranexamic acid and the transfused packed red cells cost in
average 5,180 HUF per patient in Group 1 and 15,850 HUF in Group 2. CONCLUSIONS: Intravenous
administration of tranexamic acid reduces effectively the transfusion rate and the blood loss in the
postoperative period in patients undergoing primary total hip arthroplasty. More than 1.5 million HUF and
240 units of packed red cells could be yearly saved with the introduction of this simple, safe and cheap
de Krom, M. A. P., et al. (2022). "Diagnostic tools to evaluate ankle instability caused
by a deltoid ligament rupture in patients with supination-external rotation ankle
fractures: A systematic review and meta-analysis." Injury 53(2): 724-731.
Aim Supination-external rotation (SER) ankle fractures account for the majority of ankle fractures and can be
divided into stable or unstable fractures, based on the state of the deltoid ligament. The objective of this
review was to appraise the available literature concerning diagnostic tools to evaluate deltoid ligament
integrity in patients with SER-type ankle fractures. Methods A comprehensive literature search of Pubmed
and Embase was performed up to December 2020. The outcome measures were sensitivity, specificity and
positive and negative predictive value of the diagnostic tools. A meta-analysis was performed to obtain an
overview of sensitivity, specificity and area under the curve (AUC). The methodological quality of the articles
was evaluated using Quality Assessment of Diagnostic Accuracy Studies. Results A total of 12 studies
investigating tools for deltoid ligament rupture in patients with SER-type ankle fractures were included. The
present study found sensitivity (and specificity) ranges of 0.20-0.90 (and 0.38-0.97) for clinical features,
Magnetic Resonance Imaging (MRI) 0.57-0.85 (and 0.81-1.00), ultrasonography 1.00 (and 0.89-1.00),
Malleolar Medial Fleck Sign (MMFS) 0.25 (and 0.99), conventional ankle mortise radiography 0.33-0.57 (and
0.60-0.94), gravity stress radiography 0.71-1.00 (and 0.72-0.88) and manual stress ankle radiography 0.651.00 (and 0.00-0.77). The largest AUC was found for ultrasonography, followed by MMFS, gravity stress
radiography and MRI. Conclusion Ultrasonography and gravity stress radiography seem the most accurate
diagnostic tools to evaluate deltoid ligament integrity. To strengthen this conclusion, future research should
use an identical reference test to ensure comparability of results. Nevertheless, present study is of high value
to close the knowledge gap about which presently available diagnostic tool is to be preferred to evaluate
de las Parras, F. A., E. S. Velasco and F. C. Álvarez (2016). "Pancreatitis aguda."
Medicine - Programa de Formación Médica Continuada Acreditado 12(8): 407-420.
Resumen Concepto Es la inflamación en la glándula pancreática que cursa con epigastralgia y elevación de
enzimas pancreáticas (amilasa y lipasa). Epidemiología La incidencia en España es de 15.000 casos/año.
Etiopatogenia La colelitiasis y el alcohol son las causas más frecuentes. Manifestaciones clínicas La
epigastralgia es el síntoma predominante. Un 80-90% de los casos presentan náuseas y vómitos y puede
asociarse a ictericia y a fallo multiorgánico. Diagnóstico La clínica y la elevación de enzimas pancreáticas
llevan al diagnóstico. Las técnicas de imagen (ecografía y TAC abdominal) pueden ayudar. La TAC permite
evaluar la gravedad y las complicaciones. Tratamiento Son clave el ayuno, la estabilidad hemodinámica y
eliminar el agente etiológico. Las técnicas endoscópicas están adquiriendo protagonismo en el tratamiento de
las complicaciones. Pronóstico Los reactantes de inflamación (proteína C reactiva) pueden ser útiles para la
predicción de la gravedad. Existen escalas pronósticas que ayudan en la toma de decisiones. Concept
Pancreatitis is the inflammation of pancreatic gland in which the patient presents epigastric pain an elevation
of pancreatic enzymes (amylase and lipase). Epidemiology The incidence in Spain is 15.000 cases per year.
Clinical symptoms The most frecuent sympstom is epigastric pain. 80-90% of patients present nausea and
vomits, and ictericia or multiorganic failure can be present. Diagnosis It is achieved by clinical manifestations
and elevation of pancreatic enzymes. Ultrasonography and abdominal Computarized Tomography are usefull,
and the last one enables the evaluation of severity and complications. Treatment Absolut diet, hemodynamic
stability and delete the etiological agent are imperative. Endoscopic procedures are improving its role in the
management of complications. Prognosis Acute phase reactants (as Reactive C Protein) could support in the
De Martino, E., et al. (2022). "Intramuscular lipid concentration increased in localized
regions of the lumbar muscles following 60 day bedrest." Spine J 22(4): 616-628.
de Sousa, L. M., et al. (2023). "Temporomandibular joint arthritis increases canonical
Wnt pathway expression in the articular cartilage and trigeminal ganglion in rats."
Bone Rep 18: 101649.
BACKGROUND CONTEXT: Prolonged bedrest induces accumulation of intramuscular lipid concentration
(ILC) in the lumbar musculature; however, spatial distribution of ILC has not been determined. Artificial
gravity (AG) mitigates some adaptations induced by 60 day bedrest by creating a head-to-feet force while
participants are in a supine position. PURPOSE: To quantify the spatial distribution of accumulation of ILC in
the lumbar musculature after 60 day bedrest, and whether this can be mitigated by AG exposure. STUDY
DESIGN: Prospective longitudinal study. PATIENT SAMPLE: Twenty-four healthy individuals (8 females)
participated in the study: Eight received 30 min continuous AG (cAG); Eight received 6 × 5 min AG (iAG),
interspersed with rests; Eight were not exposed to AG (CRTL). OUTCOME MEASURES: From 3T magnetic
resonance imaging (MRI), axial images were selected to assess lumbar multifidus (LM), lumbar erector spinae
(LES), quadratus lumborum (QL), and psoas major (PM) muscles from L1/L2 to L5/S1 intervertebral disc
levels. Chemical shift-based 2-echo lipid and/or water Dixon sequence was used to measure tissue
composition. Each lumbar muscle was segmented into four equal quartiles (from medial to lateral).
METHODS: Participants arrived at the facility for the baseline data collection before undergoing a 60 day
strict 6° head-down tilt (HDT) bedrest period. MRI of the lumbopelvic region was conducted at baseline and
Day-59 of bedrest. Participants performed all activities, including hygiene, in 6° HDT and were discouraged
from moving excessively or unnecessarily. RESULTS: At the L4/L5 and L5/S1 intervertebral disc levels, 60day bedrest induced a greater increase in ILC in medial and lateral regions (∼+4%) of the LM than central
regions (∼+2%; p<.05). A smaller increase in ILC was induced in the lateral region of LES (∼+1%) at L1/L2
and L2/L3 than at the centro-medial region (∼+2%; p<.05). There was no difference between CRTL and
intervention groups. CONCLUSIONS: Inhomogeneous spatial distribution of accumulation of ILC was found
in the lumbar musculature after 60 day bedrest. These findings might reflect pathophysiological mechanisms
related to muscle disuse and contribute to localized lumbar spine dysfunction. Altered spatial distribution of
ILC may impair lumbar spine function after prolonged body unloading, which could increase injury risk to
vulnerable soft tissues, such as the lumbar intervertebral discs. These novel results may represent a new
biomarker of lumbar deconditioning for astronauts, bedridden, sedentary individuals, or those with chronic
The canonical Wnt pathway participates in inflammatory diseases and it is involved in neuropathic pain. This
study evaluated the immunoexpression of the canonical Wnt signaling pathway in the articular cartilage of the
temporomandibular joint (TMJ) and along the nociceptive trigeminal pathway in arthritic rats. For this, male
Wistar rats were divided into Control (C) and Arthritic (RA) groups. Arthritis induction was performed
through subcutaneous injection of methylated bovine serum albumin (mBSA) and complete Freund Adjuvant
(CFA)/ Incomplete Freund Adjuvant (IFA) on the first 14 days (once a week), followed by 3 weekly intraarticular injections of mBSA (10 μl/joint; left TMJ). The following parameters were evaluated: nociceptive
threshold, inflammatory infiltrate, type I and III collagen birefringence, immunohistochemistry for IL-1β,
TNF-α, IL-6, Wnt10b, β-catenin, cyclin-D1 in articular cartilage, c-Myc in synovial membrane, and
immunofluorescence analysis for c-Fos, Wnt-10b and β-catenin in the trigeminal ganglion and the trigeminal
subnucleus caudalis. The RA group showed intense articular cartilage damage with proliferation of type III
collagen, increased immunoexpression of proinflammatory cytokines and Wnt-10b, β-catenin and cyclin-D1
in the articular cartilage and c-Myc in the synovial membrane. In the RA group, a reduction in the nociceptive
threshold was observed, followed by a significant increase in the expression of Wnt-10b in neurons and βcatenin in satellite cells of the trigeminal ganglion. c-Fos immunoexpression was observed in neurons,
peripherally and centrally, in arthritic rats. Our data demonstrated that TMJ arthritis in rats causes articular
cartilage damage and nociceptive behavior, with increased immunoexpression of canonical Wnt pathway in
Del Tatto, B., et al. (2022). "Arterial Embolization of Polycystic Kidneys for
Heterotopic Transplantation." J Endovasc Ther 29(6): 885-892.
INTRODUCTION: The purpose of this study was to evaluate the efficacy of polycystic kidney embolization,
performed to reduce kidney volume before heterotopic kidney transplantation, as this technique could be an
alternative to pretransplant nephrectomy. MATERIALS AND METHODS: All patients who underwent
pretransplant embolization of polycystic kidneys were included in a prospective register from June 2014 to
February 2020. All patients underwent computed tomography (CT) scan with volumetric reconstruction
(OsiriX, Bernex, Switzerland) before embolization and were then followed up at 3 and 6 months after
embolization. Primary outcome was percentage of kidney volume reduction. Secondary outcomes were 30 day
mortality and morbidity. RESULTS: Thirty-one embolizations performed on 29 patients (medium age = 55.6;
62.1% male) were included between June 2014 and February 2020. All patients were under dialysis before
embolization (9 peritoneal dialysis and 20 hemodialysis). Technical success was observed in 96.8% of cases.
Mean procedural time was 65 minutes (range = 35-106 minutes) and mean length of in-hospital stay was 3.8
days (range = 3-6 days). A volume reduction allowing a kidney transplant was obtained for 28 patients
(96.5%). The mean volume reduction was 39.9% (range = 6.01-68.2). The main observed complication was
postembolization pain in 10 cases (32.2%). One patient needed complementary nephrectomy due to
insufficient volume reduction. Twenty-three patients (79.3%) received renal transplant during follow-up with
a mean delay of 19.5 month (range = 4-54). CONCLUSION: Polycystic kidney embolization is an effective
and safe minimally invasive technique. It can be proposed as the first-choice technique for kidney transplant
Delaney, C. L., et al. (2013). "A systematic review to evaluate the effectiveness of
carnitine supplementation in improving walking performance among individuals with
intermittent claudication." Atherosclerosis 229(1): 1-9.
Delhaas, E. M., et al. (2017). "Plain radiography in patients treated with intrathecal
drug delivery using an implantable pump device." Insights Imaging 8(5): 499-511.
OBJECTIVE: To evaluate the evidence for the use of carnitine supplementation in improving walking
performance among individuals with intermittent claudication. DESIGN: Systematic review. METHODS: An
electronic search of the literature was performed using MEDLINE (PubMed), Scopus, Cochrane Central
Register of Controlled Trials and The Cochrane Library from inception through to November 2012. Search
terms included peripheral arterial disease, intermittent claudication and carnitine. Reference lists of review
articles and primary studies were also examined. Full reports of published experimental studies including
randomized controlled trials and pre-test/post-test trials were selected for inclusion. A quality assessment was
undertaken according to the Jadad scale. RESULTS: A total of 40 articles were retrieved, of which 23 did not
meet the inclusion criteria. The 17 included articles reported on a total of 18 experimental studies of carnitine
supplementation (5 pre-test/post-test; 8 parallel RCT; 5 cross-over RCT) for improving walking performance
in adults with intermittent claudication. For pre-test/post-test studies, 300-2000 mg propionyl-L-carnitine
(PLC) was administered orally or intravenously for a maximum of 90 days (7-42 participants) with
statistically significant improvements of between 74 m and 157 m in pain free walking distance and between
71 m and 135 m in maximal walking distance across 3 out of 5 studies. Similarly, PLC (600 mg-3000 mg) was
administered orally in 7 out of 8 parallel RCTs (22-485 participants), the longest duration being 12 months.
All but one of the smallest trials demonstrated statistically significant improvements in walking performance
between 31 and 54 m greater than placebo for pain free walking distance and between 9 and 86 m greater than
placebo for maximal walking distance. A double-blind parallel RCT of cilostazol plus 2000 mg oral Lcarnitine or placebo for 180 days (145 participants) did not demonstrate any significant improvement in
walking performance. Of 5 cross-over RCTs (8-20 participants), 4 demonstrated significant improvements in
walking performance following administration of 300-6000 mg L-carnitine or PLC. Compared to placebo,
pain free walking distance and maximal walking distance improved by 23-132 m and 104 m respectively
following carnitine intervention. CONCLUSIONS: Most trials demonstrated a small or modest improvement
in walking performance with administration of PLC or L-carnitine. These findings were largely independent
of level or quality of evidence, while there was some evidence that intravenous administration was more
effective than oral administration and those with severe claudication may achieve greater benefits than those
with moderate claudication. Routine carnitine supplementation in the form of PLC may therefore be a useful
adjunct therapy for management of intermittent claudication. Further research is warranted to determine the
OBJECTIVES: Intrathecal drug administration using an implanted pump system is well established in
intractable spasticity and pain. However, despite continuous advancements in manufacturing technology,
adverse events related to the pump and catheter still occur. Most of them, such as migration, damage,
disconnection and occlusion, are related to the spinal catheter. The aim of this overview is to update
radiologists on how plain radiography of the implanted delivery system for intrathecal drug administration
should be interpreted and to increase awareness for the need of urgent and timely multidisciplinary
troubleshooting. METHODS: Plain radiographic images of patients treated with intrathecal drug
administration using an implantable drug delivery system were analysed in a multidisciplinary setting at our
(university) referral centre for complications in intrathecal drug administration. RESULTS: Examples of
catheter-related adverse events are described and a proposal is made for stepwise interpretation of standard
plain radiographic images. CONCLUSIONS: Plain radiological images are the mainstay for the diagnosis of
catheter-related adverse events in intrathecal drug delivery. Radiologists play an important role in an early
diagnosis. An awareness of abnormal radiological findings seems important to avoid a life-threatening
withdrawal syndrome. TEACHING POINTS: • Untimely cessation of intrathecal drug delivery can lead to a
life-threatening withdrawal syndrome. • Initially mild symptoms can lead to an exacerbation of a withdrawal
syndrome. • Most intrathecal catheter-related problems are visible on plain radiography. • Common causes of
catheter problems are migration, lacerations, occlusion and disconnection. • Knowledge on implanted
DeMaria, P. J., et al. (2021). "Phase 1 open-label trial of intravenous administration of
MVA-BN-brachyury-TRICOM vaccine in patients with advanced cancer." J
Immunother Cancer 9(9).
BACKGROUND: MVA-BN-brachyury-TRICOM is a recombinant vector-based therapeutic cancer vaccine
designed to induce an immune response against brachyury. Brachyury, a transcription factor overexpressed in
advanced cancers, has been associated with treatment resistance, epithelial-to-mesenchymal transition, and
metastatic potential. MVA-BN-brachyury-TRICOM has demonstrated immunogenicity and safety in previous
clinical trials of subcutaneously administered vaccine. Preclinical studies have suggested that intravenous
administration of therapeutic vaccines can induce superior CD8(+) T cell responses, higher levels of systemic
cytokine release, and stronger natural killer cell activation and proliferation. This is the first-in-human study
of the intravenous administration of MVA-BN-brachyury-TRICOM. METHODS: Between January 2020 and
March 2021, 13 patients were treated on a phase 1, open-label, 3+3 design, dose-escalation study at the
National Institutes of Health Clinical Center. The study population was adults with advanced solid tumors and
was enriched for chordoma, a rare sarcoma of the notochord that overexpresses brachyury. Vaccine was
administered intravenously at three DLs on days 1, 22, and 43. Blood samples were taken to assess drug
pharmacokinetics and immune activation. Imaging was conducted at baseline, 1 month, and 3 months posttreatment. The primary endpoint was safety and tolerability as determined by the frequency of dose-limiting
toxicities; a secondary endpoint was determination of the recommended phase 2 dose. RESULTS: No doselimiting toxicities were observed and no serious adverse events were attributed to the vaccine. Vaccine-related
toxicities were consistent with class profile (ie, influenza-like symptoms). Cytokine release syndrome up to
grade 2 was observed with no adverse outcomes. Dose-effect trend was observed for fever, chills/rigor, and
hypotension. Efficacy analysis of objective response rate per RECIST 1.1 at the end of study showed one
patient with a partial response, four with stable disease, and eight with progressive disease. Three patients
with stable disease experienced clinical benefit in the form of improvement in pain. Immune correlatives
showed T cell activation against brachyury and other tumor-associated cascade antigens. CONCLUSIONS:
Intravenous administration of MVA-BN-brachyury-TRICOM vaccine was safe and tolerable. Maximum
tolerated dose was not reached. The maximum administered dose was 10(9) infectious units every 3 weeks for
three doses. This dose was selected as the recommended phase 2 dose. TRIAL REGISTRATION NUMBER:
Dembélé, B. T., et al. (2011). "[Small bowel obstruction and adhesions in general
surgery at Gabriel Toure University Hospital]." Mali Med 26(4): 12-15.
The objectives were to determine the frequency, to describe the clinical, therapeutic aspects and to evaluate
the cost of the assumption of responsibility of occlusions by supports and or adherences. It was about a
retrospective study carried out in the department of surgery general of the CHU Hôpital Gabriel TOURE from
January 1st, 2002 to December 2008. Were included in this study all the patients operated for occlusion of
hail on Brides and Adherence confirmed in per operational. We colligé 659 acute obstructions of the bowels
whose 100 occlusions of hail on supports and adherences is a frequency of 17,8%. They were 55 men (55%)
and 45 women (45%). The sex-ratio was of 1,2. The average age was 39,7 years with the extremes varying
between 15ans and 80 years. Eighty eight of our patients had surgical antecedents including 14 (16%) of
surgery known méso colic and 74 (84%) of surgery under méso colic. Twelve patients had antecedents of
contusion and untreated abdominal infections. Among the signs of the occlusive syndrome, the abdominal
pain was found at all the malades100 (100%), the vomiting (98), the stop of the matters (88) and the gases
(80). The ASP was carried out at 98 of our patients and 74 (75,5%) presented radiological images in favor of
the occlusion of hail. The leading cause of occlusion was the supports (67), the supports and adherences (18)
and adherences (15). The small intestine was hyperhémié chez14 patient, was necrosed among 16 patients and
normal in the 70 cases. The surgical treatment consisted with a section of the support among 60 patients
Adhésiolyse among 15 patients, a Adhésiolyse section among 10 patients, a résection Iléostomie among 10
patients and a résection - immediate anastomosis among 5 patients. The rate of morbidity was of 28%, it
related to the infection of the operational site 18cas, the digestive dent 6cas and the eventration 4cas.
Mortality was of 8%. Intermediate duration of hospitalization 14,8 days. The average costs of the assumption
of responsibility were of 156.900 francs CFA. CONCLUSION: Mortality and postoperative morbidity are not
Derry, S., et al. (2013). "WITHDRAWN: Single dose dipyrone for acute postoperative
pain." Cochrane Database Syst Rev 2013(11): Cd003227.
Dipyrone is a popular medicine for pain relief in many countries and is used to treat
postoperative pain, colic pain, cancer pain and migraine. Other countries (e.g. USA,
UK, Japan) have banned its use because of an association with potentially
life‐threatening blood disorders such as agranulocytosis. There was too little
information available to draw any conclusions about most of the doses and routes of
administration of dipyrone used in these studies. A single 500 mg oral dose of
dipyrone provided at least 50% pain relief to adults with moderate or severe
postoperative pain, with similar efficacy to ibuprofen 400 mg. A single 2.5 g
intravenous dose was equivalent to 100 mg intravenous tramadol for at least 50% pain
relief. Adverse effects were poorly reported, but no serious events or adverse event
withdrawals
were reported.
eng
BACKGROUND: Dipyrone (metamizole) is a non‐steroidal anti‐inflammatory drug used in some countries to
treat pain (postoperative, colic, cancer, and migraine); it is banned in others because of an association with
life‐threatening blood agranulocytosis. This review updates a 2001 Cochrane review, and no relevant new
studies were identified, but additional outcomes were sought. OBJECTIVES: To assess the efficacy and
adverse events of single dose dipyrone in acute postoperative pain. SEARCH METHODS: The earlier review
searched CENTRAL, MEDLINE, EMBASE, LILACS and the Oxford Pain Relief Database to December
1999. For the update we searched CENTRAL, MEDLINE,EMBASE and LILACS to February 2010.
SELECTION CRITERIA: Single dose, randomised, double‐blind, placebo or active controlled trials of
dipyrone for relief of established moderate to severe postoperative pain in adults. We included oral, rectal,
intramuscular or intravenous administration of study drugs. DATA COLLECTION AND ANALYSIS: Studies
were assessed for methodological quality and data extracted by two review authors independently. Summed
total pain relief over six hours (TOTPAR) was used to calculate the number of participants achieving at least
50% pain relief. Derived results were used to calculate, with 95% confidence intervals, relative benefit
compared to placebo, and the number needed to treat (NNT) for one participant to experience at least 50%
pain relief over six hours. Use and time to use of rescue medication were additional measures of efficacy.
Information on adverse events and withdrawals was collected. MAIN RESULTS: Fifteen studies tested
mainly 500 mg oral dipyrone (173 participants), 2.5 g intravenous dipyrone (101), 2.5 g intramuscular
dipyrone (99); fewer than 60 participants received any other dose. All studies used active controls (ibuprofen,
paracetamol, aspirin, flurbiprofen, ketoprofen, dexketoprofen, ketorolac, pethidine, tramadol, suprofen); eight
used placebo controls. Over 70% of participants experienced at least 50% pain relief over 4 to 6 hours with
oral dipyrone 500 mg compared to 30% with placebo in five studies (288 participants; NNT 2.4 (1.9 to 3.2)).
Fewer participants needed rescue medication with dipyrone (7%) than with placebo (34%; four studies, 248
participants). There was no difference in participants experiencing at least 50% pain relief with 2.5 g
intravenous dipyrone and 100 mg intravenous tramadol (70% vs 65%; two studies, 200 participants). No
serious adverse events were reported. AUTHORS' CONCLUSIONS: Based on very limited information,
single dose dipyrone 500 mg provides good pain relief to 70% of patients. For every five individuals given
dipyrone 500 mg, two would experience this level of pain relief who would not have done with placebo, and
Derry, S., et al. (2012). "Intracutaneous or subcutaneous sterile water injection
compared with blinded controls for pain management in labour." Cochrane Database
Syst Rev 1: Cd009107.
Di Francesco, A., et al. (2016). "Continuous intraarticular and periarticular
levobupivacaine for management of pain relief after total knee arthroplasty: A
prospective randomized, double-blind pilot study." J Orthop 13(3): 119-122.
BACKGROUND: Intracutaneous or subcutaneous injection of sterile water is rapidly gaining popularity as a
method of pain relief in labour and it is therefore essential that it is properly evaluated. Adequate analgesia in
labour is important to women worldwide. Sterile water injection is inexpensive, requires basic equipment, and
appears to have few side effects. It is purported to work for labour pain. OBJECTIVES: To determine the
efficacy of sterile water injections for relief of pain (both typical contraction pain and intractable back pain)
during labour compared to placebo (isotonic saline injections) or non-pharmacological interventions, and to
identify any relevant effects on mode and timing of delivery, or safety of both mother and baby. SEARCH
METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 May 2011),
MEDLINE, and EMBASE (January 2010 to 30 May 2011), together with reference lists in retrieved studies
and review articles. SELECTION CRITERIA: We included randomised, double blind, controlled studies
using intracutaneous or subcutaneous sterile water injections for pain relief during labour. There were no
restrictions on birth place, parity, risk, age, weight, gestation, or stage of labour. Potential comparators were
placebo (saline) and non-pharmacological interventions (e.g. hypnosis or biofeedback). DATA
COLLECTION AND ANALYSIS: Two review authors independently assessed eligibility and quality of
trials, and extracted data. We resolved any disagreements or uncertainties by discussion with a third review
author. Primary outcome measures were at least 50% pain relief, or at least 30%, pain relief, patient global
impression of change of at least 'good', mode of delivery, perinatal morbidity and mortality, maternal
complications and adverse events. Secondary outcomes were women with any pain relief, use of rescue
analgesia, and treatment group average pain relief. We made explicit judgements about potential biases in the
studies. MAIN RESULTS: We included seven studies, with 766 participants: four used intracutaneous
injections, two subcutaneous, and one both. All reported on low back pain in labour only. Methodological
quality was good, but four studies were at high risk of bias due to small size of treatment groups, incomplete
outcome data, and performance bias.All studies reported treatment group mean or median scores, finding
greater reduction in pain for sterile water. However, failure to demonstrate a normal distribution for pain
intensity or relief, and use of different scales, meant meta-analysis was inappropriate. No study reported
primary dichotomous efficacy outcomes. One reported the number self-scoring 4/10 cm or more reduction in
pain; significantly more had this outcome with sterile water (50% to 60%) than with placebo (20% to
25%).There was no significant difference between sterile water and saline for rates of caesarean section (risk
BACKGROUND: Total knee arthroplasty (TKA) can result in major postoperative pain which can impact the
recovery and rehabilitation of patients and for this reason the use of a pain-control infusion pumps (PCIP)
enhances analgesia for TKA. PURPOSE: To investigate whether a PCIP of levobupivacaine would reduce
pain in patients following TKA. METHODS: This was a prospective, randomized, controlled study conducted
in 55 patients. Criteria for participation were unilateral TKA for osteoarthritis and no allergies to
levobupivacaine. The primary outcomes measured were postoperative pain intensity on Visual Analogue
Scale (VAS) score measured at 24 h and 48 h. Other measures included amount of narcotics, presence of
adverse events, and length of hospital stay. RESULTS: PCIP-treated patients (n = 28) showed significant
reductions in VAS score at any time versus control (p < 0.01). Amount of narcotics, presence of adverse
events, and length of hospital stay were significantly less with the PCIP versus control (each p < 0.01).
CONCLUSION: The use of a mix of levobupivacaina, ketoral-trometamina, and adrenalin provides a safe and
effective means in post-operative pain relief in patients undergoing TKA. LEVEL OF EVIDENCE: Level II
Di Franco, R., et al. (2023). "Reirradiation on spine metastases: an Italian survey on
behalf of palliative care and reirradiation study groups of Italian association of
radiotherapy and clinical oncology (AIRO)." Clin Transl Oncol 25(2): 408-416.
Di Mauro, P., et al. (2021). "Systemic mastocytosis: The roles of histamine and its
receptors in the central nervous system disorders." Journal of the Neurological
Sciences 427: 117541.
AIM: This survey derived from the collaboration between the Palliative Care and Reirradiation Study Groups
of the Italian Association of Radiotherapy and Clinical Oncology (AIRO). Its aim was to obtain a real
"snapshot" on the treatments of spinal metastases, focusing on reirradiation, among radiation oncologists in
Italy. METHODS: The survey was elaborated on SurveyMonkey's online interface and was sent via e-mail to
all Radiation Oncologists of AIRO that were invited to anonymously fill in the electronic form within 60 days.
The questionnaire was prepared by the AIRO "Palliative care" and "Reirradiation" Study Groups and it
consisted of 36 questions, 19 single-choice questions, 10 multiple-choice questions and 6 open questions. The
data were analyzed and represented with tables and graphs. RESULTS: The survey shows that palliative
radiotherapy remains a field of interest for most ROs in the Italian centers. 3D Conventional Radiation
Therapy (3DCRT) alone or in combination with other techniques is the primary choice for patients with a life
expectancy of less than 6 months. For patients with a life expectancy of more than six months, there is an
increased use of new technologies, such as Volumetric Modulated Arc Therapy (VMAT). Factors considered
for retreatment are time between first and second treatment, dose delivered to spine metastasis and spinal cord
in the first treatment, vertebral stability, symptoms, and/or performance status. The most feared complication
are myelopathy followed by vertebral fracture and local recurrence. This explain an increasing focus on
patient selection and the use of high technology in the treatment of metastatic patients. CONCLUSION:
Stereotactic body radiotherapy (SBRT) and image-guided radiotherapy allow the administration of ablative
RT doses while sparing the constraints of healthy tissue in spinal metastases. However, there is still an unclear
and heterogeneous reality in the reirradiation of spinal metastases. A national registry with the aim of
clarifying the most controversial aspects of vertebral metastasis retreatments will enable better management of
Mastocytosis is a rare disease of clonal hematological disorders characterized by a pathological accumulation
of Mast Cells (MCs) in different tissues, with variable symptomatology and prognosis. Signs and symptoms of
Systemic Mastocytosis (SM) are due to pathological infiltration of MCs and to the release of chemical
mediators, mainly histamine. Patients with SM may also present with neurological symptoms or
complications. The pathophysiology of these neurological disorders remains uncertain to this day, but it can
be associated with the infiltration of tissue mastocytes, release of mastocytes' mediators or both. Moreover,
there is a lot to understand about the role of neurological symptoms in SM and knowing, for example, what is
the real frequency of neurological disorders in SM and if is present a relation between other SM subtypes,
because it has been noted that the alteration of the histamine expression may be an initiating factor for
susceptibility, gravity and progression of the epigenetic disease. In this review we explain the possible
pathophysiological mechanism about neurological symptomatology found in some patients affected by SM,
describing the role of histamine and its receptors in the nervous system and, in light of the results, what the
future prospects may be for a more specific course of treatment.
Diez, B. D., et al. (2010). "Evaluation of the exposure equivalence of oral versus
intravenous temozolomide." Cancer Chemother Pharmacol 65(4): 727-734.
Digas, G., et al. (2015). "Intra-articular injection of tranexamic acid reduce blood loss
in cemented total knee arthroplasty." Eur J Orthop Surg Traumatol 25(7): 1181-1188.
PURPOSE: Oral temozolomide is approved in many countries for malignant glioma and for melanoma in
some countries outside the USA. This study evaluated the exposure equivalence and safety of temozolomide
by intravenous infusion and oral administration. METHODS: Subjects with primary central nervous system
malignancies (excluding central nervous system lymphoma) received 200 mg/m(2) of oral temozolomide on
days 1, 2 and 5. On days 3 and 4, subjects received 150 mg/m(2) temozolomide either as a 90-min intravenous
infusion on one day or by oral administration on an alternate day. RESULTS: Ratio of log-transformed means
(intravenous:oral) of area under the concentration-time curve and maximum concentration of drug after dosing
for temozolomide and 5-(3-methyltriazen-1-yl)imidazole-4-carboxamide (MTIC) met exposure equivalence
criteria (90% confidence interval = 0.8-1.25). Treatment-emergent adverse events were consistent with those
reported previously in subjects with recurrent glioma treated with oral temozolomide, except for mostly mild
and transient injection site reactions with intravenous administration. CONCLUSIONS: This study
demonstrated an exposure equivalence of a 90-min intravenous infusion of temozolomide and an equivalent
oral dose.
The purpose of this study was to compare the efficacy of intravenous and topical tranexamic acid (TXA)
versus control group for reduction in blood loss following primary total knee arthroplasty (TKA). A total of
90 patients were prospectively allocated to each of three groups (control, intravenous IV and intra-articular)
and underwent unilateral total knee arthroplasty. In the IV group, patients received one dose of TXA of 15
mg/kg before deflation of the tourniquet, while in the intra-articular group patients received 2 g TXA via the
drain retrogradely after closure of the wound. The mean drained blood loss in control, IV and intra-articular
groups was 415 ± 24, 192 ± 21 and 121 ± 17 ml, respectively. About 43 % (control), 23 % (IV) and 17 %
(intra-articular) of each group required transfusion, and the mean transfusion was 338, 168 and 79 ml,
respectively. Preoperative hemoglobin values decreased at 24 h by 2.80 ± 0.14, 2.24 ± 0.17 and 2.26 ± 0.18
mg/dl, respectively. TXA reduced blood loss and transfusion requirement. Compared with one-dose
intravenous administration, intra-articular administration of TXA seems to be more effective in terms of
reducing drained blood loss and transfusion frequency. We recommend administration of topical TXA in
primary TKA in healthy patients to decrease perioperative blood loss.
Dimopoulos, M. A., et al. (2017). "Carfilzomib or bortezomib in relapsed or refractory
multiple myeloma (ENDEAVOR): an interim overall survival analysis of an openlabel, randomised, phase 3 trial." Lancet Oncol 18(10): 1327-1337.
BACKGROUND: The phase 3 ENDEAVOR trial was a head-to-head comparison of two proteasome
inhibitors in patients with relapsed or refractory multiple myeloma. Progression-free survival was previously
reported to be significantly longer with carfilzomib administered in combination with dexamethasone than
with bortezomib and dexamethasone in an interim analysis. The aim of this second interim analysis was to
compare overall survival between the two treatment groups. METHODS: ENDEAVOR was a phase 3, openlabel, randomised controlled trial in patients with relapsed or refractory multiple myeloma. Patients were
recruited from 198 hospitals and outpatient clinics in 27 countries in Europe, North America, South America,
and the Asia-Pacific region. Patients were aged 18 years or older, had relapsed or refractory multiple
myeloma, and had received between one and three previous lines of therapy. Patients were randomly assigned
(1:1) to receive carfilzomib and dexamethasone (carfilzomib group) or bortezomib and dexamethasone
(bortezomib group) through a blocked randomisation scheme (block size of four), stratified by International
Staging System stage, previous lines of treatment, previous proteasome inhibitor therapy, and planned route of
bortezomib delivery if assigned to the bortezomib group. Carfilzomib (20 mg/m(2) on days 1 and 2 of cycle 1;
56 mg/m(2) thereafter) was given as a 30-min intravenous infusion on days 1, 2, 8, 9, 15, and 16 of 28-day
cycles; bortezomib (1·3 mg/m(2)) was given as an intravenous bolus or subcutaneous injection on days 1, 4, 8,
and 11 of 21-day cycles. Dexamethasone (20 mg oral or intravenous infusion) was given on days 1, 2, 8, 9, 15,
16, 22, and 23 in the carfilzomib group and on days 1, 2, 4, 5, 8, 9, 11, and 12 in the bortezomib group. The
primary endpoint of ENDEAVOR, progression-free survival, has been previously reported. A stratified logrank test was used to compare overall survival between treatment groups for this prospectively planned second
interim analysis. Efficacy assessments were done in all randomly assigned patients (the intention-to-treat
population) and the safety analysis included patients who received at least one dose of study treatment. This
trial is registered with ClinicalTrials.gov, number NCT01568866, and is no longer enrolling patients.
FINDINGS: Between June 20, 2012, and June 30, 2014, 1096 patients were assessed for eligibility, of whom
929 were randomly assigned (464 to the carfilzomib group and 465 to the bortezomib group). The cutoff date
for this prespecified interim analysis was Jan 3, 2017. Median overall survival was 47·6 months (95% CI
42·5-not evaluable) in the carfilzomib group versus 40·0 months (32·6-42·3) in the bortezomib group (hazard
ratio 0·791 [95% CI 0·648-0·964], one-sided p=0·010). Grade 3 or worse adverse events were reported in 377
(81%) of 463 patients in the carfilzomib group and 324 (71%) of 456 patients in the bortezomib group, and
Dodick, D. W. (2019). "CGRP ligand and receptor monoclonal antibodies for migraine
prevention: Evidence review and clinical implications." Cephalalgia 39(3): 445-458.
