Clinical trial recruitment continues to fail at scale, with eligible patients often invisible to routine screening despite being present in electronic health records. Disease stage, treatment response, biomarker results, and clinical reasoning are frequently documented in narrative form rather than structured fields, placing eligibility-relevant information beyond the reach of conventional recruitment workflows. This narrative review examines applications of artificial intelligence (AI), and particularly large language models, across the recruitment pipeline. The evidence is organized around two ceilings. The discovery ceiling reflects the limits of identifying eligible candidates in clinical data, and current evidence suggests AI can raise it, improving discovery and screening efficiency in defined workflows. The enrollment ceiling reflects the human, logistical, ethical, and institutional barriers that persist after a patient has been identified. AI can make invisible patients visible, but visibility is not enrollment, and AI alone cannot remove these barriers. Upstream applications in trial design, predictive enrichment, site selection, and patient-facing engagement are also reviewed, together with governance requirements for equity, privacy, regulation, and workflow integration. Current evidence remains concentrated in retrospective evaluations, with limited prospective, multicenter validation and few demonstrated gains in enrollment, representativeness, or cost effectiveness. Recruitment AI is therefore best treated as a governed, human-supervised support tool that is locally validated and evaluated against downstream outcomes such as enrollment, diversity, burden, and cost.

BACKGROUND: Indoor solid fuels, outdoor air pollution (PM, PM, and PM), and heatwave are all modifiable environmental factors. However, their mixed effects on Cardiometabolic Multimorbidity (CMM) and its core component diseases (diabetes, heart disease, and stroke) remain unclear. METHODS: In this study, four diseases analysis cohorts (CMM: n = 10,273; diabetes: n = 9,893; heart disease: n = 9,536; and stroke: n = 10,466) were constructed using data from the five waves (2011, 2013, 2015, 2018, and 2020) of the CHARLS. A time-varying Cox proportional hazards model was used to estimate the hazard ratio (HR) for environmental factor exposure. The Cumulative Risk Index (CRI) and the Quantile g-computation (Qgcomp) model were employed to assess the cumulative effect and component weights of coexposure to multiple environmental factors. RESULTS: The single-exposure analysis indicated that indoor solid fuels use significantly increased heart disease (HR = 1.118, 95% CI 1.016-1.231) and stroke (HR = 1.149, 95% CI 1.007-1.310) risks. PM, PM, and PM were the most consistent risk factors for CMM, diabetes, and heart disease (all HRs > 1, P < 0.001), and heatwave was sometimes associated with higher risks of CMM, diabetes, and heart disease. The CRI analysis demonstrated that coexposure to multiple environmental factors increased the CMM, diabetes, and heart disease risks. The Qgcomp model further showed that these coexposure increased the risk of four diseases, with ORs (95% CIs) (CMM:1.650, 1.375-1.979; diabetes: 1.675, 1.475-1.903; heart disease: 1.228, 1.080-1.397; stroke: 1.205, 1.011-1.437), with indoor solid fuels use as the primary contributor. CONCLUSIONS: In conclusion, long-term coexposure to indoor solid fuels, outdoor air pollution, and heatwave increased the risk of CMM and its core component diseases. Indoor solid fuels play a main role in these effects.

Curcumin, a natural polyphenol derived from turmeric, possesses potent antioxidant properties and represents a potential cardioprotective agent capable of mitigating myocardial oxidative stress associated with rheumatoid arthritis (RA). The aim of the study was to examine the cardioprotective effect of curcumin in an experimental model of rheumatoid arthritis. The study included 104 female Wistar albino rats, divided into 8 groups (n = 13 in each group): (1) CTRL (negative control, healthy rats without treatment), (2) CUR (positive control 1, curcumin 200 mg/kg three times a week for 4 weeks orally), (3) MTX (positive control 2, methotrexate 0.75 mg/kg twice a week for 4 weeks intraperitoneally), (4) RA (positive control 3, rats with Complete Freund's adjuvant (CFA)-induced RA), (5) RA+pCUR (rats with preventive administration of curcumin + CFA-induced RA), (6) RA+tCUR (rats with CFA-induced RA + therapeutic administration of curcumin), (7) RA + MTX+pCUR (rats with preventive administration of curcumin + CFA-induced RA + methotrexate), (8) RA + MTX+tCUR (rats with CFA-induced RA + therapeutic administration of curcumin + methotrexate). Pro-oxidant levels were determined in coronary venous effluent, antioxidant enzyme activities were assessed in heart tissue homogenates, and histopathological analyses of the synovium and myocardium were performed. Curcumin, particularly in the therapeutic regimen and in combination with methotrexate, significantly reduced pro-oxidant levels and lipid peroxidation. Curcumin also increased superoxide dismutase activity and restored reduced glutathione levels, whereas improvement in catalase activity was observed predominantly in the therapeutic regimens. Histopathological analyses demonstrated that curcumin exerted a protective effect on both synovial and myocardial tissues, attenuating RA-induced structural damage, reducing edema, and preserving myocardial architecture. These findings suggest that curcumin improves myocardial redox homeostasis and may contribute to cardioprotection in experimental RA.

