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Background: Tumor programmed death-ligand 1 (PD-L1) status is useful in determining which patients may benefit from programmed death-1 (PD-1)/PD-L1 inhibitors. However, little is known about the association between PD-L1 status and tumor histopathological patterns. Using deep learning, we predicted PD-L1 status from hematoxylin and eosin (H and E) whole-slide images (WSIs) of nonsmall cell lung cancer (NSCLC) tumor samples. Materials and Methods: One hundred and thirty NSCLC patients were randomly assigned to training (n = 48) or test (n = 82) cohorts. A pair of H and E and PD-L1-immunostained WSIs was obtained for each patient. A pathologist annotated PD-L1 positive and negative tumor regions on the training samples using immunostained WSIs for reference. From the H and E WSIs, over 145,000 training tiles were generated and used to train a multi-field-of-view deep learning model with a residual neural network backbone. Results: The trained model accurately predicted tumor PD-L1 status on the held-out test cohort of H and E WSIs, which was balanced for PD-L1 status (area under the receiver operating characteristic curve [AUC] =0.80, P << 0.01). The model remained effective over a range of PD-L1 cutoff thresholds (AUC = 0.67--0.81, P ≤ 0.01) and when different proportions of the labels were randomly shuffled to simulate interpathologist disagreement (AUC = 0.63--0.77, P ≤ 0.03). Conclusions: A robust deep learning model was developed to predict tumor PD-L1 status from H and E WSIs in NSCLC. These results suggest that PD-L1 expression is correlated with the morphological features of the tumor microenvironment. [ABSTRACT FROM AUTHOR]

Background: The prevention of surgical site infection guidelines issued by the Centers for Disease Control and Prevention (CDC) recently recommended that only a single dose of preoperative antibiotics be administered to patients undergoing clean-contaminated procedures based on data from a variety of surgical disciplines. For orthopaedic procedures, where postoperative infections can have significant consequences, the existing evidence for this recommendation is widely debated.Questions/purposes: Is there a difference in postoperative infection risk when utilizing a single dose of preoperative antibiotics compared with multiple doses of perioperative antibiotics for orthopaedic procedures where implants are placed?Methods: MEDLINE, EMBASE, Google Scholar, and Cochrane were systematically reviewed for randomized controlled trials (RCTs) of a single dose of preoperative antibiotics compared with pre- and postoperative prophylaxis from 1980 to 2017 for all orthopaedic procedures where implants were being placed. Infection (both superficial and deep) as a primary outcome through all available followup was required for inclusion. Fourteen RCTs detailing 9691 orthopaedic procedures were included for analysis, including seven arthroplasty, one spine, and six general orthopaedic trials (two specific to hip fracture fixation). Pooled infection outcomes were analyzed with random-effects modeling in light of study heterogeneity. Bias was evaluated using the Cochrane risk of bias tool as well as a funnel plot for publication bias, and quality of evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Bias was largely uncertain; however, a high risk of bias was noted in four studies. No significant overall publication bias was noted. The quality of evidence was determined to be very low based on the GRADE tool, downgraded based on risk of bias, inconsistency, and imprecision. Despite the quality of evidence, the data were pooled in light of the current recommendations from the CDC to critically evaluate the recommendation that a single dose of antibiotics be utilized.Results: There were no differences in infection risk between single- versus multiple-dose groups (single: 83 of 4263 [2%], multiple: 101 of 5428 [2%]; odds ratio, 0.92 [95% confidence interval, 0.56-1.51]; p = 0.740, I = 36% for statistical heterogeneity).Conclusions: There is no difference in infection risk between a single dose and multiple doses of perioperative antibiotics for orthopaedic procedures where implants are utilized, consistent with recent recommendations. However, the quality of evidence for orthopaedic procedures is low, and a randomized study with a sufficient sample size is needed to examine the issue before universal adoption of a single antibiotic dose.Level Of Evidence: Level I, therapeutic study. [ABSTRACT FROM AUTHOR]

