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Klippel-Trénaunay syndrome (KTS) is a rare congenital vascular-overgrowth disorder within the broader spectrum of PIK3CA -related overgrowth syndromes. Although clinical, radiologic, and orthopedic manifestations are well described, the histologic spectrum of KTS-associated pathology remains under-characterized. Clinicopathologic findings from 21 patients with clinically established KTS were reviewed, including 18 with longitudinal clinical follow-up and 3 consultation cases of rare malignant mesenchymal neoplasms. Cases were identified from institutional pathology and clinical databases, and available hematoxylin and eosin-stained sections and ancillary studies were reviewed. The cohort included 11 males and 10 females. Among the 18 clinically followed patients, 12 had limb length discrepancy or asymmetric limb overgrowth, 9 had documented deep vascular malformations, 4 had intra-articular/synovial malformations, and 10 underwent initial orthopedic evaluation or intervention before age 18. Orthopedic morbidity clustered into mechanical overgrowth-related, vascular malformation-related, and soft tissue/wound-related complications. Histologic findings included superficial and/or deep slow-flow vascular malformations, ulceration and granulation tissue, hemosiderin-laden reactive synovium, and destructive hemorrhagic arthropathy. Intra-articular disease recapitulated a hemophilic arthropathy-like pattern, with hemosiderotic synovitis, papillary synovial hyperplasia, and progressive joint destruction with loss of articular cartilage, exposed subchondral bone destruction and remodeling, all attributable to long-standing intra-articular hemorrhage. Three consultation cases showed malignant mesenchymal neoplasia, including 2 angiosarcomas. Recognition of these patterns is important for pathologists evaluating specimens from patients with known or suspected KTS, particularly when findings mimic hemophilic arthropathy, diffuse-type tenosynovial giant cell tumor, nonsyndromic vascular malformation, and/or end-stage destructive arthropathy.

AI skill development is essential in health professions education (HPE), yet this type of faculty development is complex to design and implement. While competency frameworks and AI education programs are emerging, many faculty developers are themselves still building AI literacy and confidence, and practical guidance for how to design a faculty development program on AI that is accessible, skill-oriented, and responsive to rapid technological change remains limited. Although webinars and workshops can only do so much, a well-planned faculty development program can provide a great introduction to AI, alleviate fears, and inspire participants to keep growing and learning. Drawing on our experience designing and hosting the AAMC GEA AI Skill-Building Webinar Series and the current literature in AI, this article offers twelve practical tips for faculty developers who are creating AI-focused learning opportunities for everyone involved in HPE. These tips will help readers create robust AI skill-building sessions that move participants beyond awareness of AI and shift their perspectives toward applied, reflective, and responsible use of AI in HPE.

Abstract Context Menstrual irregularities have been associated with cardiovascular disease (CVD) risk, but underlying etiologies may confer distinct risk profiles. Functional hypothalamic amenorrhea (FHA) has not been evaluated as a separate risk phenotype. Objective To assess the association between FHA phenotype and incident CVD and cardiometabolic risk factors. Design Prospective cohort study with biennial follow-up from 1993 to 2019. Setting Nurses’ Health Study II cohort. Participants The sample included 52,655 premenopausal women free of CVD in 1993. FHA phenotype was defined as irregular or absent cycles without PCOS traits combined with low body mass index and/or high physical activity. Intervention None Main Outcome Measures Incident CVD (coronary heart disease [CHD; myocardial infarction or coronary revascularization] and stroke) and incident elevated cholesterol, hypertension, and type 2 diabetes (T2DM). Results During up to 26 years of follow-up, 1,007 CVD events occurred. Among women who developed CVD, the median time to the first CVD event was 17.0 years (IQR, 11.3-21.0). FHA phenotype in mid-adulthood was associated with a 62% higher risk of CVD (95% confidence interval [CI]: 1.01–2.59), driven by an almost two-fold higher risk of CHD (hazard ratio [HR] = 1.91; 95% CI: 1.11–3.27), compared with women with regular cycles. FHA was also associated with T2DM (HR = 1.86; 95% CI: 1.41–2.47), but not hypertension or elevated cholesterol. Non-FHA menstrual irregularity was associated with elevated cholesterol, hypertension, and T2DM, but not CVD. FHA in early adulthood was not associated with outcomes. Conclusions FHA phenotype in mid-adulthood was associated with increased CHD risk independent of traditional risk factors. Menstrual history may serve as an early marker of cardiometabolic risk.

Gut wall physiology in multiple sclerosis (MS) and autoimmune neurologic diseases remains underexplored. This review examines gut wall dysfunctions’ contribution to MS and autoimmune neurological disorder pathogenesis and progression. We discuss 3 inter‐related aspects of gut physiology: intestinal barrier, enteric nervous system (ENS), and mucosal immunity. We highlight the ENS as a putative target of immune injury in selected antibody‐mediated and T cell‐associated neurologic diseases. Finally, we propose a unifying framework in which the gut functions as a site of immune priming and target of autoimmune injury, bridging microbiome‐driven mechanisms in MS with ENS‐directed autoimmunity across neurologic diseases. ANN NEUROL 2026

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.