Beta-blockers (BB) are a core treatment in adult heart failure (HF) guideline directed medical therapy with evidence of reductions in mortality and HF hospitalizations. The optimal timing of BB initiation in children remains difficult to determine due to possible hemodynamic effects. We sought to analyze outcomes of pediatric HF readmission or death within 30 days of discharge after ambulatory vs. inpatient BB initiation. This retrospective analysis utilized the Advanced Cardiac Therapies Improving Outcomes Network HF registry to compare outcomes in patients with BB initiation during inpatient or outpatient encounters. Patients were excluded if BB initiation occurred prior to admission. In total, 94 patients were started on BB therapy with 69 (73.4%) during inpatient admission and 25 while outpatient. There was no difference in age or cardiac diagnosis between groups with dilated cardiomyopathy being predominant in both groups (56.5% v 36%). Both groups had similar baseline EF (33% vs. 34%, p = 0.983) and NYHA classification at time of initiation with majority being NYHA 3 or 4 (66.1% v 62.5%). There was no difference (p = 0.278) in re-admission rate between those initiated on BB inpatient (n = 10; 14.5%) vs. those initiated on BB outpatient (n = 1; 4%). There were no deaths within 30 days of discharge in either group. Initiation of pediatric BB therapy in children admitted for HF appears to be safe in both the inpatient and outpatient setting with no difference in 30-day readmission or mortality using this dataset. Continued evaluation with a larger accrual of data will be important.

PURPOSE: The CIRSE Emprint Microwave Ablation (MWA) Registry (CIEMAR) was designed to evaluate real-world effectiveness of MWA for colorectal liver metastases (CRLM). This analysis reports on local tumour control and includes post-hoc analyses of ablation margin size and confirmation software use. MATERIALS AND METHODS: Patients were eligible if MWA was indicated as part of a curative-intent strategy for ≤9 local treatment-naïve CRLM measuring ≤3 cm, with no extrahepatic disease except ≤5 lung nodules. Baseline, treatment and follow-up data from September 2019 to December 2025 were analysed. Ablation margin categories were reported locally according to centre-specific practice. The primary endpoint was the 1-year local tumour control rate after the last MWA. RESULTS: In total, 491 patients with 1083 CRLM from 30 sites in 11 countries were included. Reported margins were <5mm (12.3%), 5-10mm (35.5%) or >10mm (44.5%); for 1.5% and 6.2% of lesions, ablation was incomplete and data were missing, respectively. The 1-year local tumour control rate was 88.9% (95% CI 83.2-94.6) on a per-lesion basis and 81.2% (95% CI 77.2-84.6) on a per-patient basis. Larger margins were independently associated with lower odds of local failure (5-10 mm: OR 0.30; >10 mm: OR 0.10; both p<0.01 vs <5 mm). Use of confirmation software was associated with wider reported margins (p<0.001). CONCLUSION: MWA for CRLM achieved high 12 month local tumour control. These findings support routine verification that adequate ablation margins have been achieved, while exploratory association between confirmation software use and wider margins warrants further confirmation. TRIALS REGISTRATION: NCT03775980.

The concomitant use of ceftriaxone and proton pump inhibitors (PPIs) is common in hospital practice. However, it is unclear whether individual PPIs differ in their effects on QT interval prolongation, ventricular arrhythmia, or cardiac arrest, collectively termed as QVC events. We conducted a two-stage, real-world study. First, we screened the United States Food and Drug Administration Adverse Event Reporting System (FAERS) and the Canada Vigilance Adverse Reaction (CVAR) database with standard disproportionality measures (reporting odds ratio and proportional reporting ratio) and six drug-drug interaction (DDI) algorithms to identify combination signals that exceeded component signals. Second, we validated signal-positive combinations in the Medical Information Mart for Intensive Care IV (MIMIC-IV) intensive care unit (ICU) electronic health record (EHR) cohort by assembling adult inpatients with overlapping ceftriaxone-PPI exposures. The primary outcome was 28-day QVC events. Multivariable Cox proportional hazards models were the main analysis and complemented by propensity score matching, inverse probability of treatment weighting, and Fine-Gray competing-risk models. To address external generalisability, an additional validation was performed using ECG-ViEW II, an Asian electrocardiogram-linked real-world database. The combination of ceftriaxone and lansoprazole was significantly associated with QVC events, revealing notable DDIs (e.g., in FAERS, Ω025 = 0.54). To validate these findings, a cohort of 5,594 patients receiving ceftriaxone combined with PPIs from the MIMIC-IV database was analyzed using Cox proportional hazards models. The analyses corroborated the initial findings (lansoprazole vs. other PPIs, multivariate HR = 1.30; 95% CI: 1.10-1.54), with the risk associated with the three PPI combinations ranked as lansoprazole > pantoprazole > omeprazole. ECG-ViEW II provided supportive Asian external validation, showing a higher QVC risk for ceftriaxone plus lansoprazole than for ceftriaxone plus other PPIs. Evidence from two national pharmacovigilance systems and an ICU EHR cohort indicated that PPI choice modified cardiac safety during ceftriaxone therapy. Lansoprazole co-use confers a higher risk of QVC, whereas omeprazole appears relatively safer. Therefore, prospective confirmation is warranted.

