Journal Pre-proof Surgical factors associated with symptomatic implant removal after patella fracture Jayesh Gupta , Elizabeth A. Harkin , Katherine O’Connor , Blessing Enobun , Nathan N. O’Hara , Robert V. O’Toole PII: DOI: Reference: S0020-1383(22)00214-5 https://doi.org/10.1016/j.injury.2022.03.028 JINJ 10068 To appear in: Injury Accepted date: 14 March 2022 Please cite this article as: Jayesh Gupta , Elizabeth A. Harkin , Katherine O’Connor , Blessing Enobun , Nathan N. O’Hara , Robert V. O’Toole , Surgical factors associated with symptomatic implant removal after patella fracture, Injury (2022), doi: https://doi.org/10.1016/j.injury.2022.03.028 This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2022 Published by Elsevier Ltd. Highlights Individuals with k-wires were 4.9 times more likely to have symptomatic removal of implant. Implant prominence exceeding 5mm might be associated with increased odds of symptomatic implant removal in patients with patella fractures. Patients with BMI ≤25 and age ≤45 were more likely to have symptomatic removal of implant. 1 Surgical factors associated with symptomatic implant removal after patella fracture Jayesh Gupta, BS, Elizabeth A. Harkin, MD, Katherine O’Connor, BS, Blessing Enobun, MD, MPH, Nathan N. O’Hara, PhD, and Robert V. O’Toole, MD From the R Adams Cowley Shock Trauma Center, Department of Orthopaedics, University of Maryland School of Medicine, Baltimore, Maryland Conflict of interest and funding: N. N. O’Hara receives stock or stock options from Arbutus Medical, Inc. unrelated to this study. R. V. O’Toole is a paid consultant for Lincotek and Smith & Nephew, receives stock options from Imagen, and receives royalties from Lincotek, all unrelated to this study. This study did not receive external funding. Corresponding author Robert V. O’Toole, MD R Adams Cowley Shock Trauma Center Department of Orthopaedics University of Maryland School of Medicine 22 South Greene Street, T3R62 Baltimore, Maryland 21201 E-mail: rotoole@som.umaryland.edu Tel: 410-328-6292, Fax: 410-328-2893 2 ABSTRACT Objectives: To determine whether certain types of fixation and other factors associated with the fixation could be identified that predict an increased risk of symptomatic implant removal. Methods: We conducted a retrospective cohort study at our urban academic level 1 trauma center. Patients aged ≥18 years who underwent operative fixation for patella fracture were included. The primary outcome was symptomatic implant removal after operative fixation. Results: Of the 186 study patients (mean age, 44 [SD 17] years, 65% male), 53 patients (28.5%) underwent symptomatic implant removal. Modifiable risk factors for symptomatic implant removal included the use of Kirschner (k)-wires (OR: 4.93; 95% CI, 1.89–14.10; p < 0.001), and a trend towards significance for implant prominence >5 mm (OR: 2.57; 95% CI, 0.93–7.93; p = 0.07). Symptomatic implant removal was also less likely in patients >45 years of age (OR: 0.14; 95% CI, 0.06–0.34; p < 0.01), of a racial minority (OR: 0.40; 95% CI, 0.17–0.88; p = 0.03), and a body mass index >25 kg/m2 (OR: 0.39; 95% CI, 0.18–0.84; p = 0.02). The final model demonstrated excellent prognostic performance, with an AUC of 0.83 (0.76–0.90). Conclusion: We identified both modifiable and non-modifiable factors associated with symptomatic implant removal in patients with patella fractures. Surgeons should be aware that the use of k-wires and any implant prominence exceeding 5 mm might be associated with increased odds of symptomatic implant removal in patients with patella fractures. Keywords: symptomatic implant removal, patella fracture, k-wires, predictors 3 Introduction Symptomatic implant requiring removal after operative fixation is the most common complication of patella open reduction and internal fixation (ORIF) and has been reported with rates ranging from 17%–70% [1-5]. To our knowledge, no studies to date have identified the modifiable surgical risk factors associated with symptomatic implant removal. Previous studies have primarily focused on patella fracture characterization, operative techniques, functional outcomes after implant removal, and non-modifiable risk factors for implant removal [1-5]. Identification of modifiable surgical risk factors associated with symptomatic implant removal might allow surgeons to alter operative technique to avoid the risk of future symptomatic implant removal, and counsel patients with non-modifiable risk factors that place them at a higher risk for symptomatic implant removal. The purpose of this retrospective cohort study was to determine the surgical risk factors associated with symptomatic implant removal after ORIF of patella fractures. Our hypothesis was that certain types of fixation and other factors associated with the fixation, could be identified to predict an increased risk of symptomatic implant removal. Methods