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Purpose To assess the reliability, predictability, and discriminative capacity of 3 anatomic measurements, tibial tubercle‐trochlear groove (TT‐TG), tibial tubercle‐posterior cruciate ligament, and patellar tendon‐lateral trochlear ridge (PT‐LTR), where PT‐LTR may offer a complementary approach to assessing recurrent patellofemoral instability (PFI) risk. Methods Patients diagnosed with PFI before primary patellofemoral stabilization surgery at a single institution between 2022 and 2024 were included. A control group without PFI was propensity matched 1:1 for age, sex, and laterality. Magnetic resonance images were evaluated to measure TT‐TG, tibial tubercle‐posterior cruciate ligament, and PT‐LTR. A priori power analysis determined the cohort size. Statistical analyses compared differences between the PFI and control groups with Student t‐tests, receiver operating characteristic analyses, and area under the curve with resultant sensitivity, specificity, and an optimal cutoff. Results Patients included 50 knees with PFI (28 women, 22 men; mean age 18 ± 5 years). The control group included 50 knees (27 women, 23 men; mean age 18 ± 4 years). Excellent inter‐ and intra‐rater reliability (intraclass correlation coefficient > 0.7) was shown for TT‐TG and PT‐LTR in the PFI and control groups. The distances for TT‐TG, tibial tubercle‐posterior cruciate ligament, and PT‐LTR were significant predictors ( P ≤ .025) of PFI. The average PT‐LTR distance difference for the PFI and control groups was 7.0 mm ( P < .001). PT‐LTR showed an area under the curve of 0.80 and, when ≥4.6 mm, was 66% sensitive and 92% specific for PFI. Conclusions The PT‐LTR distance is a reliable and discriminative metric for identifying PFI in both pediatric and adult populations. A PT‐LTR cutoff value of 4.6 mm showed diagnostic discrimination and substantially high specificity for recurrent PFI, indicating strong ability to identify patients with instability. Level of Evidence Level III, retrospective case control study.

ABSTRACT Commercial antimicrobial susceptibility testing (AST) systems for gram-negative bacteria provide operational advantages over reference broth microdilution (BMD) testing, but the results produced by commercial AST systems might not be as accurate as the reference method. Assessing and comparing the performance of AST systems can be informative for clinical microbiology practice. In total, 280 clinical isolates and 100 isolates from the U.S. Centers for Disease Control and Prevention Antimicrobial Resistance Isolate Bank, including Enterobacterales and Pseudomonas aeruginosa, were intended to be tested using disk diffusion (DD) and automated commercial AST systems, such as Selux AST System (Selux Diagnostics), MicroScan (Beckman Coulter), Phoenix (Becton, Dickinson and Company), and Vitek 2 (bioMérieux). These results were compared to BMD as the reference standard. In total, 372 isolates were assessed. For Enterobacterales, the greatest frequency of very major errors was identified with cefepime by Vitek 2 (29.0%) and ertapenem by DD (9.1%); essential agreement less than 90% was identified with the following combinations: aztreonam by MicroScan (86.4%), aztreonam by Vitek 2 (88.9%), cefepime by Selux (86.3%), cefepime by Vitek 2 (76.8%), ceftazidime by Vitek 2 (89.9%), and levofloxacin by MicroScan (83.4%). For P. aeruginosa , essential agreement less than 90% was identified with the following combinations: gentamicin by Selux (87.2%), tobramycin by Selux (86.6%), and ciprofloxacin by Phoenix (88.4%). Overall, antimicrobials that had low demonstrable bias across all automated commercial AST systems included ampicillin, amoxicillin-clavulanate, ceftazidime-avibactam, ertapenem, and trimethoprim-sulfamethoxazole. Comparing commercial testing systems head-to-head against a reference standard provides insight into the strengths and weaknesses of the performance of these test systems, and these insights can subsequently inform local decisions regarding further investigations and potential operational mitigation strategies. IMPORTANCE This study assessed and compared the performance of multiple commercial antimicrobial susceptibility testing (AST) systems and disk diffusion methods. The accuracy of determining minimum inhibitory concentrations or zone diameters of antimicrobials and the associated interpretive categories were studied for 372 isolates of Enterobacterales and Pseudomonas aeruginosa . Performance of the evaluated systems revealed that multiple antimicrobial-organism combinations were below the standards typically required by regulatory agencies and clinical laboratories. These deficiencies varied across the commercial platforms and disk diffusion methods, highlighting the importance of benchmarking studies that compare the performance using identical isolates. These identified performance weaknesses may warrant further study and/or the implementation of mitigation strategies in clinical laboratory operations to prevent the reporting of errant results.