BACKGROUND: Evidence remains limited on how PM-related mortality risk has evolved under sustained air-quality improvement following the implementation of the Clean Air Action (CAA), and how such changes have influenced related health benefits. This study aimed to investigate temporal changes in short-term PM-related cardiorespiratory mortality associations and to quantify the respective contributions of PM concentration reductions and risk changes to mortality outcomes. METHODS: We conducted a multi-county time-series study in the Sichuan Basin, China, covering the period from 2014 to 2022. An extended two-stage analytical framework was applied to estimate county -specific PM-mortality associations, followed by pooled analyses. Longitudinal meta-regression was used to assess annual trends in excess risk (ER), and period-specific analyses were performed across different stages of the CAA. Scenario analyses were conducted to quantify mortality changes attributable to PM concentration reductions and to temporal changes in the exposure-response relationship. RESULTS: A significant nonlinear temporal pattern in ER per 10 μg/m increase in PM was observed (P < 0.001), characterized by an increase during 2014-2016, a decline during 2017-2019, and an increase again during 2020-2022. Corresponding ERs for the three periods were 0.7% (95% CI: 0.6%-0.9%), 0.4% (95% CI: 0.3%-0.6%), and 1.4% (95% CI: 1.2%-1.6%), respectively. Declining PM concentrations were associated with 52,831 fewer cardiorespiratory deaths, whereas changes in ER increased mortality by 10,041 deaths. The later period increase in risk was consistently observed across sexes and was more pronounced among individuals aged 65 years and older. CONCLUSIONS: Temporal increases in short-term PM-related mortality risk partially offset the health benefits achieved through reductions in PM concentrations during the later CAA period. These findings highlight the importance of incorporating time-varying health risk and population vulnerability into evaluations of air quality policies.

The Global Registry of Acute Coronary Events (GRACE) 2.0 risk score has been recommended in guidelines to orient therapeutic strategy and risk assessment for non-ST-segment elevation acute coronary syndrome (NSTE-ACS). To evaluate the incremental value of computed tomography (CT)-based coronary atherosclerosis plaque burden to GRACE 2.0 score in refining the intermediate-term prognostic accuracy and risk stratification for emergency NSTE-ACS. In this prospective cohort study, from January 2017 to January 2021, NSTE-ACS individuals were enrolled and randomly divided into a developing and validation sets by 7:3. We estimated the correlations between GRACE 2.0 score and CT findings. The primary outcomes are the incremental prognostic value of CT for the GRACE 2.0 score's efficacy in predicting 3-year mortality or myocardial infarction (MI). A total of 1248 consecutive NSTE-ACS patients undergoing CT scans were prospectively included. The risk of 3-year mortality or MI was greater in the higher CACS category (HR, 2.31 [95% CI, 1.45-3.67]), SIS category (HR, 3.37 [95% CI, 2.36-4.82]) and luminal stenosis degree (HR, 1.69 [95% CI, 1.15-2.48]) stratified by CAD-RADS (coronary artery disease reporting and Data System) 2.0 than in the lower ones. The CT-GRACE model integrating CACS category, SSS and GRACE 2.0 risk score was compared with the GRACE 2.0 risk score to evaluate their discrimination and reclassification ability in predicting 3-year mortality or MI. The C-statistics were 0.889 (0.842, 0.937) and 0.742 (0.659, 0.826) in the validation set, respectively (ΔAUC=0.147, P < 0.001). Coronary atherosclerosis plaque burden features could provide more meaningful information for GRACE 2.0 risk score to evaluate the intermediate-term prognosis for emergency NSTE-ACS.

PURPOSE: IVC segmental resection (SR) during robot-assisted radical nephrectomy and IVC thrombectomy (RARN-IVCT) is selected for wall invasion, occlusion, and collateral outflow, making direct comparison with non-segmental resection (NSR) biased. We compared the perioperative and renal safety of SR versus NSR in the overlap population. METHODS: Retrospective single-center cohort at Peking University Third Hospital (2014-2025): 120 patients with RCC and Mayo level II-IV IVC thrombus undergoing RARN-IVCT, including 45 SR and 75 NSR. Overlap weighting balanced baseline variables. Primary outcomes were AKI, ΔSCr, and ΔeGFR; secondary outcomes were complications and hospital stay, with OS assessed exploratorily. RESULTS: After weighting, no statistically significant differences were observed in AKI, ΔSCr, ΔeGFR, complications, hospital stay, or OS. SR had lower RBC transfusion volume (mean difference - 249.63 mL, 95% CI - 443.20 to - 56.05; P = 0.011). SR met non-inferiority/equivalence for hospital stay and pneumonia; renal non-inferiority was not established. Limitations include retrospective design, limited effective sample size, and unmeasured anatomic/hemodynamic confounding. CONCLUSION: In overlap patients, no statistically significant differences in renal or safety/recovery outcomes were observed, but neither renal non-inferiority nor equivalence was established. Planning should consider thrombus-wall interaction, caval patency, collateral outflow, and renal reserve.

OBJECTIVE: To examine the association between shift work and all-cause and cause-specific mortality in the U.S. population and assess whether biological age acceleration mediates this relationship. DESIGN, SETTING, AND PARTICIPANTS: A prospective cohort study included 7548 adults from the National Health and Nutrition Examination Survey (NHANES) 2005-2010, with mortality follow-up through 2019. EXPOSURE: Shift work included regular night, evening, or rotating shifts versus daytime schedules. MAIN OUTCOMES AND MEASURES: Primary outcomes were all-cause, cardiovascular (CVD), and cancer mortality. RESULTS: Among 7548 participants (mean follow-up 11.6 years), 358 deaths occurred. Shift work was associated with significantly increased all-cause mortality after full adjustment (HR = 1.52; 95% CI 1.09-2.13). CVD and cancer mortality associations were non-significant. No statistically significant interactions were observed in subgroup analyses of all-cause mortality. Shift workers showed greater PhenoAge acceleration (β = 0.39 years), which statistically accounted for 6.18% of the association between shift work and all-cause mortality. CONCLUSIONS AND RELEVANCE: Shift work was associated with higher all-cause mortality and greater PhenoAge acceleration. PhenoAge acceleration may statistically account for a small proportion of this association, although causal mediation cannot be inferred.

