In older adults hospitalized with acute heart failure and atrial fibrillation, bleeding concern often drives withholding of oral anticoagulation at discharge. Whether withholding marks a genuinely lower bleeding-risk phenotype or residual clinical vulnerability is uncertain. We examined its association with post-discharge ischemic stroke, major bleeding, and death in a predominantly older cohort.

We analyzed a registry of patients hospitalized with acute heart failure and atrial fibrillation. In a discharge-based analysis of patients discharged alive and free of stroke or major bleeding at discharge, we used stabilized inverse-probability-of-treatment weighting for discharge anticoagulation. Ischemic stroke and major bleeding were modeled with weighted Fine-Gray competing-risk regression (death as competing event) and death with weighted Cox regression, contrasting no anticoagulant versus anticoagulant. Age-restricted analyses (≥ 75, ≥ 80 years) and absolute risks were prespecified.

Among 560 patients (no anticoagulant 72, anticoagulant 488; mean age 78 years), withholding was associated with higher ischemic stroke (subdistribution hazard ratio 3.14, 95% confidence interval [CI] 1.26-7.81) and did not identify a lower bleeding-risk phenotype, with numerically higher major bleeding overall (1.98, 0.95-4.14) that reached significance among patients aged ≥ 80 years (2.41, 1.05-5.54). No significant association with death was observed (hazard ratio 1.34, 0.70-2.55). Three-year cumulative incidences of bleeding were 25.6% (no anticoagulant) versus 13.4% (anticoagulant).

Discharge anticoagulation withholding did not identify a lower post-discharge bleeding-risk phenotype but marked residual thromboembolic vulnerability, with a higher bleeding-risk trajectory, particularly among patients aged ≥ 80 years, supporting structured post-discharge anticoagulation reassessment in older adults.

Left ventricular pressure-strain loop (LV-PSL) analysis provides non-invasive myocardial-work indices by integrating strain with contemporaneous brachial systolic blood pressure. Follow-up myocardial-work assessment requires blood pressure measured at the same assessment.

To describe baseline myocardial mechanical abnormalities after percutaneous coronary intervention (PCI) for myocardial infarction and to explore associations between a 6-week enhanced external counterpulsation (EECP) program and changes in global longitudinal strain (GLS) and rehabilitation outcomes.

This single-center matched observational study was conducted from October 2021 through January 2023. It included 66 patients after PCI for myocardial infarction who completed a 6-week EECP program, 66 patients in a pre-existing matched standard-therapy comparator cohort, and 50 healthy reference participants. Baseline LV-PSL-derived myocardial-work indices were descriptive. Six-week between-group changes in GLS, peak strain dispersion (PSD), N-terminal pro-B-type natriuretic peptide (NT-proBNP), 6-min walk distance (6MWT), Seattle Angina Questionnaire (SAQ) summary score, and weekly angina frequency were analyzed using pair-aware methods with Benjamini-Hochberg false-discovery-rate (FDR) correction. A sensitivity analysis adjusted for baseline outcome value, baseline systolic blood pressure, heart rate, ST-segment-elevation myocardial infarction, ACEI/ARB/ARNI use, and calcium-channel-blocker use with pair-clustered robust standard errors.

Post-PCI patients had less negative baseline GLS and descriptively lower constructive myocardial-work values than healthy reference participants. In the matched exploratory comparison, the between-group difference in GLS change was -1.3 percentage points (95% CI, -2.0 to -0.6; P < 0.001; FDR q < 0.001). EECP exposure was also associated with larger improvements in 6MWT and SAQ score, a greater reduction in NT-proBNP, and a greater reduction in weekly angina frequency; PSD change was not different after FDR correction. The adjusted sensitivity analysis gave a GLS difference of -1.3 percentage points (95% CI, -1.9 to -0.7; P < 0.001; FDR q < 0.001).

In this non-randomized matched cohort, EECP exposure was associated with larger 6-week improvements in GLS and selected rehabilitation outcomes. Baseline LV-PSL-derived myocardial work is presented only as descriptive context; no valid longitudinal myocardial-work comparison was possible because follow-up hemodynamic measurements were unavailable. The contribution of changes in loading conditions to GLS could not be assessed.

