Citations

Once considered rare and essentially untreatable with a grim prognosis and reduced life expectancy, hypertrophic cardiomyopathy (HCM) has evolved substantially over 6 decades. Ultimately, HCM has become a contemporary global disease with pharmacologic and interventional options offering effective personalized treatment for all adverse disease pathways. Striking reduction in HCM‐related mortality to ≤0.5%/year in optimally treated cohorts is now comparable to that expected in the US general population, lower than most other disease risks to living, and 10‐fold less than the earliest estimates. The few deaths directly related to HCM are now largely attributable to advanced (end‐stage) heart failure in patients with nonobstructive HCM. Determinants of this transformation to a lower risk disease are evident in hallmark clinical inflection points and breakthroughs, including dedicated HCM programs assembling large clinical databases in which focused (and unfunded) physician‐investigators have derived data directly from patients in clinical practice. Evidence‐based observational studies report emergence of contemporary treatment strategies enhancing survival: implantable defibrillators prevent arrhythmic sudden death globally with 95% sensitive patient selection using an American Heart Association/American College Cardiology risk stratification algorithm; low‐risk, high‐benefit surgical myectomy reverses outflow obstruction and heart failure in >90% with a long‐term survival benefit; and aggressive anticoagulation has reduced embolic strokes. Recent novel pharmacologic alternatives (cardiac myosin inhibitors) are proving effective in relieving obstruction/symptom burden and changing disease management. These principles and time‐tested patient‐centered research strategies uniquely tailored to the heterogeneous HCM clinical spectrum are pivotal in providing practice insights, offering a vulnerable population more optimistic prognosis including opportunity to achieve normal longevity not available to prior generations of patients.

Background Mortality in adults with congenital heart disease (CHD) is strongly driven by disease complexity. Social determinants of health (SDOH) influence adult CHD (ACHD) health outcomes but their impact on mortality is unclear. This study examined the influence of clinical factors and SDOH on all‐cause mortality in patients with ACHD. Methods Single‐center retrospective cohort study of patients with ACHD in the Mayo ACHD Registry who had a verifiable residential address between January 1, 2004 and December 31, 2023. Clinical and SDOH indicators were extracted, including insurance type, language, rural–urban commuting area code, and a housing‐based socioeconomic index, an individual‐level measure of socioeconomic status derived from 4 objective housing characteristics and categorized into quartiles (Q1–Q4). Cox proportional‐hazards models were fitted to evaluate associations with mortality, incorporating CHD severity, arrhythmias, SDOH indicators, and other comorbidities. County of residence was included as a random effect, and model discrimination was assessed using the concordance statistic. Results Among 6134 patients with ACHD, the mean age was 38±16 years; 51% were male; 78.7% were White and 44.9% had rural residence. Independent predictors of mortality included cyanotic CHD (adjusted hazard ratio [aHR], 5.70 [95% CI, 2.90–11.23]), Fontan palliation (aHR, 4.98 [95% CI, 2.56–9.70]), ventricular tachycardia (aHR, 1.71 [95% CI, 1.16–2.52]), older age at first visit (aHR, 1.05 per year [95% CI, 1.04–1.05]), male sex (aHR, 1.19 [95% CI, 1.03–1.39]), public insurance (aHR, 1.60 [95% CI, 1.35–1.90]), rural residence (aHR, 1.25 [95%, CI 1.06–1.47]), and non‐English language (aHR 1.75 [95% CI 1.38–2.23]). The housing‐based socioeconomic index quartile was not associated with mortality. The final model achieved a concordance statistic of 0.77. Conclusions Mortality in patients with ACHD is strongly influenced by both clinical factors and SDOH, independent of socioeconomic status. Addressing barriers to care such as language, insurance, and geography is essential for improving ACHD survival particularly in those at increased mortality risk.

ABSTRACT HLA‐A*32:202 differs from HLA‐A*32:01:01:01 by two nucleotide substitutions in exons 1 and 2.

Background Kidney transplantation offers substantial clinical and economic benefits for patients with end-stage kidney disease (ESKD), yet organ shortages persist. Enhancing public awareness and health literacy regarding kidney donation is essential for effective donor recruitment. While online patient education materials are primary drivers of public perception, their readability, digital engagement, and accessibility remain underexplored barriers. Methods We analyzed the most prominent kidney donation websites identified through U.S.-based Google searches, including 11 primary organizations and 16 affiliated subdomains, for a total of 27 websites. Readability was benchmarked using Flesch-Kincaid, SMOG, and Gunning Fog indices. To assess qualitative metrics, we deployed a generative AI framework utilizing a Large Language Model (Claude) to conduct automated sentiment analysis and tone evaluation, validated by human review. We systematically mapped digital engagement features, including multimedia, interactive tools, and multilingual support, to determine content comprehensiveness. Results Websites consistently provided accurate information with a generally positive or neutral tone. Average readability exceeded recommended levels, with a combined mean grade of 12.3; 34% of websites were written at a college-level reading standard. Consensus across content was high. Multimedia elements were widely used, but engagement features were limited; only 30% of sites included extensive testimonials, and interactive tools were absent. AI-based analysis enabled standardized and reproducible evaluation, highlighting opportunities to improve accessibility, tone, and inclusivity. Conclusion Current U.S. kidney donation digital resources present a barrier to health equity due to excessive reading complexity and static engagement models. AI provides a scalable, reproducible framework to audit and optimize patient education materials. Future initiatives must leverage AI-guided content optimization to bridge the literacy gap, potentially increasing donor registration and access to transplantation.