Study participants This retrospective cohort study was completed after institutional review board approval. All patients with OTA/AO types 34A-C patella fractures who were treated with ORIF at an urban, academic level 1 trauma center from 2008 to 2018 (n = 354) were identified from electronic medical records (Figure 1) [6]. We excluded patients who underwent suture fixation with no additional use of implant, had complete patellectomy, or had a fracture in the setting of previous total knee arthroplasty. Patients younger than 18 years of age and those who did not 4 have a minimum follow-up of at least 6 weeks, as patella fractures are thought to typically require this amount of time to be healed, were also excluded. Patients were included only if they had removal of implant caused by symptomatic implant, and not for other reasons such as revision of fixation for implant failure, nonunion or infection. Outcome and predictors The primary outcome for this study was removal of symptomatic implant after ORIF of patella fractures. Patient predictors were selected based on previous literature and clinical relevance. We included candidate predictors that had minimal correlation to each other and minimal susceptibility to measurement error. Symptomatic was defined as having localized pain over the implant for no other medical reason for removal such as implant failure, nonunion or infection. Elective removal of symptomatic implant was confirmed by reviewing patient radiographs, clinic notes, and operative reports. Demographics and injury characteristics of interest were selected based on potential clinical relevance. Demographic characteristics included age, sex, race, body mass index (BMI), and injury characteristics included OTA/AO classification. Most patients had OTA/AO type 34C (86%) patella fractures with subtype 34C3 being the most common (45%). Patella ORIF was categorized as using one or more of the following fixation constructions: parallel longitudinal Kirschner (k-wires), figure-of-eight tension band, circumferential cerclage wiring, minifragment screws, cannulated screws, pins, or plates. In our unadjusted analysis of various constructs, we analyzed each as a separate event regardless of whether other constructs were also incorporated (Table 1). The amount of implant protrusion was quantified by one of the authors by viewing immediate postoperative radiographs and using measurement tool on picture archiving and communication system (PACS) IMPAX 6.5.1.1008 5 (Agfa-Gevaert, Morstel, Begium) or eUnity v6.10.1.2.15 (Client Outlook Inc., Waterloo, Ontario, Canada) system. The largest protrusion of implant from patella was measured on either anteroposterior (AP) or lateral views using standard clinical IMPAX or eUnity system. The total vertical length of the patella was measured on only the lateral radiograph. These two measurements were used to create a ratio of the amount of protrusion for each patient based on patella length to account for patella length variance among patients, and to remove magnification and other calibration issues with fluoroscopic images. Statistical analysis Previous studies suggest that a prognostic logistic regression model requires 5 to 10 study events per prognostic variable for stable results [7,8]. Based on this heuristic, our sample size was adequate to support a model containing 5 to 10 factors. We summarized patient demographics, injury characteristics, and implant characteristics as means with standard deviation (SD) for normally distributed continuous variables and medians with interquartile ranges (IQR) for skewed data. We described categorical data as counts with proportions. Patient characteristics were compared based on primary outcome, and P values were obtained using Student’s t-tests (normally distributed data), Wilcoxon rank-sum test (skewed, continuous data) or Pearson’s chi-square tests (categorical), as appropriate. To build a predictive model, all candidate predictors were considered, and we used stepwise elimination techniques, based on a minimum Akaike Information Criterion (AIC), to optimize the overall fit of the model. We report the association between prognostic factors and the outcome as odds ratios with 95% confidence intervals (CIs). The prognostic performance of the model was assessed based on discrimination and calibration. Discrimination was assessed with the area under the curve (AUC), in which a value of 1.0 indicates perfect discrimination and 6 a value of 0.5 signifies the model performs no better than chance. Calibration was evaluated by plotting the probability of symptomatic implant versus the observed outcome with a 95% confidence interval. A slope of 1.0 would indicate perfect calibration across the predicted range. To demonstrate the variation in the probability of symptomatic removal of implant based on our prognostic factors, we plotted the observed