Citations

Importance Elevated low-density lipoprotein cholesterol (LDL-C) is a modifiable risk factor for cardiovascular disease, the leading cause of premature death worldwide. Assessing the LDL-C–related burden is critical for guiding prevention and treatment strategies. Objectives To estimate the global, regional, and national burden of ischemic heart disease and ischemic stroke attributable to elevated LDL-C (relative to 35-54 mg/dL) from 1990 to 2023 and to quantify the contributions of population growth, aging, risk-deleted burden, and exposure changes to burden trends. Design, Setting, and Population This comparative risk assessment, part of the Global Burden of Disease Study 2023, estimated population-level LDL-C exposure and associated health loss in 204 countries and territories. Mean LDL-C levels were estimated using spatiotemporal gaussian process regression based on 806 studies across 161 countries. Relative risks were derived from meta-analyses of 38 randomized clinical trials. Population-attributable fractions for deaths and disability-adjusted life-years (DALYs) were estimated by age and sex for adults aged 25 years or older from 1990 to 2023, with 95% uncertainty intervals. Exposure Population-level LDL-C concentrations. Main Outcomes and Measures Population-attributable fractions, counts, and rates (all ages and age standardized per 100 000) of LDL-C–attributable deaths and DALYs from ischemic heart disease and ischemic stroke, with uncertainty intervals. Results In 2023, elevated LDL-C accounted for 3.6 million deaths (95% uncertainty interval, 2.2-5.4 million; 6.0% of global mortality) and 90.7 million DALYs (95% uncertainty interval, 58.9-123.3 million; 3.2% of DALYs). Although global all-ages rates remained stable, age-standardized death and DALY rates decreased by 45.6% and 39.5%, respectively, since 1990. In 2023, age-standardized LDL-C–attributable DALY rates were highest in Eastern Europe and lowest in high-income Asia-Pacific. One-third of the global LDL-C burden occurred in India and China. Population growth and aging drove the increasing burden, with notable regional disparities in LDL-C exposure and risk-deleted DALY rates shifting toward middle-sociodemographic settings. Conclusions and Relevance Despite declining age-standardized rates, the absolute LDL-C burden has increased since 1990 due to demographic changes and has shifted toward middle-sociodemographic countries. Measurement and surveillance gaps persist. Strengthened prevention, diagnosis, and treatment access strategies are essential to mitigate the health burden of LDL-C.

Stem cell-derived β (SC-β) cells are a promising therapy for type 1 diabetes (T1D), but their long-term efficacy is limited by immune-mediated graft rejection. Platelet-derived exosome product (PEP) has emerged as a novel immunomodulatory agent, although its effect on SC-β cell xenograft rejection remains unclear. Here, we evaluated PEP in stimulated human peripheral blood mononuclear cells (PBMCs) and in an immunocompetent mouse model of SC-β cell transplantation under the kidney capsule. Immune-related gene expression was assessed by quantitative PCR, immune cell infiltration by immunofluorescence, and graft function by circulating human insulin. In vitro, PEP reduced NK-cell-associated gene expression, including NK1.1, EOMES, and KLRK1, and increased IL-10 expression. In vivo, untreated SC-β cell xenografts showed progressive immune infiltration and loss of detectable human insulin by day 14, whereas PEP-treated grafts retained detectable insulin through day 14 across co-transplantation, pretreatment, and systemic administration strategies. PEP co-transplantation delayed, but did not prevent, xenograft rejection, with graft loss observed by day 21. This delay was associated with reduced NK1.1+ cell infiltration and lower expression of selected inflammatory and rejection-associated markers, including NK1.1, Nos2, and Nlrp3. These findings suggest that PEP modulates graft-associated immune responses and may serve as an adjunct immunomodulatory strategy for stem cell-based therapies for type 1 diabetes. Further studies are needed to evaluate sustained graft durability, safety, and translational efficacy.

