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Background: Telomeres are repetitive sequences at the end of linear chromosomes that preserve genetic information. Patients with telomere biology disorders (TBDs) are subject to multiorgan manifestations, which include the liver. However, due to the rare nature of the disorder, these manifestations are not fully characterized. Methods: Here, we describe the hepatic manifestations of patients with TBD at a large tertiary center within a specialized TBD clinic; 121 consecutive patients with TBD seen from 2017 to 2024 were included. The median age of the TBD diagnosis was 43 years old, with 60% male. The most common pathogenic/likely pathogenic variant was TERT (25%), followed by RTEL1 (10%) and TERC (7%). Results: Evidence of hepatic involvement in TBD was observed in 60% of patients (73 of 121), as determined by imaging studies or abnormal liver chemistries. Hepatic steatosis was the most prevalent imaging finding (56%), while a cholestatic pattern of liver injury was the predominant laboratory abnormality (73%). Biopsy-proven portosinusoidal vascular disorder was present in 4 patients. Findings of portal hypertension were observed in 25 patients (34%), with decompensation observed in 12 patients (16%). Traditional liver imaging modalities (computer tomography, ultrasound, and MRI) were compared with magnetic resonance elastography in 41 patients. Of these, 7 patients had abnormal magnetic resonance elastography with normal traditional imaging (17%), indicating higher sensitivity of magnetic resonance elastography to detect liver involvement. Conclusions: This study describes the liver manifestations within a cohort of patients with TBD with findings of portosinusoidal vascular disorder and hepatopulmonary syndrome similar to other cohorts and a noted higher prevalence of hepatic steatosis as compared with the general population. Liver stiffness measurements, integrated with imaging and laboratory testing, further improve characterization of hepatic manifestations in TBD.

Introduction: Flipped classroom models, which use active, case-based discussion, have shown promise across graduate medical education. Previous literature demonstrates that transitioning to a flipped classroom model resulted in significant increases in overall Orthopaedic In-Training Examination (OITE) scores. This observational study retrospectively compares foot and ankle OITE scores for orthopaedic surgery residents before and after implementation of a flipped classroom curriculum. Methods: This retrospective study reviewed OITE scores for orthopaedic residents, comparing a lecture-based curriculum (n = 49) to a flipped classroom curriculum (n = 61). Residents who started their second year in July 2020 or later were defined as treated. The curriculum is given to the postgraduate year-2 (PGY2) residents only. Percentage of correct foot and ankle questions (F&A) were analyzed via mixed-effects models using random-subject intercepts. Fixed effects included PGY, overall performance on other sections, and flipped classroom status. All statistical analyses were performed in R version 4.4.1. Results: Residents in the flipped classroom cohort demonstrated a statistically significant increase in F&A questions answered correctly. The average increase was 7% (95% confidence interval: 4%, 10%; p < 0.001). This improvement trend became clearly visible in PGY3 and grew stronger in senior residents. Specifically, PGY3 residents improved their mean percentage correct from 62.26% to 66.07% (p = 0.16). PGY4 residents improved from 69.16% to 74.83% (p = 0.013), and PGY5 residents improved from 69.03% to 75.53% (p = 0.006). Historically, approximately 75% of traditional PGY5 residents scored lower on the F&A section than on the rest of the examination. Conversely, in the flipped classroom group, approximately 75% of PGY4 and PGY5 residents scored higher on the F&A section compared with other sections Discussion: The implementation of a flipped classroom model was associated with a statistically significant improvement in resident performance on the F&A section of the OITE. The educational benefits of this curriculum appear cumulative over the course of residency, with the most substantial performance gains realized by senior residents in their fourth and fifth years of training. Level of Evidence: Level III , Observational Study. See Instructions for Authors for a complete description of levels of evidence.

