Faculty Bibliography

BACKGROUND:Contemporary data characterizing older adults admitted to cardiac intensive care units (CICUs) across diverse indications are limited. OBJECTIVES/OBJECTIVE:The objective of the study was to describe the clinical characteristics, critical care therapies, and in-hospital outcomes of older patients admitted to the CICU compared with younger adults. METHODS:The Critical Care Cardiology Trials Network is a multicenter, international registry of CICUs. Between 2017 and 2024, participating centers contributed annual ≥2-month snapshots of consecutive medical CICU admissions. Admissions were categorized into 4 age groups: <65, 65-<75, 75-<85, and ≥85 years. Outcomes included CICU and in-hospital mortality and length of stay. Multivariable models adjusted for sex, illness severity (SOFA score), lactate, and kidney function. RESULTS:Among 35,265 admissions from 50 sites, 44%, 27%, 21%, and 9% were aged <65, 65-<75, 75-<85, and ≥85 years, respectively. Acute coronary syndrome was the most common admission diagnosis among all age groups. Patients aged ≥85 years had the lowest use of mechanical circulatory support (5.5%), which consisted exclusively of intra-aortic balloon pumps. Relative to patients <65 years, adjusted ORs of in-hospital mortality were 1.53 (1.40-1.67) for 65-<75 years, 1.83 (1.67-2.01) for 75-<85 years, and 1.95 (1.72-2.22) for ≥85 years. Among cardiac arrest patients the increase in mortality with age was steeper, reaching 3.09 (2.24-4.26) for patients ≥85 years. CONCLUSIONS:Patients ≥85 years in contemporary CICUs experience survival comparable to those aged 75-<85 years, except in the setting of cardiac arrest. These findings support consideration of factors beyond chronological age in CICU triage and treatment decisions.

STUDY OBJECTIVES/OBJECTIVE:Clinical demands in the emergency department (ED) may contribute to decision and attention fatigue as clinician time-on-shift increases, impacting patient care. Emergency department pharmacists review orders and intervene to correct problems related to safety and appropriateness. This study's objective was to evaluate and characterize the rate of pharmacist interventions on ED medication orders. We hypothesized that pharmacist interventions would increase with clinician time-on-shift. METHODS:We performed a retrospective study of 2 EDs within a single health system between January 2022 and November 2023. Medication and pharmacy intervention details were extracted and linked to clinician schedules, pharmacist schedules, and ED crowding scores. Mixed-effects logistic regression modeling identified factors associated with pharmacist interventions. RESULTS:Pharmacists intervened on 9,054 (1.5%) of 622,171 medication orders placed by 308 clinicians. Pharmacy intervention rate increased with clinician time-on-shift (odds ratio 1.04 for each hour; 95% confidence interval 1.03 to 1.05), with meaningful variation in this effect between individual clinicians. Stratified by clinician type (attendings, residents, or physician assistants) and shift timing (overnight versus daytime shifts), the association between time-on-shift and pharmacy intervention rate remained positive. Stratified by site (A versus B), the association was positive at site A but not at site B. CONCLUSION/CONCLUSIONS:The likelihood of orders requiring pharmacist interventions increased as ED clinicians' time-on-shift increased. This association was consistently observed across differing clinician types and shift timing, but variable across the 2 sites of the study. Clinical staffing models and quality of care could be improved by addressing stressors and fatigue accumulation informed by this analytical model.

This study evaluates the repeatability of a 3D simultaneous

Papillary renal neoplasm with reverse polarity (PRNRP) has been proposed as a distinct subtype of renal cell neoplasm with recurrent KRAS mutations and indolent behavior. However, its epigenetic landscape is poorly understood. In this study, 12 PRNRPs and a PRNRP initially diagnosed as "papillary adenoma" were analyzed. All 13 cases underwent targeted next-generation sequencing for driver mutations. Eleven PRNRPs were profiled using the Illumina MethylationEPIC array and compared with a reference cohort of 71 common renal cell tumors. KRAS mutations were identified in 12 of 13 (92%) cases of PRNRP. Copy-number analysis from methylation profiling showed that 9 of 11 (82%) PRNRPs lacked copy-number changes. Two cases showed a focal loss of chromosome 8 and a gain of chromosome 16, respectively. Unsupervised clustering based on methylation data showed that PRNRPs form a distinct epigenetic group, separate from papillary renal cell carcinomas (pRCCs) and other major renal tumors, but with the closest affinity to clear cell papillary renal cell tumors. In addition, DNA methylation analysis suggested PRNRP may arise from the distal nephron, in contrast to pRCC, which appears to recapitulate proximal tubules. These findings support PRNRP as a subtype of renal cell neoplasm with a distinct epigenetic signature.