combination of modifiable factors (greatest amount of implant prominence and the use of k-wires) against the probability of symptomatic implant removal. The plots were stratified by age and BMI, conditioned on race. Missing predictor data accounted for less than 4% of any given variable and was imputed using multiple imputations. All statistical analyses were performed using R Version 4.0.0 (R Foundation for Statistical Computing, Vienna, Austria) and JMP Pro Version 14 (SAS, Cary, NC). Results Of the 186 patients in the study cohort, the majority were male (n = 121, 65%) and White (n = 109, 59%). The average age of the sample was 44 years (SD 17) and the median BMI was 27 kg/m2 (IQR: 23–31). Significant differences were observed between the patients with and without symptomatic implant removal based on age and BMI (p < 0.05) (Table 1). The difference in comminution between the symptomatic implant removal and control group did not reach the threshold for statistical significance (77.4% vs. 66.2%, p = 0.19). In the unadjusted analysis, we observed a difference between groups in k-wire usage (58.5% vs. 22.6%, p < 0.001), use of a figure-of-eight construct (62.3% vs. 36.8%, p = 0.003), and greatest prominence measurement (11.1 mm vs. 5.1 mm, p < 0.001). No evidence of statistically significant differences were shown for the other treatment parameters, including 7 screws (77.4% vs. 87.2%, p = 0.15), plates (3.8% vs .7.5%, p = 0.54), cerclage wires (22.6% vs. 14.3%, p = 0.24), and pins (15.1% vs 9.8%, p = 0.44). Our prognostic adjusted model identified 5 factors associated with symptomatic implant removal in patella fracture patients (Table 2, Figure 2). With regards to modifiable surgical risk factors, individuals with k-wires were 4.9 times more likely to have symptomatic removal of implant (OR: 4.93; 95% CI, 1.89–14.10; p < 0.001). We observed an association near statistical significance for any implant prominence >5 mm (OR: 2.57; 95% CI, 0.93–7.93; p = 0.07). Patients >45 years of age were 86% less likely to have symptomatic removal of implant (OR: 0.14; 95% CI, 0.06–0.34; p < 0.001). Black, Asian, and other individuals were 60% less likely to have symptomatic removal of implant (OR: 0.40; 95% CI, 0.17–0.88; p = 0.03). Patients with BMI >25 kg/m2 were 61% less likely to have symptomatic removal of implant (OR: 0.39; 95% CI, 0.18–0.84; p = 0.02). The prognostic model had a discriminative ability of AUC 0.83 (95% CI, 0.76–0.90), suggesting that the model had excellent predictive value. The calibration plot further suggests that our model performed well consistently across the prognostic range (Figure 3). Discussion Previous studies have compared patella fracture construct types to determine failure and symptomatic implant rates [1,3,4]. However, to our knowledge, this is the first study to provide a model that can predict symptomatic implant removal for patella fractures treated with ORIF based on both non-modifiable risk factors and modifiable surgical risk factors. Consistent with previous studies, we observed that symptomatic implant removal was associated with younger age, BMI <25 kg/m2, and White race. However, we also observed that there appears to be a very 8 strong signal associated with implant removal and the use of k-wires, and possibly associated with implant prominence exceeding 5 mm. Research on modifiable surgical predictors of implant removal after patella fracture is very limited. The current authors’ hypothesis that use of k-wires with greater implant prominence is associated with an increased risk of symptomatic implant removal was driven by clinical experience and previous literature on patella fractures [3,4]. Previous studies on symptomatic implant removal mostly focused on determining incidence of symptomatic implant removal, comparing implant removal rates between two specific constructs, considering the complications of specific constructs, or looking at long term functional outcomes [1-5]. The use of k-wires significantly increased odds of implant removal by nearly 5-fold. Some surgeons might find this result to be expected; however, k-wire fixation remains a very popular treatment strategy. This result is important to put before clinicians as alternative treatment options might exist that provide similar fixation results but without the high risk of symptomatic implant removal. For example, Busel et al. [9] performed a retrospective review of 50 patella fractures treated with cannulated screws with FiberWire® (Arthrex, Naples, FL) tension band and cerclage construction which showed a high risk of union (96%) and low risk of symptomatic implant removal (8%). Of note, 48/50 patients had OTA/AO 34C fractures; however, none of the 48 patients had a comminuted fracture pattern, specifically OTA/AO 34C3, thus limiting the generalizability of the cannulated screws with FiberWire® construct for more complex