Objective This study evaluates the impact of international observerships organized by Help Ukraine Group (HUG) on professional development, knowledge transfer, and clinical practice improvement in radiation oncology in Ukraine. Methods A total of 50 observerships were facilitated for Ukrainian medical professionals at 14 institutions across the USA, Canada, Europe, and Australia from 2022 to 2024, including 31 radiation oncologists and medical physicists. A survey assessed their impact on oncology care, focusing on knowledge gained, lessons learned, and challenges in implementing new techniques. The primary outcome was the success score, defined as a composite score of implementing new procedures, initiating improvement projects, and knowledge dissemination efforts. Descriptive and comparative analyses examined satisfaction and success outcomes. Results A total of 43 respondents participated in the survey (response rate 86.0%). Twenty-eight of the responders were radiation oncology professionals (67.8% radiation oncologists, 32.1% medical physicists). The median observership duration for radiation oncology professionals was four weeks, with 96.4% also attending a professional conference. Overall satisfaction was high (mean 9.5 out of 10, median 10.0, IQR 9.0-10.0) while the success score was substantial (mean 6.1 out of 10, median 7.0, IQR 5.0-8.0). Time since certification influenced success, with ≥10 years’ experience associated with higher success scores (7.4 vs. 4.7, p=0.01). Importantly, 100% of respondents learned new procedures, 89.3% reported shifts in their clinical perspective, and 60.7% successfully implemented new techniques. Subsequent knowledge dissemination in Ukraine was substantial: 82.1% provided informal training, 60.7% delivered institutional or national presentations, 39.3% incorporated materials into lectures, and 10.7% engaged in all activities. Continued mentorship with host institutions was reported by 82.1%. Conclusions Amid the war, international observerships advanced clinical practice, education, and procedures in Ukraine, demonstrating the resilience of its medical community and providing a model that other LMICs/UMICs can follow.

Belt buckle ectropion is a newly recognized mechanism of lower eyelid malposition following Mohs reconstruction. Unlike cicatricial ectropion caused by vertical skin shortage, this variant results from horizontal flap tension acting on a lax tarsus. We retrospectively reviewed three patients who developed postoperative ectropion following subciliary Mohs reconstruction without lid margin involvement. Mechanism, management, and outcomes were analyzed. In all cases, the ectropion resulted from horizontal anterior lamellar tension producing anterior tarsal tilt, confirmed by a negative forced traction test. One case resolved spontaneously, and two required lateral tarsal strip procedures, both yielding successful anatomic and functional outcomes. Belt buckle ectropion represents a distinct post-reconstructive malposition mechanism, correctable with horizontal tarsal tightening rather than skin grafting. Recognition of this pattern may prevent misclassification as cicatricial ectropion and guide appropriate surgical management.

Summary The American Society of Clinical Psychopharmacology convened a 45-member international expert task force to identify circumstances supporting the deprescribing of core psychotropic medications for major depressive disorder (MDD) and bipolar disorders. Three Delphi survey rounds plus a selective literature review identified points of consensus (predefined as ≥75% agreement) about when antidepressant, antipsychotic, mood stabiliser and sedative-hypnotic deprescribing is warranted. Twenty out of 32 statements (63%) achieved consensus across seven thematic areas. In MDD, panellists favoured discontinuing antidepressants when mechanisms of action are duplicative, adequate trials produce ≤25% improvement or loss of prior efficacy cannot be regained through dose increases or augmentations. Indefinite antidepressant maintenance in MDD was favoured after three or more lifetime episodes. In bipolar disorder, antidepressant deprescribing was favoured in the setting of rapid cycling, mixed features or emerging mania/hypomania symptoms; and discouraged if prior antidepressant cessation led to relapse. In nonpsychotic mood disorders, panellists favoured deprescribing antipsychotics that caused significant weight gain or tardive dyskinesia over adding pharmacological antidotes. Deprescribing to achieve an eventual medication-free status was considered inappropriate, in bipolar type 1, but not necessarily bipolar type 2 disorder. Although individualised circumstances necessarily inform psychopharmacology management, clinical presentations that misalign with existing pharmacotherapies may signal the desirability of cautious deprescribing.