OBJECTIVE:To systematically map and synthesise the scientific literature on substance use patterns among elite athletes, encompassing recreational substances, performance-enhancing drugs (PEDs) and polysubstance use. DESIGN/METHODS:This study was a scoping review conducted in accordance with the Joanna Briggs Institute (JBI) methodological framework and reported following the Preferred Reporting Items for Systematic Review and Meta-Analysis extension for Scoping Reviews (PRISMA-ScR) guidelines. The review protocol was prospectively registered on the Open Science Framework. DATA SOURCES/METHODS:A comprehensive search was conducted in PubMed/MEDLINE, PsycINFO, Scopus and SportDiscus from inception to March 2025. ELIGIBILITY CRITERIA FOR SELECTING STUDIES/METHODS:Eligible studies were peer-reviewed original research articles examining substance use, misuse or substance use disorders among elite athletes, including collegiate, professional, Olympic, Paralympic or national-level competitors. Both recreational substances (eg, alcohol, cannabis, nicotine, prescription drugs) and PEDs were included. RESULTS:From 3292 unique records screened, 119 studies met inclusion criteria. Alcohol was the most extensively studied substance, particularly among National Collegiate Athletic Association collegiate athletes, with consistent evidence of heavy consumption in certain sports, especially those with strong social and team-based norms. PED studies revealed marked sport-specific patterns, largely informed by anti-doping surveillance data, but offered limited insight into psychosocial mechanisms. Research on other substances and polysubstance use was heterogeneous, fragmented, and methodologically variable. Across all domains, the literature was dominated by cross-sectional designs, self-reported data and Western populations. CONCLUSION/CONCLUSIONS:The existing evidence base demonstrates substantial substance-related vulnerability among elite athletes but is characterised by significant conceptual, methodological and geographical gaps. Future research should prioritise longitudinal and theory-driven designs, broader representation of professional and non-Western athletes, integration of mental health frameworks and rigorous evaluation of prevention and intervention strategies. TRIAL REGISTRATION NUMBER/BACKGROUND:The review protocol was prospectively registered on the Open Science Framework (OSF) (DOI: 10.17605/OSF.IO/3PJDN) on 8 January 2025.

INTRODUCTION/BACKGROUND:Essential tremor is a common movement disorder that can cause substantial functional disability when symptoms become medically refractory. Stereotactic radiosurgery (SRS) is a minimal access treatment strategy for tremor control, but multicenter outcome data remain limited. METHODS:We performed a retrospective multi-institutional cohort study of 232 stereotactic radiosurgical thalamotomy procedures for medically refractory essential tremor. The median age at treatment was 76.0 years, median tremor duration was 17.0 years, median margin dose was 70.0 Gy, and median maximum dose was 140.0 Gy. The primary endpoint was clinically meaningful tremor improvement. Secondary endpoints included tremor arrest, recurrence, adverse radiation effects (AREs), and change in Fahn-Tolosa-Marín (FTM) scores. Logistic regression was used to evaluate outcome predictors. RESULTS:Significant tremor improvement was observed in 92.1% of patients, with a median time to improvement of 4.0 months. Complete tremor relief occurred in 26.1%. Symptomatic AREs occurred in 4.3%. Tremor recurrence was noted in 12.4% at median follow-up of 2 years. Among procedures, mean unilateral hand FTM score improved from 12.53 to 5.07, corresponding to a mean improvement of 7.46 points (p < 0.001). Significant improvement was also observed across tremor, writing, drawing, and drinking sub scores (all p < 0.001). On multivariable analysis, a maximum lesion dose ≥ 140 Gy was independently associated with greater odds of clinical benefit (OR 3.44, p = 0.019). CONCLUSION/CONCLUSIONS:In this multi-institutional cohort, SRS was associated with high rates of clinically meaningful tremor improvement, significant functional improvement, and durable tremor control in medically refractory essential tremor.

