Citations

Abstract Purpose Clinician educators are essential to the academic medicine workforce, yet understanding how they assess their own teaching competencies is limited. The Clinical Educator Milestones (CEMs) guide growth across key educator domains, but their use and perceived relevance remain underexplored. This study aims to (1) evaluate clinician educators’ self-reported performance on the CEMs; (2) examine differences by career level, specialty, and experience; and (3) inform faculty development efforts through a clearer understanding of educators’ perceived strengths and gaps. Method Clinician educators from 9 US academic institutions completed a self-assessment rating their performance across 4 universal pillars and 11 educational theory and practice competencies on a 1- (novice) to 5- (expert) point scale in 0.5-point increments from August to November 2024. Descriptive statistics and mean difference tests were used to analyze variation across demographic and professional characteristics. Results A total of 484 responses to at least 1 CEM were received. Respondents rated themselves highest in commitment to professional responsibilities (mean [SD], 4.30 [0.68]), teaching and facilitating learning (mean [SD], 3.96 [0.74]), and professionalism (mean [SD], 3.93 [0.73]) and lowest in medical education scholarship (mean [SD], 3.11 [1.15]), program evaluation (mean [SD], 3.33 [1.03]), and the science of learning (mean [SD], 3.43 [1.10]). Statistically significant group differences were found by years of posttraining clinical experience (F2,413 = 16.87, P < .001, η2 = .076), years of teaching experience (F2,433 = 20.87, P < .001, η2 = .088), and academic rank (F2,403 = 13.96, P < .001, η2 = .065). Conclusions This study identifies key trends in self-perceived strengths and needs among clinician educators and highlights the limited awareness of the CEM framework. As institutions aim to build effective educator development systems, the CEMs can serve as a useful structure for tailoring support to individuals and identifying institutional needs.

Abstract Background The extravascular implantable cardioverter defibrillator (EV-ICD) was designed to avoid lead-related complications associated with transvenous systems and deliver features such as anti-tachycardia pacing (ATP) and reduced generator size that provide an advantage over a subcutaneous ICD (S-ICD). As such, the EV-ICD is an attractive alternative for younger patients with genetic heart diseases (GHDs) who are not in need of permanent pacing. Objective To examine the indications, complications, and the clinical outcomes of patients with GHDs who received an EV-ICD. Methods A retrospective review of the electronic record was done for all GHD patients evaluated in genetic heart rhythm and/or cardiomyopathy clinics who had an EV-ICD implanted between 1/2021 and 2/2025. Basic demographic, ICD indications, complications, and therapy data were then extracted for all study patients. Results Overall, 23 patients (35% female; mean age 39 ± 16 years; 61% with a disease-causative genetic variant; mean LVEF 57%) with an underlying GHD (hypertrophic cardiomyopathy in 9, arrhythmogenic cardiomyopathy in 8, idiopathic ventricular fibrillation in 3, dilated cardiomyopathy in 2, and long QT syndrome in 1) had an EV-ICD implanted. For the majority, an EV-ICD was implanted for primary prevention (15/23; 65%) and represented their first ICD system (21/23; 91%). The success rate of the procedure was 96% with only one abandoned procedure because of poor R-wave sensing. Inadvertent intraprocedural lead placement in the pericardial space occurred in 1 patient with previous thoracotomy and surgically placed epicardial lead without sequelae or need for revision. Over a mean follow-up of 8±9 months, the rate of complications was low (1/23; 4%) with one electrode displacement and this patient underwent defibrillation threshold testing (DFT), the device properly detected VF and emitted a successful shock 30 J. Thus far, 2 patients have received appropriate VT/VF-terminating therapies (3 ICD shocks, 0 ATP) with successful conversion to sinus rhythm. One patient died following an electrical storm. One patient had 3 inappropriate ICD shock for sinus tachycardia while exercising followed by 1 successful shock for VF. Conclusion In this early experience, EV-ICDs appear to be safe and effective in younger patients with genetic arrhythmogenic and hypertrophic cardiomyopathies. Future studies are needed to better understand the utility of EV-ICDs in patients with cardiac channelopathies and advantages of EV-ICDs over transvenous and S-ICD systems in patients with an array of sudden death-predisposing GHDs.

