Citations

Abstract Objectives Accurate and timely prediction of physiological deterioration in hospitalized patients is essential, but existing deep learning models, which rely solely on structured electronic health record (EHR) data, generate high false-positive rates by missing crucial contextual information in clinical notes. We present DETERIO-LLM, a hybrid prediction model that selectively integrates large language models (LLMs) with a deep learning model (DETERIO) to reclassify borderline-risk alerts using narrative clinical notes. Materials and Methods This retrospective study used a cohort of 1000 inpatients (4.6% deterioration prevalence). DETERIO-LLM selectively analyzed narrative notes for alerts in the uncertainty range (scores 2.5-3.5). Performance was evaluated using sensitivity, positive predictive value (PPV), and F1 score, benchmarked against comparators including the best-established ML model, eCART. Results DETERIO-LLM significantly improved predictive precision over all comparators. At its optimal threshold, the model achieved a PPV of 30.6% and an F1 score of 37.3%, outperforming eCART. This selective integration reduced false-positive alerts by 46.5% within the uncertainty range while maintaining comparable sensitivity. Discussion This study demonstrates a practical, interpretable method for integrating LLM-derived contextual knowledge into existing structured EHR prediction workflows. By focusing LLM analysis on high-uncertainty alerts, DETERIO-LLM substantially improves clinical utility through a marked reduction in false-positive cases, which is critical for mitigating alert fatigue. Conclusion Selective LLM integration with structured EHR models offers a viable, interpretable path to improving early warning systems in clinical care by leveraging narrative context to reduce alert fatigue while enhancing predictive performance.

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.

Most genetic variants associated with complex traits are hypothesized to regulate gene expression. To understand the genetics underlying gene expression variability, we characterized 14,324 RNA-sequencing samples from the Trans-Omics for Precision Medicine program and performed expression and splicing quantitative trait locus (e/sQTL) analyses in six tissues and cell types, including whole blood ( n = 6454) and lung ( n = 1291). We detected tens of thousands of secondary cis-e/sQTLs, showing that secondary cis-e/sQTL discovery remains unsaturated. We fine-mapped UK Biobank–derived genome-wide association study (GWAS) signals from 164 traits and identified e/sQTL colocalizations for 10,611 GWAS signals, including 7096 that colocalize with secondary e/sQTLs. Our results suggest that even larger e/sQTL analyses will uncover additional secondary e/sQTLs, further benefiting GWAS interpretation.

Abstract: Extracorporeal membrane oxygenation (ECMO) is increasingly used to support patients with severe cardiac or respiratory failure. Neurological complications occur across ECMO configurations and represent a major contributor to mortality and long-term disability. Major neurological complications include ischemic and hemorrhagic stroke, hypoxic ischemic brain injury, seizures, delirium, spinal cord and peripheral nervous system injury, and brain death. The mechanisms underlying neurological injury during ECMO are multifactorial and are influenced by ECMO configuration, reflecting differences in cerebral perfusion, gas exchange, anticoagulation exposure, and precannulation physiologic insults. This review synthesizes neurological complications associated with ECMO, neurological monitoring, and outcomes.

Context.— One objective of the College of American Pathologists/American College of Medical Genetics Cytogenetics Committee is to ensure the accurate detection and clinical interpretation of abnormalities observed by fluorescence in situ hybridization (FISH) analysis when evaluating hematologic neoplasms. Objective.— To report a 20-year performance summary (2005–2024) of FISH challenges focusing on hematologic neoplasms. Design.— A retrospective review was performed from 2005 through 2024 to identify FISH challenges specifically addressing hematologic neoplasms. The overall performance of participants was evaluated to identify potential recurring errors of clinical relevance. Results.— A total of 124 hematologic neoplasm FISH challenges from 2005 to 2024 were provided to participating laboratories, including 45 paper challenges (results and/or images were provided for interpretation purposes), 43 liquid challenges (bone marrow aspirate or peripheral blood), and 36 formalin-fixed paraffin-embedded (FFPE) tissue challenges. Of the 124 challenges, 120 (97%) exceeded the required 80% consensus for grading purposes. Of the 4 failed challenges (3%), 2 (1 liquid, 1 paper) involved the interpretation of atypical FISH signal patterns; 1 (paper) involved the interpretation of FISH signal patterns correlating involvement by myeloid versus lymphoid interphase nuclei; and 1 (liquid) likely involved a specimen processing or handling error that resulted in discordant participant responses. All 36 FFPE tissue challenges exceeded the 80% consensus for grading purposes. Conclusions.— This 20-year retrospective review demonstrates that clinical cytogenomic laboratories have been and continue to be highly proficient in the detection and interpretation of FISH abnormalities associated with hematologic neoplasms.

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.