Introduction: In two-stage exchange for periprosthetic joint infection (PJI), adding antibiotics to cement spacers is the standard of care; however, little is known about optimal dosage. There is emphasis on using >3.6 g of total antibiotic, including ≥2.0 g of vancomycin, per 40 g of cement, but these recommendations lack clinical evidence. We examined whether recommended antibiotic spacer doses affect treatment success., Methods: This was a retrospective review of 202 patients who underwent two-stage exchange for PJI from 2004 to 2020 with at least 1-year follow-up. Patients were separated into high (>3.6 g of total antibiotic per 40 g of cement) and low-dose spacer groups. Primary outcomes were overall and infectious failure., Results: High-dose spacers were used in 80% (162/202) of patients. High-dose spacers had a reduced risk of overall (OR, 0.37; P = 0.024) and infectious (OR, 0.35; P = 0.020) failure for infected primary arthroplasties, but not revisions. In multivariate analysis, vancomycin dose ≥2.0 g decreased the risk of infectious failure (OR, 0.31; P = 0.016), although not overall failure (OR, 0.51; P = 0.147)., Conclusion: During two-stage exchange for PJI, spacers with greater than 3.6 g of total antibiotic may reduce overall and infectious failure for infected primary arthroplasties. Furthermore, using at least 2.0 g of vancomycin could independently decrease the risk of infectious failure., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Orthopaedic Surgeons.)

Introduction: There is no consensus on whether articulating or static spacers are superior during two-stage exchange arthroplasty for periprosthetic joint infection. We aimed to compare surgical time, need for extensile exposure, surgical costs, and treatment success for articulating and static spacers., Methods: This was a retrospective review of 229 periprosthetic joint infections treated with two-stage exchange with a minimum of one-year follow-up. For articulating and static spacers, we compared the need for extensile exposure during reimplantation and treatment failure based on an updated definition. Surgical time and costs at both stages were also compared. Subgroup analysis was performed for total knee and hip arthroplasties., Results: There was no difference in the surgical time for spacer insertion; however, articulating spacers demonstrated reduced surgical time during reimplantation (181 vs. 234 minutes, P < 0.001). In multivariate analysis, there was no difference in extensile exposures (odds ratio 2.20, P = 0.081), but treatment failure was more likely for static spacers (odds ratio 2.17, P = 0.009). Overall surgical costs for two-stage exchange were similar between groups (23,782 vs. 23,766, P = 0.495)., Conclusion: Articulating spacers demonstrated shorter surgical times and a trend toward decreased extensile exposures during reimplantation. They also had higher treatment success rates and similar surgical costs for overall two-stage exchange., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Orthopaedic Surgeons.)

Background: A megaprosthesis may be used for reconstruction in patients with massive bone loss or a periprosthetic fracture. Periprosthetic joint infection (PJI) may occur after a megaprosthesis reconstruction and may pose a major challenge. The outcomes of managing PJI in patients with a megaprosthesis is relatively unclear. The aim of this study was to investigate the clinical course and outcomes of PJI in patients with a megaprosthesis in place., Methods: From a total of 219 patients who underwent megaprosthesis replacement for non-oncologic conditions, 38 (17.4%) developed subsequent PJI. A retrospective review of the medical record was performed to ascertain the course of the PJI and treatment outcomes. Kaplan-Meier analysis was performed to evaluate the survival function, and the log-rank test was used to assess differences in outcome measures., Results: The surgical management of 33 patients with PJI included debridement, antibiotics, and implant retention (DAIR) (82%), consisting of DAIR with modular component exchange (19 patients) and DAIR without component exchange (8 patients); 2-stage exchange arthroplasty (9%); resection arthroplasty (6%); and a single-stage revision arthroplasty (3%). The Kaplan-Meier survivorship analysis demonstrated that the overall survival rate was 65.1% at 2 years. The mortality rate was 15%, with many patients undergoing salvage procedures including amputation (18%), arthrodesis (6%), and resection arthroplasty (6%)., Conclusions: The rate of PJI after megaprosthesis reconstruction, 17% in this study, appears to be very high. The management of PJI in these patients is challenging, with 1 of 3 patients undergoing failed treatment. Despite the limited options available, DAIR seems to be an appropriate treatment strategy for some of these patients. Further data on a larger cohort are needed to assess the success of various surgical procedures and predictors of failure in this challenging patient population., Level of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJSOA/A345)., (Copyright © 2021 The Authors. Published by The Journal of Bone and Joint Surgery, Incorporated. All rights reserved.)

