Procalcitonin Over the past two decades, the body of literature on the clinical usefulness of procalcitonin (PCT) in adults has grown rapidly. Although this approach has led to increased insight, it has also prompted debate regarding its potential use in diagnosis and management of severe infection. Clinicians, however, are less familiar with the use of procalcitonin. Procalcitonin • Elevation in the serum concentration of PCT is associated with systemic infection. This association has led to the proposed use of PCT as a novel biomarker of bacterial sepsis. • In an adult intensive care unit (ICU) population, we identify a specific and important question-can PCT accurately distinguish sepsis in patients with systemic inflammatory response syndrome (SIRS) who have a suspected infection? • The published evidence does not support a general claim that PCT is a useful decision support tool for diagnosing sepsis in patients who have SIRS. • PCT has a slightly better ability to exclude the diagnosis of sepsis. • • • • • • Ninety-four patients with consecutive trauma >or=16 years who were admitted to the ICU for an expected stay of >24 hours. PCT and CRP were collected at admission and every day thereafter. The American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference definition was used to identify sepsis criteria. The Sequential Organ Failure Assessment score was used to describe the severity of organ dysfunction Patients with trauma presented an early and significant increase in PCT at the moment of septic complications compared with concentrations measured 1 day before the diagnosis of sepsis: 0.85 vs. 3.32 ng/mL for PCT (p < 0.001) and 135 vs. 175 mg/L for CRP (p = not significant). The areas under the respective curve at admission in the diagnosis of sepsis were 0.787 for PCT and CRP and 0.489 , CONCLUSION: PCT plasma marks possible septic complication during systemic inflammatory response syndrome after major trauma. In addition, high PCT concentration at admission after trauma in ICU patients indicates an increased risk of septic complications. Diagnostic accuracy of PCT, WBC and, CRP for suspected acute appendicitis • RESULTS: • Seven qualifying studies (1011 suspected cases, 636 confirmed) from seven countries were identified. ROC curve analysis showed that CRP had the highest accuracy area under ROC curve 0·75, followed by WBC 0·72, and PCT 0·65. PCT was found to be more accurate in diagnosing complicated appendicitis, with a pooled sensitivity of 62 per cent and specificity of 94 per cent. • CONCLUSION: • PCT has little value in diagnosing acute appendicitis, with lower diagnostic accuracy than CRP and WBC. However, PCT has greater diagnostic value in identifying complicated appendicitis. • • • • Seven qualifying studies (1011 suspected cases, 636 confirmed) from seven countries were identified. Bivariable pooled sensitivity and specificity were 33 (95 per cent confidence interval (c.i.) 21 to 47) and 89 (78 to 95) per cent respectively for PCT, 57 (39 to 73) and 87 (58 to 97) per cent for CRP, and 62 (47 to 74) and 75 (55 to 89) per cent for WBC. ROC curve analysis showed that CRP had the highest accuracy (area under ROC curve 0·75, 95 per cent c.i. 0·71 to 0·78), followed by WBC (0·72, 0·68 to 0·76) and PCT (0·65, 0·61 to 0·69). PCT was found to be more accurate in diagnosing complicated appendicitis, with a pooled sensitivity of 62 (33 to 84) per cent and specificity of 94 (90 to 96) per cent. CONCLUSION: PCT has little value in diagnosing acute appendicitis, with lower diagnostic accuracy than CRP and WBC. However, PCT has greater diagnostic value in identifying complicated appendicitis. Given the imperfect accuracy of these three variables, new markers for improving medical decision-making in patients with suspected appendicitis are highly desirable. Copyright © 2012 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. Pediatric appendicitis • METHODS: • Subjects aged 1 to 18 years presenting with abdominal pain suspicious for acute appendicitis were enrolled. • RESULTS: • Two hundred nine subjects (59% male, 41% female) were enrolled over 6 months. One hundred fifteen subjects were histologically diagnosed with appendicitis; 94 subjects did not have appendicitis and were used as controls. Mean values of WBC, CRP, PCT, and absolute neutrophil count in subjects with definitive appendicitis were significantly higher than in subjects with no definitive appendicitis. D-Lactate levels were noncorrelative. • CRP with WBC is useful in distinguishing appendicitis from other diagnoses in pediatric subjects presenting to the ED. White blood cell count greater than >12 cells × 1000/mm(3) and CRP greater than 3 mg/dL increases the likelihood of appendicitis. D-Lactate is not a useful laboratory adjunct. dp notes the fact that PCT is missing Suspected Appendicitis • A prospective observational study was carried out in the emergency department of a university hospital. Adult patients who presented to the ED with clinically suspected appendicitis were enrolled. Each patient underwent serum PCT, CRP, and Alvarado score evaluation on admission. The results of these three measurements were analyzed in relation to the final diagnosis determined by histopathological findings or compatible computed tomography findings. • Of the 214 study patients, 113 (52.8 %) had a confirmed diagnosis of appendicitis and 58 had complicated appendicitis. For the diagnosis of appendicitis, the area under the receiving operating