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Donation after circulatory death (DCD) liver transplants (LTs) are associated with increased risk of post-LT acute kidney injury (AKI). This retrospective study aimed to examine the effect of continuous normothermic machine perfusion (NMP) on the incidence and stage of AKI in DCD LT. The incidence of AKI within 48 hours was compared between 507 NMP-DCD and 472 static cold storage (SCS)-DCD LT transplanted between January 1, 2016, and December 31, 2024. AKI developed in 337 (34%) patients. On univariate analysis, AKI rate was lower in NMP-DCD compared with SCS-DCD (28% vs. 41%, p <0.001). Stages 2 and 3 AKI at 48 hours and renal replacement therapy (RRT) within the first 3 weeks were also lower in NMP-DCD compared with SCS-DCD ( p <0.001). After adjusting for multiple recipient, donor, and intraoperative factors using multivariate logistic regression, NMP-DCD was independently associated with a 37% lower odds of AKI (aOR: 0.63, CI: 0.46–0.85, p =0.003) and 55% lower odds of stages 2 and 3 AKI (aOR: 0.45, CI: 0.29–0.69, p <0.001) compared with SCS-DCD. To mitigate for the era effect and other unmeasured confounders, an inverse probability of treatment weighting (IPTW) analysis was performed using a propensity score model with average treatment effect (ATE). After weighting for multiple factors, NMP-DCD was associated with lower odds of AKI at 48 hours (OR: 0.65, CI: 0.53–0.81, p =0.001), stages 2 and 3 AKI at 48 hours (OR: 0.60, CI: 0.42–0.85, p =0.02), and RRT at day 7 (OR: 0.31, CI: 0.13–0.65, p =0.003) compared with SCS-DCD. In conclusion, compared with SCS-DCD, NMP-DCD was independently associated with lower odds of AKI at 48 hours, of stages 2 and 3 AKI at 48 hours from LT, and of RRT requirement at day 7 from LT, an effect that extended for the first 3 post-LT weeks.

Importance Ischemic heart disease (IHD), the leading cause of death in the US, is predominantly due to modifiable risk factors. Estimates of IHD mortality attributable to risk factors provide evidence for health policy decision-making. Objective To estimate the burden of IHD death attributable to risk factors in the US from 1990-2023. Design, Setting, and Participants The Global Burden of Disease Study 2023 (GBD 2023) used vital records and a broad set of epidemiologic data to estimate IHD death rates, risk factor exposure, and relative risk curves for risk-outcome pairs for 1990-2023 for the general population. Data analysis was performed from October 2024 to December 2025. Exposure Twelve metabolic, behavioral, and environmental risk factors. Main Outcomes and Measures The primary outcomes were IHD death rates per 100 000 persons, counts, and attributable risks from 1990-2023 by age, sex, and US state. Estimates include 95% uncertainty intervals (UI). IHD death rates were estimated using ensemble modeling methods. Risk exposures were estimated using bayesian meta-regression methods. Relative risks were estimated following the Burden of Proof framework. Results In 2023, there were 473 000 IHD deaths (95% UI, 414 000-510 000) in the US, a decrease of 58.7% (95% UI, 56.8%-61.0%) in age-standardized rate since 1990. Between 2010 and 2023, there was a 19.0% decrease (95% UI, 15.0%-22.9%) for males and a 24.5% decrease (95% UI, 20.3%-29.7%) for females in IHD death rates. High systolic blood pressure (SBP), dietary risks, and high low-density lipoprotein cholesterol (LDL-C) were the leading risk factors for IHD deaths in 2023, accounting for 47.2% (95% UI, 36.4%-57.0%), 38.6% (95% UI, 17.2%-56.8%), and 28.5% (95% UI, 19.3%-39.6%) of IHD deaths, respectively. Increased exposure to several risk factors substantially increased their attributable burden for IHD deaths in 2023, with high fasting plasma glucose (FPG) increasing 38.8% (95% UI, 11.5%-81.1%) and high body mass index (BMI) increasing 54.5% (95% UI, 41.8%-66.3%) since 1990. Smoking and particulate matter pollution had the greatest decrease in attributable IHD mortality since 1990, at 33.3% (95% UI, 23.6%-41.7%) and 74.9% (95% UI, 46.7%-88.8%), respectively. Conclusion and Relevance Per the results of this systematic analysis of GBD 2023, a total of 88.7% (95% UI, 83.4%-92.5%) of IHD deaths were attributable to modifiable risk factors in the US in 2023, with high SBP, dietary risks, and high LDL-C being the greatest contributors. High BMI and high FPG showed the largest attribution increases, while exposure to other risks did not increase significantly for the population.

