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PURPOSE In large B-cell lymphoma (LBCL), use of high-dose methotrexate (HD-MTX) to prevent CNS relapse (so-called CNS prophylaxis) remains controversial. International guidelines continue to recommend HD-MTX in patients deemed ultra high risk (UHR) because of a lack of robust data specific to these subgroups. This study was designed to examine the impact of HD-MTX specifically in UHR patients. METHODS Data from two previous retrospective analyses were combined to produce a cohort of UHR patients (≥1 of the following criteria: CNS international prognostic index score 5-6; testicular, renal/adrenal, or breast involvement; ≥3 extranodal sites), treated with or without HD-MTX. The primary outcome was CNS relapse rate (isolated or concurrent with systemic relapse) measured from diagnosis with additional landmark analysis of all responding patients with no progression event at 6 months. RESULTS Analyses were performed on 1,923 patients meeting UHR criteria. No significant difference in 3-year CNS relapse rate was observed between no HD-MTX (n = 1,051) versus HD-MTX patients (n = 872), including in multivariable analyses adjusting for baseline characteristics (3-year rate, 9.3% v 8.1%; adjusted hazard ratio [HR], 1.13 [95% CI, 0.82 to 1.57]). Analyses restricted to isolated CNS relapse also confirmed no difference (5.9% v 5.7%; adjusted HR, 1.03 [95% CI, 0.69 to 1.53]). In the landmark analysis (no HD-MTX n = 782, HD-MTX n = 773), no difference in 3-year CNS relapse was observed (6.7% v 6.6%, adjusted HR, 0.95 [95% CI, 0.62 to 1.44]). CONCLUSION To our knowledge, this is the largest international comparative data set of patients with LBCL with UHR features showing no significant reduction in CNS relapse with HD-MTX in all UHR or in any individual subgroup. Despite inherent limitations of retrospective analyses, the data strongly support previous studies in suggesting HD-MTX prophylaxis has no meaningful benefit for most patients.

ABSTRACT As artificial intelligence (AI) continues to rapidly reshape health care, there is a critical need for clear frameworks for clinicians to ensure ethical, equitable, and effective integration and use of AI in patient care. Key integrations of AI include enhancing health communications, patient engagement, clinicians' training, pharmaceutical advertising, clinical decision‐making, and automation of clinical operations and workflow. However, there are growing concerns related to regulatory gaps, the spread of misinformation, security threats, patient and data privacy leaks, and widening health disparities gaps. These concerns are exacerbated by limited institutional infrastructure and limited AI literacy of clinicians and patients. Recent policy developments reflect efforts to guide responsible AI development and use. While progress has been made, the lack of standardized human oversight remains a critical gap, particularly as policies may not fully consider the challenges and complexities at institutional, societal, technical, and individual levels. Thus, herein, the Drug Information Practice and Research Network (DI PRN) of the American College of Clinical Pharmacy (ACCP) : (1) explores current and emerging multifaceted challenges, a call to action, and opportunities of AI integration in health care including examination of the regulatory, ethical, operational, and health equity implications; and (2) provides practical recommendations for responsible use of AI through DI PRN‐developed example case‐based approaches and best practices infographics to enhance AI literacy for diverse learners including clinicians, trainees, and patients. This DI PRN opinion paper highlights the importance of proactive governance frameworks and equips and empowers diverse learners with practical AI literacy tools to confidently engage with AI technologies in patient care.

Background and aims Percutaneous endoscopic gastrostomy (PEG) is an essential procedure for patients who require long-term enteral nutrition but are unable to eat orally. However, it carries a risk of bleeding, particularly in patients on anticoagulation or dual antiplatelet therapy (DAPT). This study aimed to assess the bleeding risk associated with continuing anticoagulation or DAPT during PEG placement. Methods Using the TriNetX US Collaborative Network Database, we analyzed four cohorts: patients on anticoagulants, patients not on anticoagulants, patients on DAPT, and patients on aspirin (ASP), focusing on gastrostomy-related bleeding within 7 and 30 days, along with secondary outcomes such as mortality and the need for blood transfusion or endoscopic reintervention. Results Our analysis showed no statistically significant difference in the 7-day bleeding risk between the anticoagulant and no anticoagulant groups. However, a higher 30-day bleeding risk was observed in the anticoagulant group (0.9 vs. 0.4%, P = 0.007). There was no significant difference in the incidence of severe bleeding events requiring endoscopic intervention or blood transfusion. In addition, the difference in the bleeding risk between the DAPT and ASP groups was not statistically significant within 7 and 30 days. Conclusion These findings suggest that while anticoagulant use increases the risk of minor post-PEG bleeding, it does not lead to a higher incidence of severe bleeding. Additionally, the continuation of DAPT was not associated with statistically significant increase in bleeding risk. This study provides valuable insights into the management of antithrombotic therapy in patients undergoing PEG.