Abstract Accurate, noninvasive biomarkers for diagnosis and longitudinal monitoring of metabolic dysfunction–associated steatohepatitis (MASH) remain an urgent unmet clinical need. Here, we describe an electrochemical immunoassay that involves capturing hepatic extracellular vesicles (EVs) on antibody-modified electrodes followed by detecting EV-borne biomarkers using redox active gold nanoparticles (AuNPs). The intensity of electrochemical redox signal represents a quantitative measure of biomarker abundance. Three MASH-associated biomarkers—S100A11, TNF-α, and TGF-β1—were analyzed on hepatic EVs to assess steatotic, inflammatory, and fibrotic states of the diseased liver. The electrochemical signals for individual biomarkers were added into a composite EV MASH score. Plasma samples from 28 patients with MASH, 22 healthy controls, and 27 patients with non-MASH liver disease were scored in this manner, revealing 100% accuracy in the training cohort and >90% accuracy in an independent validation cohort. Our electrochemical immunosensor represents a minimally invasive liquid liver biopsy, offering a promising alternative to solid liver biopsies for screening and monitoring of MASH. One Sentence Summary Circulating hepatic extracellular vesicles carry biomarkers of liver injury enabling accurate, minimally invasive MASH diagnosis in blood.

Abstract Purpose Bevacizumab is an effective treatment for radiation necrosis; dose dependent radiographic and edema response data are lacking. Methods Multicenter, retrospective cohort study of adult patients with primary central nervous system tumors or brain metastases who received bevacizumab for radiation necrosis between June 2021 and July 2024. Patients were grouped by bevacizumab dose (7.5 mg/kg vs 10 mg/kg administered every three weeks). Primary outcome was edema response, assessed by a blinded neuro-oncologist. Secondary outcomes included contrast enhancing disease response, clinical response, adverse events, treatment discontinuation, and re-dosing for recurrent radiation necrosis. Analyses were performed with and without adjustment for tumor type. Results 104 patients were included (7.5 mg/kg, n = 53; 10 mg/kg, n = 51). Edema response differed between dosing groups in unadjusted analyses (p = 0.032), favoring the 7.5 mg/kg cohort; however, this association was attenuated after adjustment for tumor type. Contrast enhancing disease response did not differ between groups in either unadjusted or adjusted analyses (p = 0.43). Clinical response was higher in the 7.5 mg/kg group (65.2% vs 37.8%, p = 0.013). Tumor type differed significantly between cohorts (p < 0.001), with more primary CNS tumors in the 10 mg/kg group. Rates of adverse events, treatment discontinuation, and re-dosing were similar. Conclusions While lower-dose bevacizumab was associated with greater edema reduction in unadjusted analyses, this effect was attenuated after accounting for tumor type. Importantly, 7.5 mg/kg dosing appeared sufficient for achieving edema control and contrast enhancing disease response. These findings support an individualized approach to bevacizumab dosing in radiation necrosis and highlight the need for prospective, tumor-stratified studies.