Background: The Accreditation Council for Graduate Medical Education (ACGME) case log system establishes minimum clinical experiences for anesthesiology residency. While core program requirements were last updated in 2016, case log minimums themselves have not undergone a major revision in approximately two decades. Consequently, current requirements may not fully reflect changes in anesthetic practice and the evolving scope of perioperative medicine. In anticipation of major ACGME revisions in 2027, this study aimed to develop consensus-driven recommendations for modernizing residency case logs. Methods: A three-round modified Delphi study was conducted with a nationally representative panel of 60 stakeholders, including anesthesiology residency program directors and academic and private practice anesthesiologists. Panelists evaluated a comprehensive list of potential case categories across three domains: technical skills, surgical case characteristics, and patient demographics. In Round 1, panelists proposed minimum numbers or suggested that no requirement was necessary. Rounds 2 and 3 utilized iterative feedback to determine consensus on the necessity of requirements and specific minimum thresholds. Consensus was defined as at least two-thirds agreement. Results: Sixty invited experts completed all three rounds (100% response rate). The panel reached consensus to recommend new minimum requirements across several areas not currently tracked with minimums, including arterial lines (40), central lines (20), fiberoptic intubation (10), one-lung ventilation (10), neuromonitoring (10), POCUS (10 Cardiac, 10 Lung), and NORA (20 cases). Regarding existing requirements, consensus was reached to recommend increasing total peripheral nerve blocks from 40 to 60, with added requirements for anatomic specificity, and cardiac case minimums from 20 to 25. The panel also established consensus definitions for life-threatening pathologies to standardize reporting. The panel did not achieve consensus on several areas, including, for example, whether a minimum requirement for patients younger than 3 months should be maintained. Conclusion: These findings provide stakeholder-validated recommendations to inform upcoming ACGME requirement revisions.

Importance Patients undergoing cardiac surgery with cardiopulmonary bypass often require platelet transfusions for bleeding. Platelets are routinely stored at room temperature (20-24 °C) for up to 5 to 7 days; however, cold storage (1-6 °C) may allow for increased storage duration without loss of hemostatic function. Objective To determine the maximum cold-storage duration, up to 21 days, for which cold-stored platelets (CSPs) are noninferior or superior in hemostatic efficacy to room-temperature platelets (RTPs) when transfused in actively bleeding patients undergoing cardiac surgery with cardiopulmonary bypass. Design, Setting, and Participants A phase 3, multicenter, randomized, partially blinded, adaptive, noninferiority, storage duration–ranging trial conducted in pediatric and adult patients undergoing cardiac surgery with planned cardiopulmonary bypass at 27 sites in the US and Australia from December 2021 to March 2025. Statistical analysis was conducted from September 9 to October 3, 2025. Intervention Patients were randomized 2:1 to receive CSPs with a maximum of 21 days of storage vs RTPs with a maximum of 7 days of storage. Main Outcomes and Measures The primary outcome was a hemostatic efficacy score with values ranging from 1 to 5 and higher values indicating greater bleeding. The noninferiority margin was 1 point. The success criterion was met if at least 1 cold-storage duration of 7 days or more had a posterior probability of noninferiority of at least 97.5%. The secondary outcome was 24-hour chest tube output. Results Of the 1000 patients who underwent platelet transfusion, 989 were included in the primary analysis (650 CSPs and 339 RTPs). The cohort had a mean (SD) age of 42.1 (30.1) years and 67.8% were male. CSPs were noninferior to RTPs for the primary outcome, with a probability of greater than 99.9% for all cold-storage durations. Pooled across storage durations, CSPs had a mean difference from RTPs of 0.09 (95% credible interval, −0.06 to 0.23). Median (IQR) chest tube output at 24 hours (8.9 mL/kg [5.2-15.4] for CSPs vs 8.4 mL/kg [5.5-15.9] for RTPs; difference in medians, 0.4 [95% CI, −1.0 to 1.5]) was not statistically different between study groups. In a post hoc analysis, as all storage durations were noninferior, considering the CSPs as a single group, the hemostatic efficacy score was similar between both groups: mean (SD) of 3.08 (1.15) CSPs vs 2.99 (1.10) RTPs. There were no differences in venous or arterial thrombotic events, transfusion-associated adverse events, acute respiratory distress syndrome, kidney failure, septic shock, and mortality between the study groups, except for increased reexploration rates in the CSP group. Conclusions and Relevance For patients undergoing cardiac surgery, CSPs stored up to 21 days are noninferior to RTPs for the control of active surgical bleeding. Use of CSPs may allow for increased availability of platelets by reducing wastage and shortages and may allow for incorporation of platelets into inventory at locations where platelets cannot be maintained due to the 5- to 7-day shelf life of RTPs. Trial Registration ClinicalTrials.gov Identifier: NCT04834414

This study examines the patient- and hospital-level variation in time to initiation of inpatient management among patients admitted to general medical services.

Mesothelioma is a rare cancer that originates from the mesothelial surfaces of certain sites within the body. Pleural mesothelioma is the most common type and represents approximately 85% of mesotheliomas. The NCCN Guidelines for Mesothelioma: Pleural provide recommendations for evaluation and treatment in patients with pleural mesothelioma. The NCCN Guidelines will continue to be updated annually based on available clinical evidence and panel consensus.