Abstract Context Biochemical test results are central to clinical decision-making for the diagnosis and management of Cushing syndrome (CS). With emerging research and increasing availability of different tests, updated consensus on the utility of these biomarkers is warranted. Objective To establish an updated consensus on the role of biomarkers in the diagnosis and monitoring of adrenocorticotropic hormone-dependent CS, address novel therapeutic approaches, and identify areas for future research. Design A modified 2-round Delphi panel was conducted. Consensus was defined as ≥70% agreement/disagreement for Likert-scale statements or ≥70% selection of the same option for single-choice questions. Setting Participants represented a range of international expertise. Participants Forty-one participants took part in the Delphi panel, with no attrition between rounds (one nonclinician was not required to complete the second round). An 8-member Steering Committee guided statement development. Results Of statements designed to reach consensus, 45% (14/31) and 44% (11/25) statements reached consensus in Rounds 1 and 2, respectively. Notably, most panelists reported the use of late-night salivary cortisol for diagnosis of mild CS and for monitoring following pituitary surgery or medical or radiation therapy. Most panelists responded that block-and-replace therapies can be considered in patients with cyclical or severe CS, and consensus was reached that restoration of circadian rhythm is a treatment goal for patients with CS. Conclusion Areas of alignment among experts on the diagnosis and monitoring of CS are presented. The findings from this study are intended to support clinicians in their clinical decision-making and highlight priority areas for future research.

OBJECTIVE Endovascular thrombectomy (EVT) for acute large-vessel occlusion stroke is well established, yet its role in patients presenting with minor stroke symptoms (National Institutes of Health Stroke Scale [NIHSS] score < 6) remains unclear. Prior studies have not accounted for intraprocedural factors that may influence outcomes in this subgroup. METHODS The authors analyzed 5693 patients from the STAR (Stroke and Thrombectomy and Aneurysm Registry), including 398 with low NIHSS scores, to evaluate the association between procedure time (PT) and outcomes. Among patients with low NIHSS scores, propensity score matching was used to compare outcomes between those with PT ≤ 35 versus > 35 minutes, a cutoff defined using receiver operating characteristic curve analysis. The authors performed a meta-analysis of studies reporting best medical management (BMM) outcomes in patients with low NIHSS scores. To compare these with EVT-treated patients, a matched BMM comparator cohort using stratification on pooled baseline characteristics was constructed. Outcomes included 90-day functional independence (modified Rankin Scale [mRS] scores 0–2), intracranial hemorrhage, and mortality. RESULTS PT had a stronger negative effect on outcomes in patients with low NIHSS scores compared with those with high scores, with a steeper decline in functional independence per minute of PT (slope: –0.45% vs –0.21%; p = 0.03 for interaction). Among patients with low scores, PT ≤ 35 minutes was associated with higher 90-day functional independence compared with the propensity score–matching cohort with PT > 35 minutes (82.6% vs 59.0%, p < 0.001). When benchmarked against BMM (75.2% mRS scores 0–2), patients undergoing EVT within 35 minutes had superior outcomes (85.1%, p = 0.047). In contrast, EVT with PT > 35 minutes resulted in worse outcomes than BMM (mRS scores 0–2: 59.8%, p = 0.008). The number needed to treat for PT ≤ 35 minutes was 10, whereas PT > 35 minutes yielded a number needed to harm of 6. CONCLUSIONS PT critically modulates the benefit of EVT in minor stroke. While efficient EVT yields better outcomes than BMM, prolonged procedures are associated with harm. These findings may explain prior inconsistent evidence on EVT in patients with low NIHSS scores and underscore the need to individualize procedural thresholds in this population.

Abstract Frontotemporal dementia (FTD) is characterized by selective neuronal vulnerability, yet the features that predispose specific neuron types to degeneration remain unclear. We performed single-nucleus RNA sequencing of frontoinsular cortex, a region affected early in behavioral variant FTD, across individuals with C9orf72 -associated and sporadic FTD-MND spectrum disease. By enriching for large projection neurons, we resolved molecular subtypes of layer 5 extratelencephalic neurons, including von Economo neurons, and identified selective depletion of specific layer 2/3 and layer 5 neuron subtypes, convergent across genotypes. Despite selective neuronal loss, disease-associated transcriptional changes were convergent across excitatory neuron populations, suggesting that they reflect upstream pathophysiology or shared responses to local neurodegeneration. By relating neighborhood-level depletion in disease to gene expression in controls, we found that baseline cellular respiration and ATP synthesis predict neuronal vulnerability in disease. These findings define molecular correlates of selective neuronal vulnerability in FTD and provide a framework linking cell type and state to neurodegeneration.

By acquiring the first human and equipment radiographs in space, this study demonstrated the feasibility of on-orbit radiography and expanded diagnostic capabilities for crew health and hardware evaluation.