Stroke is a leading cause of global mortality and morbidity, yet its underlying metabolic mechanisms remain largely undefined. Elucidating the causal role of blood metabolites in stroke pathogenesis is crucial for developing effective interventions. This study employed a two-sample Mendelian randomization (MR) framework to investigate the causal relationships between 1400 plasma metabolites and the risk of stroke and its subtypes. We integrated genome-wide association study (GWAS) data on metabolites from 3441 to 8299 European-ancestry individuals in the Canadian Longitudinal Study on Aging (CLSA) with European-ancestry stroke GWAS data from the MEGASTROKE consortium. IVW associations were interpreted together with Benjamini-Hochberg false-discovery-rate (FDR) correction, sensitivity analyses, and mRnd power estimates. The IVW screening analysis identified 235 nominal associations (P_IVW < 0.05) across 124 metabolites and ratios. Among the final prioritized findings, plasma free asparagine (OR = 0.852, 95% CI: 0.782-0.929, FDR = 0.033) and the glutamine-to-asparagine ratio (OR = 1.148, 95% CI: 1.068-1.235, FDR = 0.033) showed FDR-significant associations with cardioembolic stroke. Additional associations for steroid sulfates, bile-acid conjugates, and octadecenedioylcarnitine were nominally significant and supported by directionally consistent sensitivity analyses but did not pass FDR correction. Our MR analysis prioritizes amino-acid metabolism in cardioembolic stroke and suggests additional lipid-related metabolic pathways for follow-up. Because several associations were exploratory after FDR correction and all GWAS datasets were restricted to European ancestry, replication in larger and more diverse populations is warranted before clinical translation.

A 44-year old patient presents at the emergencies for a cut above his right eyebrow. Inspection reveals a bilateral bilateral xanthelasma palpebrum (XP). The blood analysis shows a normal cholesterol level: is this enough reassurance as to the patient's cardiovascular and mortality risk? This article reviews evidence showing that XP - a cholesterol papule on the eyelids - is associated with an increased risk for mortality, myocardial infarct and severe atherosclerotic disease, independently from the patient's lipid profile.

Conventional excisional haemorrhoidectomy remains the gold standard treatment for grade IV haemorrhoids, although energy-based devices may reduce postoperative pain. We performed a systematic review and meta-analysis of randomised controlled trials comparing LigaSure with conventional haemorrhoidectomy.

A systematic search of PubMed, Scopus, Web of Science and the Cochrane Central Register was performed up to July 2025. Randomised controlled trials comparing LigaSure with conventional techniques were included. Pooled risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs) were calculated using random-effects models. Heterogeneity was assessed with the I² statistic, and trial sequential analysis (TSA) was applied to assess conclusiveness.

Forty-three unique RCTs comprising 3,277 participants were analysed. LigaSure was associated with lower postoperative pain scores on days 1 and 2 and during the first and second postoperative weeks, reduced analgesic requirements and intraoperative blood loss, shorter operating time and time to return to daily activities, and lower risks of postoperative wound discharge, postoperative bleeding and acute urinary retention. No statistically significant differences were observed in immediate postoperative pain, pain on postoperative day 3 or week 4, recurrence, length of hospital stay, constipation, pruritus, surgical site infection, incomplete healing, anal fissure, anal stenosis, or faecal incontinence.

LigaSure was associated with improvements in selected early perioperative outcomes, particularly postoperative pain and return to daily activities. However, uncertainty remains for several outcomes, and evidence regarding recurrence and other long-term anorectal outcomes remains limited.

The clinical effects of dual antiplatelet therapy de-escalation after acute myocardial infarction may differ by age. We evaluated whether the efficacy and safety of de-escalation from ticagrelor to clopidogrel differed by age in stabilized patients after percutaneous coronary intervention (PCI).

This was a prespecified secondary analysis of the TALOS-AMI randomized trial. Patients event-free 1 month after PCI receiving aspirin-ticagrelor were randomly allocated to de-escalation (aspirin-clopidogrel) or continuation (aspirin-ticagrelor). The primary net clinical endpoint was a composite of major adverse cardiovascular events (cardiovascular death, myocardial infarction, stroke) and Bleeding Academic Research Consortium types 2, 3, or 5 bleeding at 1 year.

We included 2697 participants (mean age 60.0 ± 11.4 years; 16.8% women). Among patients aged <75 years (n = 2376), de-escalation reduced the primary net clinical endpoint (4.1% vs. 7.2%; adjusted hazard ratio (aHR), 0.54 [95% CI, 0.38-0.77]) and bleeding (2.8% vs. 4.9%; aHR, 0.54 [0.35-0.82]). Among patients aged ≥75 years, no significant differences were observed for the primary endpoint (6.4% vs. 11.6%; aHR0.54 [0.25-1.17]) or bleeding (3.2% vs. 7.9%; aHR, 0.41 [0.15-1.15]). Interaction testing showed no treatment effect modification by age for the primary endpoint (p for interaction = 0.978), MACE (p = 0.585), or BARC bleeding (p = 0.597). Among patients aged ≥75 years, 14/18 bleeding events occurred within 180 days.