Stellate ganglion blockade (SGB) is an uncommon but increasingly relevant therapy used to modulate the autonomic nervous system and reduce the risk of atrial fibrillation (AF). This narrative review focuses specifically on the potential therapeutic role of SGB in new-onset perioperative atrial fibrillation (POAF), a complication associated with adverse long-term outcomes that may diminish the overall benefits of surgery. SGB may reduce AF through several inflammation-mediated mechanisms, including attenuation of direct sympathetic activation and modulation of perioperative inflammatory responses. Because the clinical effects of SGB may persist beyond the expected duration of local anesthetic nerve blockade, we emphasize immunomodulation as a potential mechanism sustaining its beneficial effects and influencing longer-term outcomes. In this review, we examine the immunological effects of SGB in the context of postoperative AF, with particular emphasis on human studies most relevant to clinical practice. Available evidence suggests that, beyond nonspecific inflammation, several less commonly studied cellular components, including mast cells and T cells, may contribute to the initiation and persistence of POAF. These findings support the hypothesis that SGB may reduce POAF by limiting stellate ganglionitis driven by perioperative localized leukocyte activation. Future studies should define the extent, timing, and frequency of this inflammatory process and determine whether specific inflammatory or autonomic phenotypes can identify patients most likely to benefit from SGB.

BACKGROUND AND OBJECTIVES: Medical management options for nontraumatic subdural hematoma (SDH) remain limited, with only atorvastatin demonstrating benefit in a single phase 2 randomized clinical trial and mixed evidence for dexamethasone. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may benefit SDH outcomes. The objective of this study was to evaluate the association between GLP-1 RA use and rescue surgery rates and mortality in patients with medically managed nontraumatic SDH. METHODS: We conducted a retrospective cohort study using the TriNetX database from 2016 to 2025, including adults with SDH who were managed conservatively without surgical evacuation or middle meningeal artery embolization. Patients prescribed GLP-1 RAs were compared with nonusers. After propensity matching, rescue surgical evacuation, all-cause mortality at 1 year, and GLP-1 RA–associated adverse events were analyzed. RESULTS: A total of 134 901 patients with conservatively managed nontraumatic SDH were identified, of whom 1470 (1.1%) were GLP-1 RA users. After propensity score matching, 2922 patients remained, with 1461 in each group. At 1 year, GLP-1 RA users experienced significantly lower rates of rescue surgery (2.23% vs 3.51%; P = .046), culminating in an overall 38% reduction in relative hazard. All-cause mortality was also significantly lower for GLP-1 RA users at 1 year (16.1% vs 23.7%, P < .001), reflecting a 33% reduction in hazards. GLP-1 RA users did not experience different rates of adverse events, such as pancreatitis, gallbladder disease, or ileus/bowel obstruction (all P > .05). CONCLUSION: Among patients with medically managed nontraumatic SDH, GLP-1 RA use was associated with significantly lower rates of rescue surgery and all-cause mortality without significantly increased risk of common GLP-1 RA–related complications.

Abstract BACKGROUND [177Lu]Lu-PSMA-617 improves survival and quality of life in men with metastatic castration-resistant prostate cancer but requires substantial healthcare involvement. Our analysis evaluated the time toxicity associated with [177Lu]Lu-PSMA-617, representing the first dedicated radioligand time toxicity assessment. MATERIALS AND METHODS We conducted a multi-institutional retrospective study of patients initiating [177Lu]Lu-PSMA-617 between April 2022 and March 2023. Patients were followed from first [177Lu]Lu-PSMA-617 administration until 3 months after the final cycle, initiation of new systemic therapy, or death. Time toxicity was quantified as healthcare contact days during the at-risk interval. Associations with baseline characteristics were evaluated using negative binomial regression models. Univariate and multivariable models were performed. RESULTS Among 135 patients, median age was 69 years and median prior systemic therapies was 4. Patients completed a median of 5 [177Lu]Lu-PSMA-617 cycles over 7.6 months. Median healthcare contact days were 20 (IQR, 15–28), representing 9.5% (IQR, 6.4–13.9) of at-risk days. Fifteen patients (11%) experienced high time toxicity (&gt;1 contact day per 5 days), while 42 (31%) had low time toxicity (≤1 contact day per 14 days). Among the 57 patients who received both cycle 1 and cycle 6, mean per cycle healthcare contact days were 4 and 3.6, respectively (paired Wilcoxon signed-rank test, p = 0.04). Routine oncology visits comprised 32.7% of contact days, compared with 8.8% from hospitalizations. Lower baseline hemoglobin was independently associated with greater time toxicity (RR = 0.87; 95% CI, 0.79–0.96; p = 0.004). CONCLUSION In heavily pretreated patients, [177Lu]Lu-PSMA-617 demonstrated relatively low time toxicity, supporting it as a time-efficient therapy.