fracture patterns. In the Hoshino et al. [4] retrospective cohort study of 448 patients, the authors looked only at the modified tension band technique using either cannulated screws or k-wires, and found significantly lower symptomatic implant removal (22.6% vs. 36.8%) in the cannulated screws 9 group with no difference in postoperative infection and failure rate. A large proportion of the patients in Hoshino et al. [4] had OTA/AO 34C3 type fractures. Lebrun et al. [5] evaluated multiple fixation constructs and found that none of the patients (n = 10) who underwent tension band wiring with cannulated screws attributed their knee pain to a symptomatic implant. Additionally, none of the 10 patients required symptomatic implant removal compared with the overall symptomatic implant removal rate of 52%. We recognize the technical difficulty in using the cannulated screws and tension band technique in some comminuted fractures. However, our study and others [4,5,9] support the consideration of alternative fixation techniques when possible and if supported by the fracture type, to avoid symptomatic implant removal with no significant changes in infection and failure rates. Patients with a BMI less than 25 kg/m2 and younger than 45 years of age also appeared more likely to have symptomatic implant removal. Patients with lower BMI have less subcutaneous tissue overlying their implant, perhaps resulting in more skin irritation over the implant site. Surgeons might be less likely to offer surgery as an option for symptomatic implant to heavier and older patients because of a perceived increased risk for surgery in this population. It is also possible that younger and thinner patients might be more active on average than older and heavier patients, and thus more likely to have irritation caused by the implant. Studies looking at symptomatic implant removal for other fractures, including olecranon, tibial plateau, and tibial fractures, have found similar findings. Patients with lower BMI or younger age, or a combination of both are more likely to have symptomatic implant removal [10-12]. Minority status was also associated with less implant removal. There are several possible explanations for this finding including unmeasured confounders, but it is also possible that this is another example of implicit biases affecting disparities in care for minority patients as has been observed 10 in other areas of medicine as well as in fracture care. Dodwell et al. [13] found an association between implant removal and younger age, White race, and higher socioeconomic status in pediatric patients with femoral shaft fractures. While we did not track socioeconomic status, this study found similar trends of higher rates of implant removal in younger and White patients. In this study and ours, patients should have similar needs for implant removal, yet minorities underwent fewer implant removal procedures. This and other studies indicate that disparities in fracture care is complicated and that further studies are required to understand and address the disparity identified [13-16]. Although significant in the unadjusted analysis, implant prominence only approached statistical significance in the reduced prognostic model. Interestingly, all k-wire constructs had a prominence of greater than 5 mm. This study has many strengths. This is the first study to describe a model that accurately predicts which type of patients with patella fractures are likely to receive reoperation for symptomatic implant removal. This is also the first study that identifies modifiable surgical risk factors that can be used by surgeons to reduce the likelihood of subsequent surgeries after patella ORIF. The statistical model was developed using robust prognostic methods and the sample size is adequate to support our research question. The limitations of this study should also be considered. This is a retrospective study limited by the quality of chart review from electronic medical records. Our analysis plan attempted to account for some of the potential sources of bias and other factors typical of retrospective reviews. Although efforts were made to ensure consistent measurements across cases and controls, reviewers were not blinded to outcomes, possibly leading to bias. The retrospective nature of this study does not follow patients after symptomatic implant removal to 11 determine whether symptoms improved, but determining the efficacy of implant removal is well beyond the scope of the study. Most importantly this is not a prospective clinical trial, so our findings only show associations and not causation. Overall, this study provides insight on identifying which patients are likely to have implant removal. Surgeons should counsel young patients or those with a BMI less than 25 kg/m2 on their increased risk for subsequent reoperation for symptomatic implant removal. Surgeons should consider that the use of k-wires for patella fracture fixation might be associated with an increased risk of implant removal. Reducing unnecessary procedures not only benefits patients but also supports cost effective patient care. 12 References [1] Kumar G, Mereddy PK, Hakkalamani S, Donnachie NJ. Implant removal following surgical stabilization of patella fracture. Orthopedics. 