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.

Cirrhosis remains a major global cause of morbidity and mortality, with rapidly evolving etiologic drivers. This review summarizes the contemporary global epidemiology of cirrhosis, highlighting regional patterns and major transitions in underlying causes to inform prevention and policy. In 2021, cirrhosis and chronic liver disease accounted for ~1.4 million deaths worldwide. Although age-standardized mortality rates have declined in many regions, the absolute burden continues to rise due to population growth and aging. Reductions in hepatitis B and C–related cirrhosis, driven by vaccination, screening, and antiviral therapy, have been offset by a growing contribution from steatotic liver disease. High–sociodemographic index (SDI) regions exhibit lower mortality but increasing prevalence, reflecting improved survival and expanding metabolic risk, whereas low- and lower-middle–SDI regions continue to experience high mortality. Addressing the global burden of cirrhosis will require sustained public health investment focused on viral hepatitis elimination, alcohol-associated harm reduction, metabolic risk management, and equitable access to early detection and care.

ABSTRACT Background and Aim Determining the location of gastrointestinal (GI) bleeding is critical for guiding diagnostic and therapeutic strategies but often results in patients receiving pan‐endoscopy with upper endoscopy, colonoscopy, and small bowel capsule endoscopy, which can be unnecessary, costly, and waste limited healthcare resources. The blood urea nitrogen‐to‐creatinine ratio (BUN/Cr) may help discriminate between upper GI bleeding (UGIB) and lower GI bleeding (LGIB). This study aims to assess the diagnostic performance of the BUN/Cr in distinguishing UGIB from LGIB. Methods A literature search was conducted in MEDLINE, EMBASE, and Cochrane Library to identify diagnostic test accuracy studies published from inception through January 31, 2025, which evaluated BUN/Cr in patients with UGIB versus LGIB. A linear mixed‐effects model meta‐analysis was conducted using the “diagmeta” package. The pooled sensitivity, specificity, diagnostic odds ratio, and area under the summary receiver operating characteristic curve (AUC) were estimated, and optimal threshold was determined using the Youden index. Results Seventeen studies were included in this meta‐analysis. The pooled mean difference in BUN/Cr between UGIB and LGIB patients was 11.44 (95% confidence interval [95% CI] 8.35–14.52). At a threshold of > 30, pooled sensitivity was 38.8% (95% CI 28.1%–50.8%) and specificity was 89.3% (95% CI 81.0%–94.2%). At the optimal cut‐off of 22, sensitivity was 66.2% (95% CI 57.8%–73.7%), specificity was 71.0% (95% CI 58.5%–81.0%), and AUC was 0.740 (95% CI 0.683–0.794). Conclusion BUN/Cr demonstrates moderate diagnostic accuracy for distinguishing UGIB from LGIB, particularly at a threshold of ≥ 22. This readily accessible and inexpensive blood test may assist in early clinical triage and assessment of the location of GI bleeding, particularly in those patients where the clinical presentation is obscure.

Abstract Background Gastrointestinal (GI) cancer remains a major global health challenge. This study provides updated 2022 estimates of GI cancer incidence and mortality worldwide, along with projections of incident cases and deaths through 2050 to inform cancer control strategies. Methods In this population‐based study, data from the GLOBOCAN 2022 database were used to examine incidence and deaths associated with GI cancer. By using global demographic projections, this study estimated the projected number of incident cases and deaths until the year 2050. Results By 2050, the global burden of GI cancer is projected to reach 9.06 million incident cases (+85%) and 6.42 million deaths (+93%) from 2022. Increases in incidence are projected for both females (+87%) and males (+83%), as are increases in mortality for both females (+97%) and males (+91%). Whereas the Western Pacific region will have the highest absolute burden, with 3.88 million new cases and 2.79 million deaths, the greatest relative increase is expected in Africa, with incidence and deaths rising by 157% and 160%, respectively. As measured by the Human Development Index (HDI), the steepest increases are projected in low (+151% incidence; +152% deaths) and medium (+112% incidence; +114% deaths) HDI countries. Overall, all GI cancer types are projected to increase, led by pancreatic cancer in incidence (+95%) and colorectal cancer in deaths (+103%). Conclusions GI cancer incidence and deaths are expected to nearly double by 2050, with increases across sexes, cancer types, and regions, especially in lower HDI countries.

Importance Metabolic dysfunction–associated steatohepatitis (MASH) represents a high, underprioritized burden among noncommunicable diseases (NCDs) and people living with type 2 diabetes (T2D). Objective To identify cost-effective management approaches to prevent, detect, and treat MASH and liver fibrosis in people living with T2D. Design, Setting, and Participants This economic evaluation consisted of a generalized cost-effectiveness analysis (GCEA) that was conducted for 12 countries (Brazil, Chile, Germany, Italy, Japan, Saudi Arabia, South Africa, Spain, Sweden, Tanzania, Thailand, and the United States), across all 6 World Health Organization (WHO) regions. A cohort state-transition model simulated liver disease development and its impact on a synthetic cohort, aged 19 years and older and living with T2D, over their lifespan across 10 liver health states. Exposures Using an 80% coverage level, 14 management approaches were compared, including screening via the Fibrosis-4 (FIB-4) test and Enhanced Liver Fibrosis (ELF) test or vibration-controlled transient elastography (VCTE) as well as treatment with pharmacological and nonpharmacological interventions. Main Outcomes and Measures The main outcomes were the average cost-effectiveness ratios (ACERs) and the incremental cost-effectiveness ratios (ICERs), which were used to construct care expansion paths by ranking the management approaches in order of cost-effectiveness. The main measures were the total incremental costs and the total incremental quality-adjusted life-years (QALYs) of each intervention. Results In this GCEA, the outcomes were evaluated with respect to country-specific willingness-to-pay thresholds. The standard of care had the lowest ACERs in 8 countries (not in Chile, Germany, Saudi Arabia, or the United States). Treatment with intensive lifestyle interventions (ILIs), after screening via ELF or VCTE, was cost-effective in all countries. ILIs and treatment with semaglutide was cost-effective in 11 countries (not in Tanzania); ILIs and treatment with resmetirom was cost-effective in 8 countries (not in Brazil, South Africa, Tanzania, or Thailand). Conclusion and Relevance In this economic evaluation, screening followed by ILIs was found to be a cost-effective management approach for MASH and liver fibrosis among people living with T2D in all countries. Screening followed by pharmacological treatment was cost-effective in most countries. These results can inform health policy decision-making and further the development of WHO recommended interventions to address NCDs.