Abstract High-grade gliomas (HGGs) are aggressive tumors with poor outcomes and limited treatment options. Here, we combined genomic and transcriptomic tumor profiling with drug testing in a patient-derived 3-dimensional culture model to identify individualized treatments and predictive biomarkers. Activity of single agents targeting frequently dysregulated glioma pathways was relatively poor ex vivo and generally reflected historical patient data. However, compounds targeting PI3K, epigenetic, and survival/senescence signaling were effective in some cases. Drug sensitivity correlated with transcriptional rather than genomic features and suggested heterogeneity as a resistance mechanism. Bromodomain and extraterminal domain inhibition was particularly effective in tumors enriched in the mesenchymal transcriptional subtype, promoted proneural transition, and was overcome by upregulated PI3K signaling. Notably, combinations were largely effective, with 6 strategies exhibiting stronger efficacy than corresponding single agents in most cases (58-77%). This study identifies HGG vulnerabilities and associated biomarkers, resistance mechanisms, and effective combination strategies that warrant further clinical validation. Graphical Abstract

Abstract Background Relapsed medulloblastoma remains a significant therapeutic challenge as it is near universally fatal. The tumor microenvironment of medulloblastoma plays a critical role in tumor progression, influencing tumor growth, immune evasion, and therapeutic resistance. We hypothesized that defining tumor-immune interactions in diagnostic and relapsed medulloblastoma may uncover mechanisms of immune evasion and identify novel therapeutic targets. Methods We analyzed paired primary and recurrent RNA-sequencing data from 140 medulloblastoma patients to profile immune cell composition and validate spatial relationships within the TME. To identify key tumor-immune interactions, we developed a novel algorithm to detect receptor-ligand pairs using single-cell RNA-sequencing data. These interactions were validated across RNA and proteomic datasets. Their functional significance was empirically demonstrated in newly developed immunocompetent models of recurrent medulloblastoma that closely recapitulate the human disease. Results We observed a shift toward a heightened immunosuppressive TME at relapse. Using our algorithm, we identified biologically significant receptor-ligand interactions, most notably MIF-CD74, constitutively expressed at RNA and protein levels across medulloblastoma subgroups, at diagnosis and relapse. Disrupting MIF-CD74 interactions led to significant alterations in the tumor microenvironment, highlighting its functional significance. Conclusions Our multifaceted approach identified key tumor-immune interactions in medulloblastoma. Among these, MIF-CD74 was validated as a targetable interaction, demonstrating the utility of our integrative approach for identifying novel therapeutic targets across multiple tumor types.

BACKGROUND: Recent randomized trials have demonstrated that for patients with severe tricuspid regurgitation (TR), transcatheter tricuspid valve interventions (TTVI) improve patients’ symptoms, function, and quality of life and that the amount of health status improvement correlates with the extent of TR reduction. Defining this relationship in greater detail can potentially provide insight into device selection and patient-specific treatment goals. We therefore sought to better understand the relationship between both baseline TR severity and change in TR after TTVI and the extent of improvement in health status after TTVI. METHODS: As part of the Tri-QOL (Kansas City Cardiomyopathy Questionnaire Validation in Tricuspid Valve Disease) study, data from 11 studies of TTVI devices were transferred to the US Food and Drug Administration to harmonize and anonymize before analysis by an independent center. This secondary, observational analysis used patient-level data from the 6 single-arm studies of patients who underwent TTVI to explore the association of change in KCCQ-OS with TR grade using multivariable models, adjusted for age, sex, chronic lung disease, and baseline KCCQ-OS. The primary model included TR grade at baseline, TR grade at 1 month, and the interaction between the two. RESULTS: Among 1056 patients with ≥severe TR who underwent TTVI, mean age was 79.1±7.1 years, 60.3% were female, and mean baseline Kansas City Cardiomyopathy Questionnaire-overall summary score [KCCQ-OS] was 49.5±22.3. Baseline TR grade was severe in 33.5%, massive in 35.9%, and torrential in 30.6%. One-month after TTVI, TR was none/trace in 21.7%, mild in 27.2%, moderate in 28.1%, and ≥evere in 23.1%, while the mean change in KCCQ-OS was 17.0±21.3 points. In a multivariable model that included TR grade at baseline, TR grade at 1 month, and their interaction, there was a strong association between reduction in TR and improvement in KCCQ-OS, with no consistent evidence of a threshold of TR grade below which there was no further improvement in KCCQ-OS. However, among patients with baseline torrential TR, the extent of health status improvement plateaued for patients achieving moderate or less TR at 1 month (ie, a 3-grade improvement from baseline). CONCLUSIONS: Health status improvement after TTVI was most strongly associated with the degree of TR reduction, although there was minimal additional improvement for most patients beyond a 3-grade reduction in TR. These findings support the goal of achieving mild or less TR with TTVI, although patients with torrential TR at baseline may be well served if moderate TR can be achieved.