2010;33. https://doi.org/10.3928/01477447-20100329-14 [2] Greenberg A, Kadar A, Drexler M, Sharfman ZT, Chechik O, Steinberg EL, et al. Functional outcomes after removal of hardware in patellar fracture: Are we helping our patients? Arch Orthop Trauma Surg. 2018;138:325-30. https://doi.org/10.1007/s00402017-2852-2 [3] Hambright DS, Walley KC, Hall A, Appleton PT, Rodriguez EK. Revisiting tension band fixation for difficult patellar fractures. J Orthop Trauma. 2017;31;e66-72. https://doi.org/10.1097/BOT.0000000000000686 [4] Hoshino CM, Tran W, Tiberi JV, Black MH, Li BH, Gold SM, et al. 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Predictors of symptomatic implant removal after open reduction and internal fixation of tibial plateau fractures: a retrospective case-control study. Orthopedics. 2020;43:161-7. https://doi.org/10.3928/01477447-20200314-02 [13] Dodwell E, Wright J, Widmann R, Edobor-Osula F, Pan TJ, Lyman S. Socioeconomic factors are associated with trends in treatment of pediatric femoral shaft fractures, and subsequent implant removal in New York state. J Pediatr Orthop. 2016;36:459-64. doi: 14 10.1097/BPO.0000000000000494 [14] Sprague S, Heels-Ansdell D, Bzovsky S, Zdero R, Bhandari M, Swiontkowski M, et al. Prognostic factors for predicting health-related quality of life after intramedullary nailing of tibial fractures: a randomized controlled trial. Bone Jt Open. 2021;2:22-32. doi: 10.1302/2633-1462.21.BJO-2020-0150.R1 [15] Driesman A, Fisher N, Konda SR, Pean CA, Leucht P, Egol KA. Racial disparities in outcomes of operatively treated lower extremity fractures. Arch Orthop Trauma Surg. 2017;137:1335-40. doi: 10.1007/s00402-017-2766-z [16] Okike K, Chan PH, Prentice HA, Paxton EW, Navarro RA. Association between race and ethnicity and hip fracture outcomes in a universally insured population. J Bone Joint Surg Am. 2018;100:1126-31. doi: 10.2106/JBJS.17.01178 15 Figure Legends Figure 1: CONSORT diagram. Abbreviations: ORIF, open reduction and internal fixation. Figure 2. Probability of symptomatic removal of implant conditioned on age, body mass index, greatest amount of implant prominence, and the use of k-wires. Figure 3. Calibration plot of predicted probability of symptomatic removal of implant versus observed probability of symptomatic removal of implant. Declaration of interest N. N. O’Hara receives stock or stock options from Arbutus Medical, Inc. unrelated to this study. R. V. O’Toole is a paid consultant for Lincotek and Smith & Nephew, receives stock options from Imagen, and receives royalties from Lincotek, all unrelated to this study. This study did not receive external funding. Table 1 Patient characteristics Symptomatic Removal of Control p- (n = 133) value 37.8 (15.5) 45.9 (17.4) 0.003 23 (43.4) 42 (31.6) 0.18 White 35 (66.0) 74 (55.6) 0.14 Black 10 (18.9) 47 (35.3) Implant (n = 53) Patient and injury parameters Age, years, mean (SD) Female, n (%) Race, n (%) 16 Asian 4 (7.5) 7 (5.3) Other 4 (7.5) 5 (3.8) BMI, kg/m2, median [IQR] 27.3 [24.3, 24.3 [23.1, 29.4] 0.02 31.3] Comminution, n (%) 41 (77.4) 88 (66.2) 0.19 Treatment parameters K-wires, n (%) <0.00 31 (58.5) 30 (22.6) 1 Number of k-wires, median [IQR] <0.00 2.0 [0.0, 2.0] 0.0 [0.0, 0.0] 1 Figure 8, n (%) Number of Figure 8 knots, median [IQR] Screws, n (%) Number of screws, median [IQR] Plates, n (%) Number of plates, median [IQR] Cerclage wires, n (%) Number of cerclage knots, median [IQR] Pins, n (%) Number of pins, median [IQR] 33 (62.3) 49 (36.8) 0.003 2.0 [0.0, 5.0] 0.0 [0.0, 3.0] 0.006 41 (77.4) 116 (87.2) 0.15 2.0 [2.0, 4.0] 2.0 [2.0, 3.0] 0.12 2 (3.8) 10 (7.5) 0.54 0.0 [0.0, 0.0] 0.0 [0.0, 0.0] 0.38 12 (22.6) 19 (14.3) 0.24 0.0 [0.0, 0.0] 0.0 [0.0, 0.0] 0.20 8 (15.1) 13 (9.8) 0.44 0.0 [0.0, 0.0] 0.0 [0.0, 0.0] 0.315 Greatest prominence measurement, mm, <0.00 11.1 [6.0, 16.4] 5.1 [3.6, 8.5] median [IQR] Greatest prominence >5 mm, n (%) 1 44 (83.0) 66 (49.6) <0.00 17 1 SD, standard deviation; BMI, body mass index; IQR, interquartile range. Table 2 Factors associated with symptomatic removal of implants Symptomatic Removal of Control, Implant, n (%) Factor OR (95% CI) p-value n (%) Over 45 years of age 16 (30.2) 78 (58.6) 0.14 (0.06–0.34) <0.001 Racial minority 18 (34.0) 59 (44.4) 0.40 (0.17–0.88) 0.03 Body mass index >25 kg/m2 23 (43.4) 91 (68.4) 0.39 (0.18–0.84) 0.02 K-wires 31 (58.5) 30 (22.6) 4.93 (1.89– 14.10) <0.001 Greatest prominence >5 mm 44 (83.0) 66 (49.6) 2.57 (0.93–7.93) 0.07 OR, odds ratio; CI, confidence interval. 18 19 20 21