Background/Objectives: Acutely ill patients in hospital are at high risk for thrombosis, even post-discharge. However, the safest and most effective strategy for thromboprophylaxis in such patients is still under debate. Our aim was to compare the subcutaneous use of low-dose prophylactic enoxaparin versus intermediate-dose tinzaparin. Methods: Patients in an internal medicine clinic of a tertiary hospital in Athens, Greece, with increased risk for thrombosis (PADUA score ≥ 4) received either intermediate-dose tinzaparin (8000 anti-Xa units) or 40 mg enoxaparin as thromboprophylaxis. Efficacy and adverse effects were evaluated and compared up to 14 days post-discharge. Results: A total of 251 patients who received tinzaparin were compared with 95 patients under enoxaparin thromboprophylaxis. No statistically significant difference was found in the number of bleeding and/or clinically evident thrombotic events between the two groups [6 versus 14 bleeding (p = 0.2603) events and 0 versus 1 venous thrombotic event (p = 0.999) in the enoxaparin and tinzaparin groups, respectively]. Moreover, no difference was found in length of stay [enoxaparin: 10 days (95%CI: 9-12 days); tinzaparin: 8 days (95%CI: 8-10 days, HR = 1.18, 95%CI: 0.91-1.54, p = 0.2] or mortality [11 deaths with enoxaparin (11.58%, 95%CI: 6.59-19.55%) and 50 deaths with tinzaparin (19.92%, 95%CI: 15.45-25.30%, OR: 1.9, 95%CI: 0.94-3.83, p = 0.069)]. The use of thromboprophylaxis for two weeks post-discharge did not result in any bleeding or clinically evident thrombotic events in either group. Conclusions: In our cohort, the use of intermediate-dose tinzaparin was similar to the use of low-dose enoxaparin for patients with a high PADUA score in terms of thrombotic and/or bleeding events.

This narrative review examines how endothelin receptor antagonists (ERAs) can be used at the intersection of difficult-to-control hypertension, chronic kidney disease (CKD), and albuminuria or proteinuria. For clinicians, the central question is not receptor selectivity alone, but whether a specific agent, indication, dose, background therapy, and monitoring plan can deliver meaningful blood-pressure or kidney benefit without unacceptable fluid retention. Pulmonary arterial hypertension established the pharmacology and major safety liabilities of the class; the current implementation questions for hypertension and kidney specialists arise in systemic hypertension and proteinuric kidney disease. Aprocitentan is the first and only ERA approved for hypertension; in PRECISION, the approved 12.5-mg once-daily dose reduced placebo-corrected 24-h ambulatory systolic blood pressure by 4.2 mm Hg, with reductions of 4.2 to 5.9 mm Hg across the studied doses. In IgA nephropathy (IgAN), sparsentan reduces proteinuria and slows estimated glomerular filtration rate (eGFR) decline. Atrasentan has an established antiproteinuric effect and a favorable eGFR slope, although the prespecified week-136 eGFR contrast in the final ALIGN analysis did not reach statistical significance. Zibotentan plus dapagliflozin remains investigational. Across these settings, successful ERA use depends on careful patient selection, indication-specific interpretation of the evidence, optimized diuretic and cardiorenal therapy, and early surveillance for edema, anemia, liver-test abnormalities, and pregnancy risk, with treatment interruption or discontinuation when clinically significant volume expansion or other serious safety signals occur.

The STEEER-AF trial evaluated the effect of a structured educational program on adherence to European Society of Cardiology guidelines for atrial fibrillation.

We aimed to report the prespecified subgroup analysis of centers in Poland to evaluate regional guideline adherence and the impact of the educational intervention.

Twelve Polish centers recruiting 300 patients with atrial fibrillation were randomized 1:1 to an educational intervention for healthcare professionals or standard practice. Co-primary outcomes were patient-level adherence to class I and III European Society of Cardiology recommendations for stroke prevention and rhythm control at 6-9 months.