BACKGROUND: Monoclonal antibodies that target calcitonin gene-related peptide or the canonical
calcitonin gene-related peptide receptor have emerged as effective and well tolerated for the preventive
treatment of migraine. These large molecules appear ideally suited for migraine prevention. They have an
extended biological half-life, are administered either monthly or quarterly either by subcutaneous injection or
intravenous infusion, require minimal or no dose-titration and have the potential for a rapid onset of effect
compared to conventional oral preventive drugs. There is high selectivity and they target an important
mediator in the pathogenesis of migraine. INVESTIGATION: Phase II and pivotal phase III studies have all
yielded positive results with a favorable adverse event profile. No serious treatment-related adverse outcomes
have thus far been reported in controlled or long-term open-label extension studies. This tolerability profile
promises to improve adherence and, possibly, long-term outcomes. CONCLUSIONS: Calcitonin gene-related
peptide monoclonal antibodies are effective and well tolerated for the preventive treatment of migraine. They
have distinct advantages over currently available oral preventive drugs. While treatment-related serious
adverse events have not been observed in open-label extension studies, long-term outcomes and safety will
require broad exposure in heterogeneous patient populations in clinical practice. In addition, their safety in
women, especially during pregnancy, will require longitudinal surveillance. Given the overlapping
mechanism(s), the effectiveness of existing (triptans) and emerging (calcitonin gene-related peptide receptor
Dodick, D. W., et al. (2014). "Safety and efficacy of LY2951742, a monoclonal
antibody to calcitonin gene-related peptide, for the prevention of migraine: a phase 2,
randomised, double-blind, placebo-controlled study." Lancet Neurol 13(9): 885-892.
BACKGROUND: Migraine remains poorly treated, with few effective preventive drugs available. We
assessed the safety and efficacy of LY2951742, a fully humanised monoclonal antibody to calcitonin generelated peptide, for migraine prevention. METHODS: We did a randomised, double-blind, placebo-controlled,
phase 2 proof-of-concept study at 35 centres in the USA. Patients aged 18-65 years with four to 14 migraine
headache days per month were randomly assigned (1:1) to LY2951742 or placebo by a computerised
randomisation scheme. LY2951742 (150 mg) or placebo were given as a subcutaneous injection once every 2
weeks for 12 weeks. The primary endpoint was the mean change in number of migraine headache days per 28day period assessed at 9-12 weeks. Safety was assessed over 24 weeks, including the 12-week treatment
period and the subsequent 12 weeks after study drug administration. Patients and treating investigators were
masked to treatment allocation. Analyses were by intention to treat. A mixed-effects model of repeated
measures was used, including patient baseline value, treatment, visit, and treatment-by-visit interaction as
fixed effects, and patients as random effects. Safety measures were analysed according to the treatment
received. This study has been completed and is registered with ClinicalTrials.gov, NCT01625988.
FINDINGS: Between July 31, 2012, and Sept 18, 2013, 218 patients were randomly assigned to LY2951742
(n=108, but one patient withdrew before treatment) or placebo (n=110). The mean change from baseline to
week 12 in the number of migraine headache days was -4·2 (SD 3·1; 62·5% decrease) in the LY2951742
group compared with -3·0 (SD 3·0; 42·3% decrease) in the placebo group (least-squares mean difference -1·2,
90% CI -1·9 to -0·6; p=0·0030). Adverse events that occurred more frequently with LY2951742 than with
placebo included injection site pain, erythema, or both (21 [20%] of 107 vs seven [6%] of 110), upper
respiratory tract infections (18 [17%] vs ten [9%]), and abdominal pain (six [6%] vs three [3%]). There were
two serious adverse events reported in the treatment arm and four in the placebo arm, none of which were
deemed to be related to the study drug. INTERPRETATION: These results provide preliminary evidence that
LY2951742 might be beneficial in migraine prevention and provide support for the role of calcitonin generelated peptide in the pathogenesis of migraine. Further controlled studies are needed to assess the safety and
efficacy of monoclonal calcitonin gene-related peptide antibodies for the preventive treatment of migraine.
Doersch, K. M., et al. (2018). "Comparison of utilization of pressurized automated
versus manual hand irrigation during ureteroscopy in the absence of ureteral access
sheath." Proc (Bayl Univ Med Cent) 31(4): 432-435.
This study compared patient outcomes following irrigation applied using an automated pressure system (AP)
to hand irrigation utilizing a syringe (HI) during ureteroscopy. Retrospective chart review was performed to
evaluate ureteroscopy procedures without a ureteral access sheath. Procedures in which irrigation was applied
by AP were compared to those with HI. Statistical analyses included chi-squared tests and Student's t tests.
The AP group contained 206 procedures and the HI group, 25. The AP and HI groups were 54.9% and 36%
male, respectively. Mean ages were 53.7 ± 18.9 years in the AP group and 44.0 ± 18.5 years in the HI group.
Complication rates were 11.2% in the AP and 8.3% in the HI group (P > 0.99). One stone retrieval failure and
one stone recurrence occurred in the HI group; one patient had residual stone in the AP group. No urinary
tract infections occurred in the HI group; in the AP group, urinary tract infections occurred in 1.9% of cases.
The postoperative pain incidence was equivalent (P = 0.498). The AP group had one subcapsular hematoma;
no calyceal ruptures occurred in either group. In conclusion, irrigation applied by an automated setup appears
safe, with similar outcomes to irrigation applied with a handheld syringe.
Dohle, C. I., et al. (2013). "Pilot study of a robotic protocol to treat shoulder
subluxation in patients with chronic stroke." J Neuroeng Rehabil 10: 88.
Doi, M., et al. (2023). "Efficacy, safety, and pharmacokinetics of MR13A11A, a
generic of remifentanil, for pain management of Japanese patients in the intensive care
unit: a double-blinded, fentanyl-controlled, randomized, non-inferiority phase 3
study." J Intensive Care 11(1): 51.
BACKGROUND: Shoulder subluxation is a frequent complication of motor impairment after stroke, leading
to soft tissue damage, stretching of the joint capsule, rotator cuff injury, and in some cases pain, thus limiting
use of the affected extremity beyond weakness. In this pilot study, we determined whether robotic treatment of
chronic shoulder subluxation can lead to functional improvement and whether any improvement was robust.
METHODS: 18 patients with chronic stroke (3.9 ± 2.9 years from acute stroke), completed 6 weeks of robotic
training using the linear shoulder robot. Training was performed 3 times per week on alternate days. Each
session consisted of 3 sets of 320 repetitions of the affected arm, and the robotic protocol alternated between
training vertical arm movements, shoulder flexion and extension, in an anti-gravity plane, and training
horizontal arm movements, scapular protraction and retraction, in a gravity eliminated plane. RESULTS:
Training with the linear robot improved shoulder stability, motor power, and resulted in improved functional
outcomes that were robust 3 months after training. CONCLUSION: In this uncontrolled pilot study, the
robotic protocol effectively treated shoulder subluxation in chronic stroke patients. Treatment of subluxation
can lead to improved functional use of the affected arm, likely by increasing motor power in the trained
muscles.
BACKGROUND: The aims of this study were to evaluate the efficacy, safety, and pharmacokinetics (PK) of
continuous intravenous administration of remifentanil in mechanically ventilated patients in the intensive care
unit (ICU). METHODS: This was a multicenter, randomized, double-blinded, fentanyl-controlled, noninferiority phase 3 study. Patients aged ≥ 20 years requiring 6 h to 10 days mechanical ventilation in an ICU
and requiring pain relief were randomly assigned in a 1:1 ratio to receive either remifentanil (n = 98) or
fentanyl (n = 98). Dose was titrated from an infusion rate of 1 mL/h (remifentanil: 0.025 µg/kg/min, fentanyl:
0.1 µg/kg/h) until the target level of analgesia (behavioral pain scale [BPS] ≤ 5 or numerical rating score
[NRS] ≤ 3) was achieved by escalating the dose in 1 mL/h increasing. Administration was then adjusted to
maintain the target level of analgesia until weaning from the ventilator. The primary endpoint was the
proportion of patients who did not require rescue fentanyl. Safety was assessed according to standard
procedures. PK of remifentanil in the arterial blood was assessed in 24 patients. RESULTS: The proportion of
patients achieving the primary endpoint in the remifentanil and fentanyl groups was 100% (92/92) and 97.8%
(88/90), respectively. The difference between the groups was 2.2% (95% confidence interval, - 0.8-5.3) and
non-inferiority of remifentanil to fentanyl was verified (p < 0.0001). The incidences of any adverse events in
the remifentanil and fentanyl groups was 34 of 92 patients (37.0%) and 34 of 90 patients (37.8%),
respectively. Adverse drug reactions was 12 in 92 patients (13.0%) and 15 in 90 patients (16.7%),
respectively. In the PK analysis, blood remifentanil concentration decreased within 10 min to almost 50% of
the end of administration, suggesting rapid offset of action following discontinuation of remifentanil.
CONCLUSIONS: Remifentanil can be used safely for pain management in mechanically ventilated Japanese
patients in the ICU. TRIAL REGISTRATION: Japan Registry of Clinical Trials, jRCT2080224954.
Dong, Y., et al. (2021). "Combined topical and intravenous administration of
tranexamic acid further reduces postoperative blood loss in adolescent idiopathic
scoliosis patients undergoing spinal fusion surgery: a randomized controlled trial."
BMC Musculoskelet Disord 22(1): 663.
BACKGROUND: To indicate whether combined topical and intravenous (IV) administration of tranexamic
acid (TXA) could further reduce the blood loss after surgery for adolescent idiopathic scoliosis (AIS)
compared with IV-TXA alone. METHODS: Ninety AIS patients who underwent posterior spinal fusion were
prospectively randomized to combined group (IV + topical- TXA group) and IV-TXA alone group. TXA was
infused at a loading dose of 1 g from the beginning of the surgery with a maintenance dose of 10 mg/kg/h until
the wound was closed. In the combined group, 2 g TXA was injected retrogradely through a drain, while an
equivalent amount of normal saline was injected in the IV-TXA alone group. The drain tube was clamped for
2 h in both groups. The amount of wound drainage and transfusion rates were analyzed. RESULTS: The
drainage volume and duration of drain were significantly lower in the combined group compared with that in
the IV-TXA alone group (372.0 ± 129.7 mL vs. 545.2 ± 207.7 mL, P < 0.001;64.7 ± 13.9 h vs. 82.0 ± 12.5 h,
P < 0.001). Postoperative length of hospital stay was also significantly shorter in the combined group
(6.5 ± 1.51 days vs. 7.95 ± 1.44 days, P < 0.05). Transfusion and complication rates were comparable between
the two groups . CONCLUSIONS: IV injection of TXA combined with retrograde injection of TXA into a
drain and clamping it for 2 h could further reduce the total volume of drainage in AIS patients who underwent
spinal fusion surgery. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR1900024177 ,
Douma, M. J., et al. (2015). "Double-barrelled resuscitation: A feasibility and
simulation study of dual-intraosseous needles into a single humerus." Injury 46(11):
2239-2242.
Introduction Resuscitation can be delayed, or impaired, by insufficient vascular access. This study examines
whether dual-intraosseous needles, inserted into a single porcine humerus, can facilitate rapid and
concomitant fluid and medication delivery. Methods After inserting one- and then two-intraosseous needles
into the same porcine humerus, we determined the rate of fluid administration using (i) an infusion pump set
to 999mL/h, and (ii) a standard pressure-bag set to 300mmHg. Next, we concomitantly infused blood,
crystalloid and medications into the same medullary canal, using the two-needle set-up. Humeri were
inspected for fluid-leakage, needle-displacement, and bone damage. Results Using an infusion pump, the
mean normal-saline infusion-rate was significantly higher with dual-intraosseous needles compared to a
single-intraosseous needle: the infusion-rate was 16mL/min using dual-needles versus 8mL/min for a single
needle set-up (p<0.001). In contrast, using the pneumatic pressure-bag, the infusion rate was not statistically
different when comparing dual-intraosseous needles versus single-intraosseous: the infusion-rate was
22mL/min versus 21ml/min (p=0.4) for 500mL, and 22ml/min versus 21ml/min (p=0.64) for one-litre,
respectively. Blood product could be infused at a mean rate of 20mL/min through one needle while
tranexamic acid was simultaneously infused through a second. There were no complications with a dualintraosseous set-up (no fluid leakage; no needle-displacement; no high-pressure alarms, and no external bonefractures or internal macrohistological damage) during any of our simulated resuscitation scenarios.
Conclusions This is the first published study evaluating dual-intraosseous needles in a single bone. Despite
limitations, this preliminary study (using a porcine humerus) suggests that dual-intraosseous needles are
feasible. For critically-ill patients with limited insertion sites, dual-intraosseous (a.k.a. ‘double-barrelled
Duan, L., et al. (2023). "Comparison of continuous pericapsular nerve group (PENG)
block versus continuous fascia iliaca compartment block on pain management and
quadriceps muscle strength after total hip arthroplasty: a prospective, randomized
controlled study." BMC Anesthesiol 23(1): 233.
Duck, L., et al. (2021). "Efficacy and Safety of Lanreotide Autogel in the Treatment of
Clinical Symptoms Associated With Inoperable Malignant Intestinal Obstruction: A
Prospective Phase II Study." Clin Ther 43(12): 2136-2145.e2132.
BACKGROUND: This investigation aimed to evaluate the impact of continuous pericapsular nerve group
(PENG) block and continuous fascia iliac compartment block (FICB) on postoperative pain following total hip
arthroplasty (THA). METHODS: This prospective, randomized, and controlled trial recruited a cohort of fiftyseven patients with unilateral femoral neck fractures from Xi'an Aerospace General Hospital in northwest
China between July 2020 and November 2021. These patients were randomly assigned to two groups: the
continuous PENG block group (PENG group, n = 29) and the continuous FICB group (FICB group, n = 28).
Under ultrasound guidance, PENG block and FICB procedures were performed prior to spinal anesthesia,
utilizing 20 ml of 0.25% ropivacaine for PENG block and 30 ml of 0.25% ropivacaine for FICB.
Subsequently, a catheter was inserted. All study participants received a standardized postoperative multimodal
analgesic regimen, including intravenous administration of 30 mg Ketorolac tromethamine every eight hours
and patient-controlled neural analgesia (PCNA) after surgery. Numerical rating scale (NRS) scores at rest and
during exercise were recorded at various time points: prior to block (T0), 30 min post-blockade (T1), and 6 h
(T2), 12 h (T3), 24 h (T4), and 48 h (T5) postoperatively. Additional data collected encompassed
postoperative quadriceps muscle strength, the time of initial ambulation after surgery, the number of effective
PCNA activations, rescue analgesia requirements, and occurrences of adverse events (such as nausea and
vomiting, hematoma, infection, catheter detachment, or displacement) within 48 h following surgery.
RESULTS: In the PENG group, the resting NRS pain scores exhibited lower values at T1, T4, and T5 than
those at T0. Furthermore, exercise NRS pain scores at T1-T5 were lower in the PENG group than in the FICB
group. Similarly, during the same postoperative period, the PENG group demonstrated enhanced quadriceps
strength on the affected side compared to the FICB group. Additionally, the PENG group displayed earlier
postoperative ambulation and reduced occurrences of effective PCNA activations and rescue analgesia
requirements compared to the FICB group. CONCLUSION: Continuous PENG block exhibited superior
analgesic efficacy after THA compared to continuous FICB, promoting recovery of quadriceps strength on the
affected side and facilitating early postoperative ambulation. TRIAL REGISTRATION: This clinical trial was
registered in the China Clinical Trials Center ( http://www.chictr.org.cn ) on 20/07/2020, with the registration
PURPOSE: Inoperable malignant intestinal obstruction (IMIO) is a severe complication in patients with
cancer, usually gastrointestinal or gynecologic in origin. For patients with IMIO, there is a need to relieve
symptoms and limit nasogastric tube (NGT) use. Previous studies have suggested the efficacy of somatostatin
analogues in relieving obstruction-related symptoms, such as nausea, vomiting, and pain. The purpose of this
study was to assess the efficacy of lanreotide autogel 120 mg (LAN 120 mg) in the management of symptoms
resulting from IMIO in patients with advanced cancer. METHODS: This single-arm, multicenter study
enrolled 52 patients mostly with advanced gastrointestinal or ovarian malignant tumors (35 patients with NGT
and 17 patients without NGT). Patients received 1 deep subcutaneous injection of LAN 120 mg. Evaluations
were performed on days 7, 14, and 28. The primary end point was the percentage of responding patients
before or at day 7. Response was defined as ≤2 vomiting episodes per day (for patients without NGT at
baseline) or no vomiting recurrence (after NGT removal) during at least 3 consecutive days at any time point
between treatment and day 7. Responders at day 28 were offered a second LAN 120 mg injection and
followed up until day 56. FINDINGS: The proportion of responders in the intention-to-treat population was 24
of 52 (46.2%), which was significantly greater than the reference proportion of 30% (P = 0.0055). Patients
without NGT had a higher response (88.2%) than patients with NGT (25.7%) and had a steady trend for
clinical improvement that led to sustainable responses. Median time to response was 9 days for the overall
population, 3 days for patients without NGT, and 14 days for patients with NGT (P < 0.0001).
IMPLICATIONS: Our study is the first to use long-acting LAN 120 mg in patients with IMIO and suggests an
effect in controlling clinical symptoms in patients with and without NGT at baseline. The safety profile of
Dunn, J. A., et al. (2017). "A Comparative Outcome Study of Hamstring Versus
Tibialis Anterior and Synthetic Grafts for Deltoid to Triceps Transfers." The Journal
of Hand Surgery 42(10): 833.e831-833.e839.
Purpose To assess elbow extension strength and complications after deltoid-triceps transfers using hamstring
tendon graft compared with tibialis anterior and synthetic tendon grafts. Methods A retrospective review of
deltoid-triceps transfers in patients with tetraplegia performed between 1983 and 2014. Results Seventy-five
people (136 arms) had surgery performed, with the majority undergoing simultaneous bilateral surgery (n =
61; 81%). Tibialis anterior tendon grafts were used in 68 arms, synthetic grafts in 23 arms, and hamstring
tendon grafts in 45 arms. The average age at surgery was 31 years. Sixty-three arms (46%) were assessed
between 12 and 24 months after surgery. Seventy percent of the group (n = 54) were able to extend their
elbow against gravity (grade 3 of 5 or greater) following surgery. Seventy-nine percent of those with
hamstring grafts achieved grade 3 of 5 or more compared with 77% with tibialis anterior and 33% with
synthetic grafts. There was a statistically significant difference in postsurgery elbow extension between the
tibialis anterior group and the synthetic graft group and the hamstring and the synthetic graft group but not
between the tibialis anterior and the hamstring group. Complications occurred in 19 arms (14%), the majority
occurring immediately after surgery and associated with the wounds. The remaining complications were with
the synthetic graft group in which dehiscence of the proximal attachment occurred in 30% of the arms.
Conclusions Autologous tendon grafting is associated with achievement of antigravity elbow extension in a
Durandy, Y. (2013). "Vacuum-assisted venous drainage, angel or demon: PRO?" J
Extra Corpor Technol 45(2): 122-127.
Dvash, S., et al. (2021). "Increase rate of ruptured tubal ectopic pregnancy during the
COVID-19 pandemic." European Journal of Obstetrics & Gynecology and
Reproductive Biology 259: 95-99.
Vacuum-assisted venous drainage (VAVD) was proposed to optimize venous drainage during bypass through
femoral venous cannulation. It is currently used in both adult and pediatric surgery when siphon gravity
venous drainage is suboptimal. In pediatric surgery, the major advantages of VAVD are a significant decrease
in cardiopulmonary bypass prime volume and an improved drainage with all collateral benefits. To limit
gravity drainage, we use a two-level heart-lung machine dedicated to pediatric perfusion. The top level of the
cardiotomy reservoir is positioned at the patient atrial level, making it possible to downsize the length and
diameter of venous and arterial lines. Since 2008, a negative pressure of approximately -30 mmHg has been
used for all patients. Initiation of bypass is performed in a classical way with a cardiotomy reservoir open;
vacuum is added as soon as the maximal gravity drainage is reached. During bypass, when the blood level in
the reservoir decreases to the safety limit level, a small increase in negative pressure is used to improve
venous drainage. For weaning from bypass, the negative pressure is gradually decreased to zero, then the
reservoir is opened and the venous line progressively closed. Prime volumes were significantly reduced to 100
mL for small neonates, 125 mL for infants, and 175 mL for older children with flow up to 1.5 L/min(-1). A
low prime volume is expected to improve blood conservation and decrease donor exposure, prevent
drawbacks of transfusion (immunomodulation, infection), increase the incidence of blood-free surgery in
smaller babies, and decrease whole body systemic inflammation by decreasing surface of foreign material in
contact with blood and inflammation associated with blood transfusion. The main drawbacks described have
been retrograde flow in the venous line with cerebral air embolus and an increased incidence of gaseous
microemboli. These drawbacks are avoidable through appropriate training of perfusionists. When negative
pressure is "reasonable," complications are more theoretical than significant in clinical practice. A technique
with a benefit/drawback ratio of 1:0 is utopian, but the advantages of VAVD far outweigh any potential
Objective During the 2020 COVID-19 pandemic there was a decrease in emergency room arrivals. There is
limited evidence about the effect of this change in behavior on women's health. We aimed to evaluate the
impact of the COVID-19 pandemic on the diagnosis, treatment and complications of women presenting with a
tubal Ectopic Pregnancy (EP). Study design This is a single centre retrospective cohort study. We compared
the clinical presentation, treatment modalities and complications of all women presenting in our institution
with a tubal EP during the COVID-19 pandemic between 15 March and 15 June 2020, with women who were
treated in our institution with the same diagnosis in the corresponding period for the years 2018–2019. Results
The study group included 19 cases of EP (N = 19) that were treated between the 15 March 2020 and 15 June
2020. The control group included 30 cases of EP (N = 30) that were admitted to in the corresponding period
during 2018 and 2019. Maternal age, parity, gravity and mode of conception (natural vs. assisted) were similar
between the two groups. There was no difference in the mean gestational age (GA) according to the last
menstrual period. In the study group more women presented with sonographic evaluation of high fluid volume
in the abdomen than in the control group (53 % vs 17 %, P value 0.01). This finding is correlated with a more
advanced disease status. In the study group there was a highly statistically significant 3-fold increase in
rupture among cases (P < 0.005) and a 4-fold larger volume of blood in the entrance to the abdomen
(P < 0.002). We found that there were no cases of ruptured EP in the group of women who were pregnant after
assisted reproduction. Conclusion We found a higher rate of ruptured ectopic pregnancies in our institution
during the COVID-19 pandemic. Health care providers should be alerted to this collateral damage in the nonDvořák, M., et al. (2018). "Semi-automated set-up for exhaustive microelectromembrane extractions of basic drugs from biological fluids." Analytica
Chimica Acta 1005: 34-42.
Manual handling of microliter volumes of samples and reagents is usually prone to errors and may have direct
consequence on the overall performance of microextraction process. Direct connection of a syringe pump and
a disposable microextraction unit using flexible polymeric tubing was employed for semi-automated liquid
handling in micro-electromembrane extraction (μ-EME). A three-phase μ-EME system was formed by
consecutive withdrawal of microliter volumes of donor solution, free liquid membrane (FLM) and acceptor
solution into the unit. Excellent repeatability and accuracy of the withdrawal sequence was achieved for
solution volumes typically used in μ-EME (1–5 μL) as well as excellent correlation between the initially
withdrawn and the finally collected solution volumes. μ-EMEs were initiated by application of d.c. electric
potential to the terminal aqueous solutions and specific μ-EME parameters were optimized in order to ensure
complete transfer of model analytes from donor to acceptor solution. Exhaustive μ-EMEs of three basic drugs,
nortriptyline, papaverine and haloperidol, were achieved from 1.3 μL of acidified donor solution (10 mM HCl)
across 2.5 μL of FLM (1-ethyl-2-nitrobenzene) into 1.3 μL of acidified acceptor solution (25 mM HCl) in
10 min at 150 V. The three drugs were also exhaustively extracted from salt- and protein-containing standard
solutions, human urine and human plasma with extraction recoveries ranging from 79 to 102%. Resulting
acceptor solutions were analysed by capillary electrophoresis with ultraviolet detection (CE-UV) and the μEME-CE-UV method was characterized by good linearity (coefficients of determination ≥ 0.992), high
Ebell, M. H. and R. Grad (2017). "Top 20 Research Studies of 2016 for Primary Care
Physicians." Am Fam Physician 95(9): 572-579.
Ebisutani, C., et al. (2010). "Antibiotic prophylaxis in transcatheter treatment of
hepatocellular carcinoma: an open randomized prospective study of oral versus
intravenous administration." Intern Med 49(12): 1059-1065.
This article summarizes the top 20 original research studies and four practice guidelines of 2016, based on
regular literature surveillance and as selected by members of the Canadian Medical Association. The studies,
known as POEMs (patient-oriented evidence that matters), were rated highly because of their relevance,
validity, and potential to change practice. Key hypertension treatment findings include reduced mortality (a
benefit not demonstrated in lower-risk persons or persons with diabetes mellitus) but also an increase in harms
with a more aggressive blood pressure target in high-risk persons with hypertension and without diabetes.
Additionally, one study found that cardiovascular events are rare in patients who meet the criteria for
hypertensive urgency. Regarding respiratory conditions, the combination of fluticasone and salmeterol is
preferred to fluticasone alone in patients with moderate to severe asthma; nasal irrigation but not steam
inhalation is beneficial for patients with chronic sinus symptoms; and delayed prescriptions reduce antibiotic
use in patients with symptoms of acute respiratory infection. Studies on musculoskeletal topics found that of
the nonsteroidal anti-inflammatory drugs currently available, diclofenac is most likely to be effective for hip
or knee osteoarthritis; the benefits of opioids in patients with chronic low back pain are limited and not clearly
superior to nonsteroidal anti-inflammatory drugs; and hip radiography is not helpful for diagnosing
osteoarthritis of the hip. Regarding diabetes and obesity, the Mediterranean diet is more effective than a lowfat diet for weight loss, and aggressive blood pressure targets are not recommended in patients with diabetes,
especially older persons. Other recommendations include use of an oral syringe rather than a medicine cup to
measure liquid medications for children, and abrupt smoking cessation preceded by two weeks of nicotine
replacement via a patch, rather than a slow phasing out of tobacco use. Finally, although azithromycin has a
slightly higher failure rate than doxycycline for the treatment of chlamydia, it still cured 97% of patients in a
Edwards, J., et al. (2010). "Single dose dipyrone for acute postoperative pain."
Cochrane Database Syst Rev(9): Cd003227.
BACKGROUND: Transcatheter arterial chemoembolization (TACE) and transcatheter arterial infusion
chemotherapy (TAI) are increasingly used to treat inoperable liver malignancies. It has not been determined
whether standard oral and intravenous administration of antibiotics have different prophylactic effects against
post-TACE/TAI infection. We compared the efficacy of oral levofloxacin (LVFX) and intravenous cephazolin
(CEZ) in patients receiving TACE/TAI for hepatocellular carcinoma (HCC) using a prospective design.
PATIENTS AND METHODS: One hundred twenty-nine eligible subjects with HCC treated by TACE/TAI
were analyzed in this study. Patients were randomly assigned by the envelope method to groups who received
either intravenous infusion of CEZ at 2 g/day or oral administration of LVFX at 300 mg/day for 5 days.
Laboratory data, changes in antibiotic administration from the standard ones, duration of hospital stay, side
effects of antibiotics, and infectious complications were assessed. RESULTS: There were no significant
differences in the WBC counts and serum CRP levels between the groups; there were also no significant intergroup differences in the numbers of infectious and other adverse events. CONCLUSION: Our study findings
suggest that the results of peroral administration of LVFX for the prevention of post-procedure infectious
complications in patients receiving TACE/TAI for HCC are not inferior to those of intravenous administration
of CEZ.
BACKGROUND: Dipyrone (metamizole) is a non-steroidal anti-inflammatory drug used in some countries to
treat pain (postoperative, colic, cancer, and migraine); it is banned in others because of an association with
life-threatening blood agranulocytosis. This review updates a 2001 Cochrane review, and no relevant new
studies were identified, but additional outcomes were sought. OBJECTIVES: To assess the efficacy and
adverse events of single dose dipyrone in acute postoperative pain. SEARCH STRATEGY: The earlier review
searched CENTRAL, MEDLINE, EMBASE, LILACS and the Oxford Pain Relief Database to December
1999. For the update we searched CENTRAL, MEDLINE,EMBASE and LILACS to February 2010.
SELECTION CRITERIA: Single dose, randomised, double-blind, placebo or active controlled trials of
dipyrone for relief of established moderate to severe postoperative pain in adults. We included oral, rectal,
intramuscular or intravenous administration of study drugs. DATA COLLECTION AND ANALYSIS: Studies
were assessed for methodological quality and data extracted by two review authors independently. Summed
total pain relief over six hours (TOTPAR) was used to calculate the number of participants achieving at least
50% pain relief. Derived results were used to calculate, with 95% confidence intervals, relative benefit
compared to placebo, and the number needed to treat (NNT) for one participant to experience at least 50%
pain relief over six hours. Use and time to use of rescue medication were additional measures of efficacy.
Information on adverse events and withdrawals was collected. MAIN RESULTS: Fifteen studies tested
mainly 500 mg oral dipyrone (173 participants), 2.5 g intravenous dipyrone (101), 2.5 g intramuscular
dipyrone (99); fewer than 60 participants received any other dose. All studies used active controls (ibuprofen,
paracetamol, aspirin, flurbiprofen, ketoprofen, dexketoprofen, ketorolac, pethidine, tramadol, suprofen); eight
used placebo controls.Over 70% of participants experienced at least 50% pain relief over 4 to 6 hours with
oral dipyrone 500 mg compared to 30% with placebo in five studies (288 participants; NNT 2.4 (1.9 to 3.2)).
Fewer participants needed rescue medication with dipyrone (7%) than with placebo (34%; four studies, 248
participants). There was no difference in participants experiencing at least 50% pain relief with 2.5 g
intravenous dipyrone and 100 mg intravenous tramadol (70% vs 65%; two studies, 200 participants). No
serious adverse events were reported. AUTHORS' CONCLUSIONS: Based on very limited information,
single dose dipyrone 500 mg provides good pain relief to 70% of patients. For every five individuals given
dipyrone 500 mg, two would experience this level of pain relief who would not have done with placebo, and
Eftekhar, N., et al. (2023). "Effect of Local Ketamine Subcutaneous Injection at the
Incision Site in Reducing the Postoperative Pain Score after Transabdominal
Hysterectomy." Anesthesiol Res Pract 2023: 7782847.
Ehinger, K. H., et al. (2013). "Bioequivalence and tolerability assessment of a novel
intravenous ciclosporin lipid emulsion compared to branded ciclosporin in Cremophor
® EL." Clin Drug Investig 33(1): 25-34.
BACKGROUND: Pain control after operations is essential in decreasing the patient recovery period and
potential morbidity. Prescribing opiates is very effective, but significant side effects accompany them. This
study aims to examine the effect of local ketamine infiltration in decreasing pain intensity in patients
undergoing transabdominal hysterectomy. METHODS: In this double-blind, randomized, controlled clinical
trial, a total of 92 patients undergoing transabdominal hysterectomy aged 30-60 years were selected and
divided into two intervention and control groups randomly. For the intervention group, ketamine was injected
subcutaneously into the incision site at a dose of 0.5 mg/kg after the operation. In the control group, 5 mg
normal saline was used in the same method. Postoperative pain intensity was measured using the visual analog
scale (VAS: 0-10). The pain score and dose of administered opioids were documented at 1, 2, 4, 6, 12, and
24 hours and compared between the two groups. RESULTS: Postoperative pain intensity was significantly
lower in the intervention group than in the control group, except for hour 24. The mean amounts of
administered opioids were significantly lower in the intervention group at hours 6 and 12, as well as the total
amount of used opioids, and no significant side effects were documented. CONCLUSION: Local ketamine
subcutaneous injection in the incisional site is effective and is a safe procedure for reducing pain scores in
patients who underwent a transabdominal hysterectomy.
BACKGROUND: Ciclosporin is used as an immunosuppressant in current clinical practice but recent
research implies novel indications for the drug, such as neuro- and cardioprotection. The intravenous
formulation currently on the market, Sandimmune(®) Injection (Sandimmune(®)), uses Cremophor(®) EL as
emulsifying excipient. Cremophor(®) EL is known to cause hypersensitivity reactions in some patients,
ranging from skin reactions to potentially fatal anaphylactic shock. OBJECTIVES: The primary objective was
to assess if CicloMulsion(®), a Cremophor(®) EL-free lipid emulsion of ciclosporin for intravenous
administration, is bioequivalent to Sandimmune(®), and the secondary objective was to compare the
tolerability profiles of the two preparations. METHODS: This was a single-centre, open-label, subject-blind,
laboratory-blind, single-dose, randomized, two-treatment, two-period, two-sequence crossover study of the
pharmacokinetics of two formulations of intravenous ciclosporin. Fifty-two healthy volunteer subjects were
administered 5 mg/kg of each of the two formulations of ciclosporin as a 4-h intravenous infusion. The last
blood sample was acquired 48 h after the end of the infusion. Bioequivalence assessments according to current
guidelines were performed. RESULTS: The geometric mean ratios for CicloMulsion(®)/Sandimmune(®) (90
% confidence interval [CI]) were 0.90 (0.88, 0.92) for AUC(0-last) (area under the blood concentration-time
curve from time zero to time of last measurable concentration) and 0.95 (0.92, 0.97) for C(max) (maximum
blood concentration). For all additional variables analysed, the 90 % CIs were also within the accepted
bioequivalence range of 0.80-1.25. One anaphylactoid and one anaphylactic reaction, both classified as
serious adverse events, were reported after treatment with Sandimmune(®). No serious adverse events were
recorded after treatment with CicloMulsion(®). CONCLUSION: We have assessed the pharmacokinetics and
tolerability of a new Cremophor(®) EL-free lipid emulsion of ciclosporin, CicloMulsion(®), compared to
Sandimmune(®). The proportion of adverse events was significantly higher for the Cremophor(®) EL-based
product Sandimmune(®). We conclude that CicloMulsion(®) is bioequivalent to Sandimmune(®) and
Elsheikh, N. A. and Y. M. Amr (2016). "Calcitonin as an Additive to Local Anesthetic
and Steroid Injection Using a Modified Coronoid Approach in Trigeminal Neuralgia."
Pain Physician 19(7): 457-464.
BACKGROUND: Pharmacotherapy is the main treatment for management of trigeminal neuralgia. However,
many patients become refractory to drugs. OBJECTIVES: The present study aimed to evaluate the effect of
adding calcitonin to local anesthetic and methylprednisolone using a modified coronoid approach in
management of trigeminal neuralgia pain involving the mandibular and/or maxillary branches. STUDY
DESIGN: Randomized double blind clinical trial. SETTING: Hospital outpatient setting. METHODS: Thirtythree patients received maxillary and mandibular blocks by a modified coronoid approach. Patients were
allocated into 2 groups. Group 1 received a block with 3 mL of lidocaine 0.5% plus 40 mg of
methylprednisolone and another syringe contained 1 mL of 0.9% saline. Group 2 received a block with 3 mL
of lidocaine 0.5% plus 40 mg of methylprednisolone and another syringe contained 50 international units of
calcitonin. Pain was evaluated by visual analog scale (VAS) before the block (basal), at 2 weeks, one month
after the procedure, and monthly for one year. Duration of the effective pain relief of the first block (VAS = 3)
was reported. Repeated blockade was allowed for any patient reporting a VAS > 30 mm during one year of
follow-up and the number of blocks were reported. Adverse effects were also reported. RESULTS: A
significantly longer duration of effective pain relief was noticed in group 2 compared with group 1 (P <
0.0004) while the duration of effective pain relief of the second block in group 1 was 28.5 ± 8.9 weeks. Four
patients did not need repeated blocks in group 1 versus 15 in group 2. Six patients received 2 blocks versus 2
patients in each group, respectively. Moreover, 6 patients needed 3 blocks in group1 versus none in group 2.