INTRODUCTION: Heart failure with reduced ejection fraction (HFrEF), defined by a left ventricular ejection fraction ≤ 40%, remains a major global health challenge, associated with substantial morbidity, mortality, and impaired quality of life (QoL), particularly in patients with higher NYHA class. Sodium-glucose cotransporter-2 (SGLT2) inhibitors have emerged as a cornerstone therapy for HFrEF, significantly reducing hospitalizations and mortality regardless of glycemic status, sex, race, or comorbidities. METHODS: EVOLUTION-HF was an observational, multi-center, longitudinal cohort study involving 257 consecutive patients diagnosed with HFrEF who initiated dapagliflozin in a routine clinical setting in Greece. The primary objectives were to characterize baseline demographic and clinical features of patients newly initiated on dapagliflozin for HFrEF and to evaluate dapagliflozin treatment patterns, including discontinuation timing, reasons for discontinuation, and concomitant heart failure and glucose-lowering therapies over time. The secondary objectives are to describe patient-reported outcomes using the KCCQ-23 and to assess adherence to dapagliflozin among patients with HFrEF. RESULTS: A total of 257 patients were enrolled and the follow-up period lasted for 12 months. Significant improvements among all KCCQ-23 scores were observed from baseline to 12-months post dapagliflozin initiation, revealing that the initiation and optimization of guideline-directed medical therapy in routine clinical practice provides improvement to quality of life over time. CONCLUSIONS: Dapagliflozin was safe and well-tolerated throughout the observation period. Although benefits are observed in most patients, individuals aged > 65 years, with prior myocardial infarction, or recent hospitalizations show a diminished response, underscoring the need for tailored management and closer follow-up in these higher-risk groups.

BACKGROUND: Pulmonary arterial hypertension (PAH) causes substantial premature mortality and disability. Updated evidence comparing long-term PAH burden in China with the Group of Twenty (G20) aggregate remains limited. We assessed changes from 1990 to 2023 and projected future trends. METHODS: PAH estimates for China and the G20 aggregate were extracted from the Global Burden of Disease Study 2023. Outcomes included incidence, prevalence, deaths, disability-adjusted life years (DALYs), years lived with disability (YLDs), and years of life lost (YLLs), expressed as absolute counts and age-standardized rates. Temporal trends were assessed using Joinpoint regression. Sex-specific and age-specific patterns and demographic decomposition were examined. Autoregressive integrated moving average (ARIMA) models projected overall burden through 2050. Bayesian age-period-cohort (BAPC) models projected sex-specific patterns through 2038. RESULTS: From 1990 to 2023, incident and prevalent cases and YLDs increased in both settings, whereas deaths, DALYs, and YLLs declined. In China, prevalent cases increased by 63.5%, from 17,020.87 to 27,834.41, while the age-standardized death rate decreased by 74.3%, from 0.29 to 0.08 per 100,000 population. Similar declines in mortality-related age-standardized indicators occurred in the G20 aggregate. Females generally had higher age-standardized prevalence and YLD rates than males, although sex differences in mortality-related outcomes varied by setting. Absolute burden shifted toward older age groups. Population growth and aging contributed to increases in absolute burden, whereas epidemiological change generally acted in the opposite direction. Projections suggested continued declines in age-standardized mortality-related burden through 2050, alongside increases in incident and prevalent case numbers. CONCLUSION: Mortality-related PAH burden declined in China and the G20 aggregate, while absolute case numbers increased. Population growth and aging contributed to this divergence, underscoring the need for continued surveillance and long-term health-service planning.

BACKGROUND: Beta-blockers may improve outcomes in patients with chronic obstructive pulmonary disease (COPD) without cardiovascular disease, but randomized trials have been inconclusive. METHODS: This was a multicenter, open-label, pragmatic, phase 4 randomized trial. Patients 40 years of age or older with COPD, sinus rhythm, and no cardiovascular disease were randomly assigned in a 1:1 ratio to receive metoprolol, at a target dose of 100 mg daily, in addition to standard care or to receive standard care alone. The primary end point was the time to the first occurrence of a COPD exacerbation, cardiovascular event, or death during 1 year of follow-up. RESULTS: A total of 1695 patients underwent random assignment; their mean age was 70 years, and 62% were female. The primary end point occurred in 27% of patients assigned to receive metoprolol and in 30% assigned to receive standard care (hazard ratio, 0.87; 95% confidence interval [CI], 0.73 to 1.05; P=0.14). The corresponding hazard ratios were 0.88 (95% CI, 0.72 to 1.06) for COPD exacerbations, 0.73 (95% CI, 0.48 to 1.11) for cardiovascular events, 0.92 (95% CI, 0.48 to 1.77) for death, and 0.87 (95% CI, 0.58 to 1.28) for exacerbations requiring hospitalization. Serious adverse events occurred in 80 (9.4%) of 848 participants in the metoprolol group and 66 (7.8%) of 847 participants in the standard care group. Nonserious adverse events occurred in 293 (34.6%) of 848 patients in the metoprolol group and 247 (29.2%) of 847 in the standard care group. CONCLUSIONS: Among patients with COPD and no cardiovascular disease, metoprolol did not significantly improve the time to a composite of exacerbations, cardiovascular events, or death. (Funded by research grants from the Swedish Research Council and others; ClinicalTrials.gov number, NCT03566667.).

