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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 Undergraduate anatomy teaching in the UK has been progressively compressed, with reduced contact time and variable integration across medical programs. We examined final‐year medical students' perceptions of anatomy teaching, focusing on total contact hours, longitudinal continuity, and exposure to traditional and emerging teaching modalities. A national cross‐sectional survey was distributed to final‐year students across 40 UK medical schools between December 2024 and February 2025. Satisfaction with anatomy teaching, perceived importance of anatomy for future practice, contact hours, continuity across program years, and exposure to specific teaching modalities and technologies were assessed. Comparative analyses used non‐parametric tests and ANOVA with post hoc testing where appropriate. 628 students responded. Dissatisfaction was greatest for teaching quantity and continuity, whereas breadth, depth, and quality were rated more favourably. Students receiving more than 200 h of anatomy teaching reported significantly higher satisfaction than those receiving fewer than 200 h ( p < 0.001). Satisfaction also varied by continuity pattern, with teaching delivered continuously over three or more years associated with higher satisfaction than shorter or non‐continuous models ( p < 0.01). Cadaveric dissection was the most preferred modality, but higher satisfaction was associated with exposure to selected adjuncts, particularly 3D imaging software and 3D printed models (both p < 0.001); VR/AR showed no significant association. Perceived importance of anatomy differed by intended specialty, with students interested in surgery rating anatomy as most important ( p < 0.0001). Student dissatisfaction with UK undergraduate anatomy teaching appears to stem less from content coverage than from insufficient teaching time and poor longitudinal integration. Anatomy should be protected as a multi‐year component of the curriculum, complemented by selectively integrated adjunctive tools rather than indiscriminate technology adoption.

Abstract Anatomy is fundamental to clinical competence. However, reduced contact hours, limited cadaveric access and difficulties with technological integration raise concerns about students’ preparedness and development. The current study evaluated various practices, student perceptions, challenges, teaching quality and quantity of UK medicine anatomy education. A national cross-sectional survey was distributed to final-year medical students at 40 UK medical schools to assess teaching quality, student satisfaction, confidence and theimpact of emerging technologies and challenges associated with anatomy education. 628 students responded and 55.3% (n=347) preferred a curriculum integrating traditional teaching and emerging technologies,73.3% (n=460) were dissatisfied with teaching quantity and continuity, and 42.7% (n=268) were dissatisfied with teaching breadth and quality. Satisfaction was significantly higher for users of 3D imaging software (Users Mean=3.63 vs. Non-users=3.28;p&lt;0.001,rrb=0.172) and 3D printed simulation models (3.59 vs. 3.23;p&lt;0.001,rrb=0.181), despite familiarity among 32.3% (n=203) and 27.9% (n=175), respectively. 3D imaging software was most recognised (59.2%, n=372), followed by 3D printed simulation models (55.4%,n=348) and VR/AR (32.3%,n=203). Satisfaction was high for continuous teaching across ≥3 years (F(3,624)=24.91,p&lt;0.001) Kruskal-Wallis H test showed significant variation in perceived importance of anatomy across specialties (H(5)=75.99,p&lt;0.0001), with Surgery rating it highest (Median=5.0) and GP/Medicine lower (Median=4.0). Students are dissatisfied with the current curriculum content, structure and provision of anatomy teaching. Emerging technologies could enhance satisfaction, address limitations of cadaveric dissection and extend teaching beyond the classroom. Collaborative efforts among anatomists, clinicians and academics are essential in standardising clinically curricula and sound technological integration (VR/AR/3D models).

e18597 Background: TP53 mutations ( TP53 m) are uncommon in chronic-phase (CP) Philadelphia (Ph) chromosome–negative myeloproliferative neoplasms (MPN) but are increasingly reported in myelofibrosis (MF) and accelerated/blast phase (AP/BP). Their distribution, allelic configuration, and associated clinical outcomes have not been systematically synthesized. Methods: A PRISMA-guided search of EMBASE and PubMed (1974-July 1, 2025) identified cohort studies reporting adult Ph–negative MPNs with molecularly confirmed TP53 m. Case reports were excluded; Conference abstracts were included if cohort-level data were available. Extracted variables included demographics, MPN subtype, disease phase, TP53 allelic status (per International Consensus Classification), variant allele frequency (VAF), allogeneic hematopoietic cell transplantation (allo-HCT), median overall survival (mOS), and leukemic transformation. Given heterogeneity and lack of comparators, pooled proportions with (95% CI) were generated for descriptive variables; outcomes were summarized descriptively. Results: 10 retrospective studies met inclusion criteria. Pooled mean age was 61 years (95% CI 57.18–65.17) with male predominance (58%, 95 CI 53–63). TP53 m were uncommon in patients with Ph-negative MPN (3%, 95% CI 0–15%) but were higher in MF/AP/BP (10%, 95% CI 4–24%). Among patients with TP53 m, disease distribution included MF (35%, 95% CI 13–65%), AP/BP (33%, 95% CI 26–41%), essential thrombocythemia (ET) (10%, 95% CI 3–28%), and polycythemia vera (PV) (8%, 95% CI 4–14%). Multi-hit TP53 m accounted for 52% (95% CI 40–64%), while single-hit comprised 47% (95% CI 34–60%). The pooled mean TP53 VAF was 37.48% (95% CI 30.73–44.24%). Allo-HCT was used in 16% (95% CI 13–20%). One cohort reported leukemic transformation in 47% with a median follow-up of 9.6 months (m). Reported mOS in TP53 m CP-MF ranged from 11.6–18 m and was not reached in PV/ET, whereas AP/BP mOS ranged from 4.5–6 months. Conclusions: TP53 m Ph–negative MPNs are enriched in MF and AP/BP and frequently demonstrate multi-hit TP53 m with high VAF and associated with high leukemic transformation. Standardized molecular reporting and prospective studies are needed to refine prognostication and treatment strategies in TP53m MPN. Characteristics of patients with TP53 m MPN. Variable Pooled variables (95% CI) Age 61.18 years (57.18–65.17) Male/Female 58% (53–63)/42% (53–63) TP53 mutation in the cohort 3% (0–15) TP53 in MF/AP/BP 10% (CI 4–24) Primary myelofibrosis 35% (13–65) MPN in AP/BP 33% (26–41) Essential thrombocythemia 10% (CI 3–28) Polycythemia vera 8% (CI 4–14) Multi-hit/single-hit TP53 52% (CI 40–64) 47% (CI 34–60) TP53 VAF 37.48% (30.73–44.24) Abbreviations: MF: Myelofibrosis, AP: accelerated phase, BP: Blast phase, MPN: myeloproliferative neoplasm, VAF: Variant Allele Frequency.