No serious adverse events were reported during or after the interventional procedure. VAS was comparable in
both groups (P > 0.05). LIMITATIONS: Small sample size. CONCLUSION: Calcitonin may be a useful
additive to local anesthetic and steroid in management of trigeminal neuralgia. Also, a modified coronoid
approach for maxillary and mandibular nerve is simple, free of radiation, safe, and may be an effective
percutaneous procedure in trigeminal neuralgia. KEY WORDS: Calcitonine, modifed, coronoid approach,
Ertzgaard, P., et al. (2016). "A new way of assessing arm function in activity using
kinematic Exposure Variation Analysis and portable inertial sensors – A validity
study." Manual Therapy 21: 241-249.
Portable motion systems based on inertial motion sensors are promising methods, with the advantage
compared to optoelectronic cameras of not being confined to a laboratory setting. A challenge is to develop
relevant outcome measures for clinical use. The aim of this study was to characterize elbow and shoulder
motion during functional tasks, using portable motion sensors and a modified Exposure Variation Analysis
(EVA) and evaluate system accuracy with optoelectronic cameras. Ten healthy volunteers and one participant
with sequel after stroke performed standardised functional arm tasks. Motion was registered simultaneously
with a custom developed motion sensor system, including gyroscopes and accelerometers, and an
optoelectronic camera system. The EVA was applied on elbow and shoulder joints, and angular and angular
velocity EVA plots was calculated. The EVA showed characteristic patterns for each arm task in the healthy
controls and a distinct difference between the affected and unaffected arm in the participant with sequel after
stroke. The accuracy of the portable system was high with a systematic error ranging between −1.2° and 2.0°.
The error was direction specific due to a drift component along the gravity vector. Portable motion sensor
systems have high potential as clinical tools for evaluation of arm function. EVA effectively illustrates joint
angle and joint angle velocity patterns that may capture deficiencies in arm function and movement quality.
Next step will be to manage system drift by including magnetometers, to further develop clinically relevant
Evans, M. A., et al. (2021). "The utilization of caudal hydromorphone for fast-tracking
in congenital cardiac surgery in a tertiary-care Children's hospital: An audit." J Clin
Anesth 72: 110314.
STUDY OBJECTIVE: Our study sought to audit our institutional practice of routine single-shot caudal
epidural hydromorphone injection in children undergoing congenital cardiothoracic surgery to assess
perioperative pain control and evaluate for any caudal complications. DESIGN: Retrospective observational
study of all patients that received a caudal hydromorphone injection as part of the anesthetic for their cardiac
surgical operation between January 2017 and July 2019. SETTING: Pediatric Cardiothoracic Operating Room
(OR), Cardiac Intensive Care Unit. PATIENTS: One hundred and twenty-seven patients that received caudal
hydromorphone as part of their anesthetic for a cardiac surgical operation. INTERVENTIONS: Caudal
epidural injection performed immediately following induction of anesthesia utilizing only hydromorphone.
MEASUREMENTS: The primary outcome was well-controlled pain, defined as a score of <4/10 on rFLACC
or verbal pain scoring. Secondary outcome measures included in-OR extubation, pain service duration (from
first assessment to "sign-off"), complications related to the caudal block, intensive care unit (ICU) length of
stay (LOS), and Hospital LOS. MAIN RESULTS: One hundred and nine patients were included in the final
analysis. Pain was "well-controlled" on average in 96.3% of patients (105/109). Average pain in the 24-h postblock period was 1.67 (SD = 2.37), with median pain score of 0 [0-3]. Peak pain score remained <4/10 for the
entire 24-h post-block period in 22% of patients. 77.1% of caudal hydromorphone patients were extubated in
the operating room. The median time to heparinization post-block was 108 min, beyond the ASRA
recommendation of 60 min for neuraxial procedures. There were two caudal-related complications: one
subcutaneous injection, and one instance of a time to heparinization of less than 60 min (56 min). Neither
caudal complication led to patient harm. CONCLUSION: Caudal hydromorphone injection can safely
contribute to achieving "well-controlled" pain in the pediatric cardiac surgical population when used as a
Ezzo, J., et al. (2015). "Manual lymphatic drainage for lymphedema following breast
cancer treatment." Cochrane Database Syst Rev 2015(5): Cd003475.
Faetani, L., et al. (2021). "Safety and efficacy of mesotherapy in musculoskeletal
disorders: A systematic review of randomized controlled trials with meta-analysis." J
Rehabil Med 53(4): jrm00182.
BACKGROUND: More than one in five patients who undergo treatment for breast cancer will develop breast
cancer-related lymphedema (BCRL). BCRL can occur as a result of breast cancer surgery and/or radiation
therapy. BCRL can negatively impact comfort, function, and quality of life (QoL). Manual lymphatic drainage
(MLD), a type of hands-on therapy, is frequently used for BCRL and often as part of complex decongestive
therapy (CDT). CDT is a fourfold conservative treatment which includes MLD, compression therapy
(consisting of compression bandages, compression sleeves, or other types of compression garments), skin
care, and lymph-reducing exercises (LREs). Phase 1 of CDT is to reduce swelling; Phase 2 is to maintain the
reduced swelling. OBJECTIVES: To assess the efficacy and safety of MLD in treating BCRL. SEARCH
METHODS: We searched Medline, EMBASE, CENTRAL, WHO ICTRP (World Health Organization's
International Clinical Trial Registry Platform), and Cochrane Breast Cancer Group's Specialised Register from
root to 24 May 2013. No language restrictions were applied. SELECTION CRITERIA: We included
randomized controlled trials (RCTs) or quasi-RCTs of women with BCRL. The intervention was MLD. The
primary outcomes were (1) volumetric changes, (2) adverse events. Secondary outcomes were (1) function, (2)
subjective sensations, (3) QoL, (4) cost of care. DATA COLLECTION AND ANALYSIS: We collected data
on three volumetric outcomes. (1) LE (lymphedema) volume was defined as the amount of excess fluid left in
the arm after treatment, calculated as volume in mL of affected arm post-treatment minus unaffected arm posttreatment. (2) Volume reduction was defined as the amount of fluid reduction in mL from before to after
treatment calculated as the pretreatment LE volume of the affected arm minus the post-treatment LE volume
of the affected arm. (3) Per cent reduction was defined as the proportion of fluid reduced relative to the
baseline excess volume, calculated as volume reduction divided by baseline LE volume multiplied by 100. We
entered trial data into Review Manger 5.2 (RevMan), pooled data using a fixed-effect model, and analyzed
continuous data as mean differences (MDs) with 95% confidence intervals (CIs). We also explored subgroups
to determine whether mild BCRL compared to moderate or severe BCRL, and BCRL less than a year
compared to more than a year was associated with a better response to MLD. MAIN RESULTS: Six trials
were included. Based on similar designs, trials clustered in three categories.(1) MLD + standard
physiotherapy versus standard physiotherapy (one trial) showed significant improvements in both groups from
baseline but no significant between-groups differences for per cent reduction.(2) MLD + compression
bandaging versus compression bandaging (two trials) showed significant per cent reductions of 30% to 38.6%
OBJECTIVES: To conduct a systematic review of randomized controlled trials about the safety (number and
severity of adverse events) and efficacy (pain reduction and functional improvement) of mesotherapy in
musculoskeletal disorders, and to compare them with other therapeutic options, in accordance with the
Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. METHODS: A
search of PubMed, Cochrane Library and Scopus database resulted in an initial total of 16,253 records. A total
of 931 articles were included in the study. A final total of 7 articles, published from 1 Jan 1999 until 30 Apr
2020 were selected. Two independent reviewers selected potentially relevant studies based on the inclusion
criteria for full-text reading. They evaluated the methodological quality of each study and included only
studies of high methodological quality, according to the Physiotherapy Evidence Database scale. RESULTS:
Seven studies were included in the meta-analysis, and visual analogue scale scores before and after
mesotherapy were considered. A statistically significant reduction in visual analogue scale score in the
mesotherapy group was reported in comparison with the control group in all except 1 of the trials.
Mesotherapy was found to be a safe procedure with mild and temporary side-effects, such as nausea, fatigue,
numbness, sweating, headache, ecchymosis, bleeding, pain and local reaction at the injection site.
CONCLUSION: Mesotherapy proved to be more effective than systemic therapy in the treatment of local pain
and functional limitations caused by a variety of musculoskeletal conditions. However, because of the
heterogeneity of the analysed studies in terms of injected drugs, administration technique, associated
treatments, frequency and total number of sessions, more randomized controlled trials are needed, comparing
Fallon, M., et al. (2023). "A Randomized Placebo-Controlled Trial of the Anti-Nerve
Growth Factor Antibody Tanezumab in Subjects With Cancer Pain Due to Bone
Metastasis." Oncologist 28(12): e1268-e1278.
BACKGROUND: This phase III, randomized, double-blind, placebo-controlled, parallel-group study assessed
the efficacy and safety of tanezumab in subjects with cancer pain predominantly due to bone metastasis
receiving background opioid therapy. METHODS: Subjects were randomized (stratified by (1) tumor
aggressiveness and (2) presence/absence of concomitant anticancer treatment) to placebo or tanezumab 20 mg.
Treatment was administered by subcutaneous injection every 8 weeks for 24 weeks (3 doses) followed by a
24-week safety follow-up period. The primary outcome was change in daily average pain in the index bone
metastasis cancer pain site (from 0 = no pain to 10 = worst possible pain) from baseline to week 8. RESULTS:
LS mean (SE) change in pain at week 8 was -1.25 (0.35) for placebo (n = 73) and -2.03 (0.35) for tanezumab
20 mg (n = 72). LS mean (SE) [95% CI] difference from placebo was -0.78 (0.37) [-1.52, -0.04]; P = .0381
with α = 0.0478. The number of subjects with a treatment-emergent adverse event during the treatment period
was 50 (68.5%) for placebo and 53 (73.6%) for tanezumab 20 mg. The number of subjects with a prespecified
joint safety event was 0 for placebo and 2 (2.8%) for tanezumab 20 mg (pathologic fracture; n = 2).
CONCLUSION: Tanezumab 20 mg met the primary efficacy endpoint at week 8. Conclusions on longer-term
efficacy are limited since the study was not designed to evaluate the durability of the effect beyond 8 weeks.
Safety findings were consistent with adverse events expected in subjects with cancer pain due to bone
metastasis and the known safety profile of tanezumab. Clinicaltrials.gov identifier: NCT02609828.
Fang, C., et al. (2012). "[Safety of three-dimensional technique in patients undergoing
complicated hepatectomy]." Nan Fang Yi Ke Da Xue Xue Bao 32(8): 1116-1121.
Fanthom, T. B., et al. (2023). "Solid-Solid Interfacial Contact of Tubing Walls Drives
Therapeutic Protein Aggregation During Peristaltic Pumping." Journal of
Pharmaceutical Sciences 112(12): 3022-3034.
Featherstone, P. J. (2022). "John Henry Evans, MD: Founding Chairman of the Board
of Governors of the International Anesthesia Research Society, and a Forgotten
Pioneer of Oxygen Therapy." Anesth Analg 135(2S Suppl 1): S18-s25.
OBJECTIVE: To assess the value of abdominal three-dimensional medical image visualization system (MI3DVS) in assisting complicated hepatectomy. METHODS: Twenty-four patients undergoing complicated
hepatectomy for hepatic carcinoma or hepatic focal nodular hyperplasia were enrolled in this study. Threedimensional models of the organs, vessels and tumors were reconstructed with MI-3DVS, and virtual
operations were carried out to assess the feasibility of hepatectomy. The diameter of the liver tumors,
intraoperative blood loss and transfusion, complications, in-hospital mortality rate, and one-year survival rate
were analyzed in these cases. RESULTS: The operations were safely completed in all the cases without
perioperative deaths. The mean diameter of liver tumor was 9.8∓ 4.3 cm, and the median volumes of
intraoperative blood loss and transfusion were 800 ml and 600 ml, respectively, with a blood transfusion rate
of 91.7% (22/24). The incidence of complications was 29.2% (7/24), and the one-year survival rate was
37.5%. CONCLUSION: Three-dimensional techniques such as volumetric analysis and risk evaluation of
residual liver blood supply and drainage can increase the accuracy of surgical planning and improve the safety
of complicated hepatectomy.
Peristaltic pumping during bioprocessing can cause therapeutic protein loss and aggregation during use. Due
to the complexity of this apparatus, root-cause mechanisms behind protein loss have been long sought. We
have developed new methodologies isolating various peristaltic pump mechanisms to determine their effect on
monomer loss. Closed-loops of peristaltic tubing were used to investigate the effects of peristaltic pump
parameters on temperature and monomer loss, whilst two mechanism isolation methodologies are used to
isolate occlusion and lateral expansion-relaxation of peristaltic tubing. Heat generated during peristaltic
pumping can cause heat-induced monomer loss and the extent of heat gain is dependent on pump speed and
tubing type. Peristaltic pump speed was inversely related to the rate of monomer loss whereby reducing speed
2.0-fold increased loss rates by 2.0- to 5.0-fold. Occlusion is a parameter that describes the amount of tubing
compression during pumping. Varying this to start the contacting of inner tubing walls is a threshold that
caused an immediate 20-30% additional monomer loss and turbidity increase. During occlusion, expansionrelaxation of solid-liquid interfaces and solid-solid interface contact of tubing walls can occur simultaneously.
Using two mechanisms isolation methods, the latter mechanism was found to be most destructive and a
function of solid-solid contact area, where increasing the contact area 2.0-fold increased monomer loss by 1.6fold. We establish that a form of solid-solid contact mechanism whereby the contact solid interfaces disrupt
adsorbed protein films is the root-cause behind monomer loss and protein aggregation during peristaltic
The theoretical and practical foundations of modern oxygen therapy were established during the first half of
the 20th century. John Henry Evans, MD, inaugural chairman of the Board of Governors of the International
Anesthesia Research Society (IARS), was an early pioneer in this field. Challenging the conventional wisdom
that high concentrations of oxygen were harmful when inspired over long periods, Evans advocated the
continuous and extended administration of 100% oxygen in a wide range of conditions, using special
apparatus developed by the Toledo Technical Appliance Company (later, the McKesson Appliance
Company), which incorporated a tight-fitting facemask or nasal inhaler. In doing so, Evans became embroiled
in a conflict with Alvan Barach of Columbia University College of Physicians and Surgeons, which would
take nearly a decade to resolve. Additionally, Evans experimented with the subcutaneous injection and
intravenous infusion of oxygen, reporting significant benefits of the former in several acute inflammatory
conditions, as well as a variety of chronic ailments. While these contributions have largely been forgotten,
Evans expanded the remit of anesthesiology beyond the operating theater and the original charter of the IARS
and helped lay the foundations for the rational use of oxygen as a therapeutic agent in all areas of medicine.
Fitzgerald, K., et al. (2017). "A Highly Durable RNAi Therapeutic Inhibitor of
PCSK9." N Engl J Med 376(1): 41-51.
BACKGROUND: Inclisiran (ALN-PCSsc) is a long-acting RNA interference (RNAi) therapeutic agent that
inhibits the synthesis of proprotein convertase subtilisin-kexin type 9 (PCSK9), a target for the lowering of
low-density lipoprotein (LDL) cholesterol. METHODS: In this phase 1 trial, we randomly assigned healthy
volunteers with an LDL cholesterol level of at least 100 mg per deciliter in a 3:1 ratio to receive a
subcutaneous injection of inclisiran or placebo in either a single-ascending-dose phase (at a dose of 25, 100,
300, 500, or 800 mg) or a multiple-dose phase (125 mg weekly for four doses, 250 mg every other week for
two doses, or 300 or 500 mg monthly for two doses, with or without concurrent statin therapy); each dose
cohort included four to eight participants. Safety, the side-effect profile, and pharmacodynamic measures
(PCSK9 level, LDL cholesterol level, and exploratory lipid variables) were evaluated. RESULTS: The most
common adverse events were cough, musculoskeletal pain, nasopharyngitis, headache, back pain, and
diarrhea. All the adverse events were mild or moderate in severity. There were no serious adverse events or
discontinuations due to adverse events. There was one grade 3 elevation in the γ-glutamyltransferase level,
which was considered by the investigator to be related to statin therapy. In the single-dose phase, inclisiran
doses of 300 mg or more reduced the PCSK9 level (up to a least-squares mean reduction of 74.5% from
baseline to day 84), and doses of 100 mg or more reduced the LDL cholesterol level (up to a least-squares
mean reduction of 50.6% from baseline). Reductions in the levels of PCSK9 and LDL cholesterol were
maintained at day 180 for doses of 300 mg or more. All multiple-dose regimens reduced the levels of PCSK9
(up to a least-squares mean reduction of 83.8% from baseline to day 84) and LDL cholesterol (up to a leastsquares mean reduction of 59.7% from baseline to day 84). CONCLUSIONS: In this phase 1 trial, no serious
adverse events were observed with inclisiran. Doses of 300 mg or more (in single or multiple doses)
significantly reduced levels of PCSK9 and LDL cholesterol for at least 6 months. (Funded by Alnylam
Flisfisch, S., J. P. Woelber and W. Walther (2021). "Patient evaluations after local
anesthesia with a computer-assisted method and a conventional syringe before and
after reflection time: A prospective randomized controlled trial." Heliyon 7(2):
Flores, R. E., J. Q. Beltrán and E. Ogando-Rivas (2019). "An Affordable and Feasible
Technique for Minimally Invasive Tubular Lumbar Discectomy." World Neurosurg
129: 378-385.
OBJECTIVES: This prospective randomized controlled trial aimed to evaluate and compare patient response
to a conventional syringe and a computer-controlled local anesthetic delivery system (CCLAD) both
immediately and after reflection time, including the impact of anesthesia duration. METHODS: Twenty adult
patients (10 men and 10 women) with at least two tooth-neck defects each in different quadrants were treated
with local buccal infiltration anesthesia. Using split-mouth design, one quadrant was anesthetized using a
conventional syringe, the other with CCLAD. The time elapsed between time of injection and time of
disappearance of numbness was recorded. Patients were asked to mark on a Visual Analog Scale their visual
impression of the device regarding anxiety-inducement, their sensation of mucosal puncture, pain during
administration, and pain perception during treatment for the two different methods as well as future preference
immediately after treatment and after reflection time. RESULTS: The level of anxiety-inducement and pain
during administration were ranked three times higher with the conventional syringe (35.95%-11.85%, p <
0.001 and 21.3%-7.7%, p = 0.005, respectively). There was no difference in mean sensation of mucosal
puncture, nor a statistically significant correlation between duration of administration and time until
disappearance of numbness. Once anesthesia was administered, no pain during treatment was detected using
either method. Patients' preference of methods changed significantly with time in favor of CCLAD (p = 0.01).
CONCLUSIONS: The use of CCLAD increased patients' comfort visually and in terms of administration;
patients' preference in favor of CCLAD increased with time. CLINICAL SIGNIFICANCE: Patients'
preference of CCLAD over against the conventional syringe, even more so after reflection time, can imply the
BACKGROUND: The benefits of minimally invasive spine surgery are attainable only if hospitals have the
financial resources to acquire essential equipment. We present a surgical approach readily available to
countries where unacceptably expensive materials are the main limitation for use of minimally invasive spine
surgery. METHODS: This retrospective study included 30 patients who underwent minimally invasive spine
surgery using syringes as dilators and retractors for posterior lumbar approaches. Inclusion criteria were
lumbar radicular/back pain, degenerative disc, spondylolysis, unilateral approach, and maximum of 2 affected
spine levels. Demographic characteristics, affected radicular level, diagnosis, type and length of surgery,
hospital length of stay, MacNab criteria, complications, and resumption of daily activities were analyzed.
RESULTS: Of 30 patients, 17 (56.6%) presented with S1 radicular pain. Pain was mainly due to posterolateral
hernia (70%; n = 21) requiring 1-level discectomy. In 6 patients (20%), discectomy and an interspinous
process device were required. One patient (3.33%) underwent 2-level discectomy. All surgeries were
performed using syringes as dilators and retractors. Maximum syringe diameter used was 2 cm (20-mL
syringes) in 29 patients (96.6%) and 3 cm (60-mL syringe) in 1 patient. Average length of surgery was 1.5
hours, and average hospital stay was 1.8 days. Based on MacNab criteria, excellent, good, and fair outcomes
were achieved in 25 patients (83%), 3 patients (10%), and 2 patients (6.7%). Complications were observed in
5 patients (16.7%). CONCLUSIONS: This is a safe and feasible technique with excellent results obtained at
Foti, C., et al. (2011). "A prospective observational study of the clinical efficacy and
safety of intra-articular sodium hyaluronate in synovial joints with osteoarthritis." Eur
J Phys Rehabil Med 47(3): 407-415.
BACKGROUND: Clinical trials have demonstrated the safety and efficacy of hyaluronic acid-based products
for the treatment of synovial joints affected by osteoarthritis (OA), but data from observational studies of
normal medical practice are sparse. AIM: This study investigated the safety and efficacy of intra-articular (IA)
sodium hyaluronate (MW 1500-2000 KDa; Hyalubrix®) in the treatment of synovial joint OA. DESIGN: This
is prospective, and observational study. SETTING: This study was carried out at 47 specialist centers for
physiatrists, orthopedics and rheumatology in Italy; the enrolled population, 1266 outpatient, was
predominantly female (66%, 840/1266), with a mean age of 66 years, and a mean weight of 74 kg.
POPULATION: The Participants with OA received IA injections of the study treatment (2 mL) once per week
for 3 weeks. The knee was the joint most commonly affected by OA (right knee 802/1266 [63%]; left knee
598/1266 [47%]), and the longest median duration of disease occurred in the carpal joint (right carpal joint 40
months; left carpal joint 60 months). METHODS: The primary endpoints were tolerability and details of
usage of the IA sodium hyaluronate syringe device. Efficacy parameters included assessment of self-reported
pain via the Visual Analogue Scale (VAS), and evaluation of motor function via the Health Assessment
Questionnaire (HAQ). Quality of life (QoL) was assessed using the Euro QoL questionnaire (Clinical Trial
Registration Number: ISRCTN 42690497). RESULTS: Data from 1266 participants were collected. The
adverse event (AE) rate was 0.8% (95% CI, 0.4 to 1.5). Thirteen AEs were reported, 12 of which were mild or
moderate in severity. Only one participant discontinued study treatment following an AE. No serious adverse
events occurred. Coadministration of local anesthetic was required by up to 10% of patients. Statistically
significant improvements in VAS, HAQ and EuroQoL were recorded in multiple joints (P<0.0001 for each).
CONCLUSION: The study treatment was safe and well tolerated. CLINICAL REHABILITATION IMPACT:
. The study treatment reduced pain, improved mobility, and increased QoL in participants with OA.
Fraissenon, A., et al. (2024). "Percutaneous Sclerotherapy of Large Venous
Malformations Using Consecutive Polidocanol and Bleomycin Foam: MR Imaging
Volumetric and Quality-of-Life Assessment." J Vasc Interv Radiol 35(1): 127136.e121.
PURPOSE: To retrospectively evaluate sclerotherapy using consecutive polidocanol and bleomycin foam
(CPBF) for large untreated venous malformations (VMs) and/or those resistant to prior treatment.
MATERIALS AND METHODS: This retrospective study included all patients treated with CPBF for
untreated VMs larger than 10 mL and/or refractory to treatment between May 2016 and October 2019.
Baseline and follow-up VM volumes were measured on fat-suppressed T2-weighted magnetic resonance
(MR) imaging. Outcome was evaluated on postprocedural MR imaging volumetry and by a retrospective
survey assessing clinical response and adverse events. Imaging response was considered good for volume
reduction from 50% to 70% and excellent for volume reduction ≥70%. Symptoms and quality-of-life (QoL)
scores were compared before and after CPBF sclerotherapy. RESULTS: Forty-five patients (mean age, 16
years; range, 1-63 years; 25 males) with 57 VMs were analyzed and treated by 80 sclerotherapy. Sixty percent
(27 of 45) of patients had undergone prior treatment for VM. Median VM volume was 36.7 mL (interquartile
range, 84 mL) on pretherapy MR imaging. Good and excellent results after the last sclerotherapy were
achieved in 36% (16 of 45) and 29% (13 of 45) of patients, respectively, corresponding to a decrease of >50%
in 60% (34 of 57) of VMs. QoL score increased by at least 3 points, regardless of initial symptoms. Most
patients did not desire additional sclerotherapy owing to near complete symptomatic relief, even for patients
who did not achieve a good response. Swelling, pain, and motor impairment scores significantly improved
after CPBF. Adverse events included fever (44%, 15 of 34) and nausea/vomiting (29%, 10 of 34).
CONCLUSIONS: CPBF sclerotherapy represents an effective therapy for large and/or refractory VMs with
Frattani, F. S., et al. (2021). "Oral treatment with a chemically characterized parsley
(Petroselinum crispum var. neapolitanum Danert) aqueous extract reduces thrombi
formation in rats." J Tradit Complement Med 11(3): 287-291.
Frediani, B. and I. Bertoldi (2015). "Clodronate: new directions of use." Clin Cases
Miner Bone Metab 12(2): 97-108.
Petroselinum crispum var. neapolitanum Danert (Apiaceae) (PC), popularly known as parsley, is an herb
native to the Mediterranean region widely cultivated around the world for culinary and ethnomedicinal
purposes. The herb is traditionally used in various parts of the world to treat arterial hypertension,
hemorrhoid, nose bleeding, hyperlipidemia, and pain, among other indications. The aim of this study was to
evaluate the antithrombotic activity of an aqueous extract PC in rats. Aerial parts of a flat-leaf variety of
parsley were extracted by decoction. In vivo thrombosis in rat models as well as ex vivo assays were used in
the evaluation of PC antithrombotic effects. Intravenous administration of PC (25 mg/kg.b.w), 5 min before
thrombosis induction, reduced the venous thrombus formation by 98.2%, while oral administration
(125 mg/kg.b.w) impaired it by 76.2%. In the arterial thrombosis model, the oral administration of PC at 15 or
25 mg/kg.b.w, 60 min before thrombosis induction, increased the carotid artery occlusion time by 150%
(37.0 ± 6.44 min) and 240% (more than 60 min), respectively. A HPLC-DAD-MS/MS profile of PC extract
used in this study was provided. Apiin showed to be the most abundant phenolic compound in the extract. It
also revealed the presence of many coumaric acid derivatives. Our results indicate that PC is a potential
candidate for the development of a phytotherapeutic drug in the treatment of thromboembolic diseases and
provide a detailed chemical profile useful for controlling PC extract production in view of phytotherapy.
Clodronate is the father of bisphosphonates. For over three decades it has been subject of study in biological
and clinical areas, proving to be an extremely interesting molecule from different points of view. It has been
the first drug for osteoporosis that can be administered pulsatorily (once every 15 days or once a week). This,
along with good tolerability, has been the first cause of its success, when there were no solid data in literature
about its antifracture efficacy. There are three published studies that prove its antifracture effect: two by
McCloskey published in 2004 and 2007 on BMR, and our study about fracture prevention in corticosteroids
OP. In these studies a dose of 800 mg/day orally administered or 100 mg/week I.M. was used, and they are
basically the same if you consider that clodronate absorption, orally administered, is on average 1.9%.
However, a series of works where higher doses were used (1600 mg orally administered) with greater
effectiveness on bone mass, especially in higher risk populations, lead us to consider the use of 200 mg i.m.
formulation. First of all, we proved densitometric equivalence of 200 mg i.m./14 days and 100 mg i.m./week
in a first study; then, in a second study, we proved a greater densitometric efficacy of 200 mg/week compared
to 100 mg/week, clearer at femoral level, where the drug had not proven to prevent femoral fracture because
of inadequate bone mass increase at that level. Moreover, as for ibandronate case, monthly dose was doubled
compared to pivotal trial, in order to maximize the effects on femoral bone mass and therefore prevent femoral
fractures. Consequently, on the basis of the risk envelope, whether it is identified according to BMD and the
presence of one risk factor at least or more correctly identified through risk chart (FRAX or DeFRA), you can
put forward a differential use of 100 mg i.m. and 200 mg i.m., weekly, "off-label" or every 14 days, adjusting
doses in relation to fracture risk and painful symptoms gravity, as well as improving its ease of use and
therefore assist compliance. Common experience and clinical and biological works have proved that
clodronate has an analgesic effect that can be increased by doubling the doses. The analgesic effect is present
not only with patients with fractures, but also with patients suffering from osteoarthritis or arthritis. Therefore,
the drug would fit well in the therapeutic program of rheumatic patient, also because of its symptomatic
effects. Clodronate at small doses (2 mg) could also have protective effects on cartilage (introduction of intraarticular formulation is expected) and at 10-100 fold higher doses it has certainly anti-inflammatory effects
and more specifically antimacrophage and anticytokine effects (IL-1, IL-6, TNFalpha, PGE). These effects are
amplified by putting clodronate in monolayer liposomes. This drug, therefore, has to be considered as
adjuvant in arthritis therapy, whose origin can be linked to a strong osteoclastic activation caused by an
Fujii, K., et al. (2021). "Effectiveness of supplemental oral calcium drink in
preventing citrate-related adverse effects in peripheral blood progenitor cell
collection." Transfus Apher Sci 60(4): 103147.
Peripheral blood progenitor cells (PBPCs) are a predominant graft source in allogeneic hematopoietic cell
transplantation. Citrate-induced hypocalcemia remains the most frequent side effect of PBPC apheresis.
Although the method for preventing severe adverse events is established, more efficient prophylaxis is
required so that volunteer donors can donate PBPCs without pain and anxiety. We studied 80 healthy donors
who underwent PBPC harvest between February 2014 and June 2020. Of these, 23 donors who underwent
apheresis between February 2014 and December 2015 received only the standard prophylaxis of intravenous
calcium gluconate. Oral calcium drinks were provided to 57 donors who underwent apheresis from January
2016 to June 2020 to supplement intravenous calcium gluconate prophylaxis. The ionized calcium (ICa) levels
at multiple time intervals and the hypocalcemic symptoms were evaluated. Oral supplementation with a
calcium drink maintained significantly higher ICa levels. Analysis using the inverse probability weighted
regression adjustment method suggested that calcium drinks reduced the frequency of citrate-related reactions
by 39.2 %. Administering a prophylactic oral calcium drink before apheresis with intravenous administration
of calcium gluconate is promising to further reduce citrate-induced hypocalcemia in volunteer donors.
Fukuoka, K., et al. (2021). "Effect of Subcutaneous Adrenaline/Saline/Lidocaine
Injection on Split-Thickness Skin Graft Donor Site Wound Healing." Yonago Acta
Med 64(1): 107-112.
Gagliardi, G., et al. (2010). "Optimal treatment duration of glyceryl trinitrate for
chronic anal fissure: results of a prospective randomized multicenter trial." Tech
Coloproctol 14(3): 241-248.
BACKGROUND: Subcutaneous injection of tumescent solution, which contains local anesthetic, adrenaline,
and saline, before split-thickness skin graft harvesting, shows a significant hemostatic effect. This method can
reduce the initial bleeding from the donor site. The aim of this study is to assess the benefits of controlling the
bleeding from donor sites by tumescent injection. A randomized, controlled trial was performed to compare
the wound healing of split-thickness skin graft donor sites treated with or without tumescent injection.
METHODS: This randomized, controlled trial examined donor site healing days as the main measure of
outcome. postoperative pain, donor site ulceration, and scar quality were evaluated as secondary outcome
measures. Patients planned for split-thickness skin graft harvest were randomly assigned to receive either preharvest subcutaneous injection of local anesthetic, adrenaline, and saline solution (tumescent solution) (Group
1) or post-harvest application of adrenaline solution-soaked gauze to the skin graft donor sites (Group 2).
Donor sites were treated with calcium alginate dressings after graft harvesting. On the 10th postoperative day,
the dressings were removed and donor site healing were measured. Follow-up evaluation of scar quality was
performed 6 months after surgery. Postoperative pain was evaluated on the 1st day after operating. RESULTS:
Forty-five patients (26 males; average age 61.8 years) completed the late follow-up evaluation (6 months
postoperatively), with 26 patients in group 1 and 19 in group 2. There were no significant differences between
the two groups in any of the outcome measures. CONCLUSION: Tumescent technique provides sufficient
hemostasis in split skin graft donor sites, especially the initial bleeding just after graft harvesting, without any
negative effects. Larger series should be studied to evaluate the effect in donor site wound healing.
BACKGROUND: Chronic anal fissure (CAF) is a painful condition that is unlikely to resolve with
conventional conservative management. Previous studies have reported that topical treatment of CAF with
glyceryl trinitrate (GTN) reduces pain and promotes healing, but optimal treatment duration is unknown.
METHODS: To assess the effect of different treatment durations on CAF, we designed a prospective
randomized trial comparing 40 versus 80 days with twice daily topical 0.4% GTN treatment (Rectogesic,
Prostrakan Group). Chronicity was defined by the presence of both morphological (fibrosis, skin tag, exposed
sphincter, hypertrophied anal papilla) and time criteria (symptoms present for more than 2 months or pain of
less duration but similar episodes in the past). A gravity score (1 = no visible sphincter; 2 = visible sphincter;
3 = visible sphincter and fibrosis) was used at baseline. Fissure healing, the primary endpoint of the study,
maximum pain at defecation measured with VAS and maximum anal resting pressure were assessed at
baseline and at 14, 28, 40 and 80 days. Data was gathered at the end of the assigned treatment. RESULTS: Of
188 patients with chronic fissure, 96 were randomized to the 40-day group and 92 to the 80-day group.
Patients were well matched for sex, age, VAS and fissure score. There were 34 (19%) patients who did not
complete treatment, 18 (10%) because of side effects. Of 154 patients who completed treatment, 90 (58%) had
their fissures healed and 105 (68%) were pain free. There was no difference in healing or symptoms between
the 40- and the 80-day group. There was no predictor of fissure healing. A low fissure gravity score correlated
with increased resolution of pain (P < 0.05) and improvement of VAS score (P < 0.05) on both univariate and
multivariate analysis. A lower baseline resting pressure was associated with better pain resolution on
univariate analysis (P < 0.01). VAS at defecation and fissure healing significantly improved until 40 days (P <
0.001), while the difference between 40 and 80 days was not significant. CONCLUSION: We found no
benefits in treating CAF with topical GTN for 80 days compared to 40 days. Fissure healing and VAS
Gallidabino, M. D., et al. (2019). "Targeted and non-targeted forensic profiling of
black powder substitutes and gunshot residue using gradient ion chromatography –
high resolution mass spectrometry (IC-HRMS)." Analytica Chimica Acta 1072: 1-14.
A novel and simplified gradient IC-HRMS approach is presented in this work for forensic profiling of ionic
energetic material residues, including low-order explosives and gunshot residue (GSR). This new method
incorporated ethanolic eluents to facilitate direct coupling of IC and HRMS without auxiliary post-column
infusion pumps that are traditionally used to assist with gas phase transfer. Ethanolic eluents also enabled
better integration with an in-service protocol for direct analysis of high-order organic explosives by ICHRMS, without requiring solvent exchange before injection. Excellent method performance was achieved,
enabling both full scan qualitative and quantitative analysis, as required. In particular, linearity for 19 targeted
compounds yielded R2 > 0.99 across several orders of magnitude, with trace analysis possible at the low-mid
pg level. Reproducibility and mass accuracies were also excellent, with peak area %RSDs <10%, tR %RSDs
<0.4% and δm/z < 3 ppm. The method was applied to targeted analysis of latent fingermarks and swabbed
hand sweat samples to determine contact with a black-powder substitute containing nitrate, benzoate and
perchlorate. When combined with principal component analysis (PCA), the effect of time since handling on
recorded signals could be interpreted further in order to support forensic investigations. In a second, nontargeted application, PCA using full scan IC-HRMS data enabled classification of GSR from three different
types of ammunition. An additional 20 markers of GSR were tentatively identified in silico, in addition to the
15 anions detected during targeted analysis. This new approach therefore streamlines and adds consistency
and flexibility to forensic analysis of ionic energetic material. Furthermore, it also has implications for
targeted, non-targeted and suspect screening applications in other fields by expanding the separation space to
Gao, F., et al. (2016). "Topical fibrin sealant versus intravenous tranexamic acid for
reducing blood loss following total knee arthroplasty: A systematic review and metaanalysis." Int J Surg 32: 31-37.