Throughout the natural history of chronic kidney disease (CKD), most patients experience fatal or non-fatal cardiovascular events. In this review, we address the role of low-density lipoprotein cholesterol (LDL-C) in the excess cardiovascular risk associated with CKD and examine the impact of both traditional and novel LDL-C-lowering therapies across the entire spectrum of CKD. Current guidelines for the prevention of atherosclerotic cardiovascular disease (ASCVD), developed by European and US cardiology societies, recommend assessment of overall cardiovascular risk to tailor the intensity of preventive strategies to the individual patient's risk profile: the higher the cardiovascular risk, the more intensive the intervention should be. Novel therapies have demonstrated efficacy in achieving lower LDL-C targets, which are often unattainable with conventional treatment. The identification of vulnerable coronary plaques, rather than the mere presence of vascular lumen narrowing, represents a promising imaging target for guiding intensified preventive strategies in high-risk populations, including patients with CKD. In CKD, cardiovascular risk progressively increases as kidney function declines. Despite clear recommendations from both nephrology and non-nephrology guidelines, initiation, maintenance, and intensification of lipid-lowering treatment, as well as achievement of LDL-C targets, remain suboptimal in the CKD population. As novel lipid-lowering therapies provide additional therapeutic options for patients with CKD, there is now a compelling need to increase awareness of cardiovascular risk and integrate lipid management into the broader, longitudinal care of patients with CKD across all stages of the disease.

Cardiovascular-kidney-metabolic (CKM) syndrome encompasses obesity, type 2 diabetes, cardiovascular disease, and chronic kidney disease. Insulin resistance has traditionally been considered the primary driver, with hyperinsulinemia viewed as a compensatory response. However, emerging evidence suggests that hyperinsulinemia may precede insulin resistance in specific phenotypes and contribute to early disease mechanisms. We conducted a narrative review of the role of hyperinsulinemia in CKM syndrome. Literature searches were performed in PubMed/MEDLINE, Embase, and Scopus through December 2025. We prioritised prospective cohort studies, meta-analyses, Mendelian randomisation studies, and randomised controlled trials, and synthesised evidence across cardiovascular, renal, and metabolic domains. Sustained hyperinsulinemia is associated with myocardial hypertrophy and fibrosis through selective preservation of mitogenic signalling, contributing to heart failure phenotypes. In the kidney, it enhances sodium and glucose reabsorption, increases intraglomerular pressure, and promotes podocyte dysfunction, potentially accelerating CKD progression. Epidemiological evidence consistently shows associations between elevated fasting insulin levels and cardiovascular events, renal outcomes, and mortality across diverse populations, with meta-analytic estimates reporting a pooled relative risk of 1.46 (95% CI 1.16-1.84) for incident cardiovascular events. However, available data are largely observational and heterogeneous in exposure definitions and adjustment models. Hyperinsulinemia represents a clinically relevant and potentially modifiable component of CKM syndrome, with effects extending beyond glucose homeostasis. While causality is biologically plausible and supported by genetic and epidemiological evidence, it remains to be established through interventional studies. Recognition of hyperinsulinemia may support earlier risk stratification and mechanism-based interventions, although prospective validation is required before routine clinical implementation.

Renal biopsy is widely performed worldwide, but reported bleeding risks vary due to differences in technique, devices, operators, and patient populations. This study aimed to define the bleeding risk associated with current spring-loaded biopsy guns in a South-Asian population, identify relevant risk factors, and quantify the additional cost and hospital stay from bleeding complications. In this six-month prospective observational cohort study, all adult patients undergoing kidney biopsy at a tertiary hospital were enrolled. Demographic, clinical, radiological, procedural, and histopathological data were collected. Bleeding was defined as gross haematuria, perinephric hematoma, hemoglobin drop, transfusion requirement, or need for intervention. Factors associated with bleeding were evaluated using univariate analysis and multivariate logistic regression. Among 980 patients, overall bleeding incidence was 4.9%, with 1.6% clinically significant events. On univariate analysis, higher creatinine, urea, dialysis dependence, and ischemic heart disease were associated with bleeding, whereas diabetes mellitus was associated with lower bleeding risk. On multivariate analysis, ischemic heart disease remained independently associated with bleeding, while diabetes mellitus remained associated with lower bleeding risk. Histopathological chronicity, including glomerulosclerosis and interstitial fibrosis, was also associated with clinically significant bleeding events (requiring transfusion or intervention). Bleeding after kidney biopsy was infrequent in this cohort. Ischemic heart disease and histopathological chronicity were associated with increased bleeding risk, while procedural and operator-related factors were not significantly associated in this cohort, although these findings should be interpreted cautiously. Bleeding was associated with increased hospital stay and healthcare costs.

BACKGROUND: Stroke remains a major global health challenge and a leading cause of mortality and long-term disability worldwide. In low-income, conflict-affected countries such as Yemen, the burden is amplified by fragile healthcare systems and limited access to preventive and acute care services. Hence, this study addresses a critical awareness gap by assessing awareness of stroke risk factors, symptom recognition, prevention strategies, and stroke management among adult community members in two major urban cities in Yemen. METHODOLOGY: A cross-sectional survey design was employed using paper-based questionnaire. Participants were recruited through convenience sampling. Data analysis included descriptive statistics, non-parametric tests, correlation analysis, and bivariate logistic regression analysis. RESULTS: Our study revealed a high level of overall recognition-based awareness was observed among surveyed participants (87.9%; 95% CI: 84.7-91.1%). Specific areas of high recognition included obesity or overweight (89.4%) and high blood pressure (86.2%) as risk factors, dizziness/loss of balance (79.1%) as a symptom, and taking prescribed medications (87.2%) and regular medical checkups (86.9%) for prevention. Awareness of immediate medical care (87.7%) and future prevention medications (85.9%) also stood out in stroke management domain. A personal or family history of chronic diseases was strongly associated with greater overall stroke awareness score (p<0.001), as was a history of stroke itself (p=0.03). Bivariate regression analysis highlighted significant associations between high awareness and education level for symptoms, prevention, and stroke management domains scores (p <0.001). CONCLUSION: Despite the encouraging overall awareness, the findings highlight areas where targeted public health interventions may be warranted, particularly for less recognized aspects of stroke awareness. These should focus on reinforcing awareness, particularly concerning less recognized symptoms, and addressing disparities linked to socio-economic factors. These findings highlight the need for targeted stroke awareness interventions in urban settings, while underscoring the importance of further nationally representative studies. This study sheds light on the current level of stroke awareness and offers vital insights for policymakers and medical professionals to create culturally appropriate and successful educational campaigns.

