Citations

Abstract The 6th Edition of the World Health Organization Classification of Digestive System Tumours has introduced two new categories of gastric neuroendocrine tumors, reflecting recent data on subtypes that do not conform to the three established subtypes: type 1 (associated with autoimmune gastritis), type 2 (associated with Zollinger-Ellison Syndrome) and type 3 (sporadic). The new type 4 category is exceptionally rare and is caused by endogenous dysfunction of parietal cell proton pumps, potentially secondary to mutation of ATP4A. Type 5 gastric NETs are caused by chronic pharmacologic inhibition of the parietal cell proton pump, typically due to proton pump inhibitor use, and are increasingly common. Given the relatively low malignant potential of the new subtypes compared to sporadic (type 3) gastric NETs, it is important that clinicians and pathologists recognize these entities, limiting radical surgical resections when unnecessary.

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 Objective The validity of progression-free survival (PFS) as a surrogate for overall survival (OS) in the antibody-drug conjugate (ADCs) era remains uncertain. We evaluated the association between treatment effects on PFS and OS in randomized trials of ADCs for metastatic breast cancer (mBC) and explored the surrogate threshold effect (STE). Methods PubMed, Embase, Cochrane, and ClinicalTrials.gov were searched for published randomized controlled phase II–IV trials evaluating ADCs in mBC and reporting hazard ratios (HRs) for both PFS and OS. A meta-epidemiological approach was used. The primary metric was the ratio of hazard ratios (rHR = HR_PFS/ HR_OS), with rHR < 1 indicating a larger effect on PFS. Trial-level associations were assessed using weighted linear regression (R²) and Spearman’s correlation. Results Twenty-one trials (n = 21; 18 phase III) evaluating nine ADCs were included. The pooled rHR was 0.79 (95% CI, 0.73–0.86), indicating a larger relative effect on PFS than OS. Numerically, the largest discrepancies were observed in triple-negative disease (rHR 0.72) and trials allowing crossover (rHR 0.71). Concordant statistical significance between endpoints occurred in 76% of the trials, whereas 24% showed a significant PFS benefit without OS improvement. The trial-level association between PFS and OS was moderate (R² = 0.62; ρ = 0.67). Conclusion Treatment effects on PFS consistently exceeded those on OS, although effect directions were highly concordant between endpoints. These findings provide an exploratory framework to contextualize the relationship between PFS and OS in ADC trials, requiring further validation in diverse clinical settings.

Abstract Introduction Conversion of sleeve gastrectomy (SG) to Roux-en-Y gastric bypass (RYGB) is performed for gastroesophageal reflux disease (GERD), recurrent weight gain, and suboptimal clinical response. We compared early safety, weight loss, and healthcare utilization across indications. Methods We retrospectively analyzed adults undergoing SG-to-RYGB conversion in the 2023 MBSAQIP Participant Use File linked to the Long-Term Follow-Up file. Patients were grouped by indication as GERD, recurrent weight gain, suboptimal clinical response, or other. Baseline, operative, 30-day, and 6-month outcomes were compared using unadjusted analyses. Results Among 12,350 patients, indications were GERD in 59.2%, recurrent weight gain in 24.7%, suboptimal clinical response in 10.5%, and other in 5.6%. Patients with weight-related indications had higher baseline BMI. Major 30-day complications were uncommon and did not differ significantly across groups. Among 8,797 patients with 6-month weight data, mean percent total weight loss (%TWL) was 14.2% for recurrent weight gain, 13.3% for suboptimal clinical response, and 12.7% for both GERD and other indications (P < 0.001). The maximum absolute difference was 1.5 percentage points. Six-month intervention rates were 6.4% for GERD and 6.8% for other indications, compared with 4.2% for recurrent weight gain and 2.8% for suboptimal clinical response (P < 0.001); mortality remained uncommon. Conclusion SG-to-RYGB conversion was associated with low short-term complication rates across indications. Six-month weight loss and healthcare utilization differed in unadjusted comparisons, but weight-loss differences were modest and may reflect baseline case-mix differences.

