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.

Automated diagnostic report generation lies at the core of clinical diagnosis and can alleviate clinician shortages. Existing diagnostic report generation methods have two major limitations: they rely on unimodal inputs (e.g., images), ignoring textual biomarkers like medical history, and lack proactive dialogue capabilities to elicit personalized clinical information. To address those issues, we propose a ProActive Multimodal Agentic (PAMA) system, which performs comprehensive disease analysis by examining biomarkers in diverse sources, including multi-view medical images, medical histories, and diagnostic conversations. Built upon a knowledge graph and recommendation-based dialogue architecture, PAMA actively initiates adaptive, multi-turn conversations with patients, which is integrated with visual data for robust and reliable report generation. Specifically, PAMA actively generates adaptive multi-turn questions to collect clinically relevant background information, and then fuses the resulting dialogue context with visual representations for robust diagnostic report generation. We validate our approach on two real-world benchmark datasets, MIMIC-CXR and IU-Xray, through extensive quantitative evaluations and comparisons with state-of-the-art baselines. Furthermore, we conduct user studies to assess the realism and clinical quality of the generated reports. Finally, we present real-world case studies to examine the performance of our system across diverse scenarios, demonstrating its robustness on scalability, complexity, and data variability.

Objectives: To assess how social risk factors and socioeconomic status (SES) affect health care costs at a large, integrated health system of 45 clinics in Iowa, Minnesota, and Wisconsin. Methods: We retrospectively reviewed administrative patient cost data from January 1 through December 31, 2022. Social risk factors (lack of financial resources, food insecurity, intimate partner violence, unmet transportation needs, and housing instability) were determined with patient questionnaires. Cost z -scores were compared across all risk-factor quartiles. We used a housing-based measure to objectively determine SES. Results: We analyzed data from 410 624 patients empaneled with 689 family medicine clinicians. Self-reported risk factor data were incomplete for 219 321 patients. Costs were higher for those with higher social risk (mean cost z -score: high risk = 0.38, low risk = 0.11; P < .001). In addition, higher costs were associated with increasing age, greater medical complexity (higher Adjusted Clinical Group scores), White race, and lack of financial resources. Although we observed geographic variations in cost, urban and rural locations did not have significant cost differences. Costs were similar across all quartiles of SES, and the absolute difference in cost z -scores between the highest and lowest SES quartiles was only 0.04. The multivariate analysis, which adjusted for age, medical complexity, race, sex, and objective SES, showed that these specific associations were substantially decreased and no longer significantly associated with mean cost z -scores. Conclusions: Patient-reported social risk factors were significantly associated with increased cost of care in a large, multispecialty health system in the midwestern US. These associations were decreased in the multivariate analysis. Results should be interpreted cautiously for readers outside the midwestern US, given potential responder bias and the racial homogeneity (92% White) of the study cohort.

Radiated chronic scalp wounds with exposed bone present a significant reconstructive challenge, particularly when prior attempts have failed or when further surgery is contraindicated due to patient comorbidities or preference. We retrospectively reviewed 10 patients (2014–2024) with radiated chronic scalp wounds with exposed bone who have either failed prior reconstruction, could not medically tolerate anesthesia, or declined surgery. Patients performed daily cleansing with soap and water followed by application of Aquaphor and Silvadene. Treatment duration ranged from 1 to 73 months (mean: 29.4 mo). The area of exposed bone decreased in 6 patients (60%), remained stable in 1 (10%), and increased in 3 (30%). Three of 7 patients with wound improvement (30%) achieved complete healing. Two of 3 patients with wound progression deceased of unrelated causes. To our knowledge, no major complications occurred. These findings support wound care as a safe, and often effective, treatment when larger reconstruction is not feasible.

Prostate-specific antigen (PSA) screening has played a critical role in reducing prostate cancer mortality but remains controversial due to concerns regarding overdiagnosis, overtreatment, and inconsistent screening guidelines. In 2012, the United States Preventive Services Task Force (USPSTF) issued a grade D recommendation against PSA screening, leading to a national decline in PSA testing and prostate biopsy rates. This was followed by an increase in the incidence of metastatic prostate cancer at diagnosis. The USPSTF has since revised its recommendation to grade C, emphasizing shared decision-making for men aged 55 to 69 years. However, variability in screening recommendations across professional societies has resulted in clinical uncertainty, particularly for primary care physicians (PCPs), who frequently initiate PSA testing and urology referrals. This review provides an evidence-based overview of PSA screening tailored for the PCP. We performed a comprehensive literature review using Ovid MEDLINE, PubMed, Embase, and the Cochrane Library, including systematic reviews published between January 2020 and April 2025, and current guidelines from the American Urological Association (AUA), National Comprehensive Cancer Network (NCCN), European Association of Urology (EAU), and American Cancer Society (ACS). We summarize the evolving landscape of PSA screening and its integration with contemporary tools such as shared decision-making, multiparametric magnetic resonance imaging (mpMRI), and transperineally targeted biopsy. We advocate for initiating PSA screening between the ages of 45 and 49 in men with average or elevated risk, based on long-term evidence demonstrating the value of an early baseline PSA level and risk-stratified follow-up. This approach, coupled with improved diagnostic tools, can help PCPs navigate guideline variability and implement a rational, common-sense strategy to maximize early detection while minimizing harm.