BACKGROUND: The participation rate of exercise training among post-PCI patients with CHD is low, and their exercise behavior decisions are often influenced by bounded rationality, leading to decision-making biases. However, existing studies lack in-depth exploration. Qualitative research can provide an in-depth understanding of patients' descriptions of their exercise behaviors and their actual experiences, thereby helping to systematically identify these decision-making biases. OBJECTIVE: To explore the descriptions and related experiences of post-PCI patients with coronary heart disease regarding their own exercise behaviors, and to systematically identify the types of decision-making biases. DESIGN: A qualitative descriptive study design. METHODS: From December 2025 to February 2026, semi-structured face-to-face interviews were conducted with hospitalized post-PCI patients, and thematic analysis was used for coding and theme extraction. RESULTS: This study enrolled 20 patients. Three major bias types (information perception bias, risk perception bias, and self-regulation bias) and eight specific manifestations. These included individual cognitive fixation, authoritative information transformation, autonomous information compensation, somatic state perception, negative reference constraint, exercise risk generalization, subjective will determination, and daily activity replacement. CONCLUSION: Decision-making biases have a considerable impact on exercise behaviour in post-PCI patients with CHD. This process is profoundly influenced by immediate somatic sensations, reference to others' experiences, vague concerns about exercise risk, and the replacement of structured exercise with daily activities, leading patients to prefer decisions that afford immediate psychological safety or convenience.

INTRODUCTION: Ground-based walking training is an aerobic exercise used in supervised pulmonary rehabilitation (PR). Physical activity (PA) interventions typically promote step counts, but it is unclear whether community-based walking intensity can be targeted as aerobic exercise. This randomized controlled trial evaluated a web-based, pedometer-mediated PA intervention designed to increase walking amount and intensity. MATERIAL AND METHODS: Participants with COPD who had never enrolled in PR were randomized 1:1 to control or intervention. The intervention included individualized step-count goals, iterative feedback, educational content, and an online community forum. The Fitbit Inspire Heart Rate objectively monitored daily step counts. Participants were instructed to achieve step-count goals with as many steps of moderate-intensity as possible guided by a modified Borg rating of 4-5 for dyspnea. The primary outcome was change in PA measured as average daily step count at 12 weeks. Aerobic intensity was assessed by the Rapid Assessment of PA Questionnaire which uses self-reported moderate or vigorous PA to categorize responders as underactive or active. Linear mixed-effects models (PROC MIXED, SAS v9.4), adjusting for group, time, group*time, FEVpredicted, enrollment season, and study modality (eg, in-person, virtual, hybrid), assessed between-group change. RESULTS: Participants (57 intervention, 52 control) were 97% male, mean age 73±7 years, and baseline FEV 73±23% predicted. Baseline daily steps were 4,222±1,929 (intervention) and 4,851±2,637 (control). Intervention participants increased average daily steps by 1,410 steps/day more than controls (p=0.005). The intervention group showed greater transitions from underactive to active intensity (between-group: p=0.025), with 20 (41%) moving to active status (within-group: p=0.001). CONCLUSION: Technology-mediated community-based walking increased PA amount and intensity. These findings support further evaluation of this intervention as a potential option for ground-based walking training with objective measurement of exercise intensity.

Periodontitis is a chronic inflammatory disease associated with obesity, type 2 diabetes, and cardiovascular disease, and has become a serious public health issue. Antibacterial treatment and mechanical debridement are the main treatment strategies for periodontitis. However, side effects and bacterial resistance might lead to treatment failure. Nanotechnology systems have new opportunities for the management of periodontitis. With benefits including superior targeting and fewer side effects, drug delivery systems constructed with nanoparticles (NPs) may provide local, delayed, and regulated drug release. When combined with immunomodulatory therapy, tissue regeneration, and antibacterial therapy, a high drug loading capacity of individual medications or therapeutic combinations is made possible by the large surface area to volume ratio of nanoparticles, providing synergistic beneficial effects. This paper reviews the progress in the research and application of nanoparticle-based drug delivery systems in the treatment of periodontitis. We focused on the pathophysiology of periodontitis, introduced the rational design of nano-drug delivery systems, and concentrated on the local approaches to treatment for periodontitis. Furthermore, the future challenges and research prospects for nanoparticle-based drug delivery systems in the treatment of periodontitis are also covered in this paper.