Background Patients with substance use disorder (SUD) have high rates of hospitalization, readmission, and prolonged lengths of stay. Objectives To conduct a systematic review and meta-analysis of the impact of addiction consult services in the inpatient setting for patients with SUD. Methods Five databases were systematically searched from their earliest available records through January 2025. Two authors independently screened articles, extracted data, and assessed the quality of each study with the Newcastle-Ottawa Scale for observational studies and the Cochrane risk-of-bias tool for randomized clinical trials. Pooled odds ratios (ORs) with 95% CIs were calculated for dichotomous outcomes, and mean differences were calculated for continuous outcomes. Results The search retrieved 20 studies that met inclusion criteria. The intervention for all studies was an addiction medicine consult, but the definition of this consult varied. The meta-analysis did not detect statistically significant differences in hospital length of stay, hospital readmission, or emergency department visits at 1 year among patients who received the consult compared with those who did not; however, many of these outcomes were likely underpowered. However, addiction medicine consults significantly improved the odds of inpatient initiation of medication for SUD (OR, 7.30; 95% CI, 3.30-16.13; P <.001) and postdischarge SUD treatment linkage and adherence (OR, 3.31; 95% CI, 2.06-5.32; P <.001). Conclusion Inpatient addiction consult services are associated with increased inpatient initiation of medication for SUD treatment and postdischarge treatment linkage and adherence. No clear association was identified between the consult and readmissions, emergency department utilization, or length of stay.

Abstract Background: Plasmacytoid dendritic cell-associated acute myeloid leukemia (pDC-AML) is an emerging, rare subtype of AML characterized by the clonal proliferation of plasmacytoid dendritic cells (pDCs) at various stages of maturation. Although infrequent, this leukemia subtype is clinically aggressive and poses significant diagnostic and therapeutic challenges. Objective: This review synthesizes current knowledge on the immunophenotypic, genetic, and clinical features of pDC-AML, explores its prognostic implications, and compares it with the related entity blastic plasmacytoid dendritic cell neoplasm (BPDCN). Methods: A comprehensive literature search was conducted using databases including PubMed, Scopus, and Web of Science. Studies describing the morphology, immunophenotype, cytogenetics, molecular alterations, clinical presentation, and treatment outcomes of pDC-AML were included. Data were extracted and compiled from 16 studies encompassing 231 patients. Results: pDC-AML predominantly affects older adults (median age ~69 years) and exhibits a male predominance (~68%). It presents with diverse AML subtypes, including AML with monocytic differentiation, minimal differentiation, and secondary AML. Bone marrow pDCs range from 2.2% to 30% and exhibit variable maturation, often expressing CD123, CD303, CD304, and variably CD34 and CD117. In contrast to BPDCN, CD56 is rarely expressed, and skin or lymph node involvement is uncommon. Genetically, pDC-AML exhibits a complex landscape. RUNX1 mutations are the most common (14–78%), possibly driving pDC lineage commitment. Additional mutations include ASXL1, DNMT3A, SRSF2, FLT3, and BCOR. Chromosomal abnormalities such as chromosome 7 deletions, trisomy 13, and MLL or CBFA rearrangements are frequently observed. Compared to BPDCN—which shows high CD56 and TCL1 expression and more frequent TET2 mutations—pDC-AML is more genetically and phenotypically heterogeneous. Therapeutic responses are inconsistent. Treatments include induction chemotherapy, hypomethylating agents (e.g., azacytidine plus venetoclax), and allogeneic hematopoietic stem cell transplantation (allo-HSCT). Median overall survival ranges from 9.6 to 20 months, with frequent relapse even post-HSCT. Emerging therapies targeting CD123 (e.g., tagraxofusp) and immune-modulating agents are under investigation. Conclusion: pDC-AML is a clinically aggressive and biologically distinct AML subtype defined by clonal pDC expansion, frequent RUNX1 mutations, and suboptimal responses to current therapies. Accurate diagnosis relies on integrated immunophenotypic and genetic profiling. Despite progress, patient outcomes remain poor, underscoring the need for improved classification, prognostic markers, and targeted therapeutic strategies.