Among stabilized, event-free patients 1 month after PCI, no significant age-treatment interaction was observed; therefore, the efficacy and safety of de-escalation in older adults (≥75 years) remain uncertain.

Trial registration: ClinicalTrials.gov (NCT02018055).

To evaluate the clinical presentation, management and outcomes of adult congenital heart disease (ACHD).

This cross-sectional study was conducted at the department of pediatric cardiology and Intensive Care Unit (ICU) of NICVD, Karachi, Pakistan, from April 2021 to December 2023. Patients of either gender, aged 18 years and above and diagnosed with CHDs were analyzed. Outcomes were noted in the form of intra-operative or post-surgery mortality, and post-surgical complications.

In a total of 129 patients, 68 (52.7%) were male. The median age was 22.00 years. There were 10 (7.8%) ACHD cases who were newly diagnosed. The most common CHD types were found to be tetralogy of Fallot (TOF), atrial septal defect (ASD), and ventricular septal defect (VSD), noted in 32 (24.8%), 25 (19.4%), and 22 (17.1%) patients, respectively. Shortness of breath, cyanosis, and palpitation, were the most frequent complaints at the time of presentation, reported in 120 (93.0%), 48 (37.2%), and 44 (34.1%) patients, respectively. Cardiac catheterization was the most adopted procedure performed in 41 (31.8%) patients. Total correction, VSD closure, and ASD closure were performed in 9 (7.0%), 7 (5.4%), and 7 (5.4%) patients, respectively. No intra-operative or post-operative mortality was reported. The most frequently observed post-operative complications were left ventricular dysfunction, right ventricular dysfunction, biventricular dysfunction, and ventricular hypertrophy, noted in 39 (30.2%), 23 (17.9%), 6 (4.7%), and 3 (2.3%) patients, respectively.

The most prevalent ACHD types were TOF, ASD, and VSD. Most patients required surgical or catheter-based interventions with favorable short-term outcomes.

Although reperfusion therapy improves the prognosis of acute myocardial infarction, myocardial ischemia-reperfusion injury continues to limit its clinical benefits, with neutrophil-driven inflammatory cascades representing a central mechanism of injury amplification. This article delineates the molecular event chain of neutrophils from recruitment to effector execution: activated neutrophils damage cardiomyocytes through three principal pathways-respiratory burst, degranulation, and neutrophil extracellular traps formation-thereby establishing a positive feedback loop that exacerbates inflammatory amplification. On this basis, we summarize therapeutic strategies targeting neutrophil migration, neutrophil extracellular traps formation, intracellular signaling pathways, mitochondrial homeostasis, immune phenotypes, and targeted drug delivery systems.

Aortic dissection (AD) is a life-threatening cardiovascular disease with an extremely high mortality rate. Excessive reactive oxygen species (ROS) production and inflammatory responses in diseased vascular regions are central drivers of AD pathogenesis, leading to destruction of the aortic wall structure and fatal hemorrhage. However, conventional clinical therapies for AD cannot effectively eliminate excessive ROS at lesion sites while simultaneously exerting anti-inflammatory effects. To address these limitations, we developed a biomimetic, inflammation-targeting nanoparticle, ZIF-8@Res@PEG-FA (ZRF), to attenuate AD progression through potent antioxidant and anti-inflammatory interventions. ZRF is constructed with ZIF-8 as the core carrier, loaded with the antioxidant and anti-inflammatory agent resveratrol, and surface-modified with PEG-folic acid (PEG-FA). This nanoparticle enhances resveratrol bioavailability and leverages the inflammation-targeting capability of folic acid to preferentially accumulate in AD lesions. Under mildly acidic conditions, ZRF rapidly degrades and efficiently scavenges ROS, disrupting the oxidative stress-inflammation vicious cycle and promoting the polarization of pro-inflammatory M1 macrophages toward the anti-inflammatory M2 phenotype. Notably, ZRF also preserves the contractile phenotype of vascular smooth muscle cells (VSMCs), maintains extracellular matrix stability, and thereby delays AD progression. This study presents a promising therapeutic strategy for aortic dissection and other inflammatory vascular diseases.

Contrast-associated acute kidney injury (CA-AKI) after endovascular thrombectomy (EVT) worsens outcomes in acute ischemic stroke, but threshold-based definitions do not capture prognostic information from subthreshold changes. We tested whether early creatinine change within 48 hours of EVT conveys graded prognostic information beyond dichotomous CA-AKI.

We performed a secondary analysis of the CAN-REST (Contrast-Associated Nephropathy After Endovascular Stroke Treatment; REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT06596603) registry, a retrospective multicenter observational cohort study of 6638 EVT-treated adults with acute ischemic stroke enrolled at 73 centers in 16 countries between January 1 and December 31, 2023. Early creatinine change was quantified as the natural logarithm ratio of 48-hour creatinine to baseline creatinine (ln[48-hour/baseline creatinine]), with CA-AKI defined per Kidney Disease: Improving Global Outcomes criteria (≥0.3 mg/dL or ≥1.5× baseline rise within 48 hours). Multivariable logistic regression adjusted for prespecified baseline and periprocedural covariates examined associations with 90-day modified Rankin Scale shift and in-hospital mortality; linear versus restricted cubic spline specification was selected by likelihood ratio testing, and contrasts were estimated at ±10%, ±25%, and ±50%.