BACKGROUND: The impact of early nonfatal complications on subsequent mortality and quality of life (QOL) after contemporary transcatheter aortic valve implantation (TAVI) remains unclear. METHODS: This post-hoc substudy of the LANDMARK trial included patients with severe aortic stenosis randomized to the Myval transcatheter heart valve (THV) series or to contemporary THV (Sapien or Evolut) series. Early nonfatal complications were defined as events occurring within 30 days after TAVI in patients surviving the first 30 days and included stroke, type 3 bleeding, major vascular complications, acute kidney injury stages 2-4, moderate or severe aortic regurgitation, new permanent pacemaker implantation, or reintervention according to the VARC-3 early safety endpoint. The primary endpoint was all-cause mortality from 30 to 365 days. QOL was assessed using the Short Form-12 at baseline, 30 days, and 1 year. RESULTS: Of the 768 randomized patients, 742 were alive at 30 days. Of these, 177 (23.9%) experienced at least 1 early nonfatal complication, whereas 565 (76.1%) did not. Age (80 ± 5 years vs. 80 ± 6 years, = 0.67) and Society of Thoracic Surgeons score (median 2.6 [interquartile range: 1.6-3.9] vs. 2.6 [1.7-3.9], = 0.76) were similar between groups. Patients with early nonfatal complications had higher mortality between 30 and 365 days (8.0% vs. 3.9%, = 0.03). Early nonfatal complications were independently associated with increased 1-year mortality (hazard ratio = 2.14; 95% CI, 1.07-4.27; = 0.03). One-year QOL did not differ between groups. CONCLUSIONS: In this post-hoc, hypothesis-generating analysis, early nonfatal complications after TAVI were associated with increased 1-year mortality, whereas 1-year QOL was comparable among survivors; findings should be interpreted with caution due to potential survivor bias. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, NCT04275726.

BACKGROUND: Females with severe aortic stenosis present with distinct anatomical and clinical characteristics compared to males, which may influence outcomes following transcatheter aortic valve replacement (TAVR). We sought to investigate the prognostic impact of sex-specific differences on short- and long-term outcomes following TAVR. METHODS: PubMed, Embase, Scopus, and Web of Science were searched through August 2025 for randomized and observational studies reporting sex-specific outcomes after TAVR. Reconstructed individual patient data from published Kaplan-Meier (KM) curves were used to estimate long-term survival outcomes. RESULTS: Overall, 71 studies involving 481,353 patients were included. Compared with males, females demonstrated a higher short-term risk of adverse outcomes, including 30-day all-cause mortality (hazard ratio [HR]: 1.064, 95% CI: 1.005-1.127; = 0.033) and stroke/transient ischemic attack (HR: 1.511, 95% CI: 1.317-1.734; < 0.001). Females were also more likely to experience life-threatening bleeding (risk ratio [RR]: 1.29, 95% CI: 1.03-1.62; = 0.028), major bleeding (RR: 1.26, 95% CI: 1.13-1.41; < 0.001), and major vascular complications (RR: 1.66, 95% CI: 1.53-1.81; < 0.001). Despite these higher periprocedural risks, females demonstrated superior long-term outcomes, with lower all-cause mortality (HR: 0.812, 95% CI: 0.794-0.831; < 0.001) and cardiovascular mortality (HR: 0.837, 95% CI: 0.784-0.893; < 0.001) during follow-up extending to 10 years, whereas risks of stroke/transient ischemic attack and myocardial infarction were comparable between sexes. CONCLUSIONS: Females undergoing TAVR experience higher early risks of mortality, stroke, bleeding, and vascular complications, but exhibit a sustained long-term survival advantage compared with males, highlighting the need for sex-centered periprocedural management strategies.

BACKGROUND: Rapid identification of potentially reversible causes is essential during cardiac arrest resuscitation. The American Heart Association 5Hs and 5Ts framework is widely used as a structured cognitive aid during resuscitation. Emergency department cardiac arrest (EDCA) occurs in a distinct clinical environment and may involve different patterns of clinically identified reversible causes than out-of-hospital cardiac arrest (OHCA). We aimed to compare the distribution of clinically identified reversible causes between EDCA and OHCA. METHODS: We conducted a retrospective cohort study of adult cardiac arrest patients who received cardiopulmonary resuscitation in a tertiary emergency department between 2018 and 2024. Patients were classified as EDCA or OHCA. Reversible causes were classified using predefined operational definitions based on contemporaneous clinical documentation and available diagnostic information during resuscitation, representing clinically identified or suspected reversible causes rather than definitive etiologic diagnoses. The primary analysis compared the distribution of clinically identified reversible causes between EDCA and OHCA. Secondary exploratory analyses used Firth's penalized logistic regression with prespecified confounding adjustment. RESULTS: Among 910 patients, 275 (30.2%) had EDCA and 635 (69.8%) had OHCA. Hypoxia was the most frequently identified cause but occurred less often in EDCA (46.6% vs. 57.2%; adjusted odds ratio [aOR], 0.61; 95% CI, 0.45-0.83). Hypovolemia was identified more frequently in EDCA (33.1% vs. 23.2%; aOR 1.80, 95% CI 1.22-2.65). Cardiac tamponade was also identified more frequently in EDCA (2.9% vs. 0.6%; aOR 5.14, 95% CI 1.52-17.40). No statistically significant adjusted differences were observed for the remaining reversible causes. CONCLUSION: Among patients receiving cardiopulmonary resuscitation in the emergency department, the distribution of clinically identified reversible causes differed between EDCA and OHCA. Hypovolemia and cardiac tamponade were identified more frequently in EDCA, whereas hypoxia was identified less frequently. These findings describe patterns of clinical recognition during resuscitation rather than definitive etiologic differences and should be confirmed in multicenter studies using standardized disease-based etiologic classifications.