Background and Aim: Iron deficiency (ID) is a common condition worldwide, affecting about one-third of the population, and is particularly prevalent in heart failure (HF) patients. In HF, ID worsens symptoms such as fatigue and shortness of breath, contributing to higher hospitalization rates and mortality. Intravenous (IV) iron therapies like Ferric Carboxymaltose (FCM) and Ferric Derisomaltose (FDI) have effectively enhanced symptoms and improved quality of life. This meta-analysis examines the safety and efficacy of these iron treatments. Methods: A comprehensive literature search was conducted using PubMed, Clinical Trial.gov, and Cochrane Library databases from inception to May 2024 to identify relevant studies. All statistical analyses were conducted using R statistical software version 4.1.2. Our protocol was registered with PROSPERO (CRD#CRD42023469246). Our study included Randomized Controlled Trials (RCTs). The primary outcomes of our study includes major adverse events such as Cardiovascular Mortality, All-Cause Death, heart failure hospitalization rate, KCCQ, LVEF, MLHFQ3, and Peak Oxygen Consumption (pVO2). Results: Twenty-four RCTs with 11,333 participants were analyzed. The pooled analysis indicated that All-cause mortality risk reduction was observed with FCM [RR=0.89; 95% CI: 0.75–1.04] and FDI [RR=0.95; 95% CI: 0.81–1.12]. FCM significantly reduced composite outcomes of hospitalization for HF or cardiovascular mortality [HR=0.74; 95% CI: 0.59–0.93], while FDI showed modest effects [HR=0.86; 95% CI: 0.56–1.26]. Kansas City Cardiomyopathy Questionnaire scores improved notably with FCM [MD=5.21; 95% CI: 2.22–8.19]. Left Ventricular Ejection Fraction improvement was highest with Iron Sucrose [MD=2.92; 95% CI: 1.61–4.21]. For the Minnesota Living with Heart Failure Questionnaire (MLHFQ), Iron Sucrose also showed the most improvement [MD = -18.00; 95% CI: -38.52 to 2.52], followed by FCM and FDI. In peak oxygen consumption (pVO2), FCM exhibited modest benefits [MD = 1.25; 95% CI: -2.34 to 4.84]. The six-minute walk test (6MWT) results identified Ferrous Sulphate as the most effective [MD = 53; 95% CI: -18.85 to 124.85], followed by FCM. Conclusion: This highlights Ferric Carboxymaltose as a promising iron therapy for heart failure patients with iron deficiency. However, clinical decisions should consider patient factors, tolerability, and cost-effectiveness. Further long-term studies are needed to optimize treatment and prevent hospitalization.

Significant progress has been made in treating Coronavirus disease (COVID) – an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). An ominous turn in the pandemic is the evolving public health crisis emanating from persistent SARS-CoV-2 infection and its associated long-term impact. Long COVID or post–COVID syndrome describes protean symptoms that persist at least 3 months after the onset of acute illness and last for at least 2 months in individuals with a history of confirmed SARS-CoV-2 infection. Long COVID has become a public health concern. Millions of infected individuals are now facing chronic multi-organ failures, including neuropsychiatric, cardiovascular, pulmonary, and kidney complications. In general, the cause of long COVID syndrome is unclear but factors such as prolonged activation of immune responses, and viral persistence triggering transcription dysregulation of genes associated with normal thrombotic disease may play a role in cardiovascular complications. Although inflammatory biomarkers are reported in other disorders, it remains unclear whether similar biomarkers are associated with cardiovascular manifestations following COVID. Medications such as sulodexide directed at glycocalyx and coagulation have demonstrated benefits for long COVID in smaller studies. Here, we describe the outcomes of the symposium on the underlying cardiovascular mechanisms of the long COVID.

There is an increased risk of infection in patients with cancer that results in higher morbidity and mortality. Several risk factors can predispose these patients to infectious complications. Some such factors include immunocompromised states like neutropenia, allogeneic hematopoietic cell transplantation, and graft-versus-host disease, while others include immunosuppressive agents like corticosteroids, purine analogs, monoclonal antibodies, and other emerging cancer therapeutics like CAR T-cell therapy. The NCCN Guidelines for the Prevention and Treatment of Cancer-Related Infections address infection concerns that may be observed in these immunocompromised populations and characterize the major pathogens to which patients with cancer are susceptible, with a focus on the prevention, diagnosis, and treatment of major common and opportunistic infections. This paper highlights 2 recently updated sections of the guidelines, namely, infection concerns related to CAR T-cell therapy and antimicrobial prophylaxis recommendations, including vaccination, in patients at high-risk for infections.