Syndrome of the Trephined (SoT), also known as sunken or sinking skin flap syndrome (SSFS), is a rare sequela of decompressive craniectomy caused by an atmospheric pressure gradient over the underlying brain parenchyma following bone flap removal. Cranioplasty is the definitive treatment of SoT, although some patients are not surgical candidates or require bridging to definitive treatment. This systematic review identified 7 articles describing nonsurgical interventions for patients with SoT. Three treatment modalities emerged: external orthotics, scalp traction, and Trendelenburg positioning. These approaches demonstrated rapid improvements in neurological symptoms, including restored motor function, improved cognition, resolution of midline shifts, and, in some cases, re-expanded brain parenchyma. While these results are limited to case reports and small case series, they demonstrate promising early outcomes for the noninvasive management of Syndrome of the Trephined.

Abstract Importance and Objective Upadacitinib, an oral, reversible Janus kinase inhibitor, is approved for the treatment of moderate-to-severe Crohn’s disease (CD). Limiting corticosteroid exposure is an important goal in treating CD. This posthoc analysis evaluated the corticosteroid-sparing effects of upadacitinib in patients with CD. Design and Setting This study included pooled data from two phase 3, multicenter, double-blind induction trials and one maintenance trial. Randomization was stratified by corticosteroid use at induction baseline, with a mandatory corticosteroid taper starting at induction week 4. Efficacy was evaluated by baseline corticosteroid use and by achieving corticosteroid-free outcomes through year 2 of maintenance therapy. Safety was also assessed. Results At baseline, 34.7% (234/674) and 35.7% (124/347) of upadacitinib 45 mg and placebo-treated patients were taking corticosteroids, respectively. At induction week 12 and maintenance week 52, higher rates of upadacitinib-treated patients were corticosteroid-free among all patients and among patients with baseline corticosteroid use compared with placebo; upadacitinib-treated patients achieved higher rates of corticosteroid-free outcomes, compared with placebo, including corticosteroid-free clinical remission (stool frequency/abdominal pain score [SF/APS]: 42.7% vs 16.1%; CD activity index [CDAI]: 41.2% vs 23.4%) and corticosteroid-free endoscopic response (37.0% vs 8.1%), with similar results observed among responders to upadacitinib induction therapy at maintenance week 52. Corticosteroid-free outcomes were sustained through year 2 of maintenance therapy. The safety profile was similar to the overall population, with no new safety risks identified. Conclusions and Relevance The results from pivotal studies demonstrated that upadacitinib effectively induced early and sustainable corticosteroid-free clinical remission with a manageable safety profile in patients with moderate-to-severe CD. Clinical trial identifiers U-EXCEL, U-EXCEED, and U-ENDURE ClinicalTrials.gov numbers, NCT03345849, NCT03345836, and NCT03345823.

Introduction/Objectives: Little is known about the prevalence of patient-reported social risk factors and the use of the HOUSES Index, a simple, reliable method of assessing socioeconomic status (SES) based on publicly available housing data, in a predominantly rural, primary care population. Methods: We conducted a cross-sectional analysis of adult patients paneled to family medicine clinicians in a US Midwest health system as of December 31, 2022. Patients’ listed address determined HOUSES Index as quartile rank (Q1 lowest SES) and rural/urban status. Social risk data including housing, food, transportation, finances, and violence were collected from health record questionnaires. A mixed effect model was used to assess associations between social risk, HOUSES Index, and rurality. Results: Of the 352 355 patients included, rural patients were more likely than urban patients to report all social risk factors and had lower SES as measured by HOUSES quartiles. In the mixed effects analysis, HOUSES quartile was independently predictive of reporting an at-risk social risk factor (Q1 vs Q4 OR = 2.27, 95% CI = 2.19-2.37), but rurality was not (OR = 1.02, 95% CI = 0.97-1.07) after adjusting for HOUSES. Conclusions: The increased prevalence of social risk factors among rural residents is largely explained by individual SES measured by HOUSES Index.