Citations

ABSTRACT Objective Weight loss is frequently considered a cardinal presenting symptom for patients with Zenker diverticulum (ZD). We hypothesized that weight loss in patients with cricopharyngeal muscle dysfunction (CPMD), with or without diverticula, was associated with the length of symptoms and size of diverticulum. Methods Prospective, multicenter observational study of CPMD patients with and without diverticula reporting unintentional weight loss (+WL) or no weight loss (−WL) prior to enrollment in the Prospective Outcomes of Cricopharyngeal Hypertonicity (POuCH) database. Complications and symptom response using a patient reported outcome measure, the Eating Assessment Tool (EAT‐10), were compared. Results Of 427 patients, 101 (23.6%) were +WL. Median weight loss was 14 pounds (interquartile range [IQR] 10–25). +WL cohort had a mean age of 71.5 (standard deviation [SD] 11.5) vs. 67.9 in −WL (SD 11.6, p = 0.007). Mean preoperative EAT‐10 score was 24.7 in +WL (SD 9.7) and 14.8 in −WL (SD 8.8, p < 0.0001). Higher preoperative weight loss was associated with higher preoperative EAT‐10 ( p < 0.0001, Spearman's ρ = 0.43). Size of diverticulum was associated with WL ( p = 0.003), but weight loss was highest in both large diverticula and CP bars. Duration of symptoms was not associated with weight loss ( p = 0.30). Postoperative complications in +WL and −WL patients were similar ( p = 0.78). Conclusion Unintentional weight loss is common with ZD. Patients with worse dysphagia are more likely to have more weight loss. Weight loss does not increase with the size of the diverticulum or length of symptoms. Surgery has a similar safety profile with greater improvement in dysphagia in patients reporting weight loss. Level of Evidence 3.

Background: The purpose of this study was to determine whether placement of triangular titanium implants (TTI) suprajacent to S2-alar-iliac (S2AI) pelvic fixation screws during multilevel spinal fusion surgery for adult spine deformity reduces pelvic fixation failures. Methods: This prospective, multicenter, international, partially blinded randomized clinical trial included 222 patients scheduled for multilevel spinal fusion surgery with S2AI-based pelvic fixation. In the S2AI+TTI group, the mean age was 64.9 years, 54.1% were female, 3.7% were Hispanic, 5.5% were African American, and 1.8% were Asian. In the S2AI-alone group, the mean age was 64.8 years, 58.4% were female, 3.5% were Hispanic, 7.1% were African American, and 0.9% were Asian. Subjects were randomized to pelvic fixation using S2AI screws alone versus S2AI+TTI. Scheduled follow-up included a 24-month full-spine radiograph and a high-resolution computed tomography (CT) scan, which was independently interpreted. Results: The primary composite radiographic end point (S2AI screw breakage, lucency, or pullout, or posterior spinal rod breakage distal to S1) occurred less frequently in the S2AI+TTI group than in the S2AI-alone group (11.0% versus 20.4%, p = 0.0415). Except for rod-screw dissociation and rod fracture distal to S1, all components of the primary composite end point occurred less frequently in the S2AI+TTI group. TTI placement did not affect sagittal or coronal spinal alignment parameters. The rate of rod fracture throughout the spinal construct was slightly higher in the S2AI+TTI group (9.2% versus 5.3%) but the difference was not significant (p = 0.197). Conclusions: Placement of TTI suprajacent to S2AI screws reduced the rate of pelvic fixation failure in patients undergoing multilevel spinal fusion with pelvic fixation. Level of Evidence: Therapeutic Level I . See Instructions for Authors for a complete description of levels of evidence.

Importance Ischemic heart disease (IHD), the leading cause of death in the US, is predominantly due to modifiable risk factors. Estimates of IHD mortality attributable to risk factors provide evidence for health policy decision-making. Objective To estimate the burden of IHD death attributable to risk factors in the US from 1990-2023. Design, Setting, and Participants The Global Burden of Disease Study 2023 (GBD 2023) used vital records and a broad set of epidemiologic data to estimate IHD death rates, risk factor exposure, and relative risk curves for risk-outcome pairs for 1990-2023 for the general population. Data analysis was performed from October 2024 to December 2025. Exposure Twelve metabolic, behavioral, and environmental risk factors. Main Outcomes and Measures The primary outcomes were IHD death rates per 100 000 persons, counts, and attributable risks from 1990-2023 by age, sex, and US state. Estimates include 95% uncertainty intervals (UI). IHD death rates were estimated using ensemble modeling methods. Risk exposures were estimated using bayesian meta-regression methods. Relative risks were estimated following the Burden of Proof framework. Results In 2023, there were 473 000 IHD deaths (95% UI, 414 000-510 000) in the US, a decrease of 58.7% (95% UI, 56.8%-61.0%) in age-standardized rate since 1990. Between 2010 and 2023, there was a 19.0% decrease (95% UI, 15.0%-22.9%) for males and a 24.5% decrease (95% UI, 20.3%-29.7%) for females in IHD death rates. High systolic blood pressure (SBP), dietary risks, and high low-density lipoprotein cholesterol (LDL-C) were the leading risk factors for IHD deaths in 2023, accounting for 47.2% (95% UI, 36.4%-57.0%), 38.6% (95% UI, 17.2%-56.8%), and 28.5% (95% UI, 19.3%-39.6%) of IHD deaths, respectively. Increased exposure to several risk factors substantially increased their attributable burden for IHD deaths in 2023, with high fasting plasma glucose (FPG) increasing 38.8% (95% UI, 11.5%-81.1%) and high body mass index (BMI) increasing 54.5% (95% UI, 41.8%-66.3%) since 1990. Smoking and particulate matter pollution had the greatest decrease in attributable IHD mortality since 1990, at 33.3% (95% UI, 23.6%-41.7%) and 74.9% (95% UI, 46.7%-88.8%), respectively. Conclusion and Relevance Per the results of this systematic analysis of GBD 2023, a total of 88.7% (95% UI, 83.4%-92.5%) of IHD deaths were attributable to modifiable risk factors in the US in 2023, with high SBP, dietary risks, and high LDL-C being the greatest contributors. High BMI and high FPG showed the largest attribution increases, while exposure to other risks did not increase significantly for the population.

