Citations

Abstract INTRODUCTION Centiloid (CL) scaling standardizes amyloid positron emission tomography (PET) quantification across tracers and platforms; however, variability across software implementations may affect diagnostic classification. This study evaluated inter‐software variability and diagnostic performance across five platforms using identical 1 8 F‐florbetapir datasets. METHODS Retrospectively, 192 patients undergoing 1 8 F‐florbetapir PET/computed tomography (CT) and magnetic resonance imaging (MRI) were analyzed. CL values were generated using four US Food and Drug Administration (FDA) ‐cleared platforms and an in‐house Centiloid standard pipeline. Agreement was assessed using intraclass correlation coefficient, with bias and limits of agreement evaluated by linear modeling and Bland–Altman analysis. Diagnostic performance was assessed using receiver operating characteristic (ROC) analysis and classification against visual interpretation. RESULTS Agreement was excellent (intraclass correlation coefficient [ICC] 0.969; 95%CI 0.961–0.975). Some platforms produced systematically higher CL values versus others slightly lower. LoA reached ± 30 CL. Diagnostic accuracy was high (area under the curve [AUC]: 0.949–0.975), with sensitivity 0.923–0.968 and specificity 0.667–0.806. DISCUSSION Despite excellent agreement, systematic differences persist and may affect classification near thresholds, supporting consistent use of a single processing pipeline.

Abstract Background Adults with congenital heart disease (ACHD) represent a rapidly expanding population with evolving mortality patterns. Despite improved survival, excess mortality persists. Objective To evaluate the incidence, causes, and predictors of mortality in a contemporary ACHD cohort. Methods We performed a retrospective cohort study of adults (≥18 years) first evaluated at Mayo Clinic from 2002–2023. Baseline clinical, imaging, and electrocardiographic data were analyzed. Vital status was determined using institutional records and the Accurint national mortality database. Kaplan-Meier analysis and Cox proportional hazard models were used to evaluate mortality and identify independent predictors of mortality Results A total of 7,678 ACHD patients were included, with median age of 36.8 years and median follow-up of 11.4 years. During 78,768 patient-years of follow-up, 1,116 patients died (median age at death 57.2 years), corresponding to an annual mortality rate of 1.4%. The cumulative rate of all-cause mortality at 5, 10, 15, and 20 years was 6.9%, 12.0%, 19.0%, and 26.2%, respectively. When stratified by CHD complexity, the annual death rate in patients with severe CHD (2.4%/year) was twice that of patients with moderate or mild CHD (both 1.2%/year). Older age and ACHD subtypes, specifically, cyanotic heart disease (HR 3.9, 95% CI 2.9–5.3) and Fontan physiology (HR 3.2, 95% CI 2.3–4.4), were strongly associated with increased mortality. Additional independent predictors included male sex, ventricular dysfunction, advanced NYHA class, prior heart failure hospitalization, hypertension, smoking, coronary artery disease, renal dysfunction, and abnormal hemoglobin levels. Cardiovascular causes accounted for 57.7% of deaths with known etiology, predominantly heart failure (48.9%) and sudden cardiac death (21.9%), while non-cardiovascular causes were driven mainly by infection and malignancy. Conclusions In this large contemporary ACHD cohort, mortality was driven by ventricular dysfunction, heart failure, and systemic end-organ involvement in addition to the underlying congenital anatomy. Both cardiovascular and non-cardiovascular causes contributed significantly to mortality. These findings underscore the need for comprehensive multidisciplinary ACHD care focused on early recognition of cardiac functional decline, management of acquired comorbidities, and end-organ dysfunction.

Objective Our objective was to identify and describe the clinical characteristics and outcomes in patients with pre‐existing idiopathic inflammatory myopathies (IIMs) in the Veterans Health Administration (VHA) treated with immune checkpoint inhibitors (ICIs). Methods All veterans receiving ICI infusions were identified. Patients with at least two International Classification of Disease codes for IIM before first ICI infusion underwent chart review to identify patients with confirmed IIM by American College of Rheumatology/EULAR criteria. The demographics, cancer diagnoses, laboratory findings, clinical course, and mortality rates were reported. IIM cases were also reviewed to determine if patients developed IIM flare following ICI treatment. Results We identified 29,539 veterans who received at least one ICI infusion in the VHA between June 6, 2011, and February 14, 2023. The eight patients with confirmed IIM before ICI treatment were mostly White men with an average age of 71.7 years at first ICI infusion. The IIM diagnoses were dermatomyositis in three patients, polymyositis in two, antisynthetase syndrome in two, and one rheumatoid arthritis (RA)/myositis overlap. Cancer diagnoses were lung (two), melanoma (two), head and neck (two), kidney/other urinary (one), and mesothelioma (one). Diagnosis of IIM was made on average 3.1 years before ICI treatment. One patient had an IIM flare after ICI. No IIM flares were identified in other patients. Conclusion Our findings show that an IIM flare after ICI therapy can occur, but most patients did not develop a flare. These observations suggest ICIs can be considered as an option in patients with cancer with IIM with shared decision‐making and close monitoring.