Objective To estimate the prevalence, incidence, and disease burden of autoimmune seizures and epilepsies in Olmsted County. Methods We conducted a retrospective, population‐based study using the Rochester Epidemiology Project (1996–2019). Age‐ and sex‐standardized rates (2019 United States standard population) per 100,000 were calculated with 95% confidence intervals (95% CIs). Temporal trends in incidence were assessed over 3 consecutive 8‐year intervals (1996–2003, 2004–2011, and 2012–2019) using Poisson regression to estimate rate ratios per period and trend. Disability‐adjusted life years (DALYs), years of life lost (YLL), and years lived with disability (YLD) and 95% uncertainty intervals (95% UIs) were estimated for 2019. Results Twenty‐three patients were identified between 1996 and 2019. In 2019, the standardized prevalence of all autoimmune seizures and epilepsies was 9.81 (95% CI, 5.59–15.21) per 100,000, including autoimmune‐associated epilepsy (AAE) 7.27 (3.74–11.95) and acute symptomatic seizures secondary to autoimmune encephalitis (ASSAE) 2.55 (0.69–5.60). From 1996 to 2019, the standardized incidence was 0.50 (0.29–0.77) per 100,000 person‐years overall, with AAE 0.36 (0.19–0.59) and ASSAE 0.15 (0.05–0.30). By period, the standardized incidence of all autoimmune seizures and epilepsies suggested a rising trend from 0.28 (95% CI, 0.06–0.68) in 1996 to 2003 to 0.60 (95% CI, 0.24–1.12) in 2004–2011, then plateaued at 0.53 (95% CI, 0.21–1.00) in 2012 to 2019 (rate ratio per 8‐year interval 1.30, 95% CI, 0.71–2.38), largely driven by the seropositive subgroup. The standardized DALY rate was 26.27 (95% Uncertainly intervals [UI], 5.30–67.09) per 100,000 (YLL 20.07 [0.00–60.21] and YLD 6.20 [5.06–7.39]). Interpretation Although autoimmune seizures and epilepsies remain rare, they result in a disproportionately high disease burden. ANN NEUROL 2026;100:74–83

Abstract Aims The clinical significance of early recurrences during the blanking period following pulmonary vein isolation (PVI) remains uncertain, particularly after pulsed field ablation (PFA). This study aimed to evaluate the prognostic impact of early recurrences at 30-, 60-, and 90-day thresholds on outcomes following PFA for atrial fibrillation (AF). Methods and results Consecutive patients who underwent PFA for AF across multiple centres within the Mayo Clinic health system were included. The primary endpoint was AF-free survival. Kaplan–Meier and multivariate Cox regression analyses were performed to compare outcomes between patients with and without early recurrences using 30-, 60-, and 90-day thresholds. A total of 1162 patients were included. The estimated AF-free survival at 1 year was 70%. Early recurrences within 30-, 60-, and 90-days post-ablation were significantly associated with late recurrences beyond 90 days (hazard ratio [HR] 5.9, 95% confidence interval [CI] 4.4–7.9, P < 0.01; HR 6.6, 95% CI: 5.0–8.6, P < 0.01; and HR 9.1, 95% CI: 7.0–11.7, P < 0.01, respectively). These findings remained significant among patients undergoing continuous rhythm monitoring. Early recurrences within 30 days in this subgroup were significantly associated with a 1-year AF burden >1% or the need for repeat AF ablation (odds ratio 25.0, 95% CI: 6.6–126.8, P < 0.01). Conclusion Early recurrences following PFA are strongly predictive of long-term arrhythmia recurrence and are unlikely to represent transient inflammatory phenomena. Accordingly, the applicability of the conventional blanking interval after PFA should be reconsidered.

ABSTRACT Cataract is a leading cause of visual impairment worldwide, and its prevalence is increasing with population aging. The majority are age‐related cataracts (ARC), clinically classified into nuclear, cortical, and posterior subcapsular cataracts (PSC) by opacity location. Mechanisms of cataractogenesis remain incompletely understood. While cortical and nuclear cataracts are largely attributed to crystallin aggregation, such protein‐centric mechanisms fail to explain the early onset and axial location of PSC. Morphologically, PSC resembles posterior capsule opacification (PCO), a secondary cataract driven by epithelial–mesenchymal transition (EMT) of lens epithelial cells (LECs), suggesting LEC‐EMT may also contribute to PSC. Using clinically stratified human lens samples, we confirmed EMT marker expression across PSC subtypes. Transcriptomic profiling revealed that LECs, the lens's sole metabolically active cells, in age‐related PSC (ARC‐PSC), compared with age‐related nuclear cataract (ANC) and clear lenses, exhibit elevated EMT signatures tightly linked to senescence‐associated inflammatory signaling. Aqueous humor (AqH) profiling demonstrated a pro‐inflammatory milieu across PSC subtypes, with IL‐17A uniquely elevated in ARC‐PSC, consistent with transcriptomic findings. Integrated analyses support a model in which senescence functions as an upstream driver, whereby senescent LECs release SASP factors, including IL‐17A, that activate NF‐κB signaling to amplify inflammation, reinforce senescence, and drive EMT. In vitro, senolysis and IL‐17A blockade disrupted this loop, attenuating senescence‐ and EMT‐associated phenotypes. Collectively, our study demonstrates that senescent LECs sustain an IL‐17A–NF‐κB circuit that drives EMT and accelerates ARC‐PSC progression, positioning ARC‐PSC as a unique human context to study senescence‐induced epithelial remodeling in aging tissues.