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.

Abstract Purpose: Pancreatic ductal adenocarcinoma (PDAC) frequently recurs after neoadjuvant therapy (NT) and curative-intent resection. Although major pathologic response predicts favorable outcomes, most patients achieve only minor response with a heterogeneous recurrence risk. We asked whether the spatial organization of residual PDAC encodes clinically relevant biology beyond residual tumor burden. Experimental Design: In a retrospective cohort of 203 patients with resected PDAC treated with NT and restricted to minor pathologic response, routine hematoxylin and eosin (H&E) whole-slide images were segmented into cancer and stroma using an artificial intelligence–enabled pipeline. Spatial composition (patch density, edge density) and configuration (compactness/complexity, intermixing) were quantified and tested for associations with disease-free survival (DFS) using multivariable models adjusted for standard clinicopathologic factors. Results: Shorter DFS was associated with a fragmented, interface-rich tumor–stroma ecology featuring higher edge density and diversity and reduced homotypic aggregation, independent of clinicopathologic variables. Two spatial risk models were independently prognostic: (i) cancer mean shape index plus stromal shape index variability [adjusted hazard ratio (HR), 1.71; P = 0.003] and (ii) mean stromal patch area plus edge density (adjusted HR, 2.19; P = 0.002). Both models stratified outcomes in which pathologic response grading and residual cancer area did not. High-risk configurations were further associated with reduced intratumoral tumor-infiltrating lymphocyte (TIL) density and infiltration ratio, with relative TIL accumulation at the cancer periphery and within the stroma, consistent with an immune-excluded phenotype. Conclusions: Residual cancer–stroma topology quantified from standard H&E slides yields independent prognostic signals after NT in PDAC, provides a cellular immune correlate for spatial risk, and motivates prospective validation and spatially informed adjuvant strategies.

ABSTRACT Background and Objectives Surgery is the mainstay of treatment for localized colorectal cancer (CRC); however, little is known about survival outcomes following CRC surgery in low‐ and middle‐income countries (LMICs). Here, we examine the available data on long‐term outcomes following CRC resections in LMICs. Methods A systematic review and meta‐analysis were conducted on primary research studies reporting survival data after CRC resection with curative intent in LMICs. Disease‐free survival (DFS) and overall survival (OS) data were extracted, and random effects modelling was used to estimate the pooled survival rates. Results One hundred and fifty‐four studies representing 20,589 CRC patients were analyzed. Notably, only 27 (20%) of the 137 LMICs were represented in the literature. The pooled 5‐year OS estimate was 88% (95% CI: 77–95), 76% (69–81), and 57% (49–64) for Stages I, II, and III, respectively. 5‐year DFS estimates were 82% (71–90), 76% (67–84), and 59% (51–65) for stages I, II, and III, respectively. Combined OS and DFS estimates for all three stages were 76% and 69%, respectively. Survival rates varied considerably across the included studies and between income groups. Conclusions With the rising incidence of CRC globally, our work highlights the dearth of data on long‐term outcomes following CRC operations in most LMICs and emphasizes the urgent need for research capacity building.

Abstract Purpose: Colorectal Cancer (CRC) is a leading cause of death from cancer globally. Surgery is the mainstay of treatment for localized CRC; however, little is known about survival outcomes following CRC surgery in low- and middle-income countries (LMICs). In this study, we examine the published literature for data on long-term outcomes following CRC resections in LMICs. Methods: We systematically reviewed PubMed, Web of Science, Embase, and Global Index Medicus for original research articles reporting survival data after CRC resection with curative intent in LMICs, published between January 2005 and May 2022. LMICs were defined according to the 2020 World Bank categories. We excluded studies without English full text or involving pediatric populations (<18 years), non-primary colorectal, benign disease, and endoscopic/transanal resection only. Studies from China dominated the published literature and were excluded. Abstracts and full texts were reviewed by two independent reviewers, and a third reviewer resolved conflicts. Disease-free survival (DFS) and overall survival (OS) data were extracted, and random effects modelling was used to estimate the pooled survival rates. Results: Our search returned 32,261 articles. After deduplication, 20,729 abstracts were assessed for eligibility, with 154 articles meeting inclusion criteria, representing a total of 20,589 CRC patients. 98 (63.6%) studies were from upper-middle-income (UM) countries, 55 (35.7%) from lower-middle-income (LM) countries and only one was from a low-income (L) country. Notably, only 27 (20%) of the 137 LMICs were represented in the literature. Turkey accounted for the highest frequency (29%) of included articles. Most (60%) of the studies were retrospective cohort design, and only three (3) were randomized controlled trials. The pooled 5-year OS estimate was 88% (95% CI: 77–95) for Stage I disease, 76% (69–81) for Stage II, and 57% (49–64) for Stage III. 5-year DFS estimates were 82% (71–90), 76% (67–84), and 59% (51–65) for stages I, II and III respectively. Survival rates varied considerably between income groups, with the strongest disparity seen with Stage III OS data at 18 months: 89% in UM, 86% in LM, and 50% in L (p=0.0005). Conclusion: With the rising incidence of CRC in LMICs, our work highlights the dearth of data on long-term outcomes following CRC operations in LMICs and emphasizes the urgent need for research capacity building, especially in low-income countries. Citation Format: Oluwasegun Afolaranmi, Thomas M. Diehl, Sehar Salim Virani, Qiuyu Yang, Kenechukwu Okwunze, Adel H. Khan, Nabiha Akhlaq Mughal, Daniel Schroeder, Sheida Pourdashti, Leslie Christensen, Sadaf Khan, Syed Nabeel Zafar. Survival Following Colorectal Cancer Surgery in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis [abstract]. In: Proceedings of the 13th Annual Symposium on Global Cancer Research; 2025 Sep 16. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2025;34(12_Suppl):Abstract nr 84.