Abstract Introduction Distinct temperature patterns have long been recognized to correlate with fevers of differing etiologies. While the use of wearable sensors for high-frequency temperature monitoring (HFTM) on a near minute-by-minute basis has been shown to detect fevers earlier than standard-of-care nursing vital sign assessments in hospitalized patients, leveraging these high-resolution datasets to computationally identify unique digital signatures for real-time diagnosis of underlying fever etiology has not been widely explored. Diagnostic uncertainty is common in patients undergoing hematopoietic stem cell transplantation (HCT), with only 20–30% of febrile neutropenic episodes being microbiologically documented. We hypothesized that unique temperature patterns extracted from HFTM data collected during episodes of febrile neutropenia could be used to develop a supervised machine learning classifier capable of accurately predicting underlying fever etiology in HCT patients. Methods We analyzed 68 clinically independent fever episodes recorded in HCT patients (n=90) outfitted with an FDA-cleared wireless temperature sensor (TempTraq®, BlueSpark Technologies) that measured axillary temperature every 2 minutes throughout hospitalization. Time-series features were extracted from temperature traces spanning 1 hour before to 3 hours after fever onset and used to train a suite of machine-learning models to distinguish engraftment fevers from other fever etiologies. Model training and evaluation were performed using repeated stratified 5-fold patient-level cross-validation, yielding 100 train-test evaluations. Results Among all classification models, the logistic regression classifier provided the best overall performance and interpretability, achieving 94% specificity (95% CI, 0.84–1.0) for identifying engraftment fevers with a mean AUROC of 0.88 ± 0.10. Feature importance analysis demonstrated that both clinical variables and HFTM-derived temperature dynamics contributed to model performance, with a strong reliance on time-series features captured within the first 4 hours of fever onset. Conclusion Our study provides a demonstration that continuous temperature data collected from patients outfitted with wearable sensors can be leveraged not only for early fever detection but also for machine learning–based diagnosis of fever etiology. These findings suggest that dynamic temperature patterns contain clinically meaningful physiologic information that with further studies could support real-time diagnostic decision-making and guide safe de-escalation of empiric antibiotics during febrile neutropenia in patients undergoing intensive cancer therapy.

Treatment of participants with intermediate-risk prostate cancer with focal irreversible electroporation and radiation therapy was technically feasible and showed acceptable patient-reported outcomes and no severe adverse events over 1 year.

Abstract In response to a Cochrane review (published in April 2026) on the clinical trials of monoclonal antibodies targeting beta amyloid, this perspective outlines a number of critiques. The scientists, methodologists, subject‐matter experts, and clinicians on this perspective strongly recommend that the Cochrane editorial board consider a call for editorial response, correction of press materials, or commissioned reply to this review for four overarching reasons: (1) decision to pool antibodies that do and do not clear beta amyloid, (2) decision to include studies from a time when biomarkers of Alzheimer's disease were not available, (3) analytical and methodological limitations of the approach used, (4) conflating the distinct roles and methodological processes of systematic review and guideline methodologies, (5) contextualizing the present critique within the existing evidence‐synthesis literature, and (6) mechanistic inference beyond the scope of the presented analyses. Conclusions that may not accurately reflect treatment‐specific effects could cause significant downstream clinical and psychosocial harm to those currently undergoing treatment and their family members as well as individuals considering participation in Alzheimer's clinical trials.

Multimodality imaging plays a pivotal role in ventricular tachycardia (VT) ablation by providing critical insights into arrhythmogenic substrates and guiding procedural strategies. This updated review explores the integration of various imaging techniques, including echocardiography, cardiac magnetic resonance (CMR), multidetector computed tomography (MDCT), electroanatomical mapping (EAM), and nuclear imaging, to optimize VT ablation outcomes. Echocardiography, particularly transthoracic echocardiography (TTE), is an essential first-line tool for evaluating structural heart disease and left ventricular function. Moreover, echocardiography aids in risk stratification and procedural planning by detecting regional wall motion abnormalities and thrombus formation. Meanwhile, intracardiac echocardiography (ICE) enhances ablation precision by providing real-time catheter visualization, improving procedural success, and reducing complications such as cardiac tamponade. Nonetheless, CMR is the gold standard for myocardial tissue characterization, enabling the identification of scar burden and conduction channels critical for VT pathogenesis. Late gadolinium enhancement (LGE) facilitates preprocedural planning by localizing arrhythmogenic substrates, predicting VT recurrence risk, and informing ablation strategies. Additionally, T1- and T2-mapping techniques refine the assessment of myocardial fibrosis and inflammation, further improving patient selection and outcomes. MDCT complements CMR by offering high-resolution anatomical visualization and aids in delineating scar distribution, epicardial fat, and vascular structures, informing safe and effective ablation approaches. The integration of these imaging modalities significantly enhances VT ablation precision, reduces recurrence rates, and improves patient outcomes.