Abstract INTRODUCTION We integrate visual and quantitative metrics in white matter and medial temporal lobe to examine relationships with neuropathology in a community cohort. METHODS Postmortem in situ MRI (T1, T2, DWI) was performed in 25 human brains, followed by visual ratings (Fazekas, MTA, ERICA, Koedam). Neuropathology included ADNC, LATE-NC, hippocampal sclerosis, PART, ARTAG, Lewy pathology, and CAA. RESULTS Increased Fazekas score was linked to aging, lower education, hypertension, higher basilar artery wall thickness, and greater Braak NFT stage. WMH volume also correlated with lacunes, Thal phase, and CERAD score that was not observed using Fazekas. Hippocampal volumes were lower in elderly, less educated people and were associated with higher atrophy scores and higher Braak NFT stage. Higher amygdala volume was only associated with higher CERAD score. DISCUSSION Quantitative MRI may detect neuropathologic associations more sensitively than visual ratings. Tau pathology is a key predictor of WMH burden and hippocampal atrophy.

Abstract Background Central venous catheterization (CVC) is a fundamental procedural competency in pulmonary and critical care medicine (PCCM). Although commercially available task trainers are effective for teaching CVC placement, their high cost and logistical requirements can limit access to repeated practice. Objective To evaluate learner and faculty perceptions and usability of a newly developed CVC simulation model compared with a standard commercial task trainer and detail the technical report of the novel model’s construction. Methods We conducted a prospective educational evaluation during the PCCM CVC workshop. Participants practiced CVC placement with both the standard commercial trainer and a locally constructed simulation model developed at our institution. Teaching faculty were asked to evaluate both models from an instructional standpoint. Results Eighteen participants (15 PCCM 1st year fellows and 3 faculty instructors) evaluated the novel CVC simulation model. All fellows (n = 15, 100%) preferred the new model over a standard commercial model, with 14 (93%) reporting improved understanding of CVC insertion steps and 11 (73%) noting ease of ultrasound landmark identification. All fellows (n = 15, 100%) endorsed inclusion of the model in future workshops. Additionally, faculty instructors preferred the novel model for teaching (n = 3, 100%). All faculty supported future use of the model. The initial model development cost was approximately $288.96 with most materials’ reusable. Conclusions The novel task-aligned CVC simulation model offers a realistic, reusable, and cost-effective alternative to commercial simulators, with high learner and faculty preference and strong educational value. Its functional alignment supports integration into fellowship training, with future studies needed to assess objective skill acquisition and retention.

