Citations

INTRODUCTION: Advanced therapies infrequently achieve complete fistula closure in patients with Crohn's disease (CD). The primary objective of the STOMP2 clinical trial was to determine whether the implantable autologous cell therapy AVB-114 is effective in inducing remission of persistent Crohn's perianal fistulas versus standard of care. METHODS: Eligible patients had a single perianal fistula tract and had failed previous treatment or had documented medication intolerance to biologic or conventional CD therapy. All enrolled subjects underwent surgical fistula optimization and adipose tissue biopsy collection (to manufacture AVB-114) followed by 1:1 randomization to either standard of care (repeat fistula optimization including seton replacement) or AVB-114 implantation. The primary end point was combined fistula remission at 36 weeks, defined as closure of the external opening, no drainage of fluid despite gentle finger compression, and no collections >2 cm in at least 2 of the 3 dimensions on MRI. RESULTS: Subjects at 14 US sites were equally randomized to SoC (N = 24) or AVB-114 (N = 24). Week 36 combined remission was 8.3% and 45.8% for subjects randomized to SoC and AVB-114, respectively (38% difference, 95% CI 11%–60%; P = 0.0078). At week 36, MRI revealed no subjects with collections >2 cm, radiological improvement (≥50% decrease in the Magnetic Resonance Novel Index for Fistula Imaging in Crohn's Disease (MAGNIFI-CD) score from baseline) in 1 SoC subject and 3 AVB-114 subjects, and radiological healing (complete resolution of T2-weighted hyperintensity in fistula tract) in 2 SoC subjects and 5 AVB-114 subjects. Through week 36, there were 40 and 56 treatment emergent adverse events for SoC and AVB-114, respectively. There were no serious treatment emergent adverse events in the AVB-114 group through week 36. DISCUSSION: A significantly higher proportion of patients treated with AVB-114 achieved combined remission vs SoC, and the treatment was well tolerated. These data support the safety and efficacy of AVB-114 in persistent Crohn's perianal fistulas.

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.

Abstract Background Progressive supranuclear palsy (PSP) is a tauopathy for which there is limited understanding of epidemiological risk factors. Objective The objective of this study was to identify premorbid nonmedical and medical risk factors for PSP diagnosis in a large prospective population‐based cohort. Methods We performed a matched nested case–control study using the UK Biobank (UKB) cohort consisting of >500,000 adults aged 37 to 73 years. PSP diagnoses were identified from 2007 to censor date (August 2025) and matched 1:10 by age and sex to control subjects without parkinsonism or dementia diagnoses. We derived risk factors using an iterative logistic regression approach. Results There were 240 incident PSP diagnoses in the UKB. In the fully adjusted model, premorbid depression (odds ratio [OR], 3.22; 95% confidence interval [CI], 2.30–4.50; P < 0.001), delirium (OR, 6.76; 95% CI, 4.08–11.19; P < 0.001), and functional gastrointestinal disorders (OR, 1.91; 95% CI, 1.39–2.63; P < 0.001) were associated with increased risk. Heavy alcohol consumption was associated with higher risk compared with moderate consumption (OR, 1.65; 95% CI: 1.21–2.26; P = 0.0017). Body mass index (BMI) and alcohol consumption had nonlinear risk profiles. Cancer diagnosis was inversely associated with PSP (OR, 0.56; 95% CI, 0.40–0.79; P < 0.001). Depression and delirium diagnoses remained significant 5 to 10 years before diagnosis. Conclusions In this large prospective cohort, PSP was associated with premorbid lifestyle practices and neuropsychiatric diagnoses years before diagnosis. This suggests a long premotor phase and highlights opportunities for earlier diagnosis and further mechanistic investigation. The inverse association with cancer mirrors the relationship seen in other neurodegenerative conditions and may point toward shared mechanisms. © 2026 International Parkinson and Movement Disorder Society.

Background. Liver transplant recipients face high risks of cardiometabolic events after transplant, driven by posttransplant weight gain, diabetes, hypertension, as well as immunosuppression-related side effects. Glucagon-like peptide-1 receptor agonists (GLP1RAs) improve metabolic and cardiorenal outcomes in nontransplant populations, but their role in liver transplant recipients remains understudied. Methods. This retrospective cohort study used TriNetX data (January 2010–December 2023) to compare outcomes in liver transplant recipients prescribed GLP1RAs (semaglutide, dulaglutide, liraglutide) within 1-mo posttransplant (n = 546) versus nonusers (n = 37 153). Propensity score matching (1:1) balanced demographics, comorbidities, and medications (n = 541 per group). Outcomes included mortality, hospitalizations, cardiovascular/renal/respiratory events, and graft outcomes. Results. Over a mean follow-up 838.5 d (SD 291.9) in the GLP1RA cohort and 884.3 d (SD 313.7) in the non-GLP1RA group, GLP1RA use was associated with a 43% lower all-cause mortality (7.0% versus 12.9%; hazard ratio [HR], 0.566; 95% confidence interval [CI], 0.381-0.841) and 39% fewer hospitalizations (60.4% versus 74.5%; HR, 0.613; 95% CI, 0.530-0.710). Acute heart failure (HR, 0.386; 95% CI, 0.285-0.524), renal failure/dialysis (HR, 0.489; 95% CI, 0.413-0.579), and respiratory failure (HR, 0.484; 95% CI, 354-0.662) risks were significantly reduced. No differences were observed in graft failure/rejection, myocardial infarction, stroke, atrial fibrillation/flutter, ventricular tachycardia, or ischemic optic neuropathy. Conclusions. Early GLP1RA initiation in liver transplant recipients was associated with reduced mortality, hospitalizations, respiratory, and cardiorenal complications without compromising graft safety. These findings support GLP1RAs as a promising adjunct therapy, warranting prospective trials to confirm benefits in this high-risk population.