Greater creatinine worsening within 48 hours of EVT was independently associated with an unfavorable 90-day modified Rankin Scale shift (adjusted common odds ratio per 1-unit log-ratio increase, 1.48 [95% CI, 1.07-2.04]; linear) and in-hospital mortality (nonlinear dose-response, of larger magnitude). A 10% increase in creatinine at 48 hours-well below Kidney Disease: Improving Global Outcomes threshold-was associated with worse functional outcome (adjusted common odds ratio, 1.04 [95% CI, 1.01-1.07]) and death (adjusted odds ratio, 1.22 [95% CI, 1.13-1.32]); a 10% decrease in creatinine at 48 hours was associated with lower odds of both outcomes (adjusted common odds ratio, 0.96 [95% CI, 0.93-0.99] and 0.74 [95% CI, 0.65-0.86]). The functional-outcome association concentrated at upper modified Rankin Scale cut-points (severe disability, death); effect modification by baseline renal function was not significant.

Early creatinine change after EVT conveys graded, outcome-specific prognostic information extending below formal CA-AKI thresholds, with a dose-response detectable at changes as modest as ±10%, complementing binary CA-AKI as a framework for post-EVT renal risk assessment.

URL: https://www.clinicaltrials.gov; Unique identifier: NCT06596603.

Weight gain and associated adipose tissue remodeling have been partly linked to HIV infection and to some current antiretroviral therapy (ART) regimens in ART-naive and ART-controlled people with HIV (PWH). This review addresses recent findings on adipose tissue distribution and remodeling in PWH, receiving dolutegravir, bictegravir and/or tenofovir alafenamide (TAF), highlighting how visceral adiposity contributes to cardiometabolic comorbidities.

Preclinical models exposed to dolutegravir, bictegravir, tenofovir disoproxil fumarate (TDF) and/or TAF demonstrate alterations in adipose tissue, including mitochondrial dysfunction, fibrosis, inhibited beiging, and insulin resistance. Transcriptomic studies of abdominal subcutaneous fat from ART-controlled PWH further revealed elevated inflammation, fibrosis and insulin resistance. Increased visceral adiposity raises the risk of cardiometabolic disorders such as insulin resistance and diabetes, metabolic-dysfunction-associated steatotic liver disease and cardiovascular diseases. Reversing weight gain linked to ART, by switching regimens or adding antiobesity medications like the GLP-1 receptor agonist semaglutide, has shown potential in reducing adipose tissue remodeling, visceral adiposity and cardiometabolic risk factors.

Weight gain and increased visceral adiposity partly driven by some ARTs are associated with higher cardiometabolic risk. HIV and ART can either activate or suppress the fat beiging/browning phenotype. Reversing weight gain and visceral adiposity in at-risk PWH is a critical clinical goal.

Cell-based myocardial repair has progressed from direct cell replacement toward paracrine, engineered tissue, and cell-free strategies, but the relationship between preclinical innovation and clinical translation remains unclear. We mapped the knowledge structure and translational trajectory of this field.

Original research articles on cell therapy for myocardial infarction or heart failure published from 2004 through 2024 were retrieved from the Web of Science Core Collection. The 1,505 included records were classified as in vitro, animal, or clinical studies; animal and clinical subsets were then compared. Publication, collaboration, co-citation, citation-burst, keyword, and study-type- stratified analyses were performed using VOSviewer, CiteSpace, and the bibliometrix package in R.

Annual output increased from 34 articles in 2004 to a peak of 104 in 2012 and declined to 49 in 2024. The corpus comprised 1,190 animal and 281 clinical studies; clinical output peaked at 26 articles in 2011 and fell to 4 in 2024. The United States and China contributed the most publications, with 82 China-United States collaborations. Co-citation and burst analyses identified early bone marrow- derived and progenitor-cell trials as major intellectual landmarks. Thematic emphasis subsequently shifted toward mesenchymal stromal cells, induced pluripotent stem cell-derived cardiomyocytes, tissue engineering, extracellular vesicles, inflammation, maturation, and electrical integration. Stratified keyword analysis showed that animal studies emphasized mesenchymal stromal cells, cardiomyocytes, and extracellular vesicles. In contrast, clinical studies more often emphasized progenitor cells, bone marrow mononuclear cells, endothelial progenitor cells, and intracoronary delivery.

These findings indicate that the field has gradually shifted away from attempts at direct myocardial replacement and toward strategies that emphasize mechanistic understanding, delivery optimization, and paracrine effects. Persistent translational bottlenecks appear to have redirected research priorities across successive phases of cardiac cell therapy development.

Preclinical diversification has continued despite contraction of clinical activity, indicating that innovation has outpaced clinical translation. This bibliometric analysis identifies where the animal-clinical gap is concentrated and provides an evidence map for prioritizing reproducible, mechanism-informed, and clinically feasible strategies; it does not establish therapeutic efficacy.