Ascites development in cirrhosis reduces 5-year survival from 80% to 30%, yet substantial heterogeneity exists among patients with comparable ascites severity. This multicenter retrospective cohort study included adult liver transplant candidates with ascites at 4 United States centers (2015–2024). Latent class analysis was performed using 7 clinical variables: ascites grade, bilirubin, albumin, platelet count, estimated glomerular filtration rate, systolic blood pressure, and portal vein thrombosis. The derivation cohort (n=625) from the University of California San Francisco and Columbia University was randomly split 80/20 for model development and internal validation. External validation was performed at the University of Southern California (n=59) and Mayo Clinic (n=93). Primary outcomes were acute kidney injury (AKI) and waitlist mortality over 365 days. Three phenotypes emerged: “CKD-Metabolic” (30.4%, lowest eGFR 76.5 mL/min/1.73 m 2 ), “Vasodilatory-Synthetic Dysfunction” (38.9%, highest bilirubin 7.03 mg/dL, lowest blood pressure 117.5 mmHg), and “PVT-Intermediate” (30.7%, severe thrombocytopenia 68.1×10 3 /μL, 24.0% PVT). In validation cohorts (n=305), phenotypes demonstrated robust classification (mean posterior probability 0.823–0.855). Vasodilatory-Synthetic Dysfunction showed increased AKI risk versus CKD-Metabolic in derivation (MELD 3.0-adjusted HR 2.95, 95% CI 2.07–4.22, p <0.001) and validation cohorts (HR 3.39, 95% CI 1.93–5.94, p <0.001). Competing risk analysis revealed no mortality differences, but Vasodilatory-Synthetic Dysfunction was associated with higher transplantation rates (validation: HR 1.63, 95% CI 1.19–2.22, p =0.002). Three reproducible clinical phenotypes of ascites were identified with distinct risk profiles. The Vasodilatory-Synthetic Dysfunction phenotype was associated with a 3-fold increase in the risk of AKI that persisted after adjustment for MELD 3.0. No differences in waitlist mortality were observed, likely reflecting effective MELD-based transplant allocation that preferentially removes the highest-acuity patients from the waitlist.

ABSTRACT HLA‐C*07:1268 differs from HLA‐C*07:02:01:01 by one nucleotide substitution in exon 3.

ABSTRACT Background Gastric emptying scintigraphy (GES) is considered the standard for differentiating gastroparesis from functional dyspepsia and other foregut disorders characterized by nausea and vomiting but provides only a brief physiologic snapshot that may not accurately reflect daily function. We utilized a non‐invasive wireless patch system (WPS) to characterize multiday gastric myoelectrical activity, evaluate its relationship with GES, and assess changes following a therapeutic intervention. Methods Adults referred for GES for symptoms thought to represent gastroparesis were enrolled in a prospective study. Patients wore a WPS for up to 6 days, starting on the day of scintigraphy. Gastric myoelectrical activity was analyzed and categorized into relatively weak, relatively moderate, and relatively strong activity phenotypes. A subset of patients underwent repeat monitoring following individualized therapeutic interventions (e.g., anti‐emetics, proton pump inhibitors, lifestyle changes). Results Forty‐eight patients (mean age 44; 79% female) completed the study. GES identified delayed gastric emptying in 18%, rapid in 22%, and normal in 60% of subjects. During the 4‐h concurrent GES window, gastric activity in patients with delayed emptying was lower, but this difference did not reach statistical significance ( p = 0.08). When compared to the full multiday recording period, GES results showed no correlation with the myoelectric readings. Significant day‐to‐day variability was observed, both random and systemic. In the latter category, a “Test‐Day” dip was observed with gastric activity lowest on Day 1 (GES test day) and increasing significantly on subsequent days, stabilizing by Day 4 ( p < 0.001). Healthy control subjects recorded during normal daily routines showed no such day‐to‐day variation. In the retesting cohort, anti‐emetics produced robust increases in gastric amplitude, whereas PPIs showed minimal impact. Conclusions The WPS effectively captures distinct gastric phenotypes and quantifies physiologic responses to therapy in both gastric and intestinal regions, demonstrating its clinical utility as a robust tool for evaluating and managing foregut symptoms in real‐world settings. Importantly, the multiday WPS highlights significant day‐to‐day physiologic variability in gastric activity that extends beyond the single‐day GES ‘snapshot’.

Abstract Objective Anterior nucleus of the thalamus (ANT) deep brain stimulation (DBS) is an effective therapy for frontotemporal and limbic drug‐resistant focal epilepsies. The pulvinar nucleus (PUL) is an emerging neuromodulation target for seizure networks involving the posterior quadrant and temporal lobe. This study evaluates the safety and effectiveness of combined bilateral ANT plus PUL DBS for posterior quadrant and temporal lobe epilepsies. Methods We conducted a single‐center retrospective cohort study of patients receiving combined ANT/PUL DBS between 2021 and 2025. Outcomes included median seizure rate reduction (MSR), responder rate (RR; >50% seizure frequency reduction), and stimulation‐related side effects, assessed across ANT, PUL, and concurrent ANT/PUL stimulation settings. Acute surgical complications were evaluated. Statistical significance was assessed using two‐sided Wilcoxon signed‐rank tests with Holm–Bonferroni correction. Results Nine patients with combined ANT/PUL DBS were identified, and eight patients had sufficient follow‐up for inclusion (median follow‐up = 20 months). Posterior predominant structural abnormalities were present in eight of nine patients. There were no acute surgical complications. Three instances of transient stimulation‐related side effects resolved with parameter adjustments, whereas one patient required rescue antiseizure medication in addition to programming changes. Eight patients received periods of ANT stimulation, six PUL stimulation, and seven combined ANT/PUL stimulation. Regarding overall outcome, at last follow‐up, there was a significant 80.8% MSR ( p = .0078) and 87.5% RR, with two patients receiving ANT and six ANT/PUL stimulation. Regarding target‐specific MSR, concurrent ANT/PUL DBS (68.8% MSR) showed a trend toward superior performance relative to ANT (43.3%) and PUL DBS (17.5%) alone, although subgroup analysis of target‐specific performance did not reach statistical significance. Significance Combined four‐lead ANT/PUL DBS appears safe and effective for patients with drug‐resistant posterior quadrant and temporal lobe epilepsies. Dual‐network neuromodulation may provide greater flexibility to individually optimize neuromodulation for complex seizure networks.