Background Tirzepatide is a dual agonist for glucose‐dependent insulinotropic polypeptide and glucagon‐like peptide‐1 receptors, with proven efficacy in weight loss and improvement in cardiovascular outcomes. However, the effects of tirzepatide on the incidence of atrial fibrillation in patients with overweight or obesity remain unclear. Methods PubMed, Embase, and Cochrane Library were searched for randomized controlled trials comparing tirzepatide versus placebo for individuals with overweight or obesity. Odds ratios (ORs) with 95% credible intervals (CrIs) were pooled using a Bayesian binomial‐normal hierarchical model, appropriate for rare‐event outcomes. Results Our meta‐analysis included 10 randomized controlled trials, including 6515 individuals, of whom 4491 (68.9%) were randomized to tirzepatide. The pooled OR was 2.20 (95% CrI, 0.81–6.75) for atrial fibrillation, 2.16 (95% CrI, 0.90–5.87) for atrial arrhythmia, and 1.84 (95% CrI, 1.04–3.90) for any arrhythmia. Conclusions Tirzepatide was not associated with atrial fibrillation or atrial arrhythmia. Although higher odds of overall arrhythmias were observed, event rates were low and the findings should be interpreted cautiously.

Cerebrospinal fluid (CSF)–venous fistulas are an increasingly recognized source of spontaneous intracranial hypotension, for which endovascular embolization has emerged as an effective treatment option.1–3 Advances in diagnostic imaging have improved detection of CSF–venous fistulas throughout the cervical, thoracic, and lumbar spine; however, identification of lesions at the cranial and caudal extremes of the spine remains challenging.4 In video 1, we present the novel case of an anterior condylar confluence CSF–venous fistula arising from a hypoglossal canal nerve root sleeve diverticulum. We demonstrate the diagnostic evaluation, preprocedural planning, and transvenous embolization of the fistula using the pressure cooker technique, highlighting key technical considerations for navigating this uncommon venous anatomy. Finally, we review the patient’s postprocedural course and imaging findings demonstrating radiographic resolution of spontaneous intracranial hypotension. Video 1 Endovascular embolization of a cerebrospinal fluid–venous fistula arising from a hypoglossal canal nerve root sleeve diverticulum using a transvenous pressure cooker technique.

Abstract Meniscus surgery remains one of the most common orthopedic procedures worldwide. Successful meniscus repair requires A natomic reduction, B iologic preparation and augmentation, C ircumferential compression (ABCs), and an optimized rehabilitation protocol. Rehabilitation after surgery is critical for optimizing outcomes, yet the ideal approach remains controversial. A recent international European Union‐United States consensus task force developed recommendations for rehabilitation meniscal surgery. The group concluded that rehabilitation after meniscal repair and reconstruction should progress according to both time‐ and criterion‐based milestones. In practice, 2 rehabilitation pathways are utilized after meniscal repair: a standard protocol for biomechanically stable repairs that tolerate some weight‐bearing in full extension and a complex protocol for repairs requiring greater protection. Standard meniscal repairs (i.e., vertical longitudinal) are biomechanically stable and treated with moderate protection. During the first 4 weeks, patients are restricted to 0° to 90° of knee range of motion, partial weight‐bearing with crutches, and full knee extension during ambulation. Between weeks 4 and 8, patients progress to weight‐bearing as tolerated while avoiding loaded knee flexion beyond 90° until week 16, with emphasis on gait normalization and strengthening. From weeks 8 to 16, aerobic conditioning and strengthening continue. Pending surgeon clearance, return to running begins at week 12, plyometric exercises at week 14, and return to sport at 4 to 8 months. Complex meniscal repairs (e.g., radial or root tears) require a protective rehabilitation approach. During weeks 0 to 6, range of motion is restricted to 0° to 90° with toe‐touch weight‐bearing and full knee extension during ambulation. Range of motion and weight‐bearing progress from weeks 6 to 12, while loaded flexion beyond 90° remains restricted until week 16. Between weeks 12 and 18, aerobic conditioning and strengthening continue. Pending surgeon clearance, running begins at week 14, plyometrics at week 16, and return to sport typically occurs at 6 to 9 months.