Citations

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.

Abstract Optimal management of anticoagulation for patients with aortic mechanical heart valves (MHVs) receiving vitamin K antagonists (VKAs) undergoing gastrointestinal endoscopic procedures is clinically challenging. Risk of bleeding from an unanticipated polypectomy or biopsy further complicates this issue. Current guidelines on use of bridging with low-molecular-weight heparin (LMWH) for these procedures are based on low-quality evidence. We conducted a subanalysis of a retrospective, multicenter observational study of adult patients with aortic MHVs receiving VKAs who underwent elective gastrointestinal endoscopies (colonoscopy or upper endoscopy). We included patients who underwent the procedure between July 1, 2020, and July 1, 2023, at five centers in Canada and the United States Patients with procedures performed on separate days within a 30-day period were excluded. Efficacy and safety outcomes included thromboembolic events, major bleeding (MB), and clinically relevant non-major bleeding (CRNMB) in the 30 days post procedure. A total of 192 endoscopic procedures were analyzed. Median (interquartile range [IQR]) patient age was 66 years (58.2–72.8) and 22% were female. Warfarin was interrupted for 185 procedures (96%). Among these, 119 (64%) received LMWH bridging: 33 (17%) pre-procedure only, 10 (5%) post-procedure only, and 76 (40%) both pre- and post-procedure. Post-procedure LMWH was initiated a median (IQR) of 1 day (1–1) and discontinued 5 days post-procedure (3–8). MB occurred in two patients (1%), CRNMB in two patients (1%), and one death (0.5%) was identified; no thromboembolic events occurred. Prior to propensity score matching (PSM), post-procedure LMWH with or without pre procedure LMWH was associated with the composite outcome of MB and CRNMB (P = 0.034), although not with MB or CRNMB individually. After stepwise regression and PSM analyses, no significant differences in bleeding outcomes were observed between patients who received LMWH bridging and those who did not. Our findings indicate that although adverse thrombotic events were rare and use of post-procedure LMWH bridging was significantly associated with a small absolute increased risk of bleeding, it was not significant after PSM. Larger prospective studies are needed to better inform antithrombotic management guidelines for patients with aortic MHVs undergoing gastrointestinal endoscopy.

Abstract We aim to compare the benefits, harms, and costs of multiple plastic stents (MPS) versus covered self-expandable metallic stents (CSEMS) in the treatment of benign biliary strictures (BBS). A comprehensive database search through June 6, 2024 identified randomized controlled trials (RCT) involving adult patients with BBS comparing MPS to CSEMS in terms of stricture resolution, recurrence, technical success, number of required procedures and stents, treatment duration, all-cause mortality, adverse events, and stent migration. We utilized the Cochrane Risk of Bias (RoB) tool2 for study quality assessment. Meta-analysis following the random effects model was performed. After screening 365 references, we included 7 RCTs (high RoB) involving 594 patients. Most reported stricture etiology is chronic pancreatitis (52.4%), followed by orthotopic liver transplant (40.5%). Compared with MPS, CSEMS achieved similar efficacy and safety. However, CSEMS required fewer procedures (mean difference [MD]: −1.84 [−2.56 to −1.11]; I2 = 76%) and stents (MD: −6.04 [−9.55 to −2.52]; I2 = 93%), amounting for shorter duration of treatment (MD: −119.02 days [−137.41 to −100.62]; I2 = 96%) and savings in costs between 41 and 57% with absolute savings of 4,019$ to 9,192$ favoring CSEMS. All outcomes had a low to very low certainty of evidence (CoE), except for technical success and stricture resolution (moderate CoE). Our analysis suggests that CSEMSs are comparable to MPSs in terms of efficacy and safety. However, it shows that CSEMSs are more cost-effective. Sample size calculations from our analyses can guide the design of future studies to validate the safety profiles and determine the feasibility of the two modalities.

Abstract Coronary artery bypass graft (CABG) surgery is one of the most commonly performed surgeries in the United States. It remains the gold standard of coronary artery revascularization despite the introduction of percutaneous coronary interventions and advancements in medical therapy. First conceptualized in the 1900s, CABG underwent decades of trials, experimentation, innovations, and even failures. Despite the challenges, CABG continued to innovate, overcoming the complexities of coronary artery disease and improving patient outcomes. This manuscript aims to discuss the beginnings, evolution, and future of CABG.