Abstract Background Valvular heart disease (VHD) and atrial fibrillation (AF) frequently coexist, presenting complex clinical challenges despite advances in diagnostics and therapeutics. Together, they contribute substantially to cardiovascular mortality. However, epidemiological patterns vary across demographics and regions Methods Mortality data from 1999–2023 were obtained from the CDC WONDER database. Deaths attributed to VHD (ICD-10: I30-I52) with co-diagnosed AF (ICD-10: I48) among adults ≥ 45 were included. Age-adjusted mortality rates (AAMRs) per 1,000,000 population were calculated. Autoregressive integrated moving average (ARIMA) models were used to project mortality trends through 2035. Results From 1999 to 2023, there were 172,511 VHD and Afib-related deaths in adults ≥ 45. AAMRs increased until 2021, followed by a slight decline to 8.86. The overall AAPC for VHD with AF was 4.01%. AAMR increase was consistent across all age groups, highest seen in 65 + individuals. Males had consistently higher AAMRs than females. AAPC for males was 4.44% and for females 3.52%. Non- Hispanic White had the highest AAMR (10.56 in 2021), followed by Hispanics (4.19). Regionally, the West had the highest AAMR (11.27), followed by Mid-West (9.94). Non-metropolitan areas had higher AAMR 8.96 compared to metropolitan areas (AAMR: 7.59). Most VHD related deaths were reported in inpatient settings (n = 396,451) and 12% involved co-diagnosed AF. Conclusion Mortality associated with VHD and AF in the U.S population aged ≥ 45 has shown a concerning increase. Predictive models indicate this trend may persist, highlighting the need for early detection, equitable healthcare access and public health interventions tailored to high-risk populations.

ABSTRACT Background Critically ill patients may be overexposed to valproate because altered protein binding leads to a disproportionate free valproate fraction. The Fraser equation was derived and internally validated to estimate critically ill patients' free valproate concentrations, but it requires external validation. Methods Adult intensive care unit (ICU) patients at two academic centers with concurrently measured free and total valproate concentrations were included. Free valproate concentrations were estimated using the Fraser equation which includes total valproate, albumin and BUN concentration, and whether the patient received propofol or aspirin. The primary outcome was Fraser equation performance, assessed using Bland–Altman methods. Comparative performance against estimates from the Doré equation (an alternative predictive equation), therapeutic concordance using a target free valproate range of 5–15 mg/L, and equation improvements were explored. Results Overall, 315 patients and 556 free‐total valproate concentration pairs were included. The mean (±SD) age was 58 (±17) years and 90 (29%) patients were on valproate prior to hospital admission. The Fraser equation estimated free valproate concentrations were correlated with measured concentrations ( r = 0.728) with a negative bias (mean bias −2.77 mg/L, 95% LOA –18.9, 13.4). The Fraser equation increasingly underestimated measured concentrations as measured concentrations increased. 71% of Fraser equation estimates were therapeutically concordant (e.g., estimate and measured both within reference range) compared to 61.9% of Doré estimates ( p = 0.001). Fraser equation modifications led to minor performance improvements but did not overcome worsening underestimation with higher measured free valproate concentrations. Conclusion The Fraser equation was moderately accurate and corresponded with an appropriate interpretation for 71% of free valproate concentrations. Worse underestimation with higher measured free valproate concentrations suggests direct measurement of free valproate concentrations is warranted. While the Fraser equation could complement therapeutic decision making at centers where direct free valproate measurements are unavailable or slow to return, its accuracy is currently insufficient to replace direct measurement.