Objective Lennox–Gastaut syndrome (LGS) is a severe treatment‐resistant epilepsy. Although vagus nerve stimulation (VNS) and deep brain stimulation (DBS) are established therapies, comparative data and the impact of dual neuromodulation remain limited. We compared seizure outcomes across VNS, DBS, and combined DBS + VNS therapy in LGS. Methods This retrospective cohort study at Mayo Clinic (2005–2024) included LGS patients treated with VNS and/or DBS . Seizure frequency was assessed at 6, 12, and 24 months post‐stimulation. Responder was defined as 50% or more seizure reduction. Results Forty patients were included (42% female, median, 150 seizures/month). Eleven patients underwent sequential VNS followed by DBS and contributed data to 2 treatment epochs, yielding 3 treatment groups: VNS alone (n = 29), DBS alone (n = 12), and DBS + VNS (n = 10). At 24 months, median seizure reduction rate was comparable between VNS (50%; 95% confidence interval [ CI], 44–75%) and the overall DBS cohort (59%, 95% CI, 33–86%) ( p = 0.54). However, a significant difference emerged when comparing the 3 treatment arms ( p = 0.027). Specifically, DBS + VNS therapy yielded significantly greater median reduction rate (81%, 95% CI, 60–99%) than DBS alone (43%, 95% CI, 0–58%) ( p adj = 0.027) or VNS alone (50%, 95% CI, 44.4–75.0%) ( p adj = 0.048). Four patients attained sustained seizure freedom above 1 year at last follow‐up. Interpretation VNS and DBS provide comparable seizure reduction in LGS over a 2‐year follow‐up period. DBS + VNS was associated with further improvements in seizure reduction in this small, retrospective dataset. This possibility warrants further investigation. ANN NEUROL 2026

PURPOSE Deficient mismatch repair/microsatellite instability (dMMR, MSI-H) in biliary tract cancers (BTCs) is observed in 1%-5% of tumors. MSI-H across solid tumors has demonstrated durable response to immune checkpoint inhibitors (ICIs) regardless of the anatomic location. Here, we describe clinical outcomes and surgical conversion of MSI-H BTC treated with ICIs. Patients and Methods We conducted a multicenter, retrospective analysis of BTC patients with dMMR/MSI-H between 2017 and 2024 at Mayo Clinic, University of Michigan, and University Hospitals Seidman Cancer Center. Outcomes of interest were surgical resection rate, rate of pathologic response, 2-year overall survival (OS; time from initiation of treatment to death/last follow-up), and time to treatment discontinuation (TTD; time from initiation of treatment to cessation because of any cause). Analyses were descriptive. RESULTS Thirty patients with MSI-H BTC were identified: 19 with cholangiocarcinoma, three with gallbladder cancer, and 8 with BTC undefined. The median age at diagnosis was 61.5 years (range, 26-86). Twenty-six (86.7%) patients had advanced stage at diagnosis. Twenty-seven patients (90%) received first-line systemic therapy, and 13 (48.1%) continued onto second line. Six patients (23.1%) were restaged to resectable from advanced disease after ICI therapy and underwent resection; all remained recurrence-free at last follow-up. Of these six patients, 3 (50%) achieved a pathologic complete response. Among those receiving first-line therapy, the median TTD was 9.9 months (95% CI, 5.7 to 14.5 months) and the 2-year OS was 73% (95% CI, 56% to 94%). CONCLUSION ICI therapy in patients with MSI-H BTC demonstrated durable response and downstaged some BTC to a resectable stage. dMMR/MSI-H should be performed up-front to guide treatment decisions.

Abstract Body surface gastric mapping (BSGM) enables non-invasive measurement of gastric electrophysiology, but the signals are approximately 100 times weaker than cardiac potentials and overlap spectrally with motion artifacts, necessitating labor-intensive manual review that limits clinical scalability. We present an uncertainty-aware deep learning framework combining a signal reconstruction network with a parallel uncertainty estimation network to automate artifact correction in high-resolution BSGM. Models were trained on 2,398 multihour, 64-channel recordings from 27 international clinical sites using weak supervision, a physiology-aware loss function, and uncertainty-gated quality control. In an independent cohort of 127 patients, the system achieved relative reductions of 39% in signal reconstruction error, 9% in total data removed, and 23% in amplitude–movement correlation compared with the industry-standard Wiener filter. Improved signal fidelity altered automated clinical phenotyping in 7% of patients by recovering previously obscured gastric rhythms. Uncertainty-aware deep learning enables reliable automated artifact correction in body-surface gastric mapping, improving signal fidelity and enabling scalable clinical interpretation. The system is FDA-cleared (510(k) K252504) and deployed in clinical practice, demonstrating that data-driven artifact correction can meet regulatory requirements for medical devices and reduce dependence on specialist manual review.