Background: Patients undergoing total joint arthroplasty (TJA) following septic arthritis are at higher risk for developing periprosthetic joint infection (PJI). Minimal literature is available to guide surgeons on the optimal timing of TJA after completing treatment for prior native joint septic arthritis. This multicenter study aimed to determine the optimal timing of TJA after prior septic arthritis and to examine the role of preoperative serology in predicting patients at risk for developing PJI., Methods: A total of 207 TJAs were performed after prior septic arthritis from 2000 to 2017 at 5 institutions. Laboratory values, prior treatment, time from the initial infection, and other variables were recorded. Bivariate analyses were performed to identify the association between the time from septic arthritis to TJA and the risk of developing subsequent PJI. A subanalysis was performed between patients who underwent TJA in 1 setting (n = 97) compared with those who underwent 2-stage arthroplasties (n = 110). Receiver operating characteristic (ROC) curve analysis was performed for serum markers prior to TJA in predicting the risk of a subsequent PJI., Results: The overall PJI rate was 12.1%. Increasing time from septic arthritis treatment to TJA was not associated with a reduction of PJI, whether considering time as a continuous or categorical variable, for both surgical treatment cohorts (all p > 0.05). Although the ROC curve analysis found that the optimal threshold for timing of TJA from the initial treatment was 5.9 months, there was no difference in the PJI rate when the overall cohort was dichotomized by this threshold and when stratified by 1-stage compared with 2-stage TJA. There was no significant difference in erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level prior to conversion TJA between patients who subsequently developed PJI and those who did not., Conclusions: Serum markers have limited value in predicting subsequent PJI in patients who undergo TJA after prior septic arthritis. There was no optimal interim period between septic arthritis treatment and subsequent TJA; thus, delaying a surgical procedure does not appear to reduce the risk of PJI., Level of Evidence: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: Disclosure: The authors indicated that no external funding was received for any aspect of this work. On the Disclosure of Potential Conflicts of Interest forms, which are provided with the online version of the article, one or more of the authors checked “yes” to indicate that the author had a relevant financial relationship in the biomedical arena outside the submitted work (http://links.lww.com/JBJSOA/A279)., (Copyright © 2021 The Authors. Published by The Journal of Bone and Joint Surgery, Incorporated. All rights reserved.)