Secondary mitral regurgitation (MR) is associated with substantial cardiovascular morbidity and mortality, making accurate severity assessment essential for clinical management. Conventional 2D echocardiography has important limitations, particularly in the presence of noncircular regurgitant orifices. Three-dimensional transesophageal echocardiography (3D-TEE) enables direct measurement of Vena Contracta area (VCA) and may provide more accurate quantification of MR severity.

To assess the diagnostic value of three-dimensional transesophageal Vena Contracta area versus two-dimensional echocardiographic assessment of secondary mitral regurgitation.

This study included 52 patients with moderate-to-severe secondary MR, recruited at Alzahraa University Hospital between December 2024 and January 2026. All patients underwent TTE followed by TEE. MR severity was assessed according to current echocardiographic guidelines using an integrative approach that included qualitative, semi-quantitative, and quantitative assessments. Three-dimensional VCA was measured by both TTE and TEE using multiplanar reconstruction. Statistical analysis was performed using Jamovi version 2.3.28 for Windows, with P-values < 0.05 considered statistically significant.

The mean age of the patients studied was 58.08 ± 9.52 years, with a male-to-female ratio of 43:9. The mean PISA-derived EROA for patients with severe MR was 0.36 ± 0.09 cm², and the mean regurgitant volume for these patients was 48.6 ± 6.79 mL. VCA measured by 3D TTE (0.69 ± 0.16 cm²) showed a strong positive correlation with 3D TEE VCA (0.67 ± 0.16 cm²) (r = 0.857, p < 0.001). Bland-Altman analysis demonstrated minimal bias (0.035 cm²) and good agreement between both techniques. ROC analysis showed good diagnostic accuracy for severe MR, with slightly higher accuracy for TEE VCA (AUC = 0.874) compared with TTE VCA (AUC = 0.841).

Three-dimensional TEE-derived Vena Contracta area (3D TEE VCA) is a reliable and accurate method for assessing the severity of secondary mitral regurgitation. The strong correlation and good agreement between 3D TEE and 3D TTE VCA measurements, as well as their correlation with PISA-derived EROA, support the value of 3D VCA as a robust quantitative parameter. Moreover, our findings suggest that 3D TTE VCA may represent a feasible, less invasive alternative in selected patients; however, its use as a replacement for TEE warrants confirmation in larger multicenter studies with external validation. Larger multicenter studies with external validation are required before it can be considered a replacement for TEE.

Hypertrophic cardiomyopathy (HCM) is associated with various arrhythmias, including bradyarrhythmia. The relationship between HCM and bradyarrhythmia, and subsequent need for permanent pacemaker (PPM) implantation, remains unclear. This study aimed to evaluate the risk of bradyarrhythmia and PPM implantation in HCM patients.

This retrospective, population-based cohort study identified patients with newly diagnosed HCM from 2012 to 2017 in Taiwan's National Health Insurance Research Database. Patients with prior bradyarrhythmia or PPM implantation were excluded. A control cohort was selected by matching patients without HCM to the study cohort by age and gender in a 1:1 ratio. The primary and secondary outcomes were the occurrence of bradyarrhythmia and PPM implantation, respectively. A multivariate Cox proportional hazards regression model was used to evaluate the hazard ratios (HR) for the outcomes.

A total of 15 266 patients with a mean age of 63.8 ± 14.5 years constituted the HCM (n = 7633) and control (n = 7633) cohorts. During a follow-up period of 4.05 ± 2.03 years, HCM was associated with higher risks of bradyarrhythmia (adjusted HR: 2.15, p < 0.001) and PPM implantation (adjusted HR: 6.58, p < 0.001). In patients with HCM, the presence of AF increased the risks of both bradyarrhythmia (adjusted HR: 1.61, p < 0.001) and PPM implantation (adjusted HR: 2.12, p < 0.001), while HF increased the risks of PPM implantation (adjusted HR: 1.61, p < 0.001).

Patients with HCM had higher risks of bradyarrhythmia and PPM implantation. Patients with HCM should be carefully monitored for AF and HF, which might increase the risks of future PPM implantation.