This cohort study evaluates the reduction in risk of high-grade serous carcinoma among women undergoing opportunistic bilateral salpingectomy in Canada.

Higher-order chromatin structures (HOCS) are fundamental to genome organization, gene regulation, and cellular homeostasis. This review examines the epigenetic mechanisms shaping HOCS, including DNA methylation, histone modifications, chromatin remodeling, and RNA-based regulatory processes. We also discuss the role of architectural proteins in maintaining chromatin topology while allowing dynamic changes to chromatin structure, thereby influencing gene expression. Growing evidence indicates that disruptions in HOCS contribute to a diverse array of human diseases, including cancer, aging-related disorders, and congenital abnormalities, primarily through aberrant gene regulation. We further discuss the concept of distinct genomic areas, in which specific chromatin regions orchestrate three-dimensional (3D) genome dynamics, positioning them as potential biomarkers and therapeutic targets. By emphasizing chromatin architecture on a global scale rather than at the level of individual genes, this review underscores its emerging relevance to precision medicine. Finally, we synthesize current technical advances, outline future directions for leveraging chromatin topology in disease diagnosis and treatment, and highlight key biological insights to reshape our understanding of genome function.

Importance As gender-affirming care expands, hysterectomies for gender dysphoria are increasing, but data comparing outcomes to benign hysterectomies remain limited. Objectives The objectives of this study were to compare perioperative characteristics and 30-day outcomes between transgender and gender diverse individuals (TGDI) undergoing gender-affirming hysterectomy (GAH) and patients undergoing hysterectomy for benign indications, by surgical approach. Study Design This was a retrospective cohort study using the American College of Surgeons National Surgical Quality Improvement Program data (October 2015–December 2022). TGDI undergoing GAH were identified by gender dysphoria diagnosis and hysterectomy Current Procedural Terminology codes. Approaches included abdominal hysterectomy (AH), laparoscopic/robotic hysterectomy (L/RH), laparoscopically assisted vaginal hysterectomy (LAVH), and vaginal hysterectomy (VH). A matched cohort was created based on demographics and comorbidities. Primary outcomes were operative time, length of stay (LOS), and 30-day complications. Results A total of 975 TGDI undergoing GAH were included; 82% of GAHs were minimally invasive, mostly L/RH. GAH represented 0.7% of all benign hysterectomies, increasing over time ( P <0.001). TGDI (970) were matched to controls. In L/RH, TGDI had longer operative times (113 vs 97 min, P <0.001) but shorter LOS (0 vs 1 d, P <0.001). Similar patterns were seen in VH: longer operative times (103 vs 62 min, P <0.001) and shorter LOS (0 vs 1 d, P =0.018). In AH, TGDI had shorter LOS (1 vs 2 d, P =0.006) with similar operative times. No significant differences were found in LAVH or complications across groups. Conclusion GAH is safe with perioperative outcomes comparable to benign hysterectomy. TGDI experience shorter hospital stays and low complication rates. Promoting minimally invasive and vaginal approaches can enhance equitable, high-quality care for TGDI.

Ramdas et al. propose renaming ‘congenital myasthenic syndrome’ as ‘genetic myasthenic syndrome’. They argue that ‘congenital’ misleadingly implies neonatal onset, which may contribute to delayed diagnosis and management, and that revised nomenclature could improve patient outcomes.