PURPOSE: Efficacy and safety of topical application of a fibrin sealant (FS) compared with intravenous
administration of tranexamic acid (TXA) for reducing blood loss after total knee arthroplasty (TKA) is
controversial. We undertook a meta-analysis to compare the effects of topical application of FS or intravenous
administration of TXA on blood loss after TKA. METHODS: PubMed, Medline, Embase, Web of Science
and the Cochrane Library were searched to identify studies comparing FS with TXA for TKA patients. The
mean difference (MD) of blood loss, hemoglobin value, and odds ratios (ORs) of transfusion requirements and
adverse events in FS and TXA groups were pooled throughout the study. Relevant data were analyzed using
RevMan v5.3. RESULTS: Five studies involving 359 patients were included (181 FS vs. 178 TXA). TXA use
had a significantly lower prevalence of blood transfusion (OR = 3.14; 95% confidence interval (CI), 1.67 to
5.90, P = 0.0004) and higher hemoglobin level (MD = -1.23; 95% CI, -2.19 to -0.27, P = 0.01) than FS in the
early postoperative period. No significant difference was seen in total blood loss between the two groups
(MD = 198.06; 95% CI, -267.45 to 663.57; P = 0.40). There were no significant differences in adverse events,
superficial infections, or deep-vein thrombosis among study groups. CONCLUSIONS: Our meta-analysis
suggests that intravenous administration of TXA for patients undergoing TKA may reduce blood-transfusion
requirements and maintain higher hemoglobin levels compared with topical application of FS in the early
postoperative period. There were no significant differences in total calculated blood loss and prevalence of
complications between the two groups. However, owing to the variation of included studies, no firm
Garganeeva, A. A., et al. (2023). "[Iron deficiency in cardiac surgery patients and the
possibility of its correction at the preoperative stage]." Kardiologiia 63(7): 68-76.
Gaudinski, M. R., et al. (2019). "Safety and pharmacokinetics of broadly neutralising
human monoclonal antibody VRC07-523LS in healthy adults: a phase 1 doseescalation clinical trial." Lancet HIV 6(10): e667-e679.
Among cardio-surgical patients, the prevalence of iron deficiency conditions reaches 70 %, and anemia is
detected in less than 50% cases. Meanwhile, both anemia and latent iron deficiency are risk factors for
adverse outcomes in cardio-surgical patients. These conditions are associated with a high frequency and
greater volume of blood transfusions as well as with a longer stay in the hospital. Timely diagnosis and
correction of iron deficiency, regardless of the presence of anemia, are mandatory at the stage of preoperative
preparation. The use of oral iron medicines is limited by their low efficacy in this category of patients and a
high risk of adverse events. Intravenous iron medicines have a high potential for correcting iron deficiency,
and their efficacy and safety have been previously demonstrated. Administration of ferric carboxymaltose has
proved beneficial in studies on iron deficiency correction in cardiological and cardio-surgical patients. In
these patients, ferric carboxymaltose improved the dynamics of ferritin and hemoglobin, reduced the risk of
blood transfusion, and decreased the duration of stay in the hospital. Preoperative intravenous administration
of ferric carboxymaltose to cardio-surgical patients can improve clinical outcomes and the cost effectiveness
of cardiac surgery.
BACKGROUND: Human monoclonal antibodies that potently and broadly neutralise HIV-1 are under
development to prevent and treat HIV-1 infection. In this phase 1 clinical trial we aimed to determine the
safety, tolerability, and pharmacokinetic profile of the broadly neutralising monoclonal antibody VRC07523LS, an engineered variant of VRC01 that targets the CD4 binding site of the HIV-1 envelope protein.
METHODS: This phase 1, open-label, dose-escalation clinical trial was done at the National Institutes of
Health Clinical Center in Bethesda, MD, USA. Individuals were recruited from the greater Washington, DC,
area by IRB-approved written and electronic media. We enrolled healthy, HIV-1-negative adults aged 18-50
years. Inclusion criteria were good general health, measured through clinical laboratory tests, medical history,
and physical examination. Participants self-selected into one of seven open groups during enrolment without
randomisation. Four groups received a single intravenous dose of 1, 5, 20, or 40 mg/kg of VRC07-523LS, and
one group received a single 5 mg/kg subcutaneous dose. Two groups received three doses of either 20 mg/kg
intravenous VRC07-523LS, or 5 mg/kg subcutaneous VRC07-523LS at 12-week intervals. The primary
outcome was the safety and tolerability of VRC07-523LS, assessed by dose, route, and number of
administrations. This study is registered with ClinicalTrials.gov, NCT03015181. FINDINGS: Between Feb
21, 2017, and September 13, 2017, we enrolled 26 participants, including 11 (42%) men and 15 (58%)
women. Two (8%) participants withdrew from the study early: one participant in group 1 enrolled in the study
but never received VRC07-523LS, and one participant in group 6 chose to withdraw after a single
administration. One (4%) participant in group 7 received only one of the three scheduled administrations. 17
participants received intravenous administrations and 8 participants received subcutaneous administrations.
VRC07-523LS was safe and well tolerated, we observed no serious adverse events or dose-limiting toxic
effects. All reported local and systemic reactogenicity was mild to moderate in severity. The most commonly
reported symptoms following intravenous administration were malaise or myalgia in three (18%) participants
and headache or chills in two (12%) participants. The most commonly reported symptoms following
subcutaneous administration were pain and tenderness in four participants (50%) and malaise or headache in
three (38%) participants. INTERPRETATION: Safe and well tolerated, VRC07-523LS is a strong and
practical candidate for inclusion in HIV-1 prevention and therapeutic strategies. The results from this trial also
indicate that an HIV-1 broadly neutralising monoclonal antibody engineered for improved pharmacokinetic
Gaudinski, M. R., et al. (2018). "Safety, tolerability, and immunogenicity of two Zika
virus DNA vaccine candidates in healthy adults: randomised, open-label, phase 1
clinical trials." Lancet 391(10120): 552-562.
BACKGROUND: The Zika virus epidemic and associated congenital infections have prompted rapid vaccine
development. We assessed two new DNA vaccines expressing premembrane and envelope Zika virus
structural proteins. METHODS: We did two phase 1, randomised, open-label trials involving healthy adult
volunteers. The VRC 319 trial, done in three centres, assessed plasmid VRC5288 (Zika virus and Japanese
encephalitis virus chimera), and the VRC 320, done in one centre, assessed plasmid VRC5283 (wild-type Zika
virus). Eligible participants were aged 18-35 years in VRC19 and 18-50 years in VRC 320. Participants were
randomly assigned 1:1 by a computer-generated randomisation schedule prepared by the study statistician. All
participants received intramuscular injection of 4 mg vaccine. In VRC 319 participants were assigned to
receive vaccinations via needle and syringe at 0 and 8 weeks, 0 and 12 weeks, 0, 4, and 8 weeks, or 0, 4, and
20 weeks. In VRC 320 participants were assigned to receive vaccinations at 0, 4, and 8 weeks via single-dose
needle and syringe injection in one deltoid or split-dose needle and syringe or needle-free injection with the
Stratis device (Pharmajet, Golden, CO, USA) in each deltoid. Both trials followed up volunteers for 24
months for the primary endpoint of safety, assessed as local and systemic reactogenicity in the 7 days after
each vaccination and all adverse events in the 28 days after each vaccination. The secondary endpoint in both
trials was immunogenicity 4 weeks after last vaccination. These trials are registered with ClinicalTrials.gov,
numbers NCT02840487 and NCT02996461. FINDINGS: VRC 319 enrolled 80 participants (20 in each
group), and VRC 320 enrolled 45 participants (15 in each group). One participant in VRC 319 and two in
VRC 320 withdrew after one dose of vaccine, but were included in the safety analyses. Both vaccines were
safe and well tolerated. All local and systemic symptoms were mild to moderate. In both studies, pain and
tenderness at the injection site was the most frequent local symptoms (37 [46%] of 80 participants in VRC
319 and 36 [80%] of 45 in VRC 320) and malaise and headache were the most frequent systemic symptoms
(22 [27%] and 18 [22%], respectively, in VRC 319 and 17 [38%] and 15 [33%], respectively, in VRC 320).
For VRC5283, 14 of 14 (100%) participants who received split-dose vaccinations by needle-free injection had
detectable positive antibody responses, and the geometric mean titre of 304 was the highest across all groups
in both trials. INTERPRETATION: VRC5283 was well tolerated and has advanced to phase 2 efficacy
testing. FUNDING: Intramural Research Program of the Vaccine Research Center, National Institute of
Genovese, M. C., et al. (2020). "MRI of the joint and evaluation of the granulocytemacrophage colony-stimulating factor-CCL17 axis in patients with rheumatoid
arthritis receiving otilimab: a phase 2a randomised mechanistic study." Lancet
Rheumatol 2(11): e666-e676.
BACKGROUND: Otilimab is a human monoclonal antibody that inhibits granulocyte-macrophage colonystimulating factor (GM-CSF), a driver in many immune-mediated inflammatory conditions. We evaluated the
effect of otilimab on the GM-CSF-chemokine (C-C motif) ligand 17 (CCL17) axis and synovitis in patients
with rheumatoid arthritis. METHODS: This phase 2a, randomised, double-blind, multicentre, placebocontrolled, parallel-group study was done at nine sites across the USA, Poland, and Germany. Patients aged 18
years or older with rheumatoid arthritis per American College of Rheumatology-European League Against
Rheumatism 2010 criteria and receiving stable methotrexate were randomly assigned (3:1) by an interactive
response technology system to either subcutaneous otilimab 180 mg or placebo once weekly for 5 weeks, then
every other week until week 10 (within a 12-week treatment period), followed by a 10-week safety follow-up.
Randomisation was stratified by early rheumatoid arthritis (≤2 years since diagnosis) and established
rheumatoid arthritis (>2 years since diagnosis). Patients and study personnel (except for an unblinded
coordinator or nurse who prepared and administered the study drug) were blinded to treatment assignment; the
syringe was shielded during administration. Patients were enrolled by study investigators and allocated to a
treatment by central randomisation on the basis of a schedule generated by the sponsor. The primary endpoint
was change over time (assessed at baseline and weeks 1, 2, 4, 6, 8, 12, and 22 of follow-up) in 112
biomarkers, including target engagement biomarkers and those that may be indicative of rheumatoid arthritis
disease activity and response to otilimab. Secondary endpoints were change from baseline in synovitis, osteitis
and erosion assessed by rheumatoid arthritis MRI scoring system (RAMRIS) and rheumatoid arthritis MRI
quantitative score (RAMRIQ), and safety evaluation. The primary, secondary, and safety endpoints were
assessed in the intention-to-treat population. Biomarker and MRI endpoints were analysed for differences
between treatment groups using a repeated measures model. This study is registered with ClinicalTrials.gov,
NCT02799472. FINDINGS: Between Aug 9, 2016, and Oct 30, 2017, 39 patients were randomly assigned and
included in the analysis (otilimab n=28; placebo n=11). In the otilimab group, mean serum concentrations of
GM-CSF-otilimab complex peaked at week 4 (138·4 ng/L, 95% CI 90·0-212·9) but decreased from week 612. CCL17 concentrations decreased from baseline to week 1, remained stable to week 8, and returned to
baseline at week 12; least-squares mean ratio to baseline was 0·65 (95% CI 0·49-0·86; coefficient of variation
13·60) at week 2, 0·68 (0·53-0·88; 12·51) at week 4, 0·78 (0·60-1·00; 12·48) at week 6, and 0·68 (0·54-0·85;
11·21) at week 8. No meaningful change in CCL17 concentrations was observed with placebo. In the otilimab
Geppetti, P., et al. (2022). "Self-administered subcutaneous diclofenac sodium in acute
migraine attack: A randomized, double-blind, placebo-controlled dose-finding pilot
study." Cephalalgia 42(10): 1058-1070.
BACKGROUND: A novel formulation of diclofenac, complexed with hydroxypropyl-β-cyclodextrin (HPβ
CD) as a solubility enhancer, in a prefilled syringe for self-administered subcutaneous injection may
overcome the limitations of acute migraine treatments administered by oral, rectal, intramuscular, or
intravenous routes. METHODS: This multicentre, phase 2, double-blind, randomized, placebo-controlled,
dose-finding pilot study evaluated the efficacy, safety and tolerability of three different doses
(25/50/75 mg/1 mL) of subcutaneous diclofenac sodium in the treatment of an acute migraine attack in 122
subjects. The primary efficacy endpoint was the percentage of patients pain-free at 2 hours after the study
drug injection. RESULTS: A significantly higher percentage of patients in the 50 mg diclofenac group 14
(46.7%) were pain-free at 2 hours when compared with placebo: 9 (29.0%) (p = 0.01). The 50 mg dose proved
superior to placebo also in the majority of the secondary endpoints. The overall global impression favoured
diclofenac vs placebo. There were no adverse events leading to study withdrawal. The majority of treatmentemergent adverse events were mild. CONCLUSIONS: The 50 mg dose of this novel formulation of diclofenac
represents a valuable self-administered option for the acute treatment of migraine attacks.Trial registration:
EudraCT Registration No. 2017-004828-29.
Ghaffari, A., et al. (2021). "Does the performance of lower limb peripheral nerve
blocks differ among orthopedic sub-specialties? A single institution experience in 246
patients." Scand J Pain 21(4): 794-803.
OBJECTIVES: Continuous peripheral nerve blocks (cPNBs) have shown promising results in pain
management after orthopaedic surgeries. However, they can be associated with some risks and limitations.
The purpose of this study is to describe our experience with the cPNBs regarding efficacy and adverse events
in patients undergoing orthopedic surgeries on the lower extremity in different subspecialties. METHODS:
This is a prospective cohort study on collected data from perineural catheters for pain management after
orthopedic surgeries in lower limbs. Catheters were placed by experienced anesthesiologists using sterile
technique. After an initial bolus dose of 10-20 mL ropivacaine 0.5% (weight adjusted), the catheters were
secured and connected to disposable mechanical infusion pumps with ropivacaine 0.2% (basal infusion
rate = 6 mL/h; weight adjusted (0.2 mL/kg/h)). After catheterization, the patients were examined daily, by
specially educated acute pain service nurses. Pro re nata (PRN) or fixed boluses (10 mL bupivacaine 0.25%;
weight adjusted) with an upper limit of 4 times/day, were administered if indicated. Patients' demographic
data, physiological status, and pre-op intake of opioids and other analgesics were registered. The severity of
post-operative pain was assessed with 'Numeric Rating Scale' (NRS) and 'Face, legs, Activity, Cry,
Consolability' (FLACC) scale for adults and children, respectively. The need for additional opioids and
possible complications were registered. RESULTS: We included 547 catheters of 246 patients (Range 1-10
catheters per patient). Overall, 115 (21%) femoral, 162 (30%) saphenous, 66 (12%) sciatic, and 204 (37%)
popliteal sciatic nerve catheter were used. 452 (83%) catheters were inserted by a primary procedure, 61(11%)
catheters employed as a replacement, and 34 catheters (6.2%) used as a supplement. For guiding the
catheterization, ultrasound was applied in 451 catheters (82%), nerve stimulator in 90 catheters (16%), and
both methods in 6 catheters (1.1%). The median duration a catheter remained in place was 3 days (IQR = 2-5).
The proportion of catheters with a duration of two days was 81, 79, 73, and 71% for femoral, sciatic,
saphenous, and popliteal nerve, respectively. In different subspecialties, 91% of catheters in wound and
amputations, 89% in pediatric surgery, 76% in trauma, 64% in foot and ankle surgery, and 59% in limb
reconstructive surgery remained more than two days. During first 10 days after catheterization, the proportion
of pain-free patients were 77-95% at rest and 63-88% during mobilization, 79-92% of the patients did not
require increased opioid doses, and 50-67% did not require opioid PRN doses. In addition to 416 catheters
(76%), which were removed as planned, the reason for catheter removal was leaving the hospital in 27 (4.9%),
loss of efficacy in 69 (13%), dislodgement in 23 (4.2%), leakage in 8 (1.5%), and erythema in 4 catheters
Ghil, J., A. Zielińska and Y. Lee (2019). "Usability and safety of SB5 (an adalimumab
biosimilar) prefilled syringe and autoinjector in patients with rheumatoid arthritis."
Curr Med Res Opin 35(3): 497-502.
Ghisoni, E., et al. (2019). "Role of Mediterranean diet in preventing platinum based
gastrointestinal toxicity in gynecolocological malignancies: A single Institution
experience." World J Clin Oncol 10(12): 391-401.
OBJECTIVE: To demonstrate comparability between administration of the adalimumab biosimilar, SB5, via
prefilled syringe (PFS) and autoinjector (AI) pen based on injection site pain, patient preference, and safety in
rheumatoid arthritis (RA) patients. METHODS: In this phase 2, open-label study (NCT02565810; EudraCT
Number 2014-004887-39), adult RA patients self-administered 40 mg SB5 subcutaneously via PFS at weeks 0
and 2, followed by AI at weeks 4, 6, 8, and 10. Patients rated injection site pain from 0 (no pain) to 10 (severe
pain) using a visual numeric scale immediately and 15-30 min post-injection at weeks 0, 2, 4, and 6.
Equivalence between PFS and AI was concluded if the 97.5% confidence interval (CI) of the difference in the
injection site pain scores at weeks 2 and 6 was contained within the equivalence margin of ±5. Overall
impression and preference for PFS and AI were also evaluated. Safety was assessed up to 20 weeks after the
first injection. RESULTS: Of 49 patients enrolled, 48 completed the study. Mean injection site pain scores
were equivalent between PFS and AI immediately (2.3 vs 2.0; 97.5% CI = -0.99-0.30) and 15-30 min postinjection (0.8 vs 0.7; 97.5% CI = -0.47-0.25). The overall impression of both devices was comparable. The
overall preference of AI was higher than PFS. Treatment-emergent adverse events (TEAE) were mild-tomoderate. There were no severe or serious TEAEs reported during the study. CONCLUSIONS: In RA
patients, SB5 showed equivalent injection site pain and comparable safety when administered via PFS and AI.
BACKGROUND: Gynecological malignancies represent a major cause of death in women and are often
treated with platinum-based regimens. Patients undergoing chemotherapy suffer from alterations in nutritional
status which may worsen gastrointestinal (GI) toxicities, quality of life and affect the overall prognosis.
Indeed, assuring a good nutritional status and limiting toxicities during treatment are still major goals for
clinicians. AIM: To assess the role of Mediterranean Diet (MD) in reducing GI toxicities in patients with
gynecological cancers treated with platinum-based regimens. METHODS: We conducted an observational
study on 22 patients with gynecological tumors treated with a platinum-based chemotherapy at Candiolo
Cancer Institute FPO/IRCCS between January 2018 and June 2018. The food and frequency (FFQ) and the
Patient-Reported Outcomes Common Terminology Criteria For Adverse Events (PRO-CTCAE)
questionnaires were administered at baseline and at every Day 1 of each cycle. To evaluate the differences in
GI toxicities the study population was divided in two groups according to the currently validated
Mediterranean Diet Serving Score (MDSS) at baseline. RESULTS: Patients with high MDSS reported a trend
toward lower GI toxicities according to PRO-CTCAE at each timepoint (first evaluation: P = 0.7; second: P =
0.52; third: P = 0.01). In particular, difference in nausea frequency and gravity (P < 0.001), stomach pain
frequency and gravity (P = 0.01 and P = 0.02), abdomen bloating frequency and gravity (P = 0.02 and P =
0.03), and interference with daily activities (P = 0.02) were highly statistically significant at the end of
treatment. More than 60% of patients changed their food habits during chemotherapy mainly because of GI
toxicities. A higher reduction of food intake, both in terms of caloric (P = 0.29) and of single nutrients
emerged in the group experiencing higher toxicity. CONCLUSION: Our results show that adherence to MD
possibly reduces GI toxicity and prevents nutritional status impairment during chemotherapy treatment.
Ghosn, M., et al. (2022). "Percutaneous liver venous deprivation: outcomes in heavily
pretreated metastatic colorectal cancer patients." HPB 24(3): 404-412.
Giraldes, A. L., et al. (2016). "Tramadol wound infiltration is not different from
intravenous tramadol in children: a randomized controlled trial." J Clin Anesth 28: 6266.
Girdler, J. (2022). "Dentapen versus traditional syringe infiltration - which LA
technique is preferred by patients?" Evid Based Dent 23(3): 100-101.
Background To evaluate liver venous deprivation (LVD) outcomes in patients with colorectal liver metastasis
(CRLM) heavily pretreated with systemic and hepatic arterial infusion pump (HAIP) chemotherapies that had
an anticipated insufficient future liver remnant (FLR) hypertrophy after portal vein embolization (PVE).
Methods PVE was performed with liquid embolics using a transsplenic or ipsilateral transhepatic approach.
Simultaneously and via a trans-jugular approach, the right hepatic vein was embolized with vascular plugs.
Liver volumetry was assessed on computed tomography before and 3–6 weeks after LVD. Results Twelve
consecutive CRLM patients that underwent LVD before right hepatectomy or trisectionectomy were included,
all previously treated with systemic chemotherapy for a mean of 11.9 months. Six patients had additional
HAIP. After embolization, FLR ratio increased from 28.7% ± 5.9 to 42.2% ± 9.0 (P < 0.01). Mean kinetic
growth rate (KGR) was 3.56%/week ± 2.3, with a degree of hypertrophy (DH) of 13.8% ± 7.1. In the HAIP
subgroup, mean KGR and DH were respectively 3.58%/week ± 2.8 and 14.3% ± 8.7. No severe complications
occurred. Ten patients reached surgery after 39 days ± 7.5. Conclusion In heavily pretreated patients, LVD
safely stimulated a rapid and effective FLR hypertrophy, with a resultant high rate of resection.
STUDY OBJECTIVE: The purpose of this trial was to assess if tramadol wound infiltration is superior to
intravenous (IV) tramadol after minor surgical procedures in children because tramadol seems to have local
anesthetic-like effect. DESIGN: Randomized double-blind controlled trial. SETTING: Postanesthesia care
unit. PATIENTS: Forty children, American Society of Anesthesiologists physical status I or II, scheduled to
elective inguinal hernia repair. INTERVENTIONS: Children were randomly distributed in 1 of 2 groups: IV
tramadol (group 1) or subcutaneous infiltration with tramadol (group 2). At the end of the surgery, group 1
received 2 mg/kg tramadol (3 mL) by IV route and 3-mL saline into the surgical wound; group 2 received 2
mg/kg tramadol (3 mL) into the surgical wound and 3-mL saline by IV route. MEASUREMENTS: In the
postanesthesia care unit, patients were evaluated for pain intensity, nausea and vomiting, time to first rescue
medication, and total rescue morphine and dipyrone consumption. MAIN RESULTS: Pain scores measured
during the postanesthesia recovery time were similar between groups. Time to first rescue medication was
shorter, but not statistically significant in the IV group. The total dose of rescue morphine and dipyrone was
also similar between groups. CONCLUSIONS: We concluded that tramadol was effective in reducing
postoperative pain in children, and there was no difference in pain intensity, nausea and vomiting, or
somnolence regarding IV route or wound infiltration.
Design Single-blind randomised cross-over trial.Intervention The study compared solution deposition pain of
a maxillary lateral incisor infiltration between a computer-controlled local anaesthesia delivery device
(Dentapen) and traditional syringe. The Dentapen was given with a slow flow rate of 1.8 mL/162 sec and
ramp-up mode, and the traditional syringe infiltration was delivered at a flow rate of 1.8 ml/60 sec. Patients
were randomly assigned to a sequence to receive both interventions at two separate appointments, with each
participant acting as their own control. Patients rated the pain of each intervention using a Heft-Parker visual
analogue scale and completed a preference survey at the conclusion of the second appointment.Case selection
A total of 130 adult patients with ASA I or II were included in the study. Criteria for exclusion were patients
under 18 years of age or older than 65, allergies to local anaesthetics or sulphites, pregnant or nursing, history
of significant medical conditions (ASA III or higher), taking any medications that may affect pain assessment,
active pathosis at the injection site, or inability to give informed consent.Data analysis Differences in pain of
solution deposition for the Dentapen and traditional infiltration techniques were analysed using paired t-tests
and odds ratios. Interactions between study groups, gender and anxiety were analysed using a linear mixedeffect model with a P value <0.05.Results Solution deposition pain was significantly less (P <0.001) with the
Dentapen infiltration than the traditional infiltration. The preference survey revealed that 75% of patients
preferred the Dentapen infiltration over the traditional technique.Conclusions The findings of this clinical trial
suggest that pain during maxillary lateral incisor infiltrations can be reduced by using the Dentapen with a
Godoi, T. T. F., et al. (2022). "Platelet-Rich Plasma Gel Matrix (PRP-GM):
Description of a New Technique." Bioengineering (Basel) 9(12).
Several musculoskeletal conditions are triggered by inflammatory processes that occur along with imbalances
between anabolic and catabolic events. Platelet-rich plasma (PRP) is an autologous product derived from
peripheral blood with inherent immunomodulatory and anabolic properties. The clinical efficacy of PRP has
been evaluated in several musculoskeletal conditions, including osteoarthritis, tendinopathy, and
osteonecrosis. When used in combination with hyaluronic acid (HA), a common treatment alternative, the
regenerative properties of PRP are significantly enhanced and may provide additional benefits in terms of
clinical outcomes. Recently, a new PRP-derived product has been reported in the literature and is being
referred to as "plasma gel". Plasma gels are obtained by polymerizing plasmatic proteins, which form solid
thermal aggregates cross-linked with fibrin networks. Plasma gels are considered to be a rich source of growth
factors and provide chemotactic, migratory, and proliferative properties. Additionally, clot formation and the
associated fibrinolytic reactions play an additional role in tissue repair. There are only a few scientific articles
focusing on plasma gels. Historically, they have been utilized in the fields of aesthetics and dentistry. Given
that the combination of three products (PRP, HA, and plasma gel) could enhance tissue repair and wound
healing, in this technical note, we propose a novel regenerative approach, named "PRP-HA cellular gel
matrix" (PRP-GM), in which leukocyte-rich PRP (LR-PRP) is mixed with a plasma gel (obtained by heating
the plasma up) and HA in one syringe using a three-way stopcock. The final product contains a fibrin-albumin
network entangled with HA's polymers, in which the cells and biomolecules derived from PRP are attached
and released gradually as fibrinolytic reactions and hyaluronic acid degradation occur. The presence of
leukocytes, especially monocytes and macrophages, promotes tissue regeneration, as type 2 macrophages
(M2) possess an anti-inflammatory feature. In addition, HA promotes the viscosuplementation of the joint and
induces an anti-inflammatory response, resulting in pain relief. This unique combination of biological
molecules may contribute to the optimization of regenerative protocols suitable for the treatment of
Goldstein, M., et al. (2017). "Tranexamic Acid Prophylaxis in Hip and Knee Joint
Replacement." Dtsch Arztebl Int 114(48): 824-830.
BACKGROUND: The antifibrinolytic agent tranexamic acid (TXA) is widely used for the prevention and
treatment of hyperfibrinolytic states, such as in severe polytrauma. It can also be used for the systemic
prevention of hemorrhage in elective orthopedic procedures. In this review, we assess the efficacy and risks of
the prophylactic administration of tranexamic acid before major endoprosthetic surgery of the hip and knee.
METHODS: This review is based on pertinent articles retrieved by a selective literature search in the PubMed
and Cochrane Library databases. RESULTS: Endoprosthetic surgery of the hip and knee is often associated
with perioperative blood losses exceeding 500 mL. The prophylactic administration of tranexamic acid
immediately before such procedures has been shown in randomized, controlled trials to lessen the quantity of
intra- and postoperative bleeding and to reduce the likelihood of blood transfusion (number needed to treat
[NNT] 3.7-5.7 for knee replacement and 4.1-8.2 for hip replacement). The rate of thromboembolic events did
not differ significantly from the rate in the placebo groups. No reliable data are available on the frequency of
epileptic seizures as a complication of TXA use in knee and hip endoprosthetic surgery. On the basis of data
from other types of surgery, one may reasonably conclude that the doses of TXA used for knee and hip
endoprosthetic procedures are unlikely to cause this problem. CONCLUSION: The prophylactic intravenous
administration of tranexamic acid lessens the amount of bleeding in endoprosthetic knee and hip procedures
and reduces the likelihood of blood transfusion. According to the current state of the evidence, complications
are rare. Nonetheless, consideration of the risks and benefits implies that tranexamic acid should not be given
for this purpose to patients who have recently had urogenital bleeding, pulmonary embolism, or a myocardial
infarction, who have recently undergone percutaneous transluminal coronary angioplasty or stenting, or who
Gomaa, S., K. G. Salem and A. N. El-hoshoudy (2023). "Enhanced heavy and extra
heavy oil recovery: Current status and new trends." Petroleum.
Due to the increased demand for energy resources these days, especially due to the Russian-Ukrainian war, the
focus of the major countries is turning strongly towards improving oil production, especially heavy and extra
heavy oil, which represents 40 % of the world oil reserve. Steam-based and thermal (EOR) procedures are
promising techniques for recovering heavy oil reservoirs, but they suffer from a sequence of problems and
complications that arise after long-term application. These complications comprise steam breakthrough, steam
overlap, and steam/rock interactions. This research presents the currently applied techniques to maximize the
productivity of heavy oil, such as steam injection, cyclic steam stimulation, in-situ combustion, and steamassisted gravity drainage. Thermal technologies face numerous obstacles, as they are energy and waterintensive processes that are not environmentally friendly. The research also presents future trends in energysaving and environmentally friendly techniques that enhance heavy oil recovery through vapor extraction
(VAPEX) steam-solvent hybrid techniques, electromagnetic energy, sonication, and nanotechnology. The
findings of this review reported that all the presented techniques focus on how to reduce the oil viscosity and
in-situ upgrade the crude oil properties. In turn, these enhance both the productivity rate and oil recovery and
minimize the production cost. This article can be considered a comprehensive review of thermal recovery
methods in heavy and extra-heavy oil, in addition to screening criteria used for each method.
Gómez, A. M., et al. (2015). "Numerical and clinical precision of continuous glucose
monitoring in Colombian patients treated with insulin infusion pump with automated
suspension in hypoglycemia." Endocrinología y Nutrición (English Edition) 62(10):
485-492.
Gómez-Cardero, P. and E. C. Rodríguez-Merchán (2010). "Postoperative analgesia in
TKA: ropivacaine continuous intraarticular infusion." Clin Orthop Relat Res 468(5):
1242-1247.
Objectives Insulin pump therapy associated with continuous glucose monitoring has shown a positive clinical
impact on diabetes control and reduction of hypoglycemia episodes. There are descriptions of the performance
of this device in other populations, but its precision and accuracy in Colombia and Latin America are
unknown, especially in the routine outpatient setting. Methods Data from 33 type 1 and type 2 diabetes
patients with sensor-augmented pump therapy with threshold suspend automation, MiniMed Paradigm® Veo
™ (Medtronic, Northridge, California), managed at Hospital Universitario San Ignacio (Bogotá, Colombia)
and receiving outpatient treatment, were analyzed. Simultaneous data from continuous glucose monitoring and
capillary blood glucose were compared, and their precision and accuracy were calculating with different
methods, including Clarke error grid. Results Analyses included 2262 continuous glucose monitoringreference paired glucose values. A mean absolute relative difference of 20.1% was found for all
measurements, with a value higher than 23% for glucose levels ≤75mg/dL. Global compliance with the ISO
criteria was 64.9%. It was higher for values >75mg/dl (68.3%, 1308 of 1916 readings), than for those ≤
75mg/dl (49.4%, 171 of 346 readings). Clinical accuracy, as assessed by the Clarke error grid, showed that
91.77% of data were within the A and B zones (75.6% in hypoglycemia). Conclusions A good numerical
accuracy was found for continuous glucose monitoring in normo and hyperglycemia situations, with low
precision in hypoglycemia. The clinical accuracy of the device was adequate, with no significant safety
concerns for patients. Resumen Objetivo La terapia con bomba de insulina asociada a monitorización continua
de glucosa ha demostrado tener un impacto clínico positivo en el control de la diabetes y en la reducción de
los episodios de hipoglucemia. Aunque existen descripciones del rendimiento del dispositivo en otras
poblaciones, se desconoce su desempeño en Colombia y Latinoamérica en el contexto de la terapia
ambulatoria usual. Métodos Se analizaron los registros de 33 pacientes con diabetes mellitus tipo 1 y 2 en
terapia con monitorización continua de glucosa integrada al infusor de insulina con suspensión automática en
hipoglucemia (MiniMed Paradigm® Veo™) utilizando el Sensor Sof-Sensor™ (Medtronic, Northridge,
California) manejados en el Hospital Universitario San Ignacio (Bogotá, Colombia) y que venían recibiendo
tratamiento ambulatorio. Se compararon datos simultáneos provenientes de glucometría capilar y
monitorización continua de glucosa, calculando su validez por diferentes técnicas, incluyendo un análisis
clínico utilizando la gradilla de error de Clarke. Resultados Basados en 2.262 datos pareados se encontró una
media de la diferencia absoluta relativa para todas las mediciones del 20,1%, siendo mayor a 23% en las
BACKGROUND: Postoperative pain control is a challenge in patients undergoing TKA due to side effects
and technical limitations of current analgesic approaches. Local anesthetic infiltration through continuous
infusion pumps has been shown to reduce postoperative pain in previous studies. QUESTIONS/PURPOSES:
We assessed the effectiveness of intraarticular ropivacaine infusions in reducing pain and postoperative opioid
use after TKA and determined whether such infusions accelerate functional recovery of the patient and reduce
length of hospital stay. METHODS: In a randomized, prospective, double-blind study, two groups were
assigned: Group A (n = 25) underwent continuous intraarticular infusion with 300 mL ropivacaine 0.2% at a
speed of 5 mL/hour through an elastomeric infusion pump and Group B (n = 25) had an elastomeric pump
insertion with 300 mL saline solution at an infusion speed of 5 mL/hour. All patients had the same prosthesis
model implanted. Parameters analyzed over the first 3 days, at discharge, and 1 month later included
postoperative pain, joint function, opioid use, and length of hospital stay. RESULTS: All patients in Group A
showed a decrease in pain intensity measured by a visual analog scale and opioid use in the first 3 days. Mean
length of hospital stay was also reduced in Group A (5.72 days) compared to Group B (7.32 days). There were
no device-related complications. CONCLUSIONS: Use of an infusion pump is effective in treating pain after
TKA, reducing postoperative pain and opioid use. It also improves immediate functionality and patient
comfort, reducing the mean length of hospital stay, without increasing the risk of complications. LEVEL OF
EVIDENCE: Level I, therapeutic study. See Guidelines for Authors for a complete description of levels of
Gonella, S., et al. (2022). "Interventions to reduce arterial puncture-related pain: A
systematic review and meta-analysis." Int J Nurs Stud 126: 104131.
BACKGROUND: Arterial puncture-related pain remains unaddressed across several clinical settings.
Analgesic techniques are not routinely employed before arterial puncture despite the recommendation that
local anesthesia be used, except in emergencies. A comprehensive review of interventions aimed at reducing
arterial puncture-related pain and their potential effectiveness is lacking, and the benefit of some interventions
is uncertain. OBJECTIVE: To describe interventions aimed at reducing arterial puncture-related pain and
provide an estimate of their effectiveness. DESIGN: Systematic review and meta-analysis (PROSPERO no.
CRD42020212299). DATA SOURCE(S): PubMed, CINAHL EBSCO, EMBASE, the Cochrane Database of
Systematic Reviews, and Scopus were searched from their inception to 7 October 2020. No temporal or
language limits were applied. METHODS: Published, quantitative studies on interventions aimed at reducing
arterial puncture-related pain among adults were included. Screening, quality appraisal, and data extraction
were undertaken independently by two reviewers. Random effects meta-analyses were performed to assess the
association between interventions aimed at reducing arterial puncture-related pain and patients' perceived pain
using difference in means (MD) with 95% confidence intervals (CIs). A funnel plot and Egger test were used
to assess publication bias. RESULTS: The titles and abstracts of the 2446 identified articles were screened,
and 43 and 31 studies were finally included in the systematic review and meta-analysis, respectively.