ABSTRACT Background Inflammatory bowel disease (IBD) and myeloproliferative neoplasms (MPNs) share chronic inflammation and immune dysregulation. Aim We evaluated the incidence of MPNs among patients with IBD and clinical outcomes of IBD–MPN coexistence. Methods Two retrospective cohort analyses were conducted using the TriNetX database. First, adults with ulcerative colitis (UC) or Crohn's disease (CD) were compared with matched non‐IBD controls to estimate incident MPN risk. A coexistence second analysis included patients with UC or CD who developed MPNs and then were matched to IBD without MPN controls to assess 5‐year outcomes, including IBD‐related complications, surgical interventions, colorectal cancer (CRC) and primary sclerosing cholangitis (PSC). Medication subgroup analyses were performed to evaluate associations with MPN risk. Results After matching, 3873 patients with UC–MPN and 3474 patients with CD–MPN were included. Compared with matched non‐IBD controls, incident MPN risk was higher in UC (HR 1.60, p = 0.01) and CD (HR 1.56, p < 0.001). In CD, MPN coexistence was associated with higher risks of CRC (HR 1.52, p = 0.012), intestinal fistula (HR 2.84, p < 0.001), obstruction (HR 2.05, p < 0.001), perforation (HR 2.37, p < 0.001), small bowel resection (HR 3.69, p < 0.001) and colectomy (HR 2.10, p < 0.001). In UC, MPN coexistence was associated with higher risks of CRC (HR 1.50, p = 0.001), PSC (HR 1.75, p = 0.03) and pouchitis (HR 1.68, p = 0.003). Exposure to thiopurines (HR 1.28, p < 0.001) was associated with increased MPN risk, whereas TNF, IL‐23 and JAK inhibitors were not. Conclusions IBD is associated with increased MPN risk, and IBD–MPNs coexistence is associated with worse IBD‐related complications and malignancy risk.

Background Accreditation Council for Graduate Medical Education (ACGME) requires internal medicine (IM) residents to perform procedures considered “essential for the area of practice.” However, no guidelines or best practices exist for teaching these skills. To address this gap, a procedure training workshop (PTW) was developed. Methods IM residents attended a PTW where they practiced paracenteses, lumbar punctures (LPs), and central venous catheter (CVC) placement on ultrasound-compatible task trainers. The PTW was assessed using pre- and post-session tests and surveys. To evaluate translation into clinical practice, procedure volume, success rates, and immediate complications were tracked. Results Following implementation of the PTW, resident knowledge assessment scores increased from 67.4% to 84.1% (p < 0.001). More residents reported feeling “well-prepared” to perform or “teach others” procedures (CVC 69% from 31%, p < 0.01; LP 71% from 8%, p < 0.05; paracentesis 80% from 28%, p < 0.05) and able to perform all steps without assistance or model (CVC 54% from 28%; LP 49% from 17%, p < 0.01; paracentesis 66% from 25%, p < 0.01). Paracenteses increased from 71 (2020) to 119 (2021) to 143 (2024), while LPs increased from 87 (2020) to 156 (2021) to 135 (2024). Success rates remained stable across procedures: paracentesis (91.5% to 94.1% to 93.7%), LP (58.6% to 55.8% to 52.6%), and CVC placement (95.5% to 97.6% to 94.9%). Conclusions PTW is a valuable half-day session that equips early residents with essential procedural knowledge and hands-on practice that translates into sustained increases in bedside procedure volume.

Premature ventricular contractions (PVCs) are common arrhythmia encountered in patients with and without structural heart disease. Although often benign and asymptomatic, they may also cause palpitations, exercise intolerance, presyncope, and reduced quality of life, and in some patients can contribute to PVC-induced cardiomyopathy or trigger malignant ventricular arrhythmias. Their clinical significance depends on symptom burden, PVC frequency, ventricular function, and the presence of underlying myocardial disease. Diagnostic evaluation includes electrocardiography, ambulatory rhythm monitoring, echocardiography, exercise testing, and cardiac magnetic resonance imaging for tissue characterization and risk stratification. Management ranges from reassurance and lifestyle modification to pharmacologic therapy and catheter ablation. Beta-blockers and nondihydropyridine calcium channel blockers remain common first-line options, whereas antiarrhythmic drugs may be considered in carefully selected patients. Catheter ablation is an effective treatment for symptomatic PVCs, high PVC burden, and PVC-induced cardiomyopathy, with high procedural success rates and favorable effects on arrhythmic burden and ventricular function. Novel approaches, including electrocardiographic imaging-guided planning, pulsed field ablation, stereotactic radioablation, neuromodulation, and renal denervation, may further expand future therapeutic options. This review summarizes the pathophysiology, clinical implications, diagnostic evaluation, and contemporary management of PVCs, with emphasis on medical therapy, catheter ablation, and emerging treatments.