BACKGROUND: Peripheral arterial disease (PAD) is mainly defined by macrovascular obstruction, while microvascular dysfunction remains insufficiently characterized by conventional diagnostics. Arterial spin labeling (ASL) magnetic resonance imaging (MRI) enables non-invasive, contrast-free quantification of skeletal muscle blood flow (SMBF) in the calf, with potential applications in PAD diagnosis, risk stratification, and perioperative assessment of microcirculation. Deep learning enabled reconstruction of dynamic ASL data offers potential to generate temporally and spatially resolved high-quality perfusion maps. The purpose of this study was to determine whether this dynamic ASL could distinguish PAD from healthy controls (HCs), both on spatial and temporal domains. METHODS: Dynamic SMBF maps of the calf were acquired with 15-sec temporal resolution before, during, and after a 3-minute isometric plantar flexion exercise (hyperemia) using a MR-compatible ergometer in 10 patients with mild to severe PAD and 10 age- and sex-matched healthy volunteers. PAD was confirmed by significantly lower ankle-brachial index values compared with HCs (0.60±0.21 1.25±0.1, P<0.0001). A convolutional neural network was trained on synthetic ASL data and applied to the dynamic series to reconstruct spatiotemporal SMBF maps with full-sampling and under-sampling schemes. Regions of interest were defined in five calf muscles (medial gastrocnemius, soleus, lateral gastrocnemius, tibialis anterior, and lateral compartment) and perfusion was quantified on the SMBF maps. Linear mixed-effects modeling evaluated SMBF across time, muscle, and cohort. RESULTS: Peak exercise perfusion did not differ significantly between two cohorts across muscle groups (all P>0.05), except in the medial gastrocnemius when normalized for baseline perfusion [PAD: 54.0%±41.4 % HC: 83.4% (66.2%, 128.4%), P=0.05]. In contrast, the hyperemic recovery time constant (τ), a time-dependent kinetic parameter describing post-exercise perfusion return towards baseline, was significantly prolonged in patients with PAD across all muscle groups (P<0.05), except the tibial compartment (P=0.094). Linear mixed-effects analysis demonstrated higher resting SMBF in patients with PAD compared with controls (difference +8.3 mL/min/100 g, P=0.011), but revealed a significantly attenuated exercise-induced perfusion response, reflected by a robust time × group × muscle interaction (P<0.0001). Deep learning reconstruction of under-sampled ASL data produced SMBF maps with relatively low bias compared to fully sampled references (Bland-Altman: -1.2 to -2.0 mL/min/100 g across conditions), potentially improving temporal resolution by 100%. CONCLUSIONS: Deep learning-enhanced, temporally resolved ASL MRI identifies attenuated exercise-induced perfusion and delayed recovery after exercise in patients with PAD that are not evident using static peak perfusion metrics alone. Active hyperemia recovery kinetics provide a sensitive marker of microvascular dysfunction, while deep learning reconstruction enables high temporal resolution imaging within clinically practical scan times.

BACKGROUND: Dynamic imaging with cardiac-dedicated cadmium-zinc-telluride single-photon emission computed tomography (CZT-SPECT) enables both the absolute quantification of myocardial blood flow (MBF) and the semi-quantitative assessment of myocardial perfusion imaging (MPI). This study aimed to investigate and compare differences in quantitative and semi-quantitative outcomes between technetium-99m-tetrofosmin (Tc-TF; TF group) and technetium-99m-sestamibi (Tc-MIBI; MIBI group) using a continuous rapid dynamic acquisition protocol. METHODS: Patients with no or mild coronary artery disease (CAD) who underwent myocardial flow reserve (MFR) assessment using a CZT-SPECT continuous rapid dynamic acquisition protocol were retrospectively enrolled in the study (n=100 per group). Quantitative perfusion parameters [rest MBF (rMBF), stress MBF (sMBF), and MFR] were compared between groups for each coronary territory and the whole left ventricle (LV). Within-group coefficients of variation (CVs) and multivariate linear regression analyses were performed. Semi-quantitative perfusion indices and left ventricular functional parameters were also compared. MPI image quality was scored for both groups. Comparisons of scores and assessments of interobserver reproducibility were performed. RESULTS: No significant differences were observed in the baseline demographic and clinical characteristics between the TF and MIBI groups (all P>0.05). Quantitative flow analysis revealed no significant between-group differences in rMBF for the left circumflex (LCX) artery, right coronary artery (RCA), or the global LV (all P>0.05). In contrast, significant between-group differences were observed in rMBF in the left anterior descending (LAD) artery, as well as in sMBF and MFR across all coronary territories and global LV values (all values were higher in the MIBI group than in the TF group; all P<0.05). The within-group CVs were consistently lower in the TF group than in the corresponding MIBI group. Additionally, the CVs for rMBF were lower than those for sMBF and MFR in both groups across all coronary territories and global LV values. Multivariate linear regression analysis showed negative beta (β) coefficients for TF relative to MIBI. No significant differences were found in the semi-quantitative MPI perfusion indices or the left ventricular functional parameters between groups (all P>0.05). Image quality scores differed significantly in both between-group comparisons and within-group comparisons between stress and rest imaging (all P<0.05). Scores were lower in the TF group than in the MIBI group, suggesting better MPI image quality with TF. Additionally, rest image scores were lower than stress image scores in both groups. The intraclass correlation coefficients (ICCs) were excellent (0.869-0.957, all P<0.05). CONCLUSIONS: Under a continuous rapid dynamic acquisition protocol, Tc-TF provides conventional semi-quantitative perfusion parameters and left ventricular functional indices comparable to those obtained with Tc-MIBI, while offering superior MPI image quality. Differences in quantitative flow measurements were observed between the two tracers. These findings suggest that further head-to-head studies using positron emission tomography (PET) as the reference standard are warranted to establish TF-specific quantitative parameters.