Interventions to reduce arterial puncture-related pain included: topical anesthetics (n = 16), cryotherapy
(n = 9), local anesthetic infiltration (n = 5), narrower needle gage (n = 5), ultrasound-guided procedure
(n = 3), topical anesthetics combined with local anesthetic infiltration (n = 1), iontophoresis using anesthetics
(n = 1), engineered blood gas syringe (n = 1), jet injector (n = 1), and local massage (n = 1). Topical
anesthetics [MD -0.58, 95% CI -1.00, -0.15], cryotherapy [MD -1.13, 95% CI -1.72, -0.53], and local
anesthetic infiltration [MD -1.13, 95% CI -1.72, -0.53] reduced arterial puncture-related pain. No benefit was
found for narrower needle gage [MD -0.07, 95% CI -0.86, 0.71] or ultrasound-guided procedure [MD -1.74,
95% CI -3.51, 0.03]. No publication bias was detected. CONCLUSIONS: Local anesthetic infiltration
provided the greatest pain reduction and should be considered standard practice. Cryotherapy may be a safe,
convenient alternative to local anesthetic infiltration. Topical anesthetics had limited benefit, and their lengthy
time of onset makes them unsuitable for critical or emergency situations, though they may represent an option
when comorbid conditions make cooling impossible. Caution must be used when interpreting these results,
Goyal, A. and S. Hennayake (2010). "Prone retroperitoneoscopic approach for
heminephrectomy: Specific advantages relating to access to vascular pedicle." Journal
of Pediatric Urology 6(2): 153-156.
Introduction The lateral approach is more widely used in retroperitoneoscopic (RP) heminephroureterectomy
(HNU) due to familiar orientation and ease of conversion. The prone approach however gives early and easy
access to the vascular pedicle. The main reason for not adopting a prone approach more widely is the
perceived difficulty in lower ureteric access. We present a series of 30 HNUs where the prone approach was
utilized extremely effectively with no conversions and few complications. Methods Thirty consecutive HNUs
performed over a 4-year period (2004–2007) using a prone RP approach were included in the study.
Prospectively recorded data and notes were reviewed. Results Upper HNU was done in 17 and lower HNU in
13 patients. Mean age was 3.2 years (range 0.9–13.3). There were no transfusions or conversions. Follow-up
ultrasound showed healthy remnant moieties in all. Residual ureteric stump was seen in six patients but only
one was symptomatic requiring a further procedure. Conclusion With the prone approach the anatomy can be
demonstrated quickly and effectively. Dissection can be done easily without the need for kidney retraction as
gravity aids demonstration of the renal vascular pedicle. There is a low risk of complications arising from the
residual ureteric stump. We recommend that this approach be considered for RP HNU in all patients,
irrespective of age.
Granot, Y., et al. (2022). "Evaluation of hemodynamically significant pericardial
effusion by analysis of cardiac chambers volume by computed tomography." Br J
Radiol 95(1140): 20220106.
Griffin, P., et al. (2017). "Safety, acceptability and tolerability of uncoated and
excipient-coated high density silicon micro-projection array patches in human
subjects." Vaccine 35(48 Pt B): 6676-6684.
OBJECTIVE: Pericardial effusion may present clinically as pleuritic chest pain, dyspnea, or hemodynamic
compromise and is a frequent finding in computerized tomographic pulmonary angiography (CTPA) exams.
We hypothesized that CTPA-based analysis of the cardiac chamber volumes can be used to predict the
hemodynamic significance of pericardial effusion (HsPE) as compared with echocardiography. METHODS:
Retrospective analysis of consecutive patients who underwent CTPA and echocardiography between January
2009 and November 2017 that ruled-out acute pulmonary embolism was included. Differences in cardiac
chamber volumes were investigated in correlation to echocardiographic evidence of HsPE. RESULTS: The
final cohort included 208 patients, of whom 22 (11%) were diagnosed with HsPE. The HsPE patients had
much smaller right cardiac chamber volumes (Median 78.8 ml (IQR 72.4-89.1)) than patients without HsPE
(Median 115.1 ml (IQR 87.4-150). A decision tree for the prediction of HsPE showed multiple cutoff values.
Right atrium (RA) volume had the best accuracy (area under the curve 0.851, 95% confidence interval 0.7760.925, p < .001) for predicting the presence of HsPE. An RA volume ≤86 ml yielded a sensitivity of 95.5%, a
specificity of 64%, and a NPV of 99.2% for the presence of HsPE. CONCLUSION: CTPA-based volumetric
information with focus on the RA volume may help predict the presence of HsPE. ADVANCES IN
KNOWLEDGE: Pericardial effusion is a frequent finding in CTPA exams. Our study shows that CTPA-based
Most vaccinations are performed by intramuscular injection with a needle and syringe. However, this method
is not ideal due to limitations, such as the risk of needle-stick injury, the requirement for trained personnel to
give injections and the need to reconstitute lyophilized vaccines. Therefore, we tested an alternative delivery
technology that overcomes the problems with needle and syringe. The Nanopatch™ is an array of 10,000
silicon micro-projections per cm(2) that can be dry-coated with vaccine for skin delivery. The high number
and density of micro-projections means that high velocity application is required to achieve consistent skin
penetration. Before clinically testing a vaccine Nanopatch, this study tests the safety, tolerability and
acceptability/utility of uncoated and excipient-coated Nanopatches in healthy adults. Nanopatches were
applied to skin of the upper arm and volar forearm and left in contact with the skin for two minutes before
removal. The application sites were assessed for local skin response over 28 days. Acceptability interviews
were also performed. No unexpected adverse events directly related to the Nanopatch application were
reported. All applications of the Nanopatch resulted in an expected erythema response which faded between
days 3 and 7. In some subjects, some skin discolouration was visible for several days or up to 3 weeks after
application. The majority (83%) of subjects reported a preference for the Nanopatch compared to the needle
and syringe and found the application process to be simple and acceptable. On a pain scale from 0 to 10, 78%
of applications were scored "0" (no pain) with the average scores for less than 1. The results from this study
demonstrate the feasibility of the Nanopatch to improve vaccination by showing that application of the
product without vaccine to human skin is safe, tolerable and preferred to needle and syringe administration.
Grill, F. D., et al. (2020). "Identifying perioperative volume-related risk factors in
head and neck surgeries with free flap reconstructions – An investigation with focus
on the influence of red blood cell concentrates and noradrenaline use." Journal of
Cranio-Maxillofacial Surgery 48(1): 67-74.
Introduction The amount of fluids administered intraoperatively seems to influence the postoperative
outcome, and especially the transfusion of red blood cell concentrates (RBC) are known to have an increased
risk of postoperative complications. This prospective study focuses on patients planned with microvascular
free flap reconstruction and investigates the effect of various types and amounts of volumes given
intraoperatively and on the intensive care unit with regard to overall postoperative complications. Material
and methods In this prospective study, 52 consecutive patients planned for reconstruction with microvascular
free flaps were included. Intraoperatively administered volumes including blood products were documented
by the anesthesiologists as well as volumes given during the intensive care unit stay. Postoperative
complications were registered for the entire hospital stay. Statistical analysis was carried out correlating the
amount and type of volumes with the incidence of postoperative complications. Results The intraoperative use
of RBC showed a close to statistically significant increased risk of postoperative complications (mean/SD
concentrates: 0.5/1.1 [no complications] vs. 1.0/1.4 [complications], p = 0.058). In a multivariate analysis with
stepwise selection the use of human albumin, gelatin, or Ringer's acetate showed no correlation with
complications. The overall blood loss, however, had no significant influence on the incidence of
complications (mean/SD ml: 1187/761 [no complications] vs. 1004/600 [complications], p = 0.37). The use of
noradrenalin during reconstructive surgeries with microvascular flaps bears statistically no increased risk of
failure (mean/SD μg/kg/min: 36/23 [no flap loss] vs. 22/15 [flap loss], p = 0.289) or complications (mean/SD
μg/kg/min: 34/22 [no complications] vs. 35/23 [complications], p = 0.807). Conclusion In our investigation,
the use of crystalloids and colloids seems to have no influence on the postoperative outcome, but the use of
RBC may have an increased overall incidence of postoperative complications. A careful hemostasis to limit
the use of RBC remains essential despite available options of substitutions. The use of infusion-pumpadministered noradrenaline seems valuable to sustain a stable circulation during surgeries with microvascular
Gross, A. M., et al. (2023). "Long-term safety and efficacy of selumetinib in children
with neurofibromatosis type 1 on a phase 1/2 trial for inoperable plexiform
neurofibromas." Neuro Oncol 25(10): 1883-1894.
BACKGROUND: Selumetinib shrank inoperable symptomatic plexiform neurofibromas (PN) in children with
neurofibromatosis type 1 (NF1) and provided clinical benefit for many in our previously published phase 1/2
clinical trials (SPRINT, NCT01362803). At the data cutoff (DCO) of the prior publications, 65% of
participants were still receiving treatment. This report presents up to 5 years of additional safety and efficacy
data from these studies. METHODS: This manuscript includes data from the phase 1 and phase 2, stratum 1
study which included participants with clinically significant PN-related morbidity. Participants received
continuous selumetinib dosing (1 cycle = 28 days). Safety and efficacy data through February 27, 2021 are
included. PN response assessed by volumetric magnetic resonance imaging analysis: Confirmed partial
response (cPR) ≥20% decrease from baseline on 2 consecutive evaluations. Phase 2 participants completed
patient-reported outcome measures assessing tumor pain intensity (Numeric Rating Scale-11) and interference
of pain in daily life (pain interference index). RESULTS: For the 74 children (median age 10.3 years; range 318.5) enrolled, overall cPR rate was 70% (52/74); median duration of treatment was 57.5 cycles (range 1-100).
Responses were generally sustained with 59% (44) lasting ≥ 12 cycles. Tumor pain intensity (n = 19, P =
.015) and pain interference (n = 18, P = .0059) showed durable improvement from baseline to 48 cycles. No
new safety signals were identified; however, some developed known selumetinib-related adverse events (AEs)
for the first time after several years of treatment. CONCLUSIONS: With up to 5 years of additional
selumetinib treatment, most children with NF1-related PN had durable tumor shrinkage and sustained
improvement in pain beyond that previously reported at 1 year. No new safety signals were identified;
Gross, A. M., et al. (2020). "Selumetinib in Children with Inoperable Plexiform
Neurofibromas." N Engl J Med 382(15): 1430-1442.
BACKGROUND: No approved therapies exist for inoperable plexiform neurofibromas in patients with
neurofibromatosis type 1. METHODS: We conducted an open-label, phase 2 trial of selumetinib to determine
the objective response rate among patients with plexiform neurofibromas and to assess clinical benefit.
Children with neurofibromatosis type 1 and symptomatic inoperable plexiform neurofibromas received oral
selumetinib twice daily at a dose of 25 mg per square meter of body-surface area on a continuous dosing
schedule (28-day cycles). Volumetric magnetic resonance imaging and clinical outcome assessments (pain,
quality of life, disfigurement, and function) were performed at least every four cycles. Children rated tumor
pain intensity on a scale from 0 (no pain) to 10 (worst pain imaginable). RESULTS: A total of 50 children
(median age, 10.2 years; range, 3.5 to 17.4) were enrolled from August 2015 through August 2016. The most
frequent neurofibroma-related symptoms were disfigurement (44 patients), motor dysfunction (33), and pain
(26). A total of 35 patients (70%) had a confirmed partial response as of March 29, 2019, and 28 of these
patients had a durable response (lasting ≥1 year). After 1 year of treatment, the mean decrease in childreported tumor pain-intensity scores was 2 points, considered a clinically meaningful improvement. In
addition, clinically meaningful improvements were seen in child-reported and parent-reported interference of
pain in daily functioning (38% and 50%, respectively) and overall health-related quality of life (48% and
58%, respectively) as well as in functional outcomes of strength (56% of patients) and range of motion (38%
of patients). Five patients discontinued treatment because of toxic effects possibly related to selumetinib, and
6 patients had disease progression. The most frequent toxic effects were nausea, vomiting, or diarrhea; an
asymptomatic increase in the creatine phosphokinase level; acneiform rash; and paronychia.
CONCLUSIONS: In this phase 2 trial, most children with neurofibromatosis type 1 and inoperable plexiform
neurofibromas had durable tumor shrinkage and clinical benefit from selumetinib. (Funded by the Intramural
Research Program of the National Institutes of Health and others; ClinicalTrials.gov number,
Grzelecki, D., et al. (2021). "Efficacy of intravenous tranexamic acid administration
in revision hip arthroplasty." Orthopade 50(6): 464-470.
BACKGROUND: This study aimed to evaluate the efficiency of constant dose intravenous administration of
tranexamic acid (TXA) in reducing postoperative blood loss, hemoglobin (Hb) concentration, and the number
of transfusions in revision hip arthroplasty (RHA). METHODS: The study included 145 consecutive patients
who had undergone RHA: a TXA group (75 patients) who received two doses of TXA (1.0 g 15 min before
skin incision and 1.0 g during wound closure) and a no-TXA group (70 patients). Percentage blood loss and
quantitative blood loss were calculated. RESULTS: The percentage blood loss (23.82 ± 10.6% vs.
39.17 ± 15.1%; P < 0.001), Hb drop (2.9 ± 1.14 g/dL vs. 4.22 ± 1.4 g/dL; P < 0.001), and total blood loss
(1030 ± 477 mL vs. 1736 ± 761 mL; P < 0.001) were significantly lower in the TXA group than in the no-TXA
group on postoperative day 1. Percentage blood loss (37.5 ± 10.4% vs. 43.1 ± 12.5%; P < 0.01), Hb drop
(4.64 ± 1.5 g/dL vs. 5.22 ± 1.6 g/dL; P < 0.01) and total blood loss (1639 ± 543 mL vs. 1908 ± 681 mL;
P = 0.02) were significantly lower in the TXA group than in the no-TXA group on the 5th postoperative day.
The blood transfusion requirements were lower in the TXA group than those in the no-TXA group (30.7% vs.
71.4% of patients; P < 0.001), with a lower transfusion per patient ratio of 0.55 in the TXA group and 1.4 in
the no-TXA group. No postoperative complications were associated with TXA administration, including
deep-vein thrombosis and pulmonary embolism. CONCLUSION: Administration of TXA is an effective
Gu, X. and Y. Zhang (2021). "Clinical efficacy and safety of mecapegfilgrastim in
small cell lung cancer as primary prophylaxis of neutropenia post chemotherapy: a
retrospective analysis." Ann Palliat Med 10(7): 7841-7846.
BACKGROUND: Neutropenia is the most common adverse reaction seen in small cell lung cancer after
chemotherapy. Febrile neutropenia (FN) leads to an increase in hospitalizations and may even be lifethreatening. This paper aims to investigate the efficacy and adverse reactions of mecapegfilgrastim in the
primary prophylaxis of neutropenia in patients with small cell lung cancer after receiving intermediate risk
chemotherapy with at least one patient risk factor. METHODS: The clinical records of 106 patients with small
cell lung cancer admitted to Zhejiang Cancer Hospital from June 2019 to January 2021 were retrospectively
analyzed. Patients were divided into a mecapegfilgrastim [pegylated recombinant human granulocyte colony
stimulating factor (PEG-rhG-CSF)] group and control group, each with 53 patients. The mecapegfilgrastim
group received subcutaneous injection of mecapegfilgrastim 24 hours after the first cycle of chemotherapy,
while the control group did not receive this. The Chi-square (χ2) test or Fisher exact test were used to compare
the incidence of neutropenia, FN, and the proportion of patients administrated with full dose chemotherapy in
the two groups after the first cycle of chemotherapy. Data on adverse events after mecapegfilgrastim were also
collected. RESULTS: After the first cycle of chemotherapy, the incidence of neutropenia in the
mecapegfilgrastim group was significantly lower than that in the control group (P=0.001) and the incidence of
FN in the mecapegfilgrastim group was lower than that in the control group (P=0.118). The proportion of
patients administrated with full-dose chemotherapy in the mecapegfilgrastim group was significantly higher
than that in the control group (P=0.001). The main adverse reactions to mecapegfilgrastim were muscle pain,
fever, and fatigue. CONCLUSIONS: After receiving intermediate risk chemotherapy, the incidence of
neutropenia was significantly reduced by the primary prophylaxis of mecapegfilgrastim in patients with small
cell lung cancer. The adverse events of mecapegfilgrastim were mild and tolerable, and included muscle pain,
Guan, M., et al. (2012). "Folfox4 regimen administered through combined hepatic
arterial and systemic infusion for treatment of colorectal cancer with unresectable liver
metastases." Chin Med J (Engl) 125(20): 3640-3645.
Guan, X., et al. (2021). "Comparison of Safety between Different Kinds of Heparins
in Patients Receiving Intra-Aortic Balloon Counterpulsation." Thorac Cardiovasc Surg
69(6): 511-517.
BACKGROUND: Hepatic arterial infusion chemotherapy for liver metastases is under evaluation because of
the high target dose and low general toxicity. To investigate the efficacy and safety of a Folfox4 regimen
administered through a combined hepatic arterial and systemic infusion for the first-line treatment of
colorectal cancer (CRC) with unresectable liver metastases. METHODS: Twenty-seven CRC patients with
unresectable hepatic metastases and no prior chemotherapy were enrolled into the study. They received a
Folfox4 regimen; 1st day: HAI of oxaliplatin 85 mg/m(2) and L-folinic acid 200 mg/m(2), followed by a bolus
hepatic arterial injection of 5-fluorouracil 400 mg/m(2), then continuous HAI of 5-FU 600 mg/m(2); 2nd day:
infusion of L-folinic acid 200 mg/m(2) i.v. followed by an intravenous bolus injection of 5-Fluorouracil 400
mg/m(2), then continuous infusion of 5-fluorouracil 600 mg/m(2) i.v. The patients received HAI during the
odd cycles, and the intravenous administration of the same Folfox4 regimen during the even cycles.
RESULTS: A total of 236 treatment cycles were given with a median of 10 cycles. The therapy generated the
following results after six treatment cycles: complete response (CR) 1/27 (3.7%), partial response (PR) 17/27
(63.0%), stable disease (SD) 6/27 (22.2%), and progress disease (PD) 3/27 (11.1%). Five patients had
hepatectomy. The serum levels of both carcinoembryonic antigen (CEA) and CA19-9 were significantly
reduced (P < 0.05). A median time to progression of 11 months and a median overall survival of 24 months
were documented. The major adverse events included grade 1/2 nausea/vomiting, upper abdominal pain,
peripheral neuropathy, and neutropenia/thrombocytopenia. CONCLUSIONS: The Folfox4 regimen
administered through combined hepatic arterial and systemic infusions is efficacious and safe for the
BACKGROUND: The present study aimed to compare the effectiveness and safety of low molecularweight-heparin (LMWH) and unfractionated heparin (UFH) in acute myocardial infarction (AMI) patients
receiving intra-aortic balloon counterpulsation (IABP). MATERIALS AND METHODS: We
retrospectively analyzed a total of 344 patients receiving IABP for cardiogenic shock, severe heart failure,
ventricular septal rupture, or mitral valve prolapse due to AMI. A total of 161 patients received UFH (a bolus
injection 70 U/kg immediately after IABP, followed by infusion at a rate of 15 U/kg/hour and titration to for
50 to 70 seconds of activated partial thromboplastin time. A total of 183 patients received LMWH
(subcutaneous injection of 1.0 mg/kg every 12 hours for 5 to 7 days and 1.0 mg/kg every 24 hours thereafter).
Events of ischemia, arterial thrombosis or embolism, and bleeding during IABP were evaluated. Major
bleeding was defined as a hemoglobin decrease by >50 g/L (vs. prior to IABP) or bleeding that caused
hemodynamic shock or life-threatening or requiring blood transfusion. RESULTS: Subjects receiving UFH
and LMWH did not differ in baseline characteristics. Ischemia was noted in five (3.1%) and two (1.1%)
subjects in UFH and LMWH groups, respectively. Arterial thromboembolism occurred in three (1.9%)
subjects in the UFH group, but not in the LMWH group. Logistic regression analysis failed to reveal an
association between ischemia or bleeding with heparin type. Major bleeding occurred in 16 (9.9%) and six
(3.3%) patients in the UFH and LWMH groups, respectively (p = 0.014). Regression analysis indicated that
LMWH is associated with less major bleeding. CONCLUSION: LMWH could reduce the risk of major
bleeding in patients receiving IABP. Whether LMWH could reduce arterial thromboembolism needs further
Guimier, E., et al. (2022). "Pharmacological Approaches for the Prevention of Breast
Implant Capsular Contracture." J Surg Res 280: 129-150.
Guiu, B., et al. (2018). "Intra-arterial idarubicin_lipiodol without embolisation in
hepatocellular carcinoma: The LIDA-B phase I trial." J Hepatol 68(6): 1163-1171.
Capsular contracture is a common complication associated with breast implants following reconstructive or
aesthetic surgery in which a tight or constricting scar tissue capsule forms around the implant, often distorting
the breast shape and resulting in chronic pain. Capsulectomy (involving full removal of the capsule
surrounding the implant) and capsulotomy (where the capsule is released and/or partly removed to create more
space for the implant) are the most common surgical procedures used to treat capsular contracture. Various
structural modifications of the implant device (including use of textured implants, submuscular placement of
the implant, and the use of polyurethane-coated implants) and surgical strategies (including pre-operative skin
washing and irrigation of the implant pocket with antibiotics) have been and/or are currently used to help
reduce the incidence of capsular contracture. In this article, we review the pharmacological approaches-both
commonly practiced in the clinic and experimental-reported in the scientific and clinical literature aimed at
either preventing or treating capsular contracture, including (i) pre- and post-operative intravenous
administration of drug substances, (ii) systemic (usually oral) administration of drugs before and after surgery,
(iii) modification of the implant surface with grafted drug substances, (iv) irrigation of the implant or periimplant tissue with drugs prior to implantation, and (v) incorporation of drugs into the implant shell or filler
prior to surgery followed by drug release in situ after implantation.
BACKGROUND & AIMS: Idarubicin shows high cytotoxicity against hepatocellular carcinoma (HCC) cells,
a high hepatic extraction ratio, and high lipophilicity leading to stable emulsions with lipiodol. A doseescalation phase I trial of idarubicin_lipiodol (without embolisation) was conducted in patients with cirrhotic
HCC to estimate the maximum-tolerated dose (MTD) and to assess the safety, efficacy, and pharmacokinetics
of the drug, and the health-related quality of life achieved by patients. METHODS: Patients underwent two
sessions of treatment with a transarterial idarubicin_lipiodol emulsion without embolisation. The idarubicin
dose was escalated according to a modified continuous reassessment method. The MTD was defined as the
dose closest to that causing dose-limiting toxicity (DLT) in 20% of patients. RESULTS: A group of 15
patients were enrolled, including one patient at 10 mg, four patients at 15 mg, seven patients at 20 mg, and
three patients at 25 mg. Only two patients experienced DLT: oedematous ascitic decompensation and
abdominal pain at 20 and 25 mg, respectively. The calculated MTD of idarubicin was 20 mg. The most
frequent grade ≥3 adverse events were biological. One month after the second session, the objective response
rate was 29% (complete response, 0%; partial response, 29%) based on modified Response Evaluation
Criteria In Solid Tumours. The median time to progression was 5.4 months [95% confidence limit (CI) 3.014.6 months] and median overall survival was 20.6 months (95% CI 5.7-28.7 months). Pharmacokinetic
analysis of idarubicin showed that the mean C(max) of idarubicin after intra-arterial injection of the
idarubicin-lipiodol emulsion is approximately half the C(max) after intravenous administration. Health-related
quality of life results confirmed the good safety results associated with use of the drug. CONCLUSIONS: The
MTD of idarubicin was 20 mg after two chemolipiodolisation sessions. Encouraging safety results, and patient
responses and survival were observed. A phase II trial has been scheduled. LAY SUMMARY: There is a need
for transarterial regimens that improve the responses and survival of patients with unresectable HCC. In this
phase I trial, we showed that two sessions of treatment with a transarterial idarubicin_lipiodol emulsion
Gunduz, M. E., et al. (2021). "Effects of Combined and Alone Transcranial Motor
Cortex Stimulation and Mirror Therapy in Phantom Limb Pain: A Randomized
Factorial Trial." Neurorehabil Neural Repair 35(8): 704-716.
Phantom limb pain (PLP) is a frequent complication in amputees, which is often refractory to treatments. We
aim to assess in a factorial trial the effects of transcranial direct current stimulation (tDCS) and mirror therapy
(MT) in patients with traumatic lower limb amputation; and whether the motor cortex plasticity changes drive
these results. In this large randomized, blinded, 2-site, sham-controlled, 2 × 2 factorial trial, 112 participants
with traumatic lower limb amputation were randomized into treatment groups. The interventions were active
or covered MT for 4 weeks (20 sessions, 15 minutes each) combined with 2 weeks of either active or sham
tDCS (10 sessions, 20 minutes each) applied to the contralateral primary motor cortex. The primary outcome
was PLP changes on the visual analogue scale at the end of interventions (4 weeks). Motor cortex excitability
and cortical mapping were assessed by transcranial magnetic stimulation (TMS). We found no interaction
between tDCS and MT groups (F = 1.90, P = .13). In the adjusted models, there was a main effect of active
tDCS compared to sham tDCS (beta coefficient = -0.99, P = .04) on phantom pain. The overall effect size was
1.19 (95% confidence interval: 0.90, 1.47). No changes in depression and anxiety were found. TDCS
intervention was associated with increased intracortical inhibition (coefficient = 0.96, P = .02) and facilitation
(coefficient = 2.03, P = .03) as well as a posterolateral shift of the center of gravity in the affected hemisphere.
MT induced no motor cortex plasticity changes assessed by TMS. These findings indicate that transcranial
Guo, J., et al. (2024). "Low-dose ketamine versus morphine in the treatment of acute
pain in the emergency department: A meta-analysis of 15 randomized controlled
trials." Am J Emerg Med 76: 140-149.
OBJECTIVE: To compare the effectiveness and safety of ketamine and morphine in adult patients with acute
pain in emergency department (ED) by using a meta-analysis method. METHODS: This study was based on
the Cochrane methodology for conducting a meta-analysis. Only randomized controlled trials (RCTs) were
eligible for this study, with an experimental group that received low-dose ketamine and a control group that
received morphine. The participants were adults who had acute pain in the ED. The primary outcome
measures were the numeric rating scale (NRS) and visual analog scale (VAS). The secondary outcome
measures were the complete resolution of pain, NRS reduction ≥3 points, NRS reduction ≥50% or 60%,
change of NRS score, change of VAS score, rescue analgesia, satisfaction and adverse events. Subgroup
analysis was performed for studies with intravenous and intranasal administration of ketamine. The Review
Manager Database was used to analyze the included studies. RESULTS: 15 RCTs involving 1768 patients
were included. The ketamine group had lower NRS scores than morphine group at 30 min (MD, -0.77 [95%
CI, -0.93 to -0.61]; p < 0.00001), while the morphine had better analgesic effects at 120 min after treatment
(MD, 0.33 [95% CI, 0.15 to 051]; p = 0.0003). The subjects of complete resolution of pain in the ketamine
group performed better than those in the morphine group at 15 min (RR 3.18, 95% CI 1.75 to 5.78;
p = 0.0001). Compared with the morphine group, the ketamine group had a lower incidence of adverse events
requiring intervention (RR, 0.34 [95% CI, 0.18 to 0.66]; p = 0.001). Subgroup analysis of intravenous
ketamine showed that ketamine had lower VAS score than the morphine group at 30 min. However, also on
the 30-min VAS score, intranasal ketamine analgesia was less effective than morphine. CONCLUSIONS:
Ketamine had better analgesic effects in the early stages after treatment, while morphine maintained more
durable effects. Compared with morphine, ketamine had a lower incidence of adverse events requiring
intervention. The results of subgroup analysis showed that intravenous administration of ketamine was more
Guo, R., et al. (2023). "The Preemptive Analgesic Effect of Capsaicin Involves
Attenuations of Epidermal Keratinocytes Proliferation and Expression of ProInflammatory Mediators After Plantar Incision in Rats." J Pain Res 16: 141-149.
PURPOSE: Subcutaneous infiltration of capsaicin, which initially activates transient receptor potential
vanilloid 1 (TRPV1) receptors, can subsequently desensitize TRPV1-expressing nociceptors and induce
analgesia in different pain models. Yet, whether the modulation of keratinocytes may also contribute to the
analgesic action of capsaicin treatment remains unclear. In a rat model of postoperative pain, we tested the
hypothesis that subcutaneous injection of capsaicin inhibited the proliferation of epidermal keratinocytes and
their expression of pronociceptive inflammatory mediators after plantar incision. METHODS: The plantar
incision model was carried out in the current study. Behavioral tests were used to evaluate postoperative painrelated behaviors in rats. Immunohistochemistry was used to investigate epidermal keratinocytes proliferation
and expression of pro-inflammatory mediators in keratinocytes in rats. RESULTS: Behaviorally, plantar
incision induced robust postoperative pain hypersensitivity. However, subcutaneous pretreatment of capsaicin
(1%) but not the vehicle, prevented the development of postoperative pain. There was an increased
proliferation of keratinocytes and the expressions of interleukin-1β (IL-1β) and tumour necrosis factor-alpha
(TNF-α) in keratinocytes at 3 d and 7 d after plantar incision. However, these changes were also significantly
attenuated by capsaicin pretreatment. CONCLUSION: Our findings suggest that capsaicin pretreatment may
inhibit incision-induced keratinocytes proliferation and reduce their expression of pronociceptive
inflammatory mediators under postoperative pain conditions, which represents a peripheral non-neuronal
Guo, X. and W. Wang (2017). "Challenges and recent advances in the subcutaneous
delivery of insulin." Expert Opin Drug Deliv 14(6): 727-734.
Guth, J. J., et al. (2022). "Stress Radiography Is a Reliable Method to Quantify
Posterior Cruciate Ligament Insufficiency: A Systematic Review." Arthroscopy,
Sports Medicine, and Rehabilitation 4(5): e1851-e1860.
The morbidity of diabetes mellitus is increasing, and subcutaneous injection of exogenous insulin is well
established as an effective therapeutic strategy for reducing complications associated with the disease.
However, the pain that accompanies repeated injections is an important drawback, and can detrimentally
affect the adherence to therapy. Recently, there have been great improvements in injection devices and
techniques, including the development of microneedle systems and quantitative injection technologies, which
have increased the accuracy of injection, decreased leakage of insulin to the skin surface, and reduced pain.
Areas covered: This review highlights some limitations of current techniques for the injection of insulin and
its analogs, and describes new methodologies and strategies that have been developed in an attempt to
overcome these limitations. Furthermore, novel technologies currently under development that are potential
future prospects for insulin delivery are discussed. Expert opinion: New technologies have provided easier
and well-tolerated treatment regimens for diabetes patients. However, to further improve patients' satisfaction,
self-regulated insulin delivery, automatic adjustment of needle length, memory function to the injection
device, use of novel materials could be introduced into insulin injection. Intelligent control of insulin delivery
and soluble microneedle arrays may be important areas of future research.
Purpose To perform a systematic review of posterior tibial stress radiography techniques and radiographic
measurement methods to compare their accuracy and efficacy to aid clinicians in quantifying posterior
cruciate ligament laxity. Methods Electronic databases, including PubMed, MEDLINE, Embase.com 1947- ,
Ovid Medline 1946- , Scopus 1823- , Cochrane Central Register of Controlled Trials (CENTRAL), and
Clinicaltrials.gov 1997- were queried in December 2020. The abstracts of articles were reviewed by 2 authors
for published studies comparing posterior tibial stress radiography techniques, describing, and comparing
radiographic measurement methods, and comparing stress radiographs with instrumented knee testing. Results
The systematic review included 13 studies that satisfied the inclusion and exclusion criteria. There were 3
studies comparing stress radiography with instrumented knee devices, 6 studies comparing stress radiography
techniques, and 5 studies evaluating the reliability of radiographic measurements. Stress radiography was
more sensitive for detecting posterior tibial translation than KT-1000 and KT-2000 and was similar to the
Rolimeter knee arthrometer. The majority of studies found TELOS stress radiography to be more sensitive
than gravity or hamstring contraction stress views. Kneeling stress radiographs were found to be equivalent to
TELOS in one study and superior in another. All reported methods of radiographic measurement for posterior
tibial translation showed good-to-excellent intraobserver and interobserver reliability, and no single technique
demonstrated clear superiority. Conclusions The results of this systematic review indicate that posterior stress
radiography with TELOS and kneeling stress radiography are the most reliable methods to evaluate posterior
cruciate ligament laxity. Gravity stress and hamstring contraction can be used but may underestimate posterior
tibial translation. Radiographic measurement methods are reliable and no single method is clearly superior.
Clinical Relevance This information will allow clinicians to use various radiographic methods to objectively
Gutiérrez Zúñiga, D., et al. (2021). "Reemplazo de hombro ambulatorio: Presentación
de protocolo perioperatorio y resultados iniciales." Revista Colombiana de Ortopedia
y Traumatología 35(3): 244-252.
Resumen Introducción El reemplazo de hombro es efectivo para mejorar el dolor y la funcionalidad en
patologías crónicas del hombro. Considerando los riesgos y costos asociados a la estancia hospitalaria, realizar
este procedimiento de forma ambulatoria surge como una opción para optimizar esta estrategia terapéutica.
Materiales & Métodos Estudio observacional descriptivo prospective de pacientes operados por un mismo
cirujano con artroplastia de hombro ambulatoria (RHA) utilizando analgesia regional con bomba de infusión
elastomérica. Se registraron las escalas de ASES y SANE, el dolor, la satisfacción del paciente, las
complicaciones y reingresos a 90 días. Resultados Se intervinieron 10 pacientes de un promedio de edad de
59.6 (±3.9) años, siendo el 40% prótesis anatómicas, 50% reversas y 10% hemiartroplastia. Al cuarto día
postoperatorio el dolor por EVA fue 1,3 (±0,62) y al décimo día 2,7 (±1,1). La puntuación SANE antes del
procedimiento fue de 31 (±9,7), y 90 días después fue de 76,1 (±6,8). Todos los pacientes refirieron una alta
satisfacción. Un paciente al 3er día presentó un episodio de broncoespasmo leve, tratado de forma
ambulatoria. Un paciente presentó una infección superficial que mejoró completamente con el antibiótico oral.
No se presentaron reingresos o consultas a urgencias a 90 días. Discusión Se presentan los desenlaces a corto
plazo de la primera serie de casos en nuestro medio de RH ambulatorio. Este procedimiento puede ser
realizado de forma segura, siguiendo un protocolo estandarizado y realizando una juiciosa selección de los
pacientes. Background Shoulder arthoplasty is an effective procedure to improve pain and function in chronic
shoulder pathologies. Considering the risks and costs associated with hospital stay, performing joint
replacements on an outpatient setting emerges as an option to optimize this therapeutic strategy. Methods A
prospective analysis was performed in 10 patients undergoing same-day discharge total shoulder arthroplasty
with anatomic and reverse prostheses. Pain was managed with a continuous peripheral interscalene block
using an elastomeric infusion pump. ASES and SANE scores, pain, patient satisfaction, complications, and
readmissions after 90 days were recorded. Results 10 patients (average age 59.6 (±3.9) years) underwent
outpatient shoulder arthroplasty (50% reverse shoulder arthroplasty, 40% total shoulder arthroplasty and 10%
hemiarthroplasty). On post-operative day 4, mean visual analogue scale (VAS) for pain assessment was 1.3
(±0.62) and day 10, 2.7 (±1.1). Pre-operative SANE score was 31 (±9.7), and 90 days after the procedure was
76.1 (±6.8). All patients were satisfied with the procedure. One patient had a mild bronchospasm on day 3 that
resolved with bronchodilators on an outpatient basis. One patient had a superficial surgical site infection that
resolved completely with oral antibiotics administration. There were no re-admissions or major complications.
Haber, P., et al. (2019). "Post-licensure surveillance of trivalent adjuvanted influenza
vaccine (aIIV3; Fluad), Vaccine Adverse Event Reporting System (VAERS), United
States, July 2016-June 2018." Vaccine 37(11): 1516-1520.