This article introduces a novel, single‐operator stress ultrasound technique for evaluating medial ulnar collateral ligament (MUCL) integrity by assessing medial ulnohumeral joint (MUHJ) widening under valgus stress. Unlike prior methods requiring dual operators, specialized equipment, or the use of hand/wrist weights, this approach was designed for clinical efficiency, reproducibility, and patient comfort. By positioning the patient comfortably in a side‐lying position with the elbow flexed to 50°, MUHJ width is measured at baseline (maximally apposed) and manually stressed positions, in a manner that may reduce muscular compensation, avoid viscoelastic creep, and facilitate consistency. While additional research is needed to evaluate clinical feasibility, assess reliability, and compare our technique with previously published methods of dynamic MUCL assessment, the aim of this manuscript is to describe our technique and provide a rationale for its potential utility in musculoskeletal ultrasound practice and research.

Abstract Black/African American populations, globally, bear the greatest prostate cancer (CaP) burden compared to other racial/ethnic groups. Addressing CaP disparities in Black men is complex, requiring a patient-centered, community-centric and comprehensive approach. This study integrates iCCaRE Consortium findings and broader literature to address unmet needs in survivorship care. The iCCaRE Consortium implemented five complementary pilot studies using mixed-methods designs, including feasibility trials, qualitative research, and observational analyses across the United States and sub-Saharan Africa. Descriptive statistics, subgroup analyses, and qualitative thematic analyses were performed across these studies. Collectively, projects addressed multilevel determinants including social, behavioral, and biological drivers of disparities. Project 1 implemented a Virtual Reality Assistant (ViRA) across clinical and community settings, with ongoing evaluation in pragmatic trials. Project 2 showed strong patient preference for home-based cancer care. Project 3 enrolled demonstrated trends toward improved health-related quality of life. Project 4 identified key themes influencing survivorship experiences. Project 5 identified biological mechanisms linking stress, immune modulation, and symptom burden. The iCCaRE pilot projects demonstrate the feasibility and early impact of a consortium-based, transdisciplinary approach to addressing CaP disparities in Black men. These findings highlight the importance of integrating patient-centered interventions, community engagement, and biological insights to inform scalable strategies aimed at improving survivorship outcomes and advancing health equity. The iCCaRE Consortium demonstrates that a transatlantic, patient-centered, and multidisciplinary approach integrating social, clinical, and biological factors can generate scalable strategies to improve survivorship outcomes and advance equity in CaP care for Black men.

Background Randomized trials have shown equivocal outcomes between a direct aspiration as first-pass technique (ADAPT) and stent retriever (SR) stroke thrombectomy, yet whether specific patient subgroups benefit differentially from one technique over the other remains unknown. Methods In this retrospective multicenter cohort study, patients with large vessel occlusion were included, and those who underwent ADAPT versus SR first-pass thrombectomy (either as standalone or combined with aspiration) were compared. The primary outcome was a composite of first-pass effect (FPE, modified Thrombolysis In Cerebral Infarction (mTICI) 2c or better with one attempt) with no symptomatic intracranial hemorrhage (sICH). A causal forest model was used to estimate the conditional average treatment effect (CATE) for each patient, with larger CATEs indicating that ADAPT is expected to be more advantageous. Patients were stratified by CATEs, and outcomes were compared between treatment groups. Results Among 6700 included patients, ADAPT (n=3695, 55%) was associated with a higher rate of FPE with no sICH (39.9% vs 26.9%; adjusted OR (aOR) 2.07, 95% CI 1.77 to 2.41, P<0.001). The causal forest identified significant treatment effect heterogeneity (interaction P<0.001), where ADAPT was more advantageous in more recent years and among patients with M1 occlusions presenting in earlier time windows. Low-CATE patients showed no statistically significant difference between techniques (aOR 0.91, 95% CI 0.57 to 1.45, P=0.70), while medium- and high-CATE patients demonstrated progressively larger ADAPT advantages (aOR 2.06, 95% CI 1.67 to 2.55, and aOR 2.99, 95% CI 2.24 to 3.98, respectively, both P<0.001). Conclusions ADAPT may be superior to SR for a majority of patients, particularly in recent years, and among patients with M1 occlusions presenting in earlier time windows.