Odat, Ramez M.

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.

e14008 Background: Lung cancer is the most common cancer to metastasize to the brain. Identifying the EGFR mutation is critical for determining treatment strategies and prognosis. However, 17.26% of patients show EGFR mutation discordance between the primary tumor and CNS metastasis. On the other hand, it is not always feasible to obtain brain samples. Many studies have developed deep learning (DL) models to predict the existence of EGFR mutations using radiomics. In this paper, we aim to measure the accuracy of diagnostic tests in those studies. Methods: PubMed, Scopus, Cochrane Library and Web of Science databases were searched from inception to January 2025, to identify studies measuring the ability of DL models in differentiating between the types of EGFR mutation in patients with lung cancer brain metastases. The quality assessment of the included studies was performed using QUIPS tool. The diagnostic accuracy meta-analysis was conducted using Meta-DiSc software. Results: Nine studies were included in our systematic review and meta-analysis, encompassing 260 patients with EGFR mutant type and 264 patients with EGFR wild type. Our analysis revealed that DL approaches exhibit a high ability to differentiate between EGFR mutation types, with a sensitivity of 0.82 (95% CI: 0.73–0.88) and a specificity of 0.88 (95% CI: 0.78–0.94). Additionally, the positive likelihood ratio and negative likelihood ratio were 6.87 (95% CI: 3.5–13.3) and 0.20 (95% CI: 0.13–0.31), respectively. The diagnostic odds ratio was 33.4 (95% CI: 13.5–82.5), which is indicative of excellent diagnostic accuracy. Conclusions: DL models demonstrate exceptional diagnostic accuracy in detecting EGFR mutations in brain metastases from lung cancer. These findings highlight the potential of AI-driven approaches to enhance personalized treatment strategies and improve outcomes for patients with EGFR-mutant NSCLC brain metastases.

Cardiovascular disease (CVD) is the leading cause of mortality and morbidity worldwide. Low-dose colchicine is a novel and nonstandard management approach for patients with CVDs who are at an increased risk of adverse events. However, few studies have reported the risk of stroke with colchicine, with controversial results. This meta-analysis aimed to compare the efficacy of colchicine and placebo for stroke prevention in patients with CVD. Major electronic databases were screened for randomized controlled trials (RCTs) comparing colchicine and placebo in patients with CVDs from inception to June 2024. Pooled estimates were calculated as risk ratios (RRs) with 95% confidence intervals (CIs) using an inverse-variance random-effects model. Statistical significance was set at P < 0.05. A total of 15 RCTs encompassing 25,116 patients with CVDs were included (12,568: colchicine and 12,548: placebo). The pooled analysis demonstrated a significant reduction in stroke [RR, 0.80 (95% CI, 0.64–0.99); P = 0.04] with colchicine compared with placebo. The risk of all-cause mortality [RR, 1.00 (95% CI, 0.77–1.28)] was comparable between the 2 groups. On subgroup analysis, low-dose colchicine (0.5 mg/day) demonstrated a significantly lower risk of stroke compared with high-dose (>0.5 mg/day) colchicine, which failed to achieve statistical significance. Based on this meta-analysis, colchicine significantly reduced stroke in patients with CVDs compared with placebo. This effect was most significant with low-dose colchicine at 0.5 mg/day. However, no differences were observed in all-cause mortality. Further long-term RCTs are warranted to investigate stroke prevention using colchicine in this population.

Background: Sarcoidosis is a multisystem disorder characterized by non-caseating granulomas in various organs. While cardiac sarcoidosis (CS) is clinically rare, it has significant implications, including heart failure, ventricular arrhythmias, and sudden cardiac death. Speckle-tracking echocardiography has emerged as a promising tool for detecting subclinical myocardial dysfunction, which is cost-efficient and readily available. This meta-analysis aims to evaluate differences in functional echocardiographic parameters between patients with CS and extracardiac sarcoidosis (ECS) to improve early recognition and management. Methods: A comprehensive search of major bibliographic databases was conducted to identify studies up to December 2024. Mean differences (MDs) with 95% CIs were pooled using the inverse-variance random-effect model. Results: Seven studies with 478 patients with sarcoidosis (CS: 159 and ECS: 319) were included. Patients with CS had a significant reduction in left ventricular global longitudinal strain (MD: −2.73; 95% CI: −4.09, −1.38; p < 0.0001) and tricuspid annular plane systolic excursion (MD: −0.59; 95% CI: −1.12, −0.05; p = 0.03) compared to patients with ECS. No significant differences in the LV global circumferential strain, interventricular septum thickness, left ventricular ejection fraction, E/A ratio, E/E’ ratio, LV end-diastolic diameter, and LV end-systolic diameter were noted. Conclusions: LV GLS and TAPSE are promising parameters for the early detection of cardiac involvement in sarcoidosis, with significant prognostic implications. Although STE provides a cost-effective and accessible alternative to CMR and FDG-PET, further research is needed to standardize its use and validate diagnostic cut-offs.

ABSTRACTBackgroundAnemia is frequently observed as a comorbidity in atrial fibrillation (AF), especially in elderly patients and in those on anticoagulation. This has been associated with poor clinical outcomes. We aim to investigate the impact of anemia on clinical outcomes in patients with AF on oral anticoagulation.MethodsWe comprehensively searched PubMed, WOS, SCOPUS, EMBASE, and CENTRAL through March 2024 and conducted a prognostic systematic review and meta‐analysis. All analyses were performed using R V. 4.3.1. This meta‐analysis was registered at PROSPERO (CRD42024556023).ResultsWe included 23 studies comprising 286,781 patients for analysis. Anemia had a significant association with an 84% increase in risk of major bleeding (HR: 1.84 with 95% CI [1.59, 2.13], p < 0.01), a 32% increase in the risk of intracranial hemorrhage (HR: 1.32 with 95% CI [1.10, 1.58], p < 0.01), a 98% increase in the risk of gastrointestinal bleeding (HR: 1.98 with 95% CI [1.67, 2.35], p < 0.01), and a 91% increase in the risk of all‐cause mortality (HR: 1.91 with 95% CI [1.46, 2.51], p < 0.01). However, the impact of anemia did not significantly affect the risk of stroke, transient ischemic stroke (TIA), or systemic embolism (HR: 1.07 with 95% CI [0.93, 1.22], p = 0.36).ConclusionAnemia was significantly associated with an increased risk of major bleeding, intracranial hemorrhage, gastrointestinal bleeding, and all‐cause mortality. However, anemia did not significantly impact stroke, TIA, or systemic embolism.