BACKGROUND: Trivalent adjuvanted influenza vaccine (aIIV3; Fluad®) was approved in the United States
(U.S.) in 2015 for adults aged ≥65 years and has been in use since the 2016-17 influenza season. METHODS:
We analyzed U.S. reports for aIIV3 submitted from July 1, 2016 through June 30, 2018 to the Vaccine
Adverse Event Reporting System (VAERS), a national spontaneous reporting system. Medical records were
reviewed for serious reports. Among individuals ≥65 years of age, the relative frequency of the most
commonly reported adverse events (AEs) after aIIV3 were compared with non-adjuvanted inactivated
influenza vaccines given to adults aged ≥65 years, high-dose trivalent influenza vaccine (IIV3-HD) and
trivalent or quadrivalent vaccines (IIV3/IIV4). Data mining analyses were undertaken to identify whether AEs
for aIIV3 occurred disproportionately more than expected compared to all influenza vaccines. RESULTS:
VAERS received 630 reports after aIIV3, of which 521 (83%) were in adults aged ≥65 years; 79 (13%) in
persons <65 years and in 30 (5%) reports age was missing; 19 (3%) reports were serious, including two deaths
(0.4%) related to myocardial infarction and Sjogren's syndrome. The most common AEs reported in adults
aged ≥65 years were injection site pain (21%) and erythema (18%), with similar proportions reported for
IIV3-HD (17% and 19%, respectively) and for IIV3/IIV4 (15%, each). Except for reports related to
vaccination of inappropriate age (n = 79) and syringe malfunction (n = 6), data mining did not identify other
disproportionately reported AEs. CONCLUSIONS: Although our review of aIIV3 in VAERS did not identify
any unexpected health conditions of concern, we observed more than twice the expected number of reports
with administration of the vaccine to persons outside of the age range for which the vaccine is approved in the
Hahn, M., et al. (2015). "Radiofrequency Volumetric Thermal Ablation of Fibroids
and Laparoscopic Myomectomy: Long-Term Follow-up From a Randomized Trial."
Geburtshilfe Frauenheilkd 75(5): 442-449.
Aims: Laparoscopic myomectomy (LM) has been the gold standard treatment for uterine fibroids in women
desiring uterine conservation. To evaluate a new fibroid treatment modality - radiofrequency volumetric
thermal ablation (RFVTA) - we compare 12-month results in women who had symptomatic uterine fibroids
and who were randomized to laparoscopic ultrasound-guided RFVTA or LM. Materials and Methods: Our
study is a 1 : 1 parallel, randomized, prospective, single-center, longitudinal, comparative analysis of RFVTA
to LM for fibroid treatment in women ≥ 18 years of age who desired uterine conservation. Fifty women were
randomized intraoperatively to RFVTA (n = 25) or to LM (n = 25) after laparoscopic ultrasound mapping of
the uterus. Results: Post surgery, ablation and myomectomy subjects took pain medications for 4 days (range:
1-46) and 7 days (range: 1-83 days) respectively (p = 0.60). Ablation and myomectomy subjects missed 10.0
workdays (range: 2-86 days) and 17.0 workdays (range: 7-30 days) (p = 0.28), resumed normal activities in
20.5 days (range: 5-103 days) versus 28.0 days (range: 10-42 days) (p = 0.86) respectively. Mean symptom
severity scores decreased (improved) by - 7.8 for the ablation subjects and by - 17.9 for the myomectomy
subjects (p = 0.16). Health-related quality of life improved (increased) by 7.5 and 13.1, respectively, for the
two groups (p = 0.46). Two myomectomy subjects had pregnancies that ended in a Cesarean delivery and a
vaginal delivery of healthy infants. Two pregnancies in the RFVTA group ended in full-term vaginal
deliveries of healthy infants. Conclusions: Early postoperative recovery and twelve-month results attest to
Hajimaghsoudi, M., et al. (2016). "Comparison of local anesthetic effect of lidocaine
by jet injection vs needle infiltration in lumbar puncture." Am J Emerg Med 34(7):
1225-1229.
Hammer, G. B., et al. (2020). "Randomized Population Pharmacokinetic Analysis and
Safety of Intravenous Acetaminophen for Acute Postoperative Pain in Neonates and
Infants." J Clin Pharmacol 60(1): 16-27.
BACKGROUND: Usual routes of drug administration are often painful and invasive. Nowadays, using jet
injection has been introduced successfully, as a noninvasive and painless method of anesthetic delivery in
performing different procedures. OBJECTIVE: The objective of the study is to compare the local anesthetic
effect of lidocaine by jet injection vs needle infiltration in performing lumbar puncture in the emergency
department (ED). METHODS: A randomized single-blind controlled study was performed in 65 patients
needing lumbar puncture recruited from the ED from July to November 2014. We enrolled 44 patients and
excluded 21 patients by the exclusion criteria. Local lidocaine was delivered in 1 group by jet injector (group
B), whereas in the other group conventional method, needle infiltration was used (group A). In both groups,
intravenous midazolam 1 mg was administered as an anxiolytic drug before the procedure. Patients' pain score
(visual analog scale [VAS]) from 0 to 10 was recorded both during drug delivery and performing the
procedure itself. The observer who collected patients' data and fulfill the questionnaire was blinded to the
study. RESULTS: During lidocaine injection, the mean ± SD VAS score was 5.27 ± 1.77 in group A and 2.95
± 1.81 in group B (mean difference, 2.31; 95% confidence interval, 1.22-3.41) (P= .000). During performing
the procedure, the mean ± SD VAS score in groups A and B was 3.77 ± 1.77 vs 2.18 ± 1.50 (mean difference,
1.59; 95% confidence interval, 0.59-2.58) (P= .003). CONCLUSIONS: Injecting lidocaine by jet injector is
Intravenous administration of acetaminophen is an alternative to the oral and rectal routes, which may be
contraindicated in particular clinical settings. This randomized, placebo-controlled study of intravenous
acetaminophen (Ofirmev, Mallinckrodt Pharmaceuticals, Bedminster, New Jersey) in neonate and infant
patients with acute postoperative pain assessed pharmacokinetics (PK) and safety, in addition to efficacy and
pharmacodynamics of repeated doses administered over 24 hours. Neonate and infant patients (<2 years of
age) who were undergoing surgery or had experienced a traumatic injury and were expected to need pain
management for at least 24 hours were enrolled. Subjects were randomly assigned to receive intravenous
acetaminophen low dose, intravenous acetaminophen high dose, or placebo. A population PK model of
intravenous acetaminophen was updated by combining 581 samples from the current study of 158 neonate and
infant subjects with results from a previously developed model. The individual predicted-versus-observed
concentrations plots showed that the structural PK model fit the blood and plasma acetaminophen
concentration-versus-time profiles in the active and placebo groups. Terminal elimination half-life was
prolonged in neonates and younger infants and in intermediate and older infants similar to values in adults.
When compared with placebo, total rescue opioid consumption was similar and significantly fewer
intravenous acetaminophen patients prematurely discontinued because of treatment-emergent adverse events
(P < .01). For intravenous acetaminophen, neonates receiving 12.5 mg/kg every 6 hours had PK profiles
similar to younger, intermediate, and older infants, adolescents, and adults weighing <50 kg receiving
Hanouz, J. L., et al. (2012). "[French national survey on remifentanil utilisation for
obstetrical peridural analgesia]." Ann Fr Anesth Reanim 31(9): 682-686.
Hao, G. T., et al. (2014). "Pharmacokinetics of oxycodone hydrochloride and three of
its metabolites after intravenous administration in Chinese patients with pain."
Pharmacol Rep 66(1): 153-158.
Harbeck, N., et al. (2018). "Safety Profile of Biosimilar Filgrastim (Zarzio/Zarxio): A
Combined Analysis of Phase III Studies." Oncologist 23(4): 403-409.
OBJECTIVES: The last French survey on alternatives to neuraxial anaesthesia for labour pain was published
in 1997. However, intravenous remifentanil has become increasingly used as an option for labour analgesia.
We evaluated the use of remifentanil as an alternative to epidural analgesia in level 2 and 3 French maternities
in 2009. STUDY DESIGN: This was an internet-based French survey performed in 2009 including all level 2
and 3 maternities. Data recorded were maternity unit characteristic, alternatives to neuraxial analgesia used,
and remifentanil administration protocols. RESULTS: Two hundred and forty maternity units received the
survey and 103 responses were completed. A written institutional alternative analgesia protocol for labour
pain was present in 78%. Alternative labour analgesia included intermittent nitrous oxide inhalation (58%),
intravenous nalbuphine (52%), patient-controlled intravenous administration of remifentanil (52%) and
sufentanil (46%). Pethidine administration was reported by one maternity unit (1%). The bolus dose of
remifentanil scheduled, and background infusion varied widely between maternity units. The analgesic
efficacy of remifentanil used for labour pain was evaluated as moderate (55%) or good (43%). Two serious
adverse events were reported. CONCLUSION: Intravenous administration of remifentanil was largely
reported as an alternative to neuraxial anaesthesia for labour pain. Although remifentanil administration was
most often based on a local written protocol, bolus dose and background infusion varied widely between
OBJECTIVES: The aim of this study is to evaluate the pharmacokinetic profile of oxycodone and three of its
metabolites, noroxycodone, oxymorphone and noroxymorphone after intravenous administration in Chinese
patients with pain. METHODS: Forty-two subjects were assigned to receive intravenous administration of
oxycodone hydrochloride of 2.5, 5 or 10 mg. Plasma and urine samples were collected for up to 24 h after
intravenous administration of oxycodone hydrochloride. RESULTS: Pharmacokinetic parameters showed that
mean values of C(max), AUC(0-t) and AUC(0-∞) of oxycodone were dose dependent, whereas Tmax and
t(1/2) were not. The mean AUC(0-t) ratio of noroxycodone to oxycodone ranged from 0.35 to 0.42 over three
doses, and those of noroxymorphone, or oxymorphone, to oxycodone were ranging of 0.06-0.08 and 0.0070.008, respectively. Oxycodone and its three metabolites were excreted from urine. Approximately 10% of
unchanged oxycodone was recovered in 24 h. Most adverse events (AEs) reported were mild to moderate. The
frequently occurred AEs were dizziness, nausea, vomiting, drowsiness and fatigue. No dose-related AEs were
found. CONCLUSION: Our pharmacokinetics of oxycodone injection in Chinese patients with pain strongly
support continued development of oxycodone as an effective analgesic drug in China.
BACKGROUND: Evaluation of adverse events (AEs) in pivotal registration trials and ongoing postmarketing
surveillance is important for all biologics, including biosimilars. A combined analysis of two pivotal
registration studies was performed to strengthen evidence on safety for biosimilar filgrastim EP2006 in
patients with breast cancer receiving myelosuppressive chemotherapy, a sensitive clinical setting to confirm
biosimilarity of filgrastim. MATERIALS AND METHODS: Data were combined from two phase III studies
of biosimilar filgrastim EP2006. The U.S. registration study was a randomized, double-blind comparison of
biosimilar and reference filgrastim in women aged ≥18 years with breast cancer, receiving (neo)adjuvant
treatment with TAC (docetaxel + doxorubicin + cyclophosphamide). The European Union registration study
was a single-arm, open-label study of biosimilar filgrastim in women aged ≥18 years with breast cancer
receiving doxorubicin + docetaxel. Patients received filgrastim as a subcutaneous injection on day 2 of each
cycle for <14 days or until the absolute neutrophil count reached 10 × 10(9)/L after the expected nadir.
Results were combined for cycles 1-4. RESULTS: A total of 277 patients received biosimilar filgrastim
EP2006. Patients had a mean (± standard deviation) age of 51.1 (± 10.8) years, and 78.7% of patients had
stage II or III breast cancer. A total of 46 (20.6%) patients receiving biosimilar filgrastim had AEs considered
filgrastim-related. The most frequently reported filgrastim-related AEs were musculoskeletal or connective
tissue disorders (15.2%), including bone pain (7.2%). One death (due to pulmonary embolism) occurred of a
patient receiving biosimilar filgrastim (not considered filgrastim-related). No patient developed antidrug
antibodies during the study. CONCLUSION: Biosimilar filgrastim has a safety profile consistent with
previous filgrastim studies and is effective in preventing febrile neutropenia in patients with breast cancer.
IMPLICATIONS FOR PRACTICE: The biosimilar filgrastim EP2006 (Zarzio, Zarxio, biosimilar filgrastimsndz) has been approved in Europe since 2009 and in the U.S. since 2015. This combined analysis of two
phase III studies provides additional clinical evidence that the biosimilar filgrastim EP2006 has a safety
profile consistent with previous studies of reference filgrastim and supports large postmarketing studies of
EP2006 in Europe. Strengthening the evidence for biosimilar filgrastim can help improve acceptance of
Harrington, S. E., J. Hoffman and D. Katsavelis (2020). "Measurement of Pectoralis
Minor Muscle Length in Women Diagnosed With Breast Cancer: Reliability, Validity,
and Clinical Application." Phys Ther 100(3): 429-437.
BACKGROUND: Decreased pectoralis minor muscle length is common after primary breast cancer treatment
and can result in an abnormal position of the scapula. This position can contribute to shoulder pain and
pathomechanics and can lead to problems such as impingement syndrome, rotator cuff tears, and frozen
shoulder. Currently, there are limited reliable methods for measuring pectoralis minor length. OBJECTIVE:
The objective of this study was to examine the reliability and validity of measuring pectoralis minor length in
women diagnosed with breast cancer. DESIGN: This was a cross-sectional reliability and validity study.
METHODS: Bilateral pectoralis minor length (in centimeters) was assessed using a palpation meter in women
(N = 29) diagnosed with breast cancer by 2 licensed physical therapists who were masked to the measures.
Bilateral pectoralis minor length was also measured using a motion capture system to assess validity.
RESULTS: Intratester reliability (intraclass correlation coefficient, ICC [3,k] = 0.971; 95% confidence
interval [CI] = 0.939-0.986; standard error of measurement [SEM] = 0.16 cm) and intertester reliability
(ICC[3,k] = 0.915; 95% CI = 0.81-0.962; SEM = 0.31 cm) were excellent for the palpation meter on the
affected side and the unaffected side (intratester reliability: ICC[3,k] = 0.951; 95% CI = 0.897-0.977;
SEM = 0.19 cm; intertester reliability: ICC[3,k] = 0.945; 95% CI = 0.877-0.975; SEM = 0.22 cm). Significant
correlations were found between the motion capture system and the palpation meter on the affected side
(r = 0.87) and the unaffected side (r = 0.81). Bland-Altman plots between the palpation meter and the motion
capture system demonstrated that all the measures fell within the limits of agreement. LIMITATIONS: This
study encountered possible errors with the accuracy of the motion capture system tracking because of the
proximity of the markers and inherent volumetric restrictions. CONCLUSIONS: The palpation meter is a
reliable, valid, easily administered, and cost-effective tool for assessing pectoralis minor length in women
Hassman, H., et al. (2023). "Open-label, rapid initiation pilot study for extendedrelease buprenorphine subcutaneous injection." Am J Drug Alcohol Abuse 49(1): 4352.
Background: For patients with opioid use disorder, buprenorphine extended-release injection (BUP-XR)
achieves sustained therapeutic plasma concentrations, controls craving and withdrawal symptoms, and
improves patient outcomes. Given retention challenges during transmucosal buprenorphine (BUP-TM)
induction, assessing methods to quickly achieve sustained buprenorphine concentrations is
important.Objectives: This open-label, single-group, single-center pilot study (NCT03993392) evaluated
safety and tolerability of initiating BUP-XR following a single BUP-TM 4 mg dose.Methods: Eligible
participants abstained from short and long-acting opioids for 6 and 24 hours, respectively. If the Clinical
Opiate Withdrawal Scale (COWS) was ≥8, BUP-TM 4 mg was administered. Participants not exhibiting
hypersensitivity, precipitated opioid withdrawal (POW), or sedation symptoms within 1 hour received BUPXR 300 mg (assessed as inpatients for 48 hours and outpatients to Day 29). Endpoints were COWS score
increase ≥6, independent adjudication of POW, and opioid use.Results: Twenty-six participants (14 male)
received BUP-TM, 24 received BUP-XR, and 20 completed the study. After injection, COWS scores
decreased from pre-BUP-TM baseline of 14.6 ± 4.1 to 6.9 ± 4.1 at 6 hours and 4.2 ± 3.2 at 24 hours. Most
participants (62.5%) experienced maximum COWS scores pre-BUP-XR; 2 experienced a COWS score
increase ≥6, occurring at 1 and 2 hours post-BUP-XR. By adjudication, 2/24 participants experienced POW.
Irritability, anxiety, nausea, and pain were the most frequent adverse events (AEs) with no serious
AEs.Conclusions: Results support increased flexibility for initiating BUP-XR. Initiating BUP-XR 300 mg
following a single BUP-TM 4 mg dose was well tolerated. Although some participants initially experienced
withdrawal symptoms after injection, significant symptomatic improvement was observed in all participants
He, W. Z., et al. (2014). "[Etanercept combined with Tripterygium wilfordii
polyglycoside for treatment of rheumatoid arthritis in the elderly: a clinical study]."
Zhongguo Zhong Xi Yi Jie He Za Zhi 34(3): 267-271.
OBJECTIVE: To evaluate the efficacy and safety of etanercept plus Tripterygium wilfordii polyglycoside
(TWP) in elderly patients with active rheumatoid arthritis (RA). METHODS: Totally 46 elderly patients with
active RA were randomly assigned to the treatment group (22 cases) and the control group (24 cases). All
patients received subcutaneous injection of etanercept, 25 mg each time, twice per week. The dosage was
reduced to once per week 3 months later. Patients in the treatment group took TWP Tablet (10 mg each time,
three times per day), while those in the control group took methotrexate (MTX), 10 mg each time, once per
week. The whole course lasted for 24 weeks. Patients' rest pain, tender joint number, swollen joint number,
health assessment questionnaire (HAQ), patients' global assessment, physicians' global assessment,
erythrocyte sediment rate (ESR), C reactive protein (CRP), rheumatic factor were assessed at week 0, 4, 8, 12,
and 24. The curative effect was statistically evaluated by the United States Institute of Rheumatology ACR20,
ACR50, and ACR70 improvement criteria. Meanwhile, any adverse event was recorded and evaluated.
RESULTS: Totally 41 completed the trial, and 5 dropped off (3 in the treatment group and 2 in the control
group). Compared with the control group, there was no statistical difference in ACR20, ACR50, or ACR70 in
the treatment group (P > 0.05). Compared with before treatment in the same group, there was some
improvement in tender joint number, swollen joint number, visual analogue scale (VAS) for patients' global
assessment, VAS for physicians' global assessment, ESR, CRP, and HAQ between the two groups, showing
statistical difference (P < 0.05). Compared with the control group in the same phase, there was no statistical
difference in the treatment group (P > 0.05). There was no statistical difference in the occurrence of adverse
events between the two groups. CONCLUSIONS: Etanercept plus TWP could achieve equivalent therapeutic
effect to that of Etanercept plus MTX. The two regimens could improve clinical signs, symptoms, and QOL
Hegazy, M. W., et al. (2016). "Radiotherapy dose escalation with concurrent
chemotherapy in locally advanced cervix cancer is feasible." Clin Transl Oncol 18(1):
58-64.
BACKGROUND: To test the feasibility of radiotherapy dose escalation using volumetric arc therapy
(VMAT) and image-guided radiotherapy (IGRT) with concurrent chemotherapy in locally advanced cervix
cancer (LACC) and compare this with whole-pelvis three-dimensional conformal radiation therapy (CRT) in
terms of clinical toxicity. METHODS: Database was reviewed for all LACC patients treated during 2011 and
2012. Twenty patients who were treated with escalated dose of radiotherapy using VMAT were selected for
analysis. A matched cohort of 40 patients who had 3DCRT between 2005 and 2008 was selected as control.
Mean basal hemoglobin, average weekly hemoglobin, and maximal drop in hemoglobin were measured for
both 3DCRT and VMAT groups and treatment toxicity scored according to RTOG criteria. Charts were also
reviewed for other acute and late toxicities including the rate of compliance with prescribed treatment.
RESULTS: Mean age was 46 (30-63) and 47 years (33-67), mean tumor size was 5.5 and 5 cm and blood
transfusion rate was 55 and 45 % in CRT and VMAT groups, respectively. Hemoglobin toxicity (Grade I-II)
was encountered in 97.5 and 90 % (p 0.0.3) while Grade I-III Leukopenia was 90 and 70 % (p 0.02),
respectively. There was no Grade 3 or 4 GI or GU toxicity. CONCLUSION: VMAT/IGRT with dose
escalation is feasible in LACC without excessive toxicity as compared to CRT "Box". We propose a
randomized control trial of this novel approach of higher radiation dose and volume against the standard
Hiester, H. R., M. D. Piggott and P. A. Allison (2011). "The impact of mesh adaptivity
on the gravity current front speed in a two-dimensional lock-exchange." Ocean
Modelling 38(1): 1-21.
Hillstrom, C. and J. G. Jakobsson (2013). "Lornoxicam : pharmacology and usefulness
to treat acute postoperative and musculoskeletal pain a narrative review." Expert Opin
Pharmacother 14(12): 1679-1694.
Numerical simulations of the two-dimensional lock-exchange flow are used to evaluate the performance of
adaptive meshes as implemented in the non-hydrostatic, finite-element model Fluidity-ICOM. The lockexchange is a widely studied laboratory-scale set-up that produces two horizontally propagating gravity
currents and incorporates key physical processes associated with gravity currents over many scales, including
ocean overflows. The Froude number (non-dimensional front speed) is used to assess simulations performed
on structured-fixed, unstructured-fixed and unstructured-adaptive meshes and different adaptive mesh
configurations are compared. Fluidity-ICOM successfully captures the flow dynamics, including the
development of Kelvin–Helmholtz billows. Mesh adapts are guided by a metric which is key to the ability of
an adaptive mesh to represent the flow. The metric employed in Fluidity-ICOM is simple, based on the
curvature of the solution fields and user-defined solution field weights. Good representation of the gravity
current front region is essential to the quality of the solution and for the adaptive meshes this is achieved by
reducing the horizontal velocity field weight near the boundaries. Adaptive meshes that are configured in this
way are seen to perform as well as high-resolution fixed meshes whilst using at least one order of magnitude
fewer nodes. The Froude numbers also compare well with previously published values determined from
experimental, numerical and theoretical approaches. The substantial reduction in the number of nodes used by
the adaptive meshes is particularly encouraging as it suggests that even greater gains may be achieved in
three-dimensional simulations and larger-scale problems. Results show that successful use of the adaptive
mesh approach employed requires a clear understanding of the physics of the system and the metric. These
considerations will be vital to the effective application of adaptive mesh approaches in numerical modelling of
INTRODUCTION: Non-steroidal anti-inflammatory drugs (NSAIDS) are commonly used for acute pain
management. Lornoxicam is a nonselective NSAID for oral and intravenous administration. It has been
available for human use since two decades and there is a growing body of evidence supporting its efficacy and
tolerability for management of acute pain. AREAS COVERED: Public domain literature around the clinical
use of lornoxicam for acute pain management has been reviewed. EXPERT OPINION: There are a growing
number of clinical studies documenting lornoxicam effects for short-term treatment of acute postoperative
pain following various surgical procedures. It has in the majority of comparative studies been shown superior
as compared to paracetamol, non-inferior compared to other NSAIDs, and commonly similarly effective as
standard clinical doses of opioids, but associated with better tolerability. Its effect on other acute pain, for
example, headache, back pain, or sports injury is not well studied. Lornoxicam 8 mg twice daily is a
seemingly effective and tolerable alternative NSAID for use as sole agent or as part of multimodal analgesia
in adults. Available data does however not show any outstanding benefits or special risk. The general
precautions with regard to the use of NSAIDs, the potential risks, for example, gastrointestinal bleeding and or
cardiovascular side effects must be acknowledged.
Hinze, M., et al. (2018). "Volumetric alterations around single-tooth implants using
the socket-shield technique: preliminary results of a prospective case series." Int J
Esthet Dent 13(2): 146-170.
Hirano, K., et al. (2023). "Efficacy and feasibility of scheduled intravenous
acetaminophen administration after pancreatoduodenectomy: a propensity scorematched study." Surg Today 53(9): 1047-1056.
OBJECTIVE: To demonstrate in a prospective cohort study that immediate implantation and
provisionalization in combination with the socket-shield technique will result in volume stability of the
mucosa adherent to the inserted implant. MATERIAL AND METHODS: Patients with an indication for a
single tooth implant underwent application of the socket-shield technique and immediate implantation of a
provisional implant crown. A noninvasive volumetric measurement was performed according to the method
described by Windisch et al (2007) at baseline and 12 weeks later. The influence of potential confounders was
evaluated. Patients rated their satisfaction with the treatment, fitting accuracy of implant, intraoperative
discomfort, postoperative pain, and ability to chew soft and hard foods using visual analog scales. RESULTS:
Fifteen patients with a mean age of 49.2 ± 11.9 years were enrolled in the study. All implant sites showed
uneventful healing and no socket-shield exposures were observed. The soft tissue volume change assessed
with the mean distance change was < 0.5 mm in all cases (-0.07 ± 0.16; range -0.37 to +0.32). A slight but
significant influence of the buccal bone plate width on the soft tissue volume change was observed (b = 0.25;
P = 0.037). No influence was found for apical bone height, width of gingival tissue, buccal recession or
probing depths. The patients were highly satisfied with their treatment as well as with the pain and functional
outcomes. CONCLUSIONS: Based on preliminary data, preservation of a buccal root segment in conjunction
with immediate implant placement and provisionalization can minimize buccal contour changes after tooth
PURPOSE: The efficiency and safety of routine intravenous administration of acetaminophen after highly
invasive hepatobiliary pancreatic surgery remain unclear. In particular, there have been no studies focusing on
pancreatoduodenectomy. The present study clarified its clinical utility for patients undergoing
pancreatoduodenectomy. METHODS: We retrospectively collected 179 patients who underwent open
pancreatoduodenectomy from 2015 to 2020. The analgesic effects and adverse events in patients with
scheduled intravenous administration of acetaminophen were evaluated using propensity score matching.
RESULTS: After 40 patients from each group were selected by propensity score matching, the postoperative
liver function tests were not significantly different between the control and acetaminophen groups. No
significant differences were found in the self-reported pain intensity score or postoperative nausea and
vomiting; however, the rate of pentazocine use and the total number of additional analgesics were
significantly lower in the acetaminophen group than in the control group (p = 0.003 and 0.002, respectively).
CONCLUSION: The scheduled intravenous administration of acetaminophen did not affect the postoperative
liver function and had a good analgesic effect after pancreatoduodenectomy.
Hixson, R., et al. (2010). "Parental calculation of pediatric paracetamol dose: a
randomized trial comparing the Parental Analgesia Slide with product information
leaflets." Paediatr Anaesth 20(7): 612-619.
Hoetink, A., et al. (2020). "An In Vitro Pilot Study Comparing the Novel HemoClear
Gravity-Driven Microfiltration Cell Salvage System with the Conventional Centrifugal
XTRA™ Autotransfusion Device." Anesthesiol Res Pract 2020: 9584186.
OBJECTIVES: To compare the ability of parents to calculate and demonstrate the correct paracetamol
(acetaminophen) dose, interval, and frequency for their child when using either product information leaflets or
the Parental Analgesia Slide. BACKGROUND: Prescribing information provided with over-the-counter
medication may be a source of confusion for parents delivering analgesics to children at home. Accurate
administration is essential to ensure safe and effective treatment of children's pain or fever. The Parental
Analgesia Slide is a new device developed with the objective of improving parental dosing accuracy.
METHODS: In this prospective, randomized study, 160 parents accompanying children aged between one and
13 years old were randomly allocated to complete a paracetamol dose calculation and administration
questionnaire using one of two sources of prescribing information. Absolute percentage dose error and the
number of correct dosage intervals, frequencies, and demonstrated drug volumes were compared. RESULTS:
Use of the Parental Analgesia Slide resulted in a reduction in the absolute percentage dose error from a
median of 33.3 to 0% (P < 0.001) and an increase in the number of correct dosage intervals and frequencies
(59/80 to 70/80, P = 0.046). There was no difference in the number of correctly demonstrated drug volumes (P
= 0.082) despite a greater number of parents opting to use an oral syringe rather than a dosing spoon when
using the Slide (24/80 to 44/80, P = 0.002). CONCLUSIONS: The Parental Analgesia Slide resulted in
improved parental ability to calculate paracetamol dose, interval, and frequency while preserving their ability
BACKGROUND: In 2013, the World Health Organization reported a shortage of 17 million red blood cell
units, a number that remains growing. Acts to relieve this shortage have primarily focused on allogeneic blood
collection. Nevertheless, autologous transfusion can partially alleviate the current pressure and dependence on
blood banking systems. To achieve this, current gold standard autotransfusion devices should be
complemented with widely available, cost-efficient, and time-efficient devices. The novel HemoClear cell
salvage device (HemoClear BV, Zwolle, Netherlands), a gravity-driven microfilter, potentially is widely
employable. We evaluated its performance in the cardiac postoperative setting compared to the centrifugal
XTRA™ autotransfusion device. METHODS: In a split-unit study (n = 18), shed blood collected 18 hours
after cardiothoracic surgery was divided into two equal volumes. One-half was processed by the XTRA™
device and the other with the HemoClear blood separation system. In this paired set-up, equal washing
volumes were used for both methods. Washing effectivity and cellular recovery were determined by
measuring of complete blood count, free hemoglobin, complement C3, complement C4, and D-dimer in both
concentrate as filtrate. Also, processing times and volumes were evaluated. RESULTS: The HemoClear and
XTRA™ devices showed equal effectiveness in concentrating erythrocytes and leucocytes. Both methods
reduced complement C3, complement C4, and D-dimer by ≥90%. The centrifugal device reduced solutes more
significantly by up to 99%. Free hemoglobin load was reduced to 12.9% and 15.5% by the XTRA™ and
HemoClear, respectively. CONCLUSION: The HemoClear device effectively produced washed concentrated
red blood cells comparably to the conventional centrifugal XTRA™ autotransfusion device. Although the
centrifugal XTRA™ device achieved a significantly higher reduction in contaminants, the HemoClear device
achieved acceptable blood quality and seems promising in settings where gold standard cell savers are
Hoh, S. Y., et al. (2019). "Randomized controlled trial comparing bilateral superficial
cervical plexus block and local wound infiltration for pain control in thyroid surgery."
Asian J Surg 42(12): 1001-1008.
BACKGROUD/OBJECTIVE: Multiple approaches have been devised for pain control in patients undergoing
thyroid surgery, with local wound infiltration (LWI) of analgesia and bilateral superficial cervical plexus
block (BSCPB) among the popular choices cited. However, the results comparing these methods had either
been contradictory or equivocal. This study was carried out to assess the efficacy of BSCPB in comparison to
LWI in reducing post-operative pain, as well as any additional opioid requirement in the first 24 h after
thyroid surgery. METHODS: A prospective, double-blinded randomized controlled trial comparing the postoperative pain score between BSCPB and LWI was conducted among patients undergoing thyroid surgery.
Ropivacaine 0.50% was used in the study. Pain score was measured at 4, 12, 16 and 24 h after surgery using
the visual analog scale (VAS). Subcutaneous injection of Tramadol was given whenever the pain score was ≥4
or requested by patients. RESULTS: A total of 70 patients were recruited, with 35 patients on each arm. There
was no statistical difference in the post-operative pain score between the two groups at 4 h (p = 0.208), 12 h
(p = 0.860), 16 h (p = 0.376) and 24 h (p = 0.375) after surgery. Time to the first rescue dose of Tramadol
between the two arms was also insignificant (p = 0.949). One patient in the BSCPB arm developed transient
left upper limb weakness, which resolved 12 h after surgery. CONCLUSION: LWI remains the simplest,
safest and most economical method of pain management. While BSCPB is comparable, it does however, come
Hoiland, R. L., et al. (2020). "Nitric oxide is fundamental to neurovascular coupling in
humans." J Physiol 598(21): 4927-4939.
Holland, D., et al. (2018). "Effect of dexamethasone dose and route on the duration of
interscalene brachial plexus block for outpatient arthroscopic shoulder surgery: a
randomized controlled trial." Can J Anaesth 65(1): 34-45.
KEY POINTS: Preclinical models have demonstrated that nitric oxide is a key component of neurovascular
coupling; this has yet to be translated to humans. We conducted two separate protocols utilizing intravenous
infusion of a nitric oxide synthase inhibitor and isovolumic haemodilution to assess the influence of nitric
oxide on neurovascular coupling in humans. Isovolumic haemodilution did not alter neurovascular coupling.
Intravenous infusion of a nitric oxide synthase inhibitor reduced the neurovascular coupling response by ∼
30%, indicating that nitric oxide is integral to neurovascular coupling in humans. ABSTRACT: Nitric oxide is
a vital neurovascular signalling molecule in preclinical models, yet the mechanisms underlying neurovascular
coupling (NVC) in humans have yet to be elucidated. To investigate the contribution of nitric oxide to NVC in
humans, we utilized a visual stimulus paradigm to elicit an NVC response in the posterior cerebral circulation.
Two distinct mechanistic interventions were conducted on young healthy males: (1) NVC was assessed during
intravenous infusion of saline (placebo) and the non-selective competitive nitric oxide synthase inhibitor N(G)
-monomethyl-l-arginine (l-NMMA, 5 mg kg(-1) bolus & subsequent 50 μg kg(-1) min(-1) maintenance dose; n
= 10). The order of infusion was randomized, counterbalanced and single blinded. A subset of participants in
this study (n = 4) underwent a separate intervention with phenylephrine infusion to independently consider the
influence of blood pressure changes on NVC (0.1-0.6 μg kg(-1) min(-1) constant infusion). (2) NVC was
assessed prior to and following isovolumic haemodilution, whereby 20% of whole blood was removed and
replaced with 5% human serum albumin to reduce haemoglobin concentration (n = 8). For both protocols,
arterial and internal jugular venous blood samples were collected at rest and coupled with volumetric
measures of cerebral blood flow (duplex ultrasound) to quantify resting cerebral metabolic parameters. lNMMA elicited a 30% reduction in the peak (P = 0.01), but not average (P = 0.11), NVC response. Neither
phenylephrine nor haemodilution influenced NVC. Nitric oxide signalling is integral to NVC in humans,
PURPOSE: Dexamethasone prolongs the duration of interscalene block, but the benefits of higher doses and
perineural vs intravenous administration remain unclear. METHODS: This factorial design, double-blinded
trial randomized 280 adult patients undergoing ambulatory arthroscopic shoulder surgery at a single centre in
a 1:1:1:1 ratio. Patients received ultrasound-guided interscalene block with 30 mL 0.5% bupivacaine and 4 mg
or 8 mg dexamethasone by either the perineural or intravenous route. The primary outcome (block duration
measured as the time of first pain at the surgical site) and secondary outcomes (adverse effects, postoperative
neurologic symptoms) were assessed by telephone. In this superiority trial, the predetermined minimum
clinically important difference for comparisons between doses and routes was 3.0 hr. RESULTS: The
perineural route significantly prolonged the mean block duration by 2.0 hr (95% confidence interval [CI], 0.4
to 3.5 hr; P = 0.01), but 8 mg of dexamethasone did not significantly prolong the mean block duration
compared with 4 mg (1.3 hr; 95% CI, -0.3 to 2.9 hr, P = 0.10), and there was no significant statistical
interaction (P = 0.51). The mean (95% CI) block durations, in hours, were 24.0 (22.9 to 25.1), 24.8 (23.2 to
26.3), 25.4 (23.8 to 27.0), and 27.2 (25.2 to 29.3) for intravenous doses of 4 and 8 mg and perineural doses of
4 and 8 mg, respectively. There were no marked differences in side effects between groups. At 14
postoperative days, 57 (20.4%) patients reported neurologic symptoms, including dyspnea and hoarseness. At
six months postoperatively, only six (2.1%) patients had residual symptoms, with four (1.4%) patients'
symptoms unlikely related to interscalene block. CONCLUSION: Compared with the intravenous route,
perineural dexamethasone prolongs the mean interscalene block duration by a small amount that may or may
not be clinically significant, regardless of dose. However, the difference in mean block durations between 8
mg and 4 mg of dexamethasone is highly unlikely to be clinically important, regardless of the administration
Hooper, S. B., et al. (2016). "The timing of umbilical cord clamping at birth:
physiological considerations." Matern Health Neonatol Perinatol 2: 4.