Abstract: Cardiovascular disease (CVD) remains the leading cause of death worldwide. While advances in treatment have improved outcomes, the greatest gains in public health will come from primary prevention. Risk stratification is the foundation of CVD prevention. Traditional tools, such as pooled cohort equations (PCEs) and SCORE2, do not capture non-traditional risk factors and individual variability, driving efforts to refine existing approaches. We critically discuss emerging risk determinants for primary CVD prevention. Coronary artery calcium scoring can reclassify CVD risk but has limitations related to cost, access, and unvalidated improvements in clinical endpoints. Biomarkers such as apolipoprotein B and lipoprotein(a) may identify residual risk beyond LDL-C, particularly in patients with lipid discordance, but remain underused due to uncertain thresholds and the lack of prospective triallevel outcome data. Trials of colchicine in primary prevention have yielded mixed results, making the role of targeting inflammation unclear in CVD prevention. Polygenic risk scores can stratify genetic risk but face challenges in sensitivity, specificity, and generalizability. Multiomics approaches, while offering the promise of deeper phenotyping, lack established clinical applications and consensus on when their use is appropriate. Artificial intelligence may allow better prediction across cohorts but requires broader validation. Clonal hematopoiesis of indeterminate potential, a marker of inflammation and age-related CVD risk, lacks evidence supporting routine screening or intervention in younger, asymptomatic individuals. The proliferation of new risk stratification tools poses a key challenge: determining when additional data meaningfully alter clinical decisions. Until robust outcome-based evidence emerges, risk enhancers should guide, but not dictate, therapy in selected patients.

Abstract Introduction Bipolar disorder (BD) has been associated with increased medical burden and accelerated biological aging. Long non-coding RNAs (lncRNAs) regulate molecular pathways related to cellular senescence, inflammation, and telomere maintenance, which are implicated in both BD and aging. This study examined whether aging-related lncRNA expression reflects familial vulnerability or illness-specific effects, and whether childhood trauma and lifestyle factors modulate these signatures within a gene–environment framework. Methods In this cross-sectional study, expression levels of aging-related lncRNAs, including Antisense Non-coding RNA in the INK4 Locus (ANRIL), HOX Transcript Antisense Intergenic RNA (HOTAIR), Nuclear Enriched Abundant Transcript 1 (NEAT1), Taurine Upregulated Gene 1 (TUG1), Metastasis-Associated Lung Adenocarcinoma Transcript 1 (MALAT1), Growth Arrest-Specific 5 (GAS5), and Telomerase RNA Component (TERC), were measured in peripheral blood mononuclear cells (PBMCs) from individuals with bipolar disorder (BD) (n=68), siblings without BD diagnosis (SIB) (n=54), and healthy controls (HC) (n=70) using quantitative reverse transcription polymerase chain reaction (RT-qPCR). Childhood trauma and lifestyle were assessed using the Childhood Trauma Questionnaire (CTQ) and the Healthy Lifestyle Profile II (HPLP-II). Principal component analysis generated a composite aging-related lncRNA factor. Results At the individual transcript level, NEAT1 and TERC were elevated, whereas GAS5 was reduced, in both BD and SIB relative to HC. The aging-related lncRNA composite score was higher in BD and SIB than in HC (F = 7.315, p = 0.001). Familial liability to BD (presence vs. absence of familial liability ) showed a significant main effect on the composite score (F(1,182)=8.18, p=0.005) and interacted with childhood trauma (F(1,182)=10.14, p=0.002). In multivariable models, total CTQ and physical neglect were independently associated with lower composite scores, while familial liability remained a positive predictor (all p<0.001). Conclusions Aging-related lncRNA alterations mark familial vulnerability to BD and are shaped by childhood trauma within a gene–environment interaction framework.