BACKGROUND:CD19-directed chimeric antigen receptor T-cell (CAR T) therapy has significantly improved outcomes for patients with relapsed or refractory B-cell non-Hodgkin lymphoma (R/R B-NHL) but is frequently complicated by immune effector cell-associated neurotoxicity syndrome (ICANS), a major cause of morbidity and mortality. Preclinical and early phase clinical studies suggest that interleukin-1 blockade with anakinra may mitigate ICANS without impairing CAR T efficacy. However, real-world data evaluating the efficacy and safety of prophylactic anakinra remain limited. OBJECTIVES/OBJECTIVE:We performed a retrospective analysis comparing CAR T toxicities and clinical outcomes among patients treated with prophylactic anakinra versus controls using inverse probability of treatment weighting (IPTW), hypothesizing that anakinra prophylaxis would be associated with decreased severe ICANS. STUDY DESIGN/METHODS:In 2023, our institution implemented a policy for anakinra prophylaxis for high-risk patients based on promising early phase data. We conducted a single-center retrospective cohort study of 176 adult patients with R/R B-NHL who received CD19 CAR T therapy between 2018 and 2025. The analysis was restricted to patients meeting institutional criteria for anakinra prophylaxis (age ≥65 years or receipt of a CD28 costimulatory domain CAR T product), excluding those with baseline ICE score <8. Patients treated with anakinra in the post-policy era were compared with patients treated prior to the implementation of the policy. Inverse probability of treatment weighting (IPTW) was used to balance baseline clinical and disease-related covariates between groups. RESULTS:After IPTW, patients receiving prophylactic anakinra had a higher incidence of any-grade ICANS compared with those who did not (40.0% vs 23.0%, p = 0.03), while rates of grade ≥3 ICANS were similar between groups (p = 0.62). In multivariate regression, anakinra prophylaxis was associated with increased odds of any-grade ICANS (aOR 3.22; 95% CI 1.39-7.46) but not grade ≥3 ICANS (aOR 1.84; 95% CI 0.61-5.5). Rates of all-grade CRS were comparable (p = 0.74); however, in multivariate regression, anakinra prophylaxis was associated with increased odds of grade ≥3 CRS (aOR 17.83; 95% CI 1.30-245.21), though the estimate was imprecise due to sparse events. Grade ≥3 infections were more common in the anakinra cohort (21.5% vs 7.3%; p = 0.01) by day 30 and by day 90 (27.1% vs 10.4%; p = 0.01). Grade ≥3 infections remained associated with use of anakinra in multivariate regression (day 30: aOR 7.08; 95% CI 1.90-26.30, p = 0.004) (day 90: (aOR 5.59; 95% CI 1.83-17.04; p = 0.003). No differences in response rates, event-free or overall survival were observed between groups. CONCLUSION/CONCLUSIONS:In this single-center historical comparison of high-risk patients receiving CD19 CAR T cells, prophylactic anakinra did not reduce severe ICANS and was associated with increased immune-mediated toxicities and infectious complications. Causal inference is limited by policy-driven treatment assignment, residual temporal confounding, and limited practical overlap. These findings suggest the need for caution in routine use of anakinra prophylaxis outside of clinical trials and underscore the importance of prospective studies to better define optimal toxicity mitigation strategies.

BACKGROUND:Data on the differential impact of interventions on subsequent myocardial infarction (MI) type are limited. OBJECTIVES/OBJECTIVE:This post-hoc analysis was done to evaluate the 30-day rate of subsequent MI by type (ie, type 1 and 2) among patients enrolled in the MINT (Myocardial Ischemia and Transfusion; NCT02981407) trial. METHODS:Subdistribution HRs and cumulative incidences of subsequent MI types were computed using Fine-Gray subdistribution models that accounted for the competing risk of death and other MI types, if applicable. Effect modification of treatment strategy by index MI type was tested using log-binomial regression models. RESULTS:Among 3,504 MINT trial patients, 275 (7.8%) had a 30-day subsequent MI, of which 118 (43%) were type 2 MI, 79 (28%) were uncertain MI type, 40 (15%) were type 4 MI, and 38 (14%) were type 1 MI. The rate of subsequent type 2 MI in patients randomized to the restrictive vs liberal transfusion was 3.5% (n = 61) vs 3.2% (n = 57) (HR: 1.07; 95% CI: 0.74-1.53) as compared with a subsequent type 1 MI rate of 1.3% (n = 23) vs 0.9% (n = 15) (HR: 1.53; 95% CI: 0.80-2.94). CONCLUSIONS:Among patients with MI and anemia, subsequent MI occurred within 30 days in 7.8% of patients, with type 2 MI occurring 3 times more often than type 1 MI. A differential effect of the restrictive vs liberal transfusion strategy on the type of subsequent MI (eg, type 1 vs type 2) was not observed.