Portal vein thrombosis (PVT) is a significant complication of cirrhosis. Nonselective beta-blockers (NSBBs) are standard therapy for portal hypertension, but their effect on PVT risk remains uncertain.

To assess whether NSBB use after variceal band ligation increases PVT risk and to compare outcomes among propranolol, carvedilol and no NSBB therapy.

We conducted a retrospective cohort study using the TriNetX US Collaborative Network (> 110 million patients). Adults with cirrhosis and portal hypertension who underwent variceal band ligation (2010-2024) were included. Patients were stratified by NSBB exposure and matched 1:1 on 12 clinical variables. The primary outcome was incident PVT; secondary outcome was all-cause mortality. Kaplan-Meier analysis evaluated time-to-event outcomes.

After matching (n = 4296 per group), NSBB use was associated with higher PVT incidence compared with no NSBBs (9.5% vs. 5.4%; RR 1.765, 95% CI 1.500-2.077). Propranolol was associated with increased PVT risk, whereas carvedilol showed similar PVT incidence to controls and significantly lower mortality compared with both propranolol and no NSBB use.

Propranolol use was linked to increased PVT risk, while carvedilol did not elevate PVT risk and was associated with improved survival. Beta-blocker selection may meaningfully influence outcomes in cirrhosis.

Chronic arsenic exposure causes neurological damage, but the underlying mechanisms remain incompletely understood. This study investigated whether Saposhnikoviae Radix (SR) aqueous extract protects against arsenic-induced neurotoxicity by modulating pyroptosis. Kunming mice were exposed to NaAsO₂ (10 mg/kg) with or without SR (3, 6, 12 g/kg). NaAsO₂ exposure induced anxiety-like behaviors and spatial memory deficits, accompanied by widespread neuronal damage (hippocampal pyramidal cell disarray, cerebellar Purkinje cell loss, and cortical vacuolation) and upregulation of pyroptosis-related proteins (NLRP3, Cleaved-Caspase-1, GSDMD-N, IL-1β, IL-18) in brain tissues. SR treatment significantly ameliorated these behavioral and pathological changes. In HT22 cells, NaAsO₂ (12.5 μM) reduced cell viability, increased LDH release, induced pyroptotic ultrastructural features (membrane blebbing and pore formation), and upregulated pyroptosis markers; SR (400 μg/mL) effectively reversed these effects. Mechanistically, SR suppressed the NLRP3/Caspase-1/GSDMD axis activation, as confirmed by both protein and mRNA analyses. These findings demonstrate that SR aqueous extract attenuates arsenic-induced central nervous system injury through specific inhibition of the pyroptosis pathway, providing an experimental basis for the potential use of traditional Chinese medicine in preventing environmental metalloid-induced neurotoxicity.

Background/Objectives: Computed tomography perfusion is widely used in acute ischemic stroke, but its performance is less reliable for lacunar and infratentorial infarcts. This technical review examines the acquisition and processing factors that influence their detectability. Methods: A targeted technical review of PubMed/MEDLINE, Scopus, and Web of Science was performed, focusing on acquisition, reconstruction, vascular input selection, deconvolution, filtering, spatial sampling, automated classification, posterior circulation stroke, and lacunar infarction. Results: Detectability depends on lesion size and contrast, posterior fossa artifacts, spatial and temporal resolution, vascular curve quality, mathematical stabilization, and automated thresholds. Larger cerebellar infarcts may remain visible, whereas brainstem, deep cerebellar, and perforator lesions are more vulnerable. Temporal maps and direct review of parametric images may reveal abnormalities absent from automated summaries. Conclusions: This technical review shows that computed tomography perfusion should be interpreted as a derived estimate rather than a direct representation of cerebral hemodynamics. Negative automated findings do not exclude lacunar or infratentorial infarction when clinical suspicion remains high.