Abstract Most clinical large language model (LLM) benchmarks rely on clean, concise vignettes that do not reflect the noisy, long-form documentation typical of real clinical records. How LLM performance degrades under realistic chart conditions remains poorly characterised. Here we test whether structured retrieval workflows protect National Institutes of Health Stroke Scale (NIHSS) scoring accuracy under systematic context stress. Using 100 de-identified acute stroke cases and a fully crossed 4 x 4 x 3 x 3 condition matrix (144 conditions per case), we vary context acquisition method, document length, distractor load and critical-information position across four Gemini models (57,047 retained runs). Structured retrieval reduces mean absolute error (MAE) from 4.58 to 2.96 points relative to non-agentic baselines (mean gain 1.62 MAE points; 95% CI 1.57–1.67; 35% relative reduction), with consistent gains across all 36 stress combinations. Lower-cost models show disproportionately larger gains (2.76 versus 0.45 MAE points). Tool-retrieved pipelines outperform retrieval-augmented generation in 33 of 36 combinations. These findings indicate that retrieval architecture, rather than model scale alone, is a tractable lever for robust, equitable clinical LLM deployment.

ABSTRACT Braak and others have proposed that Lewy body pathology (LBP) in Parkinson’s disease (PD) may arise not only in the brain but alternatively from an initial site in the gastrointestinal (GI) tract with subsequent passage to the central nervous system CNS through the vagus nerve or other routes. We tested this hypothesis by using both immunohistochemistry (IHC) and RT QuIC a form of alpha synuclein seed amplification assay (SAA) to detect alpha synuclein LBP in samples from selected brain regions and 10 GI tract sites taken from autopsies of 50 PD subjects and 128 elderly subjects without parkinsonism or dementia including 34 with IHC identified CNS incidental Lewy body disease (ILBD) and 94 with no Lewy body IHC pathology detected (NLB). A positive SAA or IHC result was restricted to the GI tract in only 2 subjects while LBP by either SAA or IHC was restricted to the brain in 11 subjects. To fairly compare GI-only with brain-only synucleinopathy, however, we would have to do SAA on brain samples from all ILBD and NLB cases in at least 4 critical brain regions: olfactory bulb, medulla, pons, and amygdala. Further SAA of brain regions is estimated, based on the proportional results to date, to potentially identify 21 additional brain-only LBP subjects, for a total of 32, if it were done on all of the NLB subjects. From this brain-only LBP is estimated to be 16 times more common than GI-only LBP. To assess the clinical impact of SAA-positive GI sites we found that the number of positive sites per subject is significantly correlated with UPDRS motor score and SCOPA-AUT GI related scores including those for salivation, straining, constipation, and bowel movement.

Abstract Introduction Evaluate large language models (LLMs) for scoring medical student essays, and compare various prompting techniques and models. Methods OpenAI GPT scored 51 medical student reflection essays (15 real, 36 fabricated) using a previously-reported 6-point rubric (April-May 2025). We compared 29 prompt-model conditions by systematically varying the LLM prompts (including the persona, scoring rubric, few-shot learning [exemplars], chain-of-thought reasoning, and temperature), fine-tuning, and model (including GPT-4.1, GPT-4.1-mini, GPT-o4-mini, and GPT-4-Turbo). Outcomes were accuracy (compared with human raters, measured using single-score intraclass correlation coefficient [ICC] and mean absolute difference [MAD; zero indicates perfect agreement]), within-condition reproducibility, and cost. Results Across all conditions, it took mean (SD) 3.73 (3.12) seconds to score 1 essay. The cost to score 100 essays was USD $0.04 for GPT-4.1-mini, $0.21 for GPT-4.1, $0.57 for GPT-4.1 with 3 exemplars, and $2.00 for fine-tuned GPT-4.1. When the one-time cost of fine-tuning was amortized across 10,000 essays, the cost for fine-tuned GPT-4.1 was $0.20 per 100. Accuracy was “almost perfect” (ICC >0.80) for 28/29 conditions (97%). Fine-tuned models were more accurate than non-fine-tuned models (MAD difference –0.24 [95% CI, –0.34, –0.14]). Conditions with exemplars were more accurate than those without (MAD difference –0.44 [CI, –0.57, –0.31]). Accuracy progressively decreased as 6, 3, 1, and 0 rubric levels were explicitly defined in the prompt (P<.001). Contrary to hypotheses, accuracies for chain-of-thought prompts and variations in temperature and persona were not significantly different from the baseline prompt. Reproducibility ICC was >0.80 for 28/29 conditions (97%). Discussion Automated LLM essay scoring demonstrated near-perfect accuracy and reproducibility for most prompt-model conditions. Fine-tuned models and prompts with exemplars had higher accuracy but higher cost. Fine-tuned models had lower per-essay costs for larger essay volumes. For smaller volumes, non-fine-tuned GPT-4.1 provided excellent results at moderate cost. GPT-4.1-mini provided very good results at low cost.