characteristic (ROC) curve is 0.74 for Alvarado score, 0.69 for PCT, and 0.61 for CRP. Overall, the Alvarado score has the best discriminative capability among the three tested markers. We adopted two cutoff point approaches to harness both ends of the diagnostic value of a biomarker. PCT levels were significantly higher in patients with complicated appendicitis. For diagnosis of complicated appendicitis, a cutoff value of 0.5 ng/mL had a sensitivity of 29 % and a specificity of 95 %, while a cutoff value of 0.05 ng/ml had a sensitivity of 85 % and a specificity of 30 % in diagnosing complicated appendicitis. For those with a PCT value in the gray zone, clinical findings may play a more important role. • The study does not support the hypothesis that PCT may be useful for screening ED patients for appendicitis. However, determination of the PCT level may be useful for risk assessment of ED patients with suspected complicated appendicitis. Discriminative value of PCT, interleukin-6 (IL-6), and CRP for suspected sepsis. • Of 336 enrolled subjects, 60% had definite infection, 13% possible infection, and 27% no infection. Of those with infection, 202 presented with sepsis, 28 with severe sepsis, and 17 with septic shock. Overall, 21% of subjects were septicemic. PCT, IL6, and CRP levels were higher in septicemia (median PCT 2.3 vs. 0.2 ng/mL; IL-6 178 vs. 72 pg/mL; CRP 106 vs. 62 mg/dL; p < 0.001). Biomarker concentrations increased with likelihood of infection and sepsis severity. Using receiver operating characteristic analysis, PCT best predicted septicemia (0.78 vs. IL-6 0.70 and CRP 0.67), but CRP better identified clinical infection (0.75 vs. PCT 0.71 and IL-6 0.69). A PCT cutoff of 0.5 ng/mL had 72.6% sensitivity and 69.5% specificity for bacteremia, as well as 40.7% sensitivity and 87.2% specificity for diagnosing infection. no biomarker independently predicted discharge to a higher level of care. • In adult emergency department patients with suspected sepsis, PCT, IL-6, and CRP highly correlate with several infection parameters, but are inadequate at discriminating and cannot be used independently as diagnostic tools. WBC, CRP & PCT • A total of 10 studies looking into PCT tests and 8 studies looking into CRP tests were included in the final analysis. The prevalence of bacterial sepsis was 304 of 1031 (29.5%) in PCT studies and 741 of 1316 (56.3%) in CRP studies. In terms of area under the receiver operating characteristic curve, PCT had comparable discrimination to CRP (area under the curve: 0.75 versus 0.74). PCT was not as sensitive as the CRP test. The pooled sensitivity of PCT was 0.59 as compared with 0.75 for CRP. PCT was more specific than sensitive whereas CRP was more sensitive than specific in this population. The pooled specificity was 0.76 for PCT and 0.62 for CRP. PCT had greater likelihood ratio positive (2.50) making it the better rule-in test. • Of three markers potentially useful for diagnosing bacterial sepsis in children with fever and neutropenia, PCT had comparable diagnostic accuracy to CRP. Serum PCT as a diagnostic test • • • • for sepsis, severe sepsis, or septic shock in adults in intensive care units or after surgery or trauma, alone and compared with CRP. To draw and compare the summary receiver operating characteristics curves for procalcitonin and C-reactive protein from the literature. Thirty-three studies fulfilled inclusion criteria (3,943 patients, 1,828 males, 922 females; mean age: 56.1 yrs; 1,825 patients with sepsis, severe sepsis, or septic shock; 1,545 with only systemic inflammatory response syndrome); Global mortality rate was 29.3%. Global odds ratios for diagnosis of infection complicated by systemic inflammation were 15.7 for the 25 studies (2,966 patients) using procalcitonin and 5.4 for the 15 studies (1,322 patients) using CRP. The summary receiver operating characteristics curve for procalcitonin was better than for CRP. In the 15 studies using both markers, the Q* was significantly higher for procalcitonin than for C-reactive protein (0.78 vs. 0.71, p = .02), the former test showing better accuracy. Procalcitonin represents a good biological diagnostic marker for sepsis, severe sepsis, or septic shock, difficult diagnoses in critically ill patients. Procalcitonin is superior to C-reactive protein. Procalcitonin should be included in diagnostic guidelines for sepsis and in clinical practice in intensive care units. In Summary • • • • • • • • Procalcitonin has a slightly better ability to exclude the diagnosis of sepsis. PCT plasma marks possible septic complications during systemic inflammatory response syndrome after major trauma. High PCT concentration at admission after trauma in ICU patients indicates an increased risk of septic complications PCT has little value in diagnosing acute appendicitis, with lower diagnostic accuracy than CRP and WBC. PCT has greater diagnostic value in identifying complicated appendicitis. Of three markers potentially useful for diagnosing bacterial sepsis in children with fever and neutropenia, PCT had comparable diagnostic accuracy to CRP. PCT represents a good biological diagnostic marker for sepsis, severe sepsis, or septic shock, difficult diagnoses in critically ill patients. PCT is superior to Creactive protein. PCT should be included in diagnostic guidelines for sepsis and in clinical practice in intensive care units. Clinicians, however, are less familiar with the use of PCT. You cannot bill for this to detect sepsis