IMPORTANCE/UNASSIGNED:T-cell-engaging bispecific antibodies (BsAbs) are increasingly used in B-cell non-Hodgkin lymphoma (NHL) and multiple myeloma (MM). As these agents transition into earlier courses of therapy and broader clinical use, understanding their safety profile is critical. While second primary malignant neoplasms (SPMs) represent a key long-term safety signal, small sample sizes, single-arm trials, short follow-up, and heterogeneous reporting have limited reliable estimation of their frequency. OBJECTIVE/UNASSIGNED:To estimate the frequency of reported SPMs after BsAb therapy and evaluate whether study-level characteristics and reporting definitions influence observed estimates. DATA SOURCES/UNASSIGNED:PubMed and Embase were searched from inception through October 1, 2025, following a prespecified protocol registered in PROSPERO. STUDY SELECTION/UNASSIGNED:Clinical trials and real-world studies of BsAbs in adults with NHL or MM reporting SPM outcomes. DATA EXTRACTION AND SYNTHESIS/UNASSIGNED:Data were extracted following PRISMA guidelines. Pooled SPM frequencies were calculated using random-effects meta-analysis of single proportions. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Reported SPM occurrence during available follow-up was categorized as (1) total SPMs reported, (2) SPMs leading to treatment discontinuation, and (3) SPMs leading to death. RESULTS/UNASSIGNED:Of 494 records, 20 studies (26 cohorts; 2551 patients) met inclusion criteria. Among 8 studies (10 cohorts; 1003 patients) reporting total SPMs, random-effects meta-analysis yielded a pooled estimated proportion of 3.5% (95% CI, 1.8-6.9) at a median (range) follow-up of 17.4 (5.7-25.6) months. Disease-specific estimates were 3.8% (95% CI, 2.3-6.3) for NHL and 3.4% (95% CI, 0-76.7) for MM. A total of 6 studies (8 cohorts; 748 patients) reporting SPMs leading to treatment discontinuation showed a pooled estimate of 2.2% (95% CI, 1.5-3.1). A total of 19 studies (24 cohorts; 2330 patients) reporting SPMs leading to death yielded a pooled estimate of 1.4% (95% CI, 1.1-1.9). In exploratory meta-regression analyses of prespecified study-level covariates (follow-up duration, disease category, prior therapy courses, and age), no variables were associated with total SPM estimates. CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this systematic review and meta-analysis, despite relatively short follow-up, SPMs were a measurable and clinically relevant complication of BsAb therapy. Heterogeneous and inconsistent reporting currently complicates their comprehensive assessment, highlighting the need for standardized long-term safety surveillance in clinical trials examining BsAbs.

PURPOSE/UNASSIGNED:Orbital fractures are a major reason for ophthalmologic consultation in the emergency department. In this study, we studied ocular signs associated with intervention and compared 4 previously published protocols to identify which best identified higher risk patients in need of consultation. METHODS/UNASSIGNED:We performed a retrospective cross-sectional study of patients from the BALCITE (BALtimore Consultation, Inpatient, and Trauma of the Eye) database who received ophthalmologic consultation. Our primary outcomes were the ocular and orbital signs associated with receiving intervention. Our secondary outcome identified the most sensitive and specific screening algorithm for orbital fractures by comparing four existing protocols (HOPE+CT, STOP, MEE, and UTH) to our large independent cohort. RESULTS/UNASSIGNED: < 0.001). The STOP tool had the highest sensitivity of 96.3%, demonstrating a potential 29% reduction in hospital fracture consults, followed by MEE, with a sensitivity of 93.1%. The HOPE+CT tool had the highest specificity of 95.6%. CONCLUSION/UNASSIGNED:The presence of an APD and periorbital laceration are strong indicators of urgent ophthalmologic treatment in the setting of acute orbital fractures. Supportive implementation of the STOP and MEE algorithms can effectively screen orbital fracture patients to help triage in the acute setting, improve resource utilization, and reduce healthcare costs.