While it is now recognized that umbilical cord clamping (UCC) at birth is not necessarily an innocuous act,
there is still much confusion concerning the potential benefits and harms of this common procedure. It is most
commonly assumed that delaying UCC will automatically result in a time-dependent net placental-to-infant
blood transfusion, irrespective of the infant's physiological state. Whether or not this occurs, will likely
depend on the infant's physiological state and not on the amount of time that has elapsed between birth and
umbilical cord clamping (UCC). However, we believe that this is an overly simplistic view of what can occur
during delayed UCC and ignores the benefits associated with maintaining the infant's venous return and
cardiac output during transition. Recent experimental evidence and observations in humans have provided
compelling evidence to demonstrate that time is not a major factor influencing placental-to-infant blood
transfusion after birth. Indeed, there are many factors that influence blood flow in the umbilical vessels after
birth, which depending on the dominating factors could potentially result in infant-to-placental blood
transfusion. The most dominant factors that influence umbilical artery and venous blood flows after birth are
lung aeration, spontaneous inspirations, crying and uterine contractions. It is still not entirely clear whether
gravity differentially alters umbilical artery and venous flows, although the available data suggests that its
influence, if present, is minimal. While there is much support for delaying UCC at birth, much of the debate
has focused on a time-based approach, which we believe is misguided. While a time-based approach is much
easier and convenient for the caregiver, ignoring the infant's physiology during delayed UCC can potentially
Hornung, A. L., et al. (2022). "Do total shoulder arthroplasty implants corrode?" J
Shoulder Elbow Surg 31(11): 2381-2391.
BACKGROUND: Total shoulder arthroplasty (TSA) has become the gold-standard treatment to relieve joint
pain and disability in patients with glenohumeral osteoarthritis who do not respond to conservative treatment.
An adverse reaction to metal debris released due to fretting corrosion has been a major concern in total hip
arthroplasty. To date, it is unclear how frequently implant corrosion occurs in TSA and whether it is a cause
of implant failure. This study aimed to characterize and quantify corrosion and fretting damage in a single
anatomic TSA design and to compare the outcomes to the established outcomes of total hip arthroplasty.
METHODS: We analyzed 21 surgically retrieved anatomic TSAs of the same design (Tornier Aequalis
Pressfit). The retrieved components were microscopically examined for taper corrosion, and taper damage was
scored. Head and stem taper damage was quantitatively measured with a non-contact optical coordinatemeasuring machine. In selected cases, damage was further characterized at high magnifications using scanning
electron microscopy. Energy-dispersive x-ray spectroscopy and metallographic evaluations were performed to
determine underlying alloy microstructure and composition. Comparisons between groups with different
damage features were performed with independent-samples t tests; Mann-Whitney tests and multivariate
linear regression were conducted to correlate damage with patient factors. The level of statistical significance
was set at P < .05. RESULTS: The average material loss for head and stem tapers was 0.007 mm(3) and 0.001
mm(3), respectively. Material loss was not correlated with sex, age, previous implant, or time in situ (P > .05).
We observed greater volume loss in head tapers compared with stem tapers (P = .002). Implants with evidence
of column damage had larger volumetric material loss than those without such evidence (P = .003). Column
damage aligned with segregation bands within the alloy (preferential corrosion sites). The average angular
mismatch was 0.03° (standard deviation, 0.0668°), with negative values indicating distal engagement and
positive values indicating proximal engagement. Implants with proximal engagement were significantly more
likely to have column damage than those with distal engagement (P = .030). DISCUSSION: This study has
shown not only that the metal components of TSA implants can corrode but also that the risk of corrosion can
be reduced by (1) eliminating preferential corrosion sites and (2) ensuring distal engagement to prevent fluid
House, G., et al. (2016). "A feasibility study to determine the benefits of upper
extremity virtual rehabilitation therapy for coping with chronic pain post-cancer
surgery." Br J Pain 10(4): 186-197.
BACKGROUND: Persistent pain in shoulder and arm following post-surgical breast cancer treatment can lead
to cognitive and physical deficits. Depression is also common in breast cancer survivors. Virtual reality
therapy with integrative cognitive and physical rehabilitation has not been clinically trialed for this
population. The novel BrightArm Duo technology improved cognition and upper extremity (UE) function for
other diagnoses and has great potential to benefit individuals coping with post-surgical breast cancer pain.
OBJECTIVES: The aim of this study was to explore the feasibility of BrightArm Duo therapy for coping with
post-surgical chronic pain and associated disability in breast cancer survivors with depression. METHODS:
BrightArm Duo is a robotic rehabilitation table modulating gravity loading on supported forearms. It tracks
arm position and grasping strength while patients play three-dimensional (3D) custom integrative
rehabilitation games. Community-dwelling women (N = 6) with post-surgical breast cancer pain in the upper
arm trained on the system twice a week for 8 weeks. Training difficulty increased progressively in game
complexity, table tilt and session length (20-50 minutes). Standardized assessments were performed before
and after therapy for pain, cognition, emotion, UE function and activities of daily living. RESULTS: Subjects
averaged upwards of 1300 arm repetitions and 850 hand grasps per session. Pain intensity showed a 20%
downward trend (p = 0.1) that was corroborated by therapist observations and participant feedback. A total of
10 out of 11 cognitive metrics improved post-training (p = 0.01) with a significant 8.3-point reduction in
depression severity (p = 0.04). A total of 17 of 18 range of motion metrics increased (p < 0.01), with five
affected-side shoulder improvements above the Minimal Clinically Important Difference (8°). In all, 13 out of
15 strength and function metrics improved (p = 0.02) with lateral deltoid strength increasing 7.4 N on the
affected side (p = 0.05). CONCLUSION: This pilot study demonstrated feasibility of using the BrightArm
Duo Rehabilitation System to treat cancer survivors coping with upper body chronic pain. Outcomes indicate
Huang, D., et al. (2022). "Intravenous nicorandil during primary percutaneous
coronary intervention in patients with ST-Elevation myocardial infarction: Rationale
and design of the Clinical Efficacy and Safety of Intravenous Nicorandil (CLEAN)
trial." Am Heart J 244: 86-93.
BACKGROUND: The efficacy and safety of intravenous infusion of nicorandil during primary percutaneous
coronary intervention (PCI) in patients with ST-elevation myocardial infarction (STEMI) remain uncertain.
OBJECTIVES: The primary objective of the CLinical Efficacy and sAfety of intravenous Nicorandil
(CLEAN) trial is to evaluate the long-term efficacy and safety of intravenous administration of nicorandil as
adjuncts to reperfusion therapy in patients with STEMI undergoing primary PCI. DESIGN: The CLEAN trial
is a multicenter, randomized, double-blind, placebo-controlled trial that will enroll 1,500 patients from 40
centers across china. patients were randomly (1:1) assigned to receive intravenous nicorandil (6 mg as a bolus
before reperfusion, followed by 48 hours of continuous infusion at a dose of 6 mg/h after coronary
intervention) or the same dose of placebo according to randomization. The primary efficacy outcome was a
composite of death from cardiovascular causes, nonfatal myocardial infarction, target vessel revascularization,
and unplanned hospitalization for heart failure within 12 months. The secondary efficacy outcomes included
the individual components of the combined efficacy endpoint, incidence of slow coronary flow after PCI, and
incidence of complete ST-segment resolution at 2 hours after PCI. the safety outcomes included the incidence
of hypotension after drug infusion and other adverse events during medication. SUMMARY: CLEAN will
determine whether the addition of intravenous nicorandil as adjuncts to reperfusion therapy reduces the major
adverse cardiovascular events in STEMI patients undergoing primary PCI. TRIAL REGISTRATION:
Hughes, J. D., et al. (2021). "Graft healing does not influence subjective outcomes and
shoulder kinematics after superior capsule reconstruction: a prospective in vivo
kinematic study." J Shoulder Elbow Surg 30(7s): S48-s56.
BACKGROUND: A viable treatment option for young patients with massive, irreparable rotator cuff tears is
arthroscopic superior capsule reconstruction (SCR). SCR theoretically improves shoulder stability and
function and decreases pain. However, no prospective studies to date have correlated magnetic resonance
imaging (MRI) healing with in vivo kinematic data. The purpose of this study was to evaluate the association
between graft healing and in vivo kinematics, range of motion (ROM), strength, and patient-reported
outcomes (PROs). METHODS: Ten patients (8 men and 2 women; mean age, 63 ± 7 years) with irreparable
rotator cuff tears underwent arthroscopic SCR with dermal allograft. Strength was measured with isometric
internal rotation and external rotation (ER) at 0° of abduction, ER at 90° of abduction, and scapular-plane
abduction, whereas ROM was measured during shoulder flexion, abduction, and ER and internal rotation at
90° of abduction both before and 1 year after SCR. PROs included American Shoulder and Elbow Surgeons,
Western Ontario Rotator Cuff Index, and Disabilities of the Arm, Shoulder and Hand surveys that were
collected before and 1 year after SCR. Synchronized biplane radiographs were collected at 50 images/s before
and 1 year after SCR while patients performed 3 trials of scapular-plane abduction. A validated volumetric
tracking technique with submillimeter accuracy determined 6-df glenohumeral and scapular kinematics. The
acromiohumeral distance (AHD), humeral head translation, and scapulohumeral rhythm (SHR) were
calculated from the in vivo kinematics. Healing at 5 locations was evaluated on 1-year postoperative MRI
scans: anterior and posterior glenoid, anterior and posterior humerus, and posteriorly along the infraspinatus.
Each subject was given a score from 0 to 5 based on number of sites healed. RESULTS: Of the 10 patients, 9
(90%) had complete (n = 4) or partial (n = 5) healing of the graft whereas 1 (10%) had complete failure at the
glenoid. No correlation existed between MRI healing and the AHD, SHR, strength, ROM, or PROs. American
Shoulder and Elbow Surgeons, Western Ontario Rotator Cuff Index, and Disabilities of the Arm, Shoulder
and Hand scores all significantly improved from before to 1 year after SCR regardless of graft healing.
CONCLUSIONS: The rate of complete or partial graft healing on MRI mimics findings of prior reports in the
literature. MRI healing was correlated with humeral head anterior-posterior translation but not with the static
and dynamic AHDs, SHR, humeral head superior-inferior translation, ROM, strength, or PROs 1 year after
SCR. All PROs improved significantly from before to 1 year after SCR regardless of graft status on MRI.
In vivo kinematic changes were small after SCR and not clinically significant, and the data suggest that
Huisman, M., et al. (2014). "Feasibility of volumetric MRI-guided high intensity
focused ultrasound (MR-HIFU) for painful bone metastases." J Ther Ultrasound 2: 16.
BACKGROUND: Magnetic resonance-guided high intensity focused ultrasound (MR-HIFU) has recently
emerged as an effective treatment option for painful bone metastases. We describe here the first experience
with volumetric MR-HIFU for palliative treatment of painful bone metastases and evaluate the technique on
three levels: technical feasibility, safety, and initial effectiveness. METHODS: In this observational cohort
study, 11 consecutive patients (7 male and 4 female; median age, 60 years; age range, 53-86 years) underwent
13 treatments for 12 bone metastases. All patients exhibited persistent metastatic bone pain refractory to the
standard of care. Patients were asked to rate their worst pain on an 11-point pain scale before treatment,
3 days after treatment, and 1 month after treatment. Complications were monitored. All data were
prospectively recorded in the context of routine clinical care. Response was defined as a ≥2-point decrease in
pain at the treated site without increase in analgesic intake. Baseline pain scores were compared to pain scores
at 3 days and 1 month using the Wilcoxon signed-rank test. For reporting, the STROBE guidelines were
followed. RESULTS: No treatment-related major adverse events were observed. At 3 days after volumetric
MR-HIFU ablation, pain scores decreased significantly (p = 0.045) and response was observed in a 6/11
(55%) patients. At 1-month follow-up, which was available for nine patients, pain scores decreased
significantly compared to baseline (p = 0.028) and 6/9 patients obtained pain response (overall response rate
67% (95% confidence interval (CI) 35%-88%)). CONCLUSIONS: This is the first study reporting on the
volumetric MR-HIFU ablation for painful bone metastases. No major treatment-related adverse events were
observed during follow-up. The results of our study showed that volumetric MR-HIFU ablation for painful
bone metastases is technically feasible and can induce pain relief in patients with metastatic bone pain
refractory to the standard of care. Future research should be aimed at standardization of the treatment
procedures and treatment of larger numbers of patients to assess treatment effectiveness and comparison to the
Hulse, W., et al. (2020). "Warming blood products for transfusion to neonates: In vitro
assessments." Transfusion 60(9): 1924-1928.
BACKGROUND: Blood products may be transfused into neonates at temperatures at or below room
temperature. The benefits and risks of warming blood to 37°C are not defined in this population or with the
equipment used in neonates. Physiologic warming might enhance product effectiveness or decrease
transfusion-associated hypothermia. STUDY DESIGN AND METHODS: We utilized an in vitro model of
neonatal transfusions, with a syringe pump, blood tubing, and 24-gauge catheter and compared current
practice (cold products) vs an inline blood warmer. Transfusions were performed rapidly (30 minutes) and
slower (120 minutes) to model emergent vs routine situations. We tested red blood cells, fresh-frozen plasma,
apheresis platelets (PLTs), and cold-stored low-titer group O whole blood. We used infrared detectors and
inline probes to measure temperatures at the origin and at the simulated patient. We assessed warmer-induced
damage by measuring plasma hemoglobin and hematocrit (seeking hemolysis), fibrinogen (seeking activation
of coagulation), and PLT count and TEG-MA (seeking PLT destruction or dysfunction). RESULTS: The
cold-stored products were 4.2 ± 1.0°C (mean ± SD) at the origin and 21.5 ± 0.1°C at the patient. With the
inline warmer, products were 37.8 ± 0.6°C at the warmer and 32.6 ± 1.7°C at the patient during a 30-minute
infusion, but were 34.5 ± 2.1 with a foil sheath covering the terminal tubing. We found no warmer-induced
damage using any metric. CONCLUSION: In simulated neonatal intensive care unit (NICU) transfusions, an
inline blood warmer can deliver blood products at near-physiologic temperatures with no detected damage.
We suggest in vivo testing of warmed NICU transfusions, assessing product effectiveness and hypothermia
Ilfeld, B. M. (2011). "Continuous Peripheral Nerve Blocks in the Hospital and at
Home." Anesthesiology Clinics 29(2): 193-211.
Ilfeld, B. M. (2017). "Continuous Peripheral Nerve Blocks: An Update of the
Published Evidence and Comparison With Novel, Alternative Analgesic Modalities."
Anesth Analg 124(1): 308-335.
A continuous peripheral nerve block (CPNB) consists of a percutaneously inserted catheter with its tip
adjacent to a target nerve/plexus through which local anesthetic may be administered, providing a prolonged
block that may be titrated to the desired effect. In the decades after its first report in 1946, a plethora of data
relating to CPNB was published, much of which was examined in a 2011 Anesthesia & Analgesia article. The
current update is an evidence-based review of the CPNB literature published in the interim. Novel insertion
sites include the adductor canal, interpectoral, quadratus lumborum, lesser palatine, ulnar, superficial, and
deep peroneal nerves. Noteworthy new indications include providing analgesia after traumatic rib/femur
fracture, manipulation for adhesive capsulitis, and treating abdominal wall pain during pregnancy. The
preponderance of recently published evidence suggests benefits nearly exclusively in favor of catheter
insertion using ultrasound guidance compared with electrical stimulation, although little new data are
available to help guide practitioners regarding the specifics of ultrasound-guided catheter insertion (eg,
optimal needle-nerve orientation). After some previous suggestions that automated, repeated bolus doses
could provide benefits over a basal infusion, there is a dearth of supporting data published in the past few
years. An increasing number of disposable infusion pumps does now allow a similar ability to adjust basal
rates, bolus volume, and lockout times compared with their electronic, programmable counterparts, and a
promising area of research is communicating with and controlling pumps remotely via the Internet. Large,
prospective studies now document the relatively few major complications during ambulatory CPNB, although
randomized, controlled studies demonstrating an actual shortening of hospitalization duration are few. Recent
evidence suggests that, compared with femoral infusion, adductor canal catheters both induce less quadriceps
femoris weakness and improve mobilization/ambulation, although the relative analgesia afforded by each
remains in dispute. Newly published data demonstrate that the incidence and/or severity of chronic, persistent
postsurgical pain may, at times, be decreased with a short-term postoperative CPNB. Few new CPNB-related
complications have been identified, although large, prospective trials provide additional data regarding the
incidence of adverse events. Lastly, a number of novel, alternative analgesic modalities are under
development/investigation. Four such techniques are described and contrasted with CPNB, including singleinjection peripheral nerve blocks with newer adjuvants, liposome bupivacaine used in wound infiltration and
Inagaki, Y., et al. (2022). "The Efficacy and Safety of Dexmedetomidine for Sedation
During Surgery Under Epidural or Spinal Anesthesia: A Randomized, Double-Blind,
Placebo-Controlled Study." Yonago Acta Med 65(1): 14-25.
BACKGROUND: Only a few studies have been reported on the use of dexmedetomidine for sedating surgical
patients requiring epidural or spinal anesthesia. We conducted a randomized, double-blind, placebocontrolled, parallel-group study at 12 hospitals in Japan. METHODS: Adult patients were randomly allocated
to receive an intravenous administration of placebo or dexmedetomidine at 0.067, 0.25, 0.5 or 1.0 µg/kg over
10 min after epidural or spinal anesthesia. All dexmedetomidine groups received dexmedetomidine 0.2-0.7
µg/kg/h to maintain an Observer's Assessment of Alertness/Sedation Scale (OAA/S) score of ≤ 4; however,
propofol was administered to rescue patients who exceeded this score. Surgery was then started 15 min after
study drug infusion in patients with OAA/S score of ≤ 4. The primary endpoint was the percentage of patients
not requiring rescue propofol to achieve and maintain an OAA/S score of ≤ 4. RESULTS: Of the 120 enrolled
and randomized patients, 119 were treated the study: 22 received placebo and 97 received dexmedetomidine
(23-25 patients per dose). Significantly more patients did not require propofol in the dexmedetomidine 0.5 and
1.0 µg/kg groups (68.0% and 80.0%, respectively) compared to the placebo group (22.7%) (P = 0.003 and P <
0.001, respectively). Common adverse events (AEs) were protocol-defined respiratory depression, bradycardia
and hypotension. There was no significant difference in the incidence of AEs between the dexmedetomidine
and the placebo groups. CONCLUSION: We concluded that loading doses of 0.5 and 1.0 µg/kg
dexmedetomidine, followed by an infusion at a rate of 0.2-0.7 µg/kg/h, provide effective and well-tolerated
sedation for surgical patients during epidural or spinal anesthesia. Clinical trials.gov identifier:
Ipaktchi, K., J. Wingfield and S. Colakoglu (2019). Fasciotomy: Upper Extremity.
Compartment Syndrome: A Guide to Diagnosis and Management. C. Mauffrey, D. J.
Hak and I. M. Martin. Cham (CH), Springer
Copyright 2019, The Author(s). 59-66.
Early fasciotomy is the standard of care for upper extremity compartment syndrome (UECS) and may prevent
the development of irreversible contractures of forearm and hand musculature, a pathology initially described
by Volkmann (VOLKMAN Centralblat fur hirurgie 8:801–803, 1881). Compartment syndrome (CS) is a
feared orthopedic complication and common cause for permanent functional damage and limb loss as well as
one of the most common causes for litigation in orthopedic surgery (DePasse et al. J Am Acad Orthop Surg
25:e109–e113, 2017; Marchesi et al. Injury 45(Suppl 6):S16–S20, 2014). CS of the forearm is the second
most common cause of CS in the extremities given the injury proneness of the upper extremity and hand as a
prime organ of prehension and grasp (Leversedge et al. J Hand Surg Am 36:544–559, 2011). Given this
important physiologic function, one can argue that the functional loss due to an established CS is higher than
that of the lower extremity. For UECS, a high level of alertness to clinical symptoms such as pain to passive
stretch and increasing pain or analgesic requirements is key to not miss the diagnosis in the alert patient.
UECS shares common etiologies for CS seen in other body areas: either an external reduction of CS size such
as external pressure from casts, dressings, and gravity or increase in compartmental size as seen in bleeding
and fracture displacement, microvascular barrier damage in ischemia, burn injury, and envenomations
(Leversedge et al. J Hand Surg Am 36:544–559, 2011). Several additional etiologies are pertinent to UECS
such as iatrogenic extravasations of intravenous fluids, upper extremity arterial catheterizations (Omori et al.
Orthopedics 36:e121–e125, 2013), and electrical trauma (Lee et al. J Am Acad Orthop Surg, 2018). UECS is
most commonly encountered in the forearm, which has three designated compartments (i.e., the lateral
(mobile wad), the dorsal extensor, and the volar) of which contains the bulk of muscle mass in the flexor
compartment. There are ten designated hand compartments which can be affected in hand compartment
syndrome as seen, for instance, in crushing injuries (exploded hand syndrome), fractures and dislocations, as
well as extravasations. When performing fasciotomies for UECS, special emphasis must be placed to
decompress the muscles of the deep flexor compartment due to their nonredundant blood supply which makes
them especially prone to ischemic damage (Inoue and Taylor Plast Reconstr Surg 98:195–210, 1996).
Ismael, G., et al. (2012). "Subcutaneous versus intravenous administration of
(neo)adjuvant trastuzumab in patients with HER2-positive, clinical stage I-III breast
cancer (HannaH study): a phase 3, open-label, multicentre, randomised trial." Lancet
Oncol 13(9): 869-878.
BACKGROUND: A subcutaneous formulation of trastuzumab has been developed, offering potential
improvements in patient convenience and resource use compared with the standard intravenous infusion of the
drug. We compared the pharmacokinetic profile, efficacy, and safety of the subcutaneous and intravenous
formulations in patients with HER2-positive early breast cancer. METHODS: The HannaH study was a phase
3, randomised, international, open-label, trial in the (neo)adjuvant setting. Patients with HER2-positive,
operable, locally advanced or inflammatory breast cancer were randomly assigned to eight cycles of
neoadjuvant chemotherapy administered concurrently with trastuzumab every 3 weeks either intravenously (8
mg/kg loading dose, 6 mg/kg maintenance dose) or subcutaneously (fixed dose of 600 mg); 1:1 ratio.
Chemotherapy consisted of four cycles of docetaxel (75 mg/m(2)) followed by four cycles of fluorouracil (500
mg/m(2)), epirubicin (75 mg/m(2)), and cyclophosphamide (500 mg/m(2)), every 3 weeks. After surgery,
patients continued trastuzumab to complete 1 year of treatment. Coprimary endpoints were serum trough
concentration (C(trough)) at pre-dose cycle 8 before surgery (non-inferiority margin for the ratio between
groups of 0·80) and pathological complete response (pCR; non-inferiority margin for the difference between
groups of -12·5%), analysed in the per-protocol population. This study is registered with ClinicalTrials.gov,
number NCT00950300. FINDINGS: 299 patients were randomly assigned to receive intravenous trastuzumab
and 297 to receive subcutaneous trastuzumab. The geometric mean presurgery C(trough) was 51·8 μg/mL
(coefficient of variation 52·5%) in the intravenous group and 69·0 μg/mL (55·8%) in the subcutaneous group.
The geometric mean ratio of C(trough) subcutaneous to C(trough) intravenous was 1·33 (90% CI 1·24-1·44).
107 (40·7%) of 263 patients in the intravenous group and 118 (45·4%) of 260 in the subcutaneous group
achieved a pCR. The difference between groups in pCR was 4·7% (95% CI -4·0 to 13·4). Thus subcutaneous
trastuzumab was non-inferior to intravenous trastuzumab for both coprimary endpoints. The incidence of
grade 3-5 adverse events was similar between groups. The most common of these adverse events were
neutropenia (99 [33·2%] of 298 patients in the intravenous group vs 86 [29·0%] of 297 in the subcutaneous
group), leucopenia (17 [5·7%] vs 12 [4·0%]), and febrile neutropenia (10 [3·4%] vs 17 [5·7%]). However,
more patients had serious adverse events in the subcutaneous group (62 [21%] of 297 patients) than in the
intravenous group (37 [12%] of 298); the difference was mainly attributable to infections and infestations (24
[8·1%] in the subcutaneous group vs 13 [4·4%] in the intravenous group). Four adverse events led to death
(one in the intravenous group and three in the subcutaneous group), all of which occurred during the
Itzhaki, M. H., et al. (2024). "Insights from home parenteral nutrition infusion data."
Nutrition 120: 112347.
Objective Patients with chronic intestinal failure use home parenteral nutrition infusion support. Noncompliance of home parenteral nutrition treatment is well documented, especially if clinical resources are
remote. Objective delivery data from Infusion Pump reports have the potential to support treatment progress
and planning. The aim of this study was to report the efficacy and accuracy of the Eitan Insights digital health
platform for home parenteral nutrition use (a platform providing data-driven insights from the pump-recorded
data). Methods A prospective, single-center observational study of 20 patients treated with home parenteral
nutrition ≥3 d/wk was conducted over 2022. The patients recorded the pre- and postinfusion home parenteral
nutrition bag weight, duration of infusion, and alarms. We compared manual records to the pump data.
Repeated measures analysis of variance was used for statistical analysis. Results A total of 45 data sets were
collected, with no adverse events noted. In multiple comparisons between patient factors and descriptive
statistics, there was no significant difference between manually recorded and pump-recorded data for volume
infused (mean values of manual versus pump were 1707 ± 362 mL and 1708 ± 405 mL; P = 0.939) and
infusion duration (mean values of manual versus pump iwere 9h 43 min ± 2.48 SD versus 9h 45 min ± 2.41
SD; P = 0.858). Conclusion The data collected by the digital platform accurately reflect patients’ infusion
data. This connected device has the potential to allow clinicians to be more informed and assess treatment
Iyer, C. P., et al. (2010). "Gastric bypass and On-Q pump: effectiveness of Soaker
Catheter system on recovery of bariatric surgery patients." Surgery for Obesity and
Related Diseases 6(2): 181-184.
Jain, M., et al. (2017). "Tralokinumab pharmacokinetics and tolerability when
administered by different subcutaneous injection methods and rates " Int J Clin
Pharmacol Ther 55(7): 606-620.
Background The continuous infusion of ropivacaine is effective in controlling pain for a wide variety of
surgical procedures and reducing opioid adverse effects and dependency. The present study assessed the
efficacy of ropivacaine infusion using the I-Flow dual Soaker Catheter system at the surgical site for bariatric
surgery recovery at the Dallas Veterans Affairs Medical Center Hospital (Dallas, TX). We hypothesized that
patients receiving ropivacaine would report lower levels of morphine requirement and pain, would have
shorter hospital stays, and would return to ambulating faster than patients in the control group. Methods A
total of 45 patients undergoing Roux-en-Y gastric bypass surgery were randomized to 1 of 2 treatment groups,
with a target study population of 50 patients, receiving either .2% ropivacaine (n = 24) or saline solution (n =
21). Before incision closure, the surgeon infiltrated the surrounding tissues with 30 mL of ropivacaine (.5%)
or saline solution. The catheter was then placed in both the subfascial space and subcutaneously. Next, the
infusion pump was connected to the Soaker Catheters to complete the system design and deliver solution to
the surgical site. Results No significant differences were found in the pain scores, morphine requirement, or
length of stay between the 2 groups. The ropivacaine group interval to sitting up was one half day shorter than
that of patients receiving saline (P = .038). Conclusions Patients receiving ropivacaine were found to ambulate
much more quickly than did the control group patients. This could be very beneficial in reducing the
complications from blood clots and improving patient recovery and overall well-being after surgery by
OBJECTIVE: Tralokinumab, administered as two 1-mL subcutaneous injections every 2 weeks, at the target
dose 300 mg, has been shown to improve lung function in patients with asthma. This study evaluated the
pharmacokinetic (PK) and tolerability profile of tralokinumab 300 mg when administered by different rates of
subcutaneous injection, as part of a pilot investigation of new injection regimens. METHODS: This phase I
study randomized 60 healthy adults to receive 300 mg tralokinumab, as two 1-mL subcutaneous injections,
each delivered over 10 seconds, or one 2-mL injection delivered over 10 seconds (12 mL/min), 1 minute (2
mL/min), or 12 minutes (0.167 mL/min). RESULTS: No differences in the PK profile of tralokinumab were
observed between cohorts. Immediately following injection, injection-site pain intensity (mean (SD)) was
lowest following 0.167 mL/min injection (5.1 mm (8.0) via visual analog scale (VAS)) and greatest following
12 mL/min injection (41 mm (27.7) via VAS); with mean injection-site pruritus intensity low for all
participants. Two types of local injection-site reactions were observed: erythema (58.3%) and
hematoma/bleeding (18.3%). All treatment-emergent adverse events were mild. CONCLUSIONS:
Tralokinumab 300 mg is well tolerated, with comparable PK, when administered by a single 2-mL injection at
different rates of subcutaneous injection vs. two 1-mL injections. .
Jälevik, B. and G. Klingberg (2014). "Pain sensation and injection techniques in
maxillary dento-alveolar surgery procedures in children--a comparison between
conventional and computerized injection techniques (The Wand)." Swed Dent J 38(2):
67-75.
Jelsing, E. J., E. Maida and J. Smith (2013). "A simple technique to restore needle
patency during percutaneous lavage and aspiration of calcific rotator cuff
tendinopathy." Pm r 5(3): 242-244.
Local anesthesia, especially palatal injection, is often associated with fear and anxiety. The aim was to
compare the sensation of pain when using palatal block technique with computerized injection technique
(CIT), to conventional infiltration technique with traditional syringe in surgical procedures involving the
palate. Patients referred for bilateral minor maxillary surgical treatments were randomized for traditional
infiltration anesthesia on one side and palatal block anesthesia with CIT on the other side. AMSA and P-ASA
approaches were used with CIT. The sensation of pain was scored by the VAS scale. Twenty-eight patients
were included in the study, where of 17 (61%) were girls. The median age was 14.8 yrs. (12.6 - 17.8).
Bilateral exposure of palatal impacted canines was the most common treatment. The injection pain was
significantly lower, (p = 0.009), when using the CIT injection compared to conventional injection. However,
with time-consuming surgery, additional CIT analgesic solution had to be injected in the buccal gingiva when
suturing, in one fourth of the cases. Patients sedated with nitrous oxide seemed to benefit less from CIT.
Computerized injection techniques, including P-ASA and AMSA approaches, reduces the sensation of pain
when carrying out less time-consuming palatal dental surgery, especially in non-sedated teenagers.
Calcific rotator cuff tendinopathy caused by symptomatic calcium hydroxyapatite crystal deposition is a wellestablished cause of shoulder pain. In refractory or acutely symptomatic cases, sonographically guided
percutaneous lavage and aspiration can significantly reduce pain in approximately 60%-92% of cases.
Although the complication rate of sonographically guided percutaneous lavage and aspiration is apparently
low, needle clogging attributable to impacted calcific debris has been described by several authors and in our
experience can occur in daily practice. Traditionally, an inability to relieve the obstruction via needle
repositioning or increased syringe plunger pressure has required needle removal and replacement. In this
article, we outline a simple technique that can be used to restore patency of the obstructed lavage needle
without necessitating needle removal and replacement.
Jennings, J. M., et al. (2020). "The James A. Rand Young Investigator's Award:
Traditional Intravenous Fluid vs. Oral Fluid Administration in Primary Total Knee
Arthroplasty: A Randomized Trial." J Arthroplasty 35(6s): S3-s9.
Jindal, A., et al. (2024). Amniocentesis. StatPearls. Treasure Island (FL), StatPearls
Publishing
Copyright © 2024, StatPearls Publishing LLC.
BACKGROUND: Optimal perioperative fluid management has not been established in patients undergoing
orthopedic surgical procedures. Our purpose was to investigate the effects of perioperative fluid management
(ie, preoperative, intraoperative, and postoperative) on patients undergoing total knee arthroplasty (TKA).
METHODS: One hundred thirty patients who met inclusion criteria undergoing primary unilateral TKA were
prospectively randomized into traditional (TFG) vs oral (OFG) perioperative fluid management groups. The
primary outcome was change in body weight (BW). Secondary outcome measures included knee motion, leg
girth, bioelectrical impendence, quadriceps activation, functional outcomes testing, Knee injury and
Osteoarthritis Outcome Score JR, VR-12, laboratory values, vital signs, patient satisfaction, pain scores, and
adverse events. RESULTS: The TFG had increased BW the evening of surgery (7.0 ± 4.3 vs 3.0 ± 3.9, P <
.0001), postoperative day (POD) #1 (9.1 ± 4.3 vs 4.7 ± 3.9, P < .0001), and POD #2 (6.2 ± 5.0 vs 4.4 ± 4.0,
P = .032). Bioelectrical impedance showed less limb edema in the OFG (4.2 ± 29.7 vs 17.8 ± 30.3, P < .0001)
on POD #1. Urine specific gravity differences were seen preoperatively between groups (OFG, more hydrated,
P = .002). Systolic blood pressure decrease from the baseline was greater in the OFG on arrival to the floor
(19.4 ± 13.5 vs 10.6 ± 12.8, P < .0001) and 8 (23.4 ± 13.3 vs 17.0 ± 12.9, P = .006) and 16 (25.8 ± 13.8 vs
25.8 ± 13.8, P = .046) hours after floor arrival. The TFG had more urine output on POD #1 (3369 mL ± 1343
mL vs 2435 mL ± 1151 mL, P < .0001). The OFG were more likely to go home on POD #1 than the TFG (63
vs 56, P = .02). CONCLUSION: Oral fluid intake with IVF restriction in the perioperative period after TKA
may offer short-term benefits with swelling and BW fluctuations. The authors continue to limit perioperative
Prenatal diagnosis enables the diagnosis of a broad spectrum of chromosomal abnormalities, gene disorders,
X-linked conditions, neural tube defects, and infections to be made before the birth of the fetus. The various
invasive prenatal diagnostic tests are amniocentesis, chorionic villus sampling, and fetal blood sampling or
cordocentesis. Amniocentesis Amniocentesis is an invasive technique. This technique removes amniotic fluid
from the uterine cavity using a needle. This procedure is performed transabdominally and under ultrasound
guidance by a trained obstetrician. It was first performed for the diagnosis of genetic diseases (sex
determination) of the fetus by Fuchs and Riis in 1956. It is performed for diagnostic and therapeutic purposes,
including for diagnostic evaluation in the form of chromosomal, biochemical, histopathological, and microbial
assessments. When performed as a therapeutic procedure, it is done to reduce the volume of amniotic fluid in
patients with polyhydramnios. The amniotic fluid obtained consists of fetal exfoliated cells, transudates, fetal
urine, and lung secretions. Amniocentesis can be performed from 15 weeks of gestation to delivery, with an
attributable risk of loss in experienced hands of 0.13% in singletons. Earlier the attributable risk is greater
than chorion villus sampling (CVS), which provides similar data from 11 to 15 weeks. There is an increased
risk of amnionic fluid leakage of 1 to 2%, most of which corresponds to decreased activity in days and fetal
demise, which is usually much rarer than the risk of demise attributable to the indication for the procedure,
except in low-risk women with no maternal risks indicating the procedure, and talipes equinovarus,
presumably from oligohydramnios. Counseling of the couple is necessary regarding the procedure's
indications, risks, benefits, and limitations. This can be complex, as the individual circumstances leading to
risk, including maternal age, parental family history, maternal serum screening, sonographic signs of
chromosomal and other problems, and population history, can vary significantly. The benefit of possible
pregnancy termination also varies depending on the patient's education, religious and ethical preferences, and,
at present, state law. Chorionic Villus Sampling It is a prenatal invasive procedure and is done under
ultrasound guidance. This procedure uses ultrasonography to guide the catheter or needle into the chorion
frondosum. It is done abdominally and is followed by tissue aspiration (chorionic villi) for genetic or
chromosomal analysis with a syringe containing tissue culture media. It is done in the first trimester for
prenatal diagnosis between 10 to 14 weeks. Depending on the position of the uterus and bladder, the patient's
gestational age, and placental localization, it can be performed transabdominally or transcervically. The safer
and earlier termination of pregnancy is possible as karyotype results are available within 7 to 10 days,
Joethy, J. and B. K. Tan (2016). "Precise breast implant placement using percutaneous
chest wall markings." Indian J Plast Surg 49(2): 234-238.