Chronic venous leg ulcers (VLUs) affect approximately 1% of adults, and up to 30% remain unhealed by 12 months of standard therapy, with rates of recurrence approaching 70%. The chronicity and treatment resistance cannot be explained by the traditional view that venous hypertension alone causes the pathogenesis of VLUs. This narrative review synthesizes evidence from PubMed, Web of Science, and Scopus (2016-April 2026), including original research, systematic reviews, meta-analyses, and clinical trials on the pathophysiology, diagnosis, and treatment of VLU, with a focus on biofilm, inflammation, and microvascular dysfunction. The reviewed studies were critically appraised. The current integrated framework offers a potential mechanistic roadmap for understanding the pathogenesis of VLUs and may help justify integrated therapeutic strategies. This review evaluates the existing evidence, identifies controversies, and highlights areas of knowledge that require further investigation. We analyze emerging data to propose a unified, conceptually distinct framework focused on the reciprocal, self-perpetuating interactions between biofilm, inflammation, and microvascular dysfunction, a triad that may offer a more comprehensive explanation for clinical heterogeneity and therapeutic resistance than venous hypertension alone. Future research should focus on the development of clinically available biofilm diagnostics, rigorous studies of combination therapies and elucidation of molecular links between components of the triad. We suggest that a transition to mechanism-based approaches targeting simultaneously may hold promise for transforming outcomes for millions of people affected by this debilitating condition.

Background/Objectives: Postbiotics are increasingly recognized as biologically active products of microorganisms with emerging potential as microbiome-inspired therapeutic interventions. While most microbiome-based strategies focus on modifying microbial composition, restoration of microbial signaling has received comparatively less attention. This review examines postbiotics through the lens of microbial signaling restoration and proposes a unified Metabolite-Immune-Redox (MIR) axis linking microbial-derived signals with immune regulation, redox homeostasis, endothelial integrity, and host resilience. Methods: This narrative review synthesizes current evidence on postbiotics, microbial metabolites, structural microbial components, and extracellular vesicles, with emphasis on their roles in immunometabolic regulation, redox biology, endothelial function, and host-directed interventions. Results: Current evidence suggests that short-chain fatty acids, indole derivatives, bile acid metabolites, and microbial extracellular vesicles are important mediators of host-microbe communication. These signals influence interconnected pathways involving mitochondrial function, inflammasome activity, immune calibration, endothelial and glycocalyx homeostasis, and disease tolerance. The review highlights the endothelium as an underrecognized therapeutic target and discusses biomarkers, including soluble thrombomodulin, von Willebrand factor, and D-dimer, as potential tools for identifying patients most likely to benefit from host-directed interventions. Major translational challenges include product heterogeneity, incomplete mechanistic characterization, uncertain exposure-response relationships, and unresolved regulatory considerations. Conclusions: The proposed MIR axis provides a hypothesis-generating framework for understanding how restoration of microbial signaling may contribute to precision host-directed therapeutic strategies. Further mechanistic and clinical studies are needed to validate this concept and define its translational potential in inflammatory, infectious, and critical illness settings.

Atherosclerotic cardiovascular disease (CVD) remains a leading cause of worldwide morbidity and mortality, despite well-established/effective pharmacological therapies. A substantial component of the residual risk is inflammatory. The importance of inflammation and immune mediators in the pathophysiology has been recognised over the past two decades and, importantly, treatment with percutaneous coronary intervention (PCI) also results in an inflammatory response and associated adverse outcomes. Multiple biochemical pathways have been implicated with various identified biomarkers, such as high-sensitivity C-reactive protein which is now recognised as a marker of cardiovascular risk. Proteins such as interleukins (IL) IL-1 and IL-6 or larger protein complexes such as the NLRP3 inflammasome all play a key role in both the pathophysiology of atherosclerosis and inflammation relating to PCI. This knowledge has led to advances in pharmacological therapies and multiple pre-clinical and clinical trials, but to date, colchicine is the only treatment with sufficiently robust evidence from large-scale clinical trials to be recommended in multinational guidelines. Other therapies at present lack this level of evidence, and identification of other potential therapies is an important next step in treating inflammation post-PCI. Furthermore, the potential routine use of colchicine periprocedurally for PCI and its biochemical and clinical effects in this context are not yet fully established, requiring further investigation to identify its effect on specific inflammatory mediators and whether this translates to clinical outcomes.