Aims Two-stage exchange arthroplasty with an antibiotic-eluting cement spacer remains the predominant strategy in the USA for managing chronic periprosthetic joint infection (PJI) following total hip arthroplasty (THA). The aim of this study was to evaluate a commercially available, partially intraoperatively fabricated articulating high-dose antibiotic cement spacer, focusing on survival, complications, and patient-reported outcomes. Methods A total of 298 patients (302 THAs) underwent two-stage exchange arthroplasty for PJI using a specific articulating antibiotic spacer between August 2005 and May 2022. Patients with a previous failed two-stage exchange were excluded, although 121 THAs (302, 40%) had undergone previous PJI-related procedures. The mean age of the patients was 65 years (SD 11), the mean BMI was 32 kg/m 2 (SD 7), and 116 (38%) were female. Most patients were classified as McPherson host B (158; 52%) and limb grade 2 (165; 55%), and 265 (88%) met the 2011 Musculoskeletal Infection Society criteria. The mean follow-up was six years (2 to 16). Results At five years after reimplantation, survival free of reinfection, aseptic rerevision, any rerevision, or any reoperation were 89% (95% CI 85.2 to 93.1), 93% (95% CI 89.3 to 96.1), 86% (95% CI 81.3 to 90.3), and 80% (95% CI 74.7 to 84.9), respectively. Dislocation accounted for most aseptic rerevisions (15/20). McPherson host C (HR 3.7 (95% CI 1.4 to 9.6); p = 0.007) and limb grade 3 (HR 3.3 (95% CI 1.0 to 11.1); p = 0.049) were significantly associated with an increased risk of reinfection. The mean Harris Hip Score at the latest follow-up was 76 (29 to 100). A total of 17 patients underwent revision or removal of a spacer for concerns about persistent infection and two for dislocation of the spacer. Eight patients underwent a non-rerevision reoperation during the spacer interval for wound drainage (n = 5), dislocation of the spacer (n = 2), and perispacer fracture (n = 1). A total of 26 spacer-related complications were treated nonoperatively (15 perispacer fractures, 11 dislocations). Dislocation of the spacer was strongly associated with dislocation after reimplantation (HR 6.2 (95% CI 2.3 to 16.9); p < 0.001). Conclusion This commercially available, partially intraoperatively fabricated articulating spacer showed excellent reinfection-free five-year survival (89%). Spacer-related fracture and dislocation each occurred in 5% of patients. Dislocation of the spacer significantly increased the risk of dislocation following reimplantation, supporting the use of higher-stability bearings in these high-risk patients. Cite this article: Bone Joint J 2026;108-B(9):1104–1112.

Purpose To evaluate implantation rates, time to implantation, and predictors of implantation following matrix‐induced autologous chondrocyte implantation (MACI) biopsy for knee chondral defects. Methods Patients undergoing MACI biopsy or implantation for symptomatic knee chondral defects from 2017 to 2024 at a single institution were reviewed. At a minimum 1‐year follow‐up, the decision to proceed with implantation, recurrent symptoms, complications, and reoperations were assessed. Kaplan‐Meier analysis estimated time to implantation, and multivariable logistic regression identified predictors of MACI implantation. Results A total of 208 knees in 202 patients (mean age 28.0 ± 10.9 years, range 11‐59) underwent MACI biopsy for 243 chondral defects (patella [38%], femoral condyle [34%], and trochlea [26%]). At a mean follow‐up of 4.3 years (range 1.0‐8.3), 64 knees (31%) proceeded to second‐stage MACI implantation. Among 144 knees not implanted, 87 (60%) reported symptom improvement, and 26 (18%) had persistent symptoms. The remaining 22% did not undergo implantation due to another cartilage procedure, insurance denial, or pending scheduling. Patients who underwent biopsy at the home institution had a shorter time from biopsy to implantation compared with those biopsied at outside institutions (6.1 vs 13.1 months, P = .001). Median time to implantation was 9.4 months (95% confidence level: 7.2‐12.2) for home biopsies. Lower body mass index was associated with progression to implantation after adjusting for covariates (odds ratios 0.92, P = .019). Patients implanted within 4 months had larger chondral defects (4.0 vs 3.0 cm 2 , P = .045). At a mean 4.1‐year follow‐up, 6 patients (8%) experienced postoperative complications, including 3 (4%) who required revision chondroplasty. Conclusions MACI biopsy for knee chondral defects resulted in approximately one‐third of patients proceeding to MACI implantation, at a median of 9.4 months after biopsy. Lower body mass index was associated with higher likelihood of progression to implantation, larger chondral defects with earlier implantation, and among patients who did not proceed to implantation, approximately 60% reported symptom improvement following concomitant chondroplasty at the time of biopsy. Level of Evidence Level IV, retrospective case series.