Joo, C. W., et al. (2023). "Insulin syringe for anesthesia in ptosis surgery: a
randomized, fellow eye-controlled clinical study." Int Ophthalmol 43(8): 2721-2730.
Joseph, D., et al. (2022). "Assessment of the Pharmacokinetics and Safety of
Spesolimab, a Humanised Anti-interleukin-36 Receptor Monoclonal Antibody, in
Healthy Non-Japanese and Japanese Subjects: Results from Phase I Clinical Studies."
Clin Pharmacokinet 61(12): 1771-1787.
BACKGROUND: Traditionally, pre-operative breast markings are usually made using an indelible marker.
These markings are at risk of being removed by pre-operative cleaning, positional changes and parenchymal
changes post-incision. We present our approach to breast surgery with rib or intercostal markings using
methylene blue. METHODS: Using an indelible marker, markings are made on the breast and the
inframammary crease. A blue needle (23 G) mounted on a 1 ml syringe is prepared, and aliquots of 0.1 ml of
methylene blue are injected. Excessive infiltration and pre-operative local anaesthetic infiltration result in
diffusion of the dye and difficulty with accuracy. Dye is injected directly over the bony periosteum closest to
the inframammary fold. RESULTS: We achieved good symmetry of bilateral breast implants. Photographs
were taken pre-operative and 3 months post-operative and were evaluated independently by medical officers.
All results were rated as good or very good. We had 39 patients and follow-up was between 3 and 24 months.
There were no implant-related complications. CONCLUSIONS: For accurate implant placement, a fixed
position must be found. Our technique utilises the relative immobility of the ribs for accurate implant
placement. Disadvantages to our method were few, and we had two cases of dizziness or patients feeling faint
due to pain. There is also a potential allergic or anaphylaxis reaction, but we did not experience any allergic
reaction.
PURPOSE: Unlike ordinary 30-gauge needles, insulin syringe needles are thinner and shorter and have a
comparatively blunt tip. Therefore, insulin syringes may reduce injection discomfort, bleeding, and edema by
minimizing tissue damage and vascular penetration. This study aimed to evaluate the potential benefits of
using insulin syringes for local anesthesia in ptosis surgery. METHODS: This randomized, fellow eyecontrolled study included 60 patients (120 eyelids), conducted at a university-based hospital. An insulin
syringe was used on one eyelid, and a conventional 30-gauge needle was used on the other. Patients were
instructed to score pain in both eyelids using a visual analog scale (VAS) ranging from 0 (no pain) to 10
(unbearable pain). Ten minutes after the injection, two observers scored degrees of hemorrhage and edema in
both eyelids on five- and four-pointing grading scales (0-4 and 0-3) for each value, and the average score
between the two observers was calculated and compared. RESULTS: The VAS score was 5.17 in the insulin
syringe group and 5.35 in the 30-gauge needle group (p = 0.282). Ten minutes after the anesthesia, the median
hemorrhage scores were 1.00 and 1.75 (p = 0.010), and the median eyelid edema scores were 1.25 and 2.00
(p = 0.007) in the insulin syringe and 30-gauge needle groups, respectively (Fig. 1). CONCLUSION: Injecting
local anesthesia using an insulin syringe significantly reduces hemorrhage and eyelid edema, but not injection
pain, before skin incision. Insulin syringes are useful in patients at high risk of bleeding because they can
BACKGROUND AND OBJECTIVE: The interleukin-36 signalling pathway is associated with pathogenesis
of a number of inflammatory diseases. Spesolimab is a selective, humanised, IgG1 antibody that targets the
interleukin-36 receptor. We aimed to evaluate the pharmacokinetics, safety and tolerability of single and
multiple doses of spesolimab in healthy non-Japanese and Japanese subjects. METHODS: Five phase I
clinical studies (three placebo-controlled dose-escalation, two open-label) were conducted in healthy
volunteers; single or multiple doses of spesolimab were administered by intravenous infusion or subcutaneous
injection. Plasma samples were collected to investigate the pharmacokinetics of spesolimab and evaluate
changes with respect to dose, frequency of dosing, formulation and injection site. Immunogenicity, safety and
tolerability were also assessed. RESULTS: Intravenous spesolimab exhibited target-mediated drug disposition
at low doses (0.01-0.3 mg/kg) and linear kinetics at doses ≥ 0.3 mg/kg. Steady state was not attained after the
fourth weekly dose because of the long half-life (3-5 weeks). Bioavailability of subcutaneous spesolimab
increased with increasing dose over the range of 150-600 mg and was higher when administered to the thigh
than to the abdomen. The pharmacokinetic profile was consistent between Japanese and non-Japanese
subjects. Positive anti-drug antibody responses occurred during the terminal phase of the spesolimab
concentration-time profile in 26.7-33.3% and 16.7-37.5% of subjects receiving intravenous and subcutaneous
spesolimab, respectively. The impact of anti-drug antibodies on spesolimab pharmacokinetics was low in
healthy volunteers, with the impact on spesolimab plasma concentrations only observed in a few subjects at
higher titres (≥ 11,400). No serious adverse events were reported; intravenous doses up to 1200 mg were well
tolerated in healthy volunteers. CONCLUSIONS: The pharmacokinetic profile and safety data obtained from
these phase I clinical studies have been used to guide spesolimab dosing in clinical studies of patients with
interleukin-36-mediated diseases. CLINICAL TRIAL REGISTRATION: For Studies 1-5, NCT02525679,
Juif, P. E., et al. (2019). "Influence of Rifampin-Mediated Organic AnionTransporting Polypeptide 1B1/1B3 Inhibition on the Pharmacokinetics of
Clazosentan." Clin Transl Sci 12(5): 440-444.
Jun, S. Y., et al. (2017). "Pharmacokinetics and Tolerance of the Phage EndolysinBased Candidate Drug SAL200 after a Single Intravenous Administration among
Healthy Volunteers." Antimicrob Agents Chemother 61(6).
Clazosentan is a selective endothelin A receptor antagonist in development for the prevention and treatment of
vasospasm postsubarachnoid hemorrhage. It is a substrate of organic anion-transporting polypeptide 1B1/1B3
based on preclinical data. This randomized, double-blind, two-period, cross-over study investigated the
pharmacokinetics, safety, and tolerability of an intravenous infusion of clazosentan (15 mg/hour for 3 hours)
after the intravenous administration of placebo or rifampin (600 mg/100 mL in 30 minutes). A total of 14
healthy male participants were enrolled resulting in 13 completers. Clazosentan exposure was three to four
times higher after organic anion-transporting polypeptide 1B1/1B3 inhibition, as reflected by the geometric
mean ratio (90% confidence interval) of area under the plasma concentration-time curve from zero to infinity:
3.88 (3.24-4.65). Clearance and volume of distribution decreased to a similar extent. Elimination half-life was
not affected. A similar pattern but a higher incidence and frequency of adverse events were observed when
clazosentan was given with rifampin than with placebo.
Kagwa, S., et al. (2015). "Ultrasound guided transversus abdominis plane versus sham
blocks after caesarean section in an Ugandan village hospital: a prospective,
randomised, double-blinded, single-centre study." Lancet 385 Suppl 2: S36.
This study was a phase 1, single-center, randomized, double-blind, placebo-controlled, single-dosing, and
dose-escalating study of intravenous SAL200. It is a new candidate drug for the treatment of antibioticresistant staphylococcal infections based on a recombinant form of the phage endolysin SAL-1. The study
evaluated the pharmacokinetics, pharmacodynamics, and tolerance among healthy male volunteers after the
intravenous infusion of single ascending doses of SAL200 (0.1, 0.3, 1, 3, and 10 mg/kg of body weight).
SAL200 was well tolerated, and no serious adverse events (AEs) were observed in this clinical study. Most
AEs were mild, self-limiting, and transient. The AEs reported in more than three participants were fatigue,
rigors, headache, and myalgia. No clinically significant values with respect to the findings of clinical
chemistry, hematology, and coagulation analyses, urinalysis, vital signs, and physical examinations were
observed, and no notable trends in our electrocardiogram (ECG) results for any tested dose were noticed. A
greater-than-dose-proportional increase with regard to systemic exposure and the maximum serum
concentration was observed when the SAL200 dose was increased from 0.1 mg/kg to 10 mg/kg. This
investigation constitutes the first-in-human phase 1 study of an intravenously administered, phage endolysinbased drug. (This study has been registered at ClinicalTrials.gov under identifier NCT01855048 and at the
Clinical Research Information Service [https://cris.nih.go.kr/cris/] under identifier KCT0000968.).
BACKGROUND: Transversus abdominis plane (TAP) block provides 12-24 h of analgesia to the parietal
peritoneum and abdominal wall, and are best used combined with oral or intravenous medications. Despite
ease of use, a large margin of safety, and a high success rate, TAP blocks remain under used in settings where
patients could most benefit from their use. Previous studies have used oral or intravenous narcotics for
supplementation. However, the efficacy of TAP blocks in low-resourced settings where patients do not have
dependable access to these medications is unknown. This study examines TAP block analgesic efficacy after
caesarean section in a poorly resourced setting. We compared the post-operative status of 170 women with
self-administered paracetamol-diclofenac with or without TAP blocks. We hypothesised that the block would
decrease pain at 8 h, 16 h, and 24 h at rest, with coughing and upon standing. METHODS: Between Oct 31,
and Dec 28, 2013, 180 women were enrolled and randomly assigned to receive either TAP or sham blocks
after caesarean section. Bi-institutional (Mbarara Regional Referral Hospital and Massachusetts General
Hospital) institutional review board approval was obtained for this single-centre study. After informed written
consent, patients received TAP or sham blocks after caesarian section. Inclusion criteria for enrolment were:
age 18 years or older, weight at least 50 kg, no allergies to study medications, otherwise healthy (American
Society of Anesthesiologists classification status I or II), and having undergone elective, urgent, or emergent
caesarian section under spinal anaesthesia without sedation. Under ultrasound guidance, 20-25 mL of 0·25%
bupivacaine (epinephrine 1:400 000) were injected near the triangles-of-Petit. Sham blocks consisted of a
transducer with a needleless syringe pressed over each flank. In the post-anaesthesia recovery area, all patients
received 1000 mg paracetamol and 50 mg diclofenac, orally, to be continued on an 8-h schedule for 3 days. A
skilled (masked) research nurse collected all data. The primary outcomes measured were numerical rating
scale at 8 h, 16 h, and 24 h at rest, with coughing, and upon standing. The association between the pain scores
at each time and type of treatment (TAP vs sham blocks) was assessed using general linear model with
repeated measures. Demographics were compared using the two sample t-test (appendix). FINDINGS: 170
patients completed the study; 86 in the sham group and 84 in the study group. Demographics (age, weight, and
parity) were similar between both study groups. One participant from the sham group was missing parity
information (appendix). Preliminary data analysis showed reduced pain scores at all times, and with all
degrees of movement for the TAP group (appendix). The largest reduction in pain was at 8 h (resting 33%,
coughing 36%, and standing 44%). With time, the pain scores of the TAP group changed a little, whereas a
Kahlberg, A., et al. (2018). "Volumetric analysis of aneurysm thrombosis after
thoracic endovascular aortic repair predicts postoperative changes in platelet count
and coagulation parameters." J Cardiovasc Surg (Torino) 59(3): 419-427.
Kalina, R., et al. (2021). "[Effect of a Single Dose of Tranexamic Acid Administered
during Anterior Cruciate Ligament Reconstruction Using Hamstrings: a Randomized
Clinical Study]." Acta Chir Orthop Traumatol Cech 88(3): 184-190.
BACKGROUND: The aim of this study was to investigate the predictors of blood count changes and
coagulation parameters alterations after thoracic aortic endovascular repair (TEVAR). METHODS: Fifty
patients (41 males, age 72±7 years) submitted between 2007 and 2009 to elective TEVAR for non-dissecting
aortic lesions, without major associated surgical procedures, were analyzed. Blood count and coagulation
parameters were recorded pre-operatively and daily up to postoperative day 5. The volume of new thrombus
formed after TEVAR (TV) was calculated comparing pre- and post-operative computed tomography scans
with a semi-automatic method by two independent examiners. Pre- intra-, and postoperative variables,
including TV, were tested for a possible effect on changes in laboratory values and transfusion requirements
using a stepwise multiple regression model analysis. RESULTS: In the multivariable model, TV and
associated surgical procedures were significantly associated with maximum platelets decrease (P=0.021, and
P=0.029, respectively), while only TV remained a significant predictor for maximum prothrombin time
increase (P=0.003). Maximum aneurysm diameter (P=0.041), procedural time (P=0.027), and TV (P=0.047)
were also significant predictors of transfusion requirement. CONCLUSIONS: TEVAR is associated with
consumption of platelets and coagulative factors, which seems to be associated with the amount of
perioperative aneurysm thrombosis. The latter may also help to predict perioperative transfusion requirement.
PURPOSE OF THE STUDY Anterior cruciate ligament reconstruction is one of the most common
reconstruction surgeries. The unintended consequences of the surgery are hemarthrosis, blood loss, knee
swelling and postoperative pain. The purpose of the study was to evaluate the effect of a single dose of
intravenous tranexamic acid (TXA) on the postoperative parameters and functional status of the knee joint 3
months after surgery. MATERIAL AND METHODS It is a prospective randomised clinical study. An
intravenous injection of TXA equivalent to 15 mg/kg in 100 ml of saline solution was administered to the test
group during the surgery (20 minutes before the end of the surgery). The control group was administered 100
ml of saline solution without TXA. In both groups, the following parameters were evaluated preoperatively
and postoperatively (on Day 1 and Day 10 and at 1 month and 3 months): thigh circumference at 1 cm above
the patella, Coupens and Yates (CY) score for swelling, and pain score (VAS). At 24 hours after the surgery,
the blood loss (secretion into the drain) and decrease in hemoglobin (Hb) and hematocrit (HCT) levels
compared to the preoperative levels were assessed. The functional status of the knee joint was assessed based
on the Lysholm knee scoring scale and the IKDC subjective knee evaluation form preoperatively, or at 1 and 3
months postoperatively. RESULTS In the test group, a significantly lower blood loss was detected 24 hours
after the surgery. The mean difference of 128 ml compared to the control group was both statistically and
practically significant (p < 0.001, d =1.42). The test group showed a lower decrease in Hb and HCT levels
postoperatively compared to the control group, although with no statistical significance. On the first
postoperative day, slightly better results of the thigh circumference at 1 cm above the patella and of the CY
score were observed in the test group. However, during the follow-up check performed postoperatively on
Day 10, the differences in the thigh circumference at 1 cm above the patella, CY score and pain VAS score
were negligible. The differences in the functional status of the knee joint between the two groups ascertained
during the check performed 1 month and 3 months after the surgery were insignificant. DISCUSSION Our
study, just like other studies, confirms a significant effect of a single dose of intravenous TXA on the volume
of blood loss and early postoperative swelling, which are the parameters affecting the early postoperative
course. Even though the intervention does not affect the subsequent result of surgery, it can undoubtedly be of
benefit perioperatively. There is a fairly limited number of randomised clinical studies on this topic in
literature, with most of them published in the last 7 years. Further research should, among other things,
optimise the protocol and identify a suitable candidate for TXA administration in patients undergoing an ACL
Kantarjian, H. M., et al. (2013). "Phase I study assessing the safety and tolerability of
barasertib (AZD1152) with low-dose cytosine arabinoside in elderly patients with
AML." Clin Lymphoma Myeloma Leuk 13(5): 559-567.
INTRODUCTION: Barasertib is the pro-drug of barasertib-hydroxy-quinazoline pyrazole anilide, a selective
Aurora B kinase inhibitor that has demonstrated preliminary anti-AML activity in the clinical setting.
PATIENTS AND METHODS: This Phase I dose-escalation study evaluated the safety and tolerability of
barasertib, combined with LDAC, in patients aged 60 years or older with de novo or secondary AML.
Barasertib (7-day continuous intravenous infusion) plus LDAC 20 mg (subcutaneous injection twice daily for
10 days) was administered in 28-day cycles. The MTD was defined as the highest dose at which ≤ 1 patient
within a cohort of 6 experienced a dose-limiting toxicity (DLT) (clinically significant adverse event [AE] or
laboratory abnormality considered related to barasertib). The MTD cohort was expanded to 12 patients.
RESULTS: Twenty-two patients (median age, 71 years) received ≥ 1 treatment cycle (n = 6, 800 mg; n = 13,
1000 mg; n = 3, 1200 mg). DLTs were reported in 2 patients (both, National Cancer Institute Common
Terminology Criteria for Adverse Events grade 3 stomatitis/mucositis; 1200 mg cohort). The most common
AEs were infection (73%), febrile neutropenia (59%), nausea (50%), and diarrhea (46%). Barasertib plus
LDAC resulted in an overall response rate (International Working Group criteria) of 45% (n = 10/22;
according to investigator opinion). CONCLUSION: The MTD of 1000 mg barasertib in combination with
LDAC in older patients with AML was associated with acceptable tolerability and preliminary anti-AML
Katheria, A. C., et al. (2017). "Providing a Placental Transfusion in Newborns Who
Need Resuscitation." Front Pediatr 5: 1.
Kaya, O., et al. (2023). "Fluoroscopy guided without contrast injection for ganglion
impar blockade in traumatic coccydynia: Description a modified approach and 1-year
results." Ulus Travma Acil Cerrahi Derg 29(3): 395-401.
Over the past decade, there have been several studies and reviews on the importance of providing a placental
transfusion to the newborn. Allowing a placental transfusion to occur by delaying the clamping of the
umbilical cord is an extremely effective method of enhancing arterial oxygen content, increasing cardiac
output, and improving oxygen delivery. However, premature and term newborns who require resuscitation
have impaired transitional hemodynamics and may warrant different methods to actively provide a placental
transfusion while still allowing for resuscitation. In this review, we will provide evidence for providing a
placental transfusion in these circumstances and methods for implementation. Several factors including cord
clamping time, uterine contractions, umbilical blood flow, respirations, and gravity play an important role in
determining placental transfusion volumes. Finally, while many practitioners agree that a placental transfusion
is beneficial, it is not always straightforward to implement and can be performed using different methods,
making this basic procedure important to discuss. We will review three placental transfusion techniques:
delayed cord clamping, intact umbilical cord milking, and cut-umbilical cord milking. We will also review
resuscitation with an intact cord and the evidence in term and preterm newborns supporting this practice. We
will discuss perceived risks versus benefits of these procedures. Finally, we will provide key straightforward
concepts and implementation strategies to ensure that placental-to-newborn transfusion can become routine
Kërveshi, A., et al. (2014). "Local irrigation of the surgical field with antibiotics in the
end of procedure reduces the infection rate in herniated lumbar disc surgery." Mater
Sociomed 26(6): 398-400.
BACKGROUND: This study presents a new fluoroscopy-controlled approach in patients with chronic
traumatic coccydynia by applying ganglion impar block using the needle-inside-needle technique from the
intercoccygeal region without the administration of contrast material. With this approach, the cost and
possible side effects of using contrast material can be prevented. In addition, we examined the long-term
effect of this method. METHODS: The study was designed retrospectively. The marked area was entered with
a 21-gauge needle syringe, and 3 cc of 2% lidocaine was administered subcutaneously by local infiltration. A
25-gauge 90 mm spinal needle was inserted into the guide 21-gauge 50 mm needle tip. The location of the
needle tip was controlled under fluoroscopy, and 2 mL of 0.5% bupivacaine and 1 mL of be-tamethasone
acetate were mixed and administered. RESULTS: A total of 26 patients with chronic traumatic coccydinia
participated in the study between 2018 and 2020. The average procedure time was approximately 3.19 min.
The mean time of pain relief of more than 50% was 1.25±1.22 (1st min-72 h) min. The mean Numerical pain
rating scale scores were 2.38±2.26 at 1 h, 2.50±2.30 at 6 h, 2.50±2.21 at 24 h, 3.73±2.20 at 1 month,
4.46±2.14 at 6 months 1 and 5.23±2.52 at 1 year. CONCLUSION: Our study shows that as an alternative in
patients with chronic traumatic coccydynia, the long-term results of the needle-inside-needle method from the
intercoccygeal region without contrast material are safe and feasible.
INTRODUCTION: Reported rate of infections after lumbar discectomy is 1%-15 %. This complication may
result in disability or even the death. AIM: The aim of the study is to assess the rate of infection associated
with lumbar discectomies when combined systemic and local antibiotic prophylaxis was employed.
PATIENTS AND METHODS: In this retrospective study we analyzed all patients operated for herniated
lumbar disc from 2009 -2012 in our institute. Beside of receiving systemic prophylaxis with 2g of Cefazoline,
all patients had their operative field irrigated at the end of operation with Amikacin sulfate injection. Wound
was considered infected when local and systemic signs of infection were revealed and were associated with
elevated ESR, leukocytosis and elevated CRP. Assessment of infection is done by neurosurgeon during the
hospitalization and later at outpatient's clinic along postoperative course of three months. RESULTS: A total
of 604 patients were operated, of those 285 patients (47.2 %) females and 319 males (52.8 %), 12 patients
were operated on two levels (1.98 %). Average patient age was 32.5 years (range 20-65 years) Localization of
herniated disc was: in L/2-L/3 20 patients or 3.3 %, the L/3-L/4 level 42 patients or 7 % , the L/4 -L /5 262
patients or 43.3 % at the level L/V- S/1 280 patients or 46.3 %. Three patients (0.49%) developed wound
infection, two of them superficial infection only with local signs: local pain, redness and leakage. They were
treated with oral antibiotics. One with deep wound infection. He presented with local and systemic signs and
treated with i.v antibiotics. All the cultures from wound swab revealed staphylococcus aureus.
CONCLUSION: Prophylaxis with systemic antibiotic (Cefazoline 2.0) intravenous administration 30 minutes
before the incision and irrigation of operative field with local antibiotic Amikacine sulfate at the end of
procedure reduces the infection rate in patients operated for herniated lumbar disc when compared with
Khalil, K. G., et al. (2015). "Operative Intercostal Nerve Blocks With Long-Acting
Bupivacaine Liposome for Pain Control After Thoracotomy." The Annals of Thoracic
Surgery 100(6): 2013-2018.
Khanal, G., et al. (2018). "Towards bedside washing of stored red blood cells: a
prototype of a simple apparatus based on microscale sedimentation in normal gravity."
Vox Sang 113(1): 31-39.
Background Postthoracotomy pain is quite intense. Epidural analgesia (EPI) has long been the gold standard
but is often associated with hypotension and urinary retention. The recent availability of liposomal
bupivacaine formulation (Exparel) stimulated us to use it for multilevel intercostal nerve blocks (IB) injected
during open thoracotomy. Methods We reviewed the records of 85 patients who had open thoracotomies for
lung, pleural, or mediastinal pathologies between March 2010 and December 2013. Clinical variables; pain
score; supplemental narcotic utilization on day 1, 2, and 3; postoperative pulmonary complications; and
hospital length of stay were compared in the 2 groups. Results In all, 53 patients in the IB group had similar
clinical data compared to 32 in the EPI group. There were statistically significant lower mean pain scores on
days 1 and 3, but no significant difference in pain score on day 2. Supplemental narcotic utilization was not
different between the 2 groups. There was a significant decrease in pulmonary complications in the IB group
(4 of 53) compared to the EPI group (8 of 32).The total length of hospital stay was 7.4 days in the IB group
versus 9.3 days in EPI group (p < 0.05). Conclusions It appears that intraoperative IB with bupivacaine
liposome at 6 levels during thoracotomy provided significantly better pain control in postoperative days 1 and
3, compared to EPI in this retrospective study. This technique is simple, safe, and reproducible. It does not
require epidural space invasion, infusion pumps, or another service to comanage the postoperative pain
BACKGROUND AND OBJECTIVES: Infusion of by-products of red blood cell (RBC) storage-induced
degradation as well as of the residual plasma proteins and the anticoagulant-preservative solution contained in
units of stored blood serve no therapeutic purpose and may be harmful to some patients. Here, we describe a
prototype of a gravity-driven system for bedside washing of stored RBCs. MATERIALS AND METHODS:
Stored RBCs were diluted to 10% haematocrit (Hct) with normal saline, matching the conventional washing
procedure. The dilute RBC suspensions were passed through a column of coiled tubing to allow RBC
sedimentation in normal gravity, thus separating them from the washing solution. Washed RBCs were
collected using bifurcations located along the tubing. Washing efficiency was quantified by measuring Hct,
morphology, deformability, free haemoglobin and total-free protein. RESULTS: The gravity-driven washing
system operating at 0·5 ml/min produced washed RBCs with final Hct of 36·7 ± 3·4% (32·3-41·2%, n = 10)
and waste Hct of 3·4 ± 0·7% (2·4-4·3%, n = 10), while removing 80% of free haemoglobin and 90% of totalfree protein. Washing improved the ability of stored RBCs to perfuse an artificial microvascular network by
20%. The efficiency of washing performed using the gravity-driven system was not significantly different than
that of conventional centrifugation. CONCLUSIONS: This proof-of-concept study demonstrates the
feasibility of washing stored RBCs using a simple, disposable system with efficiency comparable to that of
conventional centrifugation, and thus represents a significant first step towards enabling low-cost washing of
Kheirabad, M. K., et al. (2023). "Vascular outcomes of early deflation of radial artery
band following coronary angiography: A controlled clinical trial." J Vasc Nurs 41(2):
56-61.
Kiany, F., et al. (2022). "Evaluation of post laparoscopic cholecystectomy pain after
subcutaneous injection of lidocaine at port site versus lidocaine spray on gallbladder
bed after cholecystectomy: a randomized controlled trial." Langenbecks Arch Surg
407(7): 2853-2859.
The present study aimed to investigate the effect of early deflation of the transradial (TR) band on the
vascular outcomes of patients who have undergone coronary angiography through transradial access (TRA).
The present controlled clinical trial included all patients who had undergone elective coronary angiography
through TRA. The participants (n=70) met the inclusion criteria and were selected using convenient sampling.
Then, they were randomly assigned to the intervention and control groups, using block randomization. Data
collection tools included a questionnaire on demographic and related clinical data, including the history of
diabetes, hypertension, hypercholesterolemia, heart failure and vascular disease, and the checklist of postangiographic complications, including duration of the procedure, systolic and diastolic blood pressures
measured before and after the procedure, and assessments of radial artery occlusion (RAO), hematoma and
pain. The intervention group had their TR band on the artery for 1.5 hours after the procedure. Then, the cuff
of the band was deflated at a speed of 5 cc every 15 minutes, using a syringe. However, the TR band was kept
in place for 2 hours in the control group, followed by the deflation with the same speed. The pressure
application time was recorded in both groups from the removal of sheaths until complete hemostasis. The
patients with early deflation of the TR band experienced less pain compared to those with typical deflation
(P=0.003). However, the variables of hematoma development (P=0.062) and RAO (P=0.371) were not
significantly different between the patients with typical and early deflation of the TR band. The present study
concluded that the patients with early deflation of the TR band experienced less pain compared to those with
typical deflation. Therefore, deflating the TR band after cardiac angiography at 1,5 hours has similar efficacy
PURPOSE: The efficacy of intraperitoneal (IP) and incisional use of local anesthesia in laparoscopic
cholecystectomy is a promising subject regarding post-operative pain control. In this study, we aim to
compare these methods using lidocaine as the local anesthetic. METHODS: This study was a double-blinded
randomized controlled trial. Eighty-two patients, candidates for laparoscopic cholecystectomy, were included.
Participants were randomly divided into two equal groups; the instillation group and the infiltration group. In
the instillation group, a 2% lidocaine ampule was instilled in the gallbladder bed after removal of the
gallbladder. In the infiltration group, a 2% lidocaine ampule was injected subcutaneously into the port sites
before making the incisions for the insertion of laparoscopic ports. RESULTS: The mean age of patients were
41.66 ± 14.44 and 48.05 ± 17.03 years in the instillation and infiltration groups, respectively. The etiologies
recorded in this study were: acute calculous cholecystitis (29.3%), symptomatic gallstone (68.3%), and polyp
(2.4). The pain severity, evaluated at six different times, from immediately after awakening from anesthesia to
24 h after the operation, was not significantly different between the two groups (p-value = 0.329).
Consumption of nonsteroidal anti-inflammatory drugs and narcotics, were statistically lower in the instillation
group (p-value = 0.013 and 0.003, respectively). However, hospitalization period, time spent to return to
normal bowel movements and oral diet, and postoperative nausea/vomiting were not significantly significant
between the groups. CONCLUSION: IP instillation of lidocaine following laparoscopic cholecystectomy
offers post-operative pain relief and is associated with lower analgesic consumption in comparison to
Kim, H. J., et al. (2016). "Evaluation of fluid warmer safety using hemorheologic
analysis with outdated human blood." Clin Hemorheol Microcirc 62(1): 13-17.
Kim, H. K., et al. (2017). "Incidence and risk factors of hypotension after intravenous
fosphenytoin administration." J Clin Pharm Ther 42(5): 561-566.
PURPOSE: A newly developed fluid warmer (ThermoSens®) has a direct blood warming plate, which can
result in hemolysis or red blood cell injury during heating. Therefore, to evaluate the safety of heating blood
products with a fluid warmer, we conducted laboratory tests to study hemolysis and erythrocyte rheology.
METHODS: We used outdated human blood taken from a Korean blood bank. Packed red blood cells mixed
with 100 mL isotonic saline was passed through the fluid warmer. Blood flow was achieved by either gravity
or 300 mmHg pressure. Blood samples were analyzed before and after heating for hemolysis marker and
erythrocyte rheology parameters. RESULTS: The temperatures at the outlet were higher than 38°C at gravity
and 300 mmHg pressure, respectively. There were no significant differences in hemolysis markers
(hemoglobin, hematocrit, lactate dehydrogenase, and plasma free hemoglobin) or erythrocyte rheology
(deformability, disaggregating shear stress, and aggregation index) between before and after heating (p > 0.05)
except LDH at gravity (p = 0.0001). CONCLUSION: The ThermoSens® fluid warmer caused no erythrocyte
injury or negative effects on rheology during heating. Regarding medical device development, hemorheologic
analysis can be useful for safety evaluation of medical devices that directly contact blood for temperature
modulation.
WHAT IS KNOWN AND OBJECTIVE: Fosphenytoin (FOS) administered intravenously offers several
benefits over intravenously administered phenytoin, including a faster infusion rate, decreased pain and
irritation at the infusion site, and fewer cardiovascular complications. However, some studies suggest that the
intravenous administration of FOS in some patients may also induce adverse cardiovascular events. Here, we
investigated the clinical characteristics of patients who experienced hypotension following an intravenous
infusion of a FOS loading dose. METHODS: We reviewed the medical records of consecutive patients who
received an intravenous (IV) dose of FOS between July 2013 and June 2015. Various clinical and
demographic parameters were analysed, including comorbidities, drug history, seizure aetiology and type,
incidence of hypotension/cardiac arrhythmia and the dosing data (ie the total dose, concentration and FOS IV
infusion rate). Hypotension was defined as a ≥20 mm Hg decrease in systolic blood pressure or a ≥10 mm Hg
decrease in diastolic blood pressure during or after FOS IV infusion. These parameters were compared
between patients with and without hypotension. RESULTS AND DISCUSSION: Of the 28 included patients,
11 (39%) had hypotension associated with an IV infusion of FOS, two of whom also had an atrioventricular
block. Most patients (22/28, 79%) who received an IV infusion of FOS had status epilepticus (SE). The
presence of SE was significantly associated with the development of hypotension (P=.026); hypotension
occurred in half of the patients with SE, but did not occur in six patients without SE. Hypotension was also
associated with old age (≥60 years, P=.034) and the presence of a systemic infection (P=.04). WHAT IS NEW
AND CONCLUSION: Our study shows that hypotension associated with an IV infusion of FOS is not a rare
adverse event, especially in patients with SE. Moreover, we found that old age and the presence of a systemic
infection increased the risk of hypotension. These findings suggest that FOS should be infused under careful
Kim, J.-E., et al. (2019). "Risk Factors of Postoperative Spinal Epidural Hematoma
After Biportal Endoscopic Spinal Surgery." World Neurosurgery 129: e324-e329.
Background Although postoperative spinal epidural hematoma is a rare complication, it can cause severe
neurologic complications. Studies regarding biportal endoscopic spinal surgery, a type of minimally invasive
spinal surgery technique, have been recently reported. The purpose of our study is to report the incidence and
risk factors of postoperative hematoma after biportal endoscopic spinal surgery. Methods The subjects
included 310 patients that underwent biportal endoscopic spinal surgery from 2015 to 2017. Magnetic
resonance imaging (MRI) was performed in all patients before surgery, and also after surgery to identify
epidural hematoma. Using electronic medical records, perioperative factors such as age, sex, operation name,
operation level, water infusion pump usage, thrombin-containing hemostatic agent, and anticoagulant
medication were statistically analyzed in the aspect of postoperative hematoma. Results The overall
occurrence rate of postoperative hematoma was 23.6% (n = 94). A total of 304 levels (76.4%) were without
hematoma according to the postoperative MRI among the total 398 levels. Six patients underwent revision
surgery of hematoma evacuation. Female sex, old age (>70 years), preoperative anticoagulation medication,
and usage of intraoperative water infusion pump were significantly correlated to the occurrence of
postoperative hematoma. Conclusions Although symptomatic postoperative hematoma was extremely rare at
1.9%, radiologic hematoma confirmed by postoperative MRI was higher at 23.6%. The perioperative risk
factors of postoperative hematoma after biportal endoscopic spinal surgery include female sex, older age (>70
years), preoperative anticoagulation medication, usage of intraoperative water infusion pump, and surgery
Kim, S., et al. (2017). "Pharmacokinetics and safety of a single dose of the novel
necrosis inhibitor LC28-0126 in healthy male subjects." Br J Clin Pharmacol 83(6):
1205-1215.
AIMS: A novel necrosis inhibitor, LC28-0126, is expected to have a cellular protective effect from ischaemic
reperfusion injury in acute myocardial infarction. The objective of this study was to investigate the safety,
tolerability and pharmacokinetics of LC28-0126 after a single intravenous administration in healthy male
subjects. METHODS: The study was a dose-block-randomized, double-blind, placebo-controlled, single
ascending dose, first-in-human trial. Subjects were randomly assigned to receive 0.3, 1, 3, 10, 25, 50, 100 or
200 mg of LC28-0126. LC28-0126 was infused for 30 min and 5 min in cohorts 1 and 2, respectively. An
interim analysis to assess the tolerability and pharmacokinetics was conducted in each dose group. Blood
samples were taken to determine plasma LC28-0126 concentrations from predose to 48 or 144 h postdose, and
urine samples were taken from predose to 48 or 72 h postdose. RESULTS: Overall, 89 subjects were
randomly assigned to the dose groups of the two cohorts. LC28-0126 was well tolerated, and no serious
adverse events were reported. LC28-0126 showed rapid disposition in the distribution phase. Overall, the
fraction of unchanged LC28-0126 excreted during the 48 or 72 h after administration was below 5%. The
systemic exposure of LC28-0126 tends to be increased in a dose-proportional manner in the dose range of 0.3200 mg. CONCLUSIONS: A single intravenous dose of LC28-0126 was safe and well tolerated up to 200 mg.
Furthermore, LC28-0126 demonstrated a predictable pharmacokinetic profile after a single intravenous
Kim, S., et al. (2024). "Cryogenic flow boiling in microgravity: Effects of reduced
gravity on two-phase fluid physics and heat transfer." International Journal of Heat
and Mass Transfer 218: 124751.
Kim, S. J., et al. (2019). "Short-term daily teriparatide improve postoperative
functional outcome and fracture healing in unstable intertrochanteric fractures." Injury
50(7): 1364-13