Introduction: Orthopaedic surgery residency has become increasingly competitive for medical school applicants with at least one in five applicants not matching annually. For unmatched applicants, the new application cycle is a perplexing and disconcerting period, where unique decisions must be addressed by the applicant. We aimed to investigate the risk factors and outcomes of unmatched orthopaedic applicants., Methods: This was a retrospective study using a survey-based questionnaire administered electronically to medical students annually from 2016 to 2019 immediately after match day. Applicant responses totaled 934 completed surveys, of which 81 identified themselves as unmatched from the previous year and reapplied for a subsequent cycle. Variables collected through the survey included demographics, United States Medical Licensing Examination scores, Electronic Residency Application Service application characteristics, and interim year pursuits. A univariate analysis was performed with an alpha level of 0.05 denoting statistical significance., Results: Overall, 58.0% of unmatched applicants subsequently matched into an orthopaedic residency. Applicants who pursued a research year or surgical internship after initially not matching had a subsequent match rate of 52.1% and 64.0%, respectively (p = 0.46). Of those who matched, 19.1% were Alpha Omega Alpha (AOA) compared with 2.9% in the unmatched group (p = 0.04). When stratified by gender, 83.3% of women matched subsequently compared with 50.8% of men (p = 0.02). There were no differences in Step 1 scores (242.5 vs. 240.7, p = 0.60), Step 2 clinical knowledge (CK) scores (248.3 vs. 244.5, p = 0.60), or the number of publications (15.6 vs. 10.9, p = 0.25) between applicants who matched or did not match, respectively., Discussion: Our findings demonstrate that most orthopaedic applicants matched during their subsequent attempt. Women and those with AOA status had a significantly higher match rate than their counterparts. There was no difference in outcomes between those who pursued a research year or surgical internship, Step 1 or 2CK scores, or the number of publications. Further study is warranted to properly analyze risk factors for not matching on a subsequent attempt., Level of Evidence: Prognostic Level IV., (Copyright © 2020 The Authors. Published by The Journal of Bone and Joint Surgery, Incorporated. All rights reserved.)

Background: Culture-negative periprosthetic joint infection (PJI) is a challenging condition to treat. The most appropriate management of culture-negative PJI is not known, and there is immense variability in the treatment outcome of this condition. The purpose of this study was to elucidate the characteristics, outcomes, and risk factors for failure of treatment of culture-negative PJI., Methods: A retrospective review of 219 patients (138 hips and 81 knees) who had undergone surgery for the treatment of culture-negative PJI was performed utilizing a prospectively collected institutional PJI database. PJIs for which the results of culture were unavailable were excluded. An electronic query and manual review of the medical records were completed to obtain patient demographics, treatment, microbiology data, comorbidities, and other surgical characteristics. Treatment failure was assessed using the Delphi consensus criteria., Results: The prevalence of suspected culture-negative PJI was 22.0% (219 of 996), and the prevalence of culture-negative PJI as defined by the Musculoskeletal Infection Society (MSIS) was 6.4% (44 of 688). Overall, the rate of treatment success was 69.2% (110 of 159) in patients with >1 year of follow-up. Of the 49 culture-negative PJIs for which treatment failed, 26 (53.1%) subsequently had positive cultures; of those 26, 10 (38.5%) were positive for methicillin-sensitive Staphylococcus aureus . The rate of treatment success was greater (p = 0.019) for patients who had 2-stage exchange than for those who underwent irrigation and debridement., Conclusions: The present study demonstrates that culture-negative PJI is a relatively frequent finding with unacceptable rates of treatment failure. Every effort should be made to isolate the infecting organism prior to surgical intervention, including extending the incubation period for cultures, withholding antibiotics prior to obtaining culture specimens, and possibly using newly introduced molecular techniques., Level of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Background: Abnormal patellar height is associated with anterior knee pain and several conditions that affect the patellofemoral joint. The aim of this study was to 1) report the incidence of patella alta and patella baja and 2) investigate whether the normal limits of the Insall-Salvati ratio is applicable in adult Middle-Easterners., Methods: A radiographic review of the lateral radiographs of 736 Middle-Eastern knees were performed. Patellar tendon length (TL) and the patellar length (TP) was digitally measured and the ratios of these measures was used to calculate the Insall-Salvati ratio., Results: The overall mean TL/PL ratio was 1.20±0.17. The Insall-Salvati ratio was higher (p=0.0013) in males (1.22± 0.12) than in females (1.18±0.17). According to our measurement, the recommended levels for defining abnormal patellar position should be 0.86 for patella baja and 1.54 for patella alta., Conclusion: The use of TL/PL ratio demonstrated a higher incidence of patella alta and a higher mean TL/PL ratio compared to other techniques. The normal ranges for the TL/PL differs from western populations and may be attributed to lifestyle differences.