Background: The optimal self-expandable metallic stent (SEMS) choice for endoscopic drainage of unresectable extrahepatic malignant biliary obstruction (MBO) with endoscopic retrograde cholangiopancreatography (ERCP) remains unclear due to limited randomized controlled trial (RCT) evidence. Prior meta-analyses have relied on observational data, introducing heterogeneity and bias. To overcome these limitations, an RCT-only network meta-analysis (NMA) was performed to evaluate the efficacy and safety of SEMS types. Methods: A literature search was conducted to identify RCTs assessing fully covered SEMS (FCSEMS), partially covered SEMS (PCSEMS), and/or uncovered SEMS (UCSEMS) for ERCP drainage of unresectable extrahepatic MBO. Study outcomes included recurrent biliary obstruction (RBO), specific causes of RBO, overall survival (OS), and adverse events (AEs). A frequentist NMA was performed to estimate hazard ratios (HRs) and incidence rate ratios (IRRs) with their 95% confidence intervals and overall P-scores. Results: Ten RCTs (1,659 patients) were included. There were no significant differences in time to RBO, incidence of any RBO, or OS between stent types. UCSEMS had the lowest rates of stent migration, tumor overgrowth, and sludge occlusion, whereas FCSEMS most effectively prevented tumor ingrowth. AE rates were similar across groups; however, only FCSEMS, but not PCSEMS, had significantly higher rates of acute cholecystitis than UCSEMS in patients with an intact gallbladder. Conclusion: There were no differences in RBO, OS, or AE excluding acute cholecystitis between each SEMS type, although each type has its advantages and disadvantages. FCSEMS was associated with a higher risk of acute cholecystitis, emphasizing careful patient selection, particularly regarding gallbladder status.

Importance Timely identification of aortic stenosis (AS) is essential for appropriate clinical management, yet screening remains limited by dependence on comprehensive echocardiography and trained imaging personnel. Objective To develop and validate a deep learning algorithm for detection of moderate or greater AS and prospectively evaluate its performance using artificial intelligence (AI)–guided focused cardiac ultrasound (FoCUS) acquired by novice operators. Design, Setting, and Participants This diagnostic study included retrospective algorithm development and validation and prospective evaluation of AI-guided FoCUS across Mayo Clinic sites in the Midwest, Arizona, and Florida. The model was developed using 6753 patients and evaluated in internal validation (n = 852), internal test (n = 844), and validation (n = 1912) cohorts. Performance was assessed on FoCUS acquired by experienced sonographers (n = 602) and prospectively by novice operators (n = 1302). The retrospective model development and validation cohorts comprised studies performed from January 2005 through September 2022. Prospective study was conducted in 2 enrollment periods from June to August 2024 and from June to September 2025. Participants from both periods were combined to comprise the final prospective cohort. Exposure AI-guided FoCUS acquisition and automated deep learning–based assessment for detection of moderate or greater AS. Main Outcomes and Measures Detection of moderate or greater AS. Performance was assessed using area under the receiver operating characteristic curve (AUROC), sensitivity, specificity, and positive predictive value. Results The model demonstrated excellent discrimination in the internal test cohort (AUROC, 0.99; 95% CI, 0.98-1.00) and geographically distinct validation cohorts in Arizona (AUROC, 0.99; 95% CI, 0.97-1.00) and Florida (AUROC, 0.99; 95% CI, 0.96-1.00). Among FoCUS examinations acquired by experienced sonographers, sensitivity was 95% (95% CI, 82-99) and specificity was 97% (95% CI, 95-98). In the prospective novice-operator cohort, 1258 of 1302 examinations (96.6%) were suitable for automated analysis. Sensitivity was 93% (95% CI, 82-99) and specificity was 96% (95% CI, 95-97). Expert review of AI-positive and uninterpretable examinations increased the positive predictive value from 49.4% to 91.1%, with sensitivity of 85.4%. Conclusions and Relevance A deep learning algorithm accurately detected moderate or greater AS across validation cohorts in this study. In prospective evaluation, novice operators were able to acquire AI-guided FoCUS examinations that enabled accurate detection of moderate or greater AS. These findings support a scalable strategy that may expand access to AS detection in settings with limited echocardiography resources.