AbstractEUS-guided gallbladder drainage (EUS-GBD) using lumen apposing metal stents (LAMS) has excellent technical and short-term clinical success for acute cholecystitis (AC). The goals of this study were to determine the long-term clinical outcomes and adverse events (AEs) of EUS-GBD with LAMS.A multicenter, retrospective study was conducted at 18 US tertiary care institutions. Inclusion criteria: any AC patient with attempted EUS-GBD with LAMS and minimum 30-day post-procedure follow-up. Long-term clinical success was defined as absence of recurrent acute cholecystitis (RAC) > 30 days and long-term AE was defined as occurring > 30 days from the index procedure.A total of 109 patients were included. Technical success was achieved in 108 of 109 (99.1%) and initial clinical success in 106 of 109 (97.2%). Long-term clinical success was achieved in 98 of 109 (89.9%) over a median follow-up of 140 days (range 30–1188). On multivariable analysis (MVA), acalculous cholecystitis (odds ratio [OR] 15.93, 95% confidence interval [CI] 1.22–208.52, P = 0.04) and the occurrence of a LAMS-specific AE (OR 63.60, 95% CI 5.08–799.29, P <0.01) were associated with RAC. AEs occurred in 38 of 109 patients (34.9%) at any time, and in 10 of 109 (9.17%) > 30 days from the index procedure. Most long-term AEs (7 of 109; 6.42%) were LAMS-specific. No technical or clinical factors were associated with occurrence of AEs. LAMS were removed in 24 of 109 patients (22%). There was no difference in RAC or AEs whether LAMS was removed or not.EUS-GBD with LAMS has a high rate of long-term clinical success and modest AE rates in patients with AC and is a reasonable destination therapy for high-risk surgical candidates.

AbstractExtended oral antibiotic prophylaxis (EOAP) has been suggested to reduce rates of periprosthetic joint infection (PJI) postoperatively after total joint arthroplasty (TJA). The purpose of this multicenter study is to define how many TJA patients are considered high risk for developing PJI based on published EOAP criteria and determine whether this status is associated with socioeconomic or demographic factors. All primary and aseptic revision TJAs performed in 2019 at three academic medical centers were reviewed. High-risk status was defined based on prior published EOAP criteria. Area deprivation index (ADI) was calculated as a measure of socioeconomic status. Data were reported as means with standard deviation. Both overall and institutional differences were compared. Of the 2,511 patients (2,042 primary and 469 revision) in this cohort, 73.3% met criteria for high risk (primary: 72.9% [1,490] and revision: 74.6% [350]). Patient's race or age did not have a significant impact on risk designation; however, a larger proportion of high-risk patients were women (p = 0.002) and had higher Elixhauser scores (p < 0.001). The mean ADI for high-risk patients was higher (more disadvantaged) than for standard-risk patients (64.0 [20.8] vs. 59.4 [59.4]) (p < 0.001). Over 72% of primary and revision TJA patients at three medical centers met published criteria for EOAP. These patients were more often women, had more comorbidities, and lived in more disadvantaged areas. Our findings suggest that most patients qualify for EOAP, which may call for more stringent criteria on who would benefit extended antibiotic prophylaxis.

Study Design. Prospective multicenter study data were used for model derivation and externally validated using retrospective cohort data. Objective. Derive and validate a prognostic model of benefit from bracing for adolescent idiopathic scoliosis (AIS). Summary of Background Data. The Bracing in Adolescent Idiopathic Scoliosis Trial (BrAIST) demonstrated the superiority of bracing over observation to prevent curve progression to the surgical threshold; 42% of untreated subjects had a good outcome, and 28% progressed to the surgical threshold despite bracing, likely due to poor adherence. To avoid over-treatment and to promote patient goal setting and adherence, bracing decisions (who and how much) should be based on physician and patient discussions informed by individual-level data from high-quality predictive models. Materials and Methods. Logistic regression was used to predict curve progression to <45° at skeletal maturity (good prognosis) in 269 BrAIST subjects who were observed or braced. Predictors included age, sex, body mass index, Risser stage, Cobb angle, curve pattern, and treatment characteristics (hours of brace wear and in-brace correction). Internal and external validity were evaluated using jackknifed samples of the BrAIST data set and an independent cohort (n=299) through estimates of discrimination and calibration. Results. The final model included age, sex, body mass index, Risser stage, Cobb angle, and hours of brace wear per day. The model demonstrated strong discrimination ( c -statistics 0.83–0.87) and calibration in all data sets. Classifying patients as low risk (high probability of a good prognosis) at the probability cut point of 70% resulted in a specificity of 92% and a positive predictive value of 89%. Conclusion. This externally validated model can be used by clinicians and families to make informed, individualized decisions about when and how much to brace to avoid progression to surgery. If widely adopted, this model could decrease overbracing of AIS, improve adherence, and, most importantly, decrease the likelihood of spinal fusion in this population.

Endosomal sorting complexes required for transport (ESCRTs) promote the invagination of vesicles into the lumen of endosomes, the budding of enveloped viruses, and the separation of cells during cytokinesis. These processes share a topologically similar membrane scission event facilitated by ESCRT-III assembly at the cytosolic surface of the membrane. The Snf7 subunit of ESCRT-III in yeast binds directly to an auxiliary protein, Bro1. Like ESCRT-III, Bro1 is required for the formation of intralumenal vesicles at endosomes, but its role in membrane scission is unknown. We show that overexpression of Bro1 or its N-terminal Bro1 domain that binds Snf7 enhances the stability of ESCRT-III by inhibiting Vps4-mediated disassembly in vivo and in vitro. This stabilization effect correlates with a reduced frequency in the detachment of intralumenal vesicles as observed by electron tomography, implicating Bro1 as a regulator of ESCRT-III disassembly and membrane scission activity.