Purpose Radioligand therapy (RLT) with [ 177 Lu] Lu-PSMA-617 has shown significant benefits in metastatic castration-resistant prostate cancer (mCRPC), including prolonged overall survival (OS) and progression-free survival (PFS), as well as improved quality of life. For patients previously treated with [ 177 Lu]Lu-PSMA-617 who subsequently experience disease progression, retreatment with [ 177 Lu] Lu-PSMA-617 has emerged as a potential approach, yet data on the outcomes of RLT retreatment remains limited. This study aimed to assess the efficacy and safety of retreatment RLT in mCRPC. Methods Clinical and imaging data of patients who underwent at least two cycles of [ 177 Lu] Lu-PSMA-617, followed by a second course of treatment with [ 177 Lu] Lu-PSMA-617 between March 2018 and December 2024, were retrospectively reviewed. Endpoints included biochemical response, imaging response, toxicity, PSA-PFS, rPFS, and OS. Radiologic and biochemical responses were evaluated using RECIST 1.1 criteria and PSA levels, respectively. Results A total of 589 patients underwent [ 177 Lu] Lu-PSMA-617 RLT, of whom 20 (3.4%, 20/589) received RLT retreatment. The median age was 71.3 years (range: 63.7–95.2), and the median follow-up was 73.3 months (95% CI, 35.7–77.2 months) after the initial treatment and 21.7 months (95% CI, 16.9–26.0 months) after retreatment. The initial treatment involved a median of 4.5 cycles (range: 2–6). Following the first course of RLT, 15 patients (75%, 15/20) had exhibited a &gt;50% decline in PSA levels, including 9 who achieved a &gt;90% decrease. Additionally, 12 patients (60%, 12/20) had demonstrated a complete or partial imaging response, while 3 (15%, 3/20) patients had stable disease, and 5 (25%, 5/20) patients had progressive radiologic disease. Patients received a median of 4 retreatment cycles (range, 1–6), and the median interval between initial RLT and retreatment RLT was 33.1 months (IQR, 16.2–48.9 months; range, 10.7–58.8 months). A PSA decline of ≥50% was observed in 9 out of 20 patients (45%, 9/20). An imaging response was observed in 10 patients (50%, 10/20), with 4 achieving a complete response and 6 achieving a partial response, whereas 10 patients (50%, 10/20) showed progression. The median PSA-PFS was 9.8 months (95% CI, 4.1–17.9 months), and the median rPFS was 8.2 months (95% CI, 3.3–17.9 months). Eight deaths occurred during follow-up. The estimated Kaplan Meier OS rates were 83.6% at 12 months (95% CI, 57.3%–94.4%) and 53.7% at 24 months (95% CI, 28.3%–73.7%). Grade 2 renal toxicity was observed in one patient (5%, 1/20). Three patients (15%, 3/20) developed Grade 2 anemia. Notably, no grade 3 or grade 4 adverse events were observed during either treatment period. Conclusion In our cohort, retreatment with [¹ 77 Lu]Lu-PSMA-617 RLT was associated with biochemical and imaging responses in some patients, with observed survival outcomes that support further investigation. However, given the retrospective single-arm design and small sample size, large prospective studies are needed to more rigorously evaluate the safety, efficacy, and optimal patient selection for retreatment RLT.