Complete case analysis included 262 patients. Baseline oral anticoagulant prescription was 96.3%. At follow-up, adherence to stroke prevention guidelines was 76.6% in the intervention group and 70.9% in the control group (adjusted risk ratio, 1.12; 95% confidence interval, 0.99-1.27). For rhythm control, guideline adherence reached 53.1% in the intervention group compared with 26.9% in the control group (adjusted risk ratio 1.75; 95% confidence interval, 1.16-2.64). Educational engagement was robust, with learners spending a median of 11.5 hours on the platform.

Following structured professional education, absolute adherence to rhythm control recommendations was substantially higher in the Polish cohort. A near-optimal baseline oral anticoagulant prescription rate limited the capacity for measurable improvement in stroke prevention. These findings are hypothesis-generating and highlight the need for targeted education aligned with local healthcare infrastructure.

Ferroptosis is a regulated form of cell death driven by iron-dependent lipid peroxidation, characterized by disruption of iron homeostasis, imbalance in the antioxidant system, and accumulation of lipid peroxides. Its core execution machinery is highly conserved across tissues, whereas disease-specific upstream nodes dictate pathway activation and progression in different pathological contexts. In autoimmune hepatitis (AIH), ferroptosis is governed by a "bidirectional imbalance" between enhanced pro-death signals and compromised anti-death protective mechanisms, further modulated by endocrine and metabolic factors. This imbalance collectively lowers the ferroptosis threshold in hepatocytes, amplifying their susceptibility to ferroptotic cell death. Although hepatocyte ferroptosis has been observed in experimental cholestasis models, these models do not directly represent the pathological process of primary biliary cholangitis (PBC). In PBC patients, recent studies have identified ferroptosis signals in monocyte-derived macrophages, but ferroptosis in biliary epithelial cells remains unconfirmed. In primary sclerosing cholangitis (PSC), despite elevated oxidative stress markers, the absence of core ferroptosis executioner molecules precludes any definitive link to ferroptosis. This review comprehensively summarizes the ferroptosis regulatory network and its disease-specific manifestations across autoimmune liver diseases, with a focus on AIH-specific nodes as potential precision intervention targets. We also propose a phase-based therapeutic framework and discuss safety considerations, as well as key challenges for clinical translation.

Atherosclerosis (AS), the pathological basis of cardiovascular diseases, remains a leading global cause of mortality. Its pathogenesis involves chronic inflammation, impaired clearance of apoptotic cells (efferocytosis), and lipid dysregulation within the arterial wall. The CD47-SIRPα signaling axis, a key immune checkpoint, has been identified as a critical regulator integrating these processes in the atherosclerotic plaque microenvironment. This review systematically details the multifaceted role of the aberrantly activated CD47-SIRPα axis in driving AS progression. We elaborate on its molecular architecture and how it pathologically inhibits macrophage efferocytosis by disrupting cytoskeletal dynamics and integrin-mediated adhesion. The axis concurrently sustains a pro-inflammatory state within plaques and disrupts cholesterol homeostasis by promoting lipid influx and inhibiting efflux, thereby accelerating foam cell formation. We further evaluate emerging therapeutic strategies targeting this axis, including monoclonal antibodies, engineered SIRPα-Fc fusion proteins, and multifunctional nanocarriers designed for plaque-targeted delivery. These approaches aim to restore efferocytosis, mitigate inflammation, and resolve lipid accumulation. While preclinical results are encouraging, challenges such as cell-type-specific effects, potential on-target hematological toxicity, and the need for precise delivery persist. Therapeutic modulation of the CD47-SIRPα axis presents a promising immunometabolic strategy for AS. Future directions should focus on developing cell- or context-selective modulators to enhance safety, identifying biomarkers for patient stratification, and rationally combining these novel agents with established lipid-lowering and anti-inflammatory therapies to address the residual risk in atherosclerotic cardiovascular disease.

This meta-analysis evaluated the associations between the Fibrosis-4 index (FIB-4) and overall stroke, ischemic stroke, hemorrhagic outcomes, poor functional outcome, and all-cause mortality.

PubMed, Embase, and the Cochrane Library were searched from inception to November 4, 2025. Cohort and cross-sectional studies evaluating categorical or continuous FIB-4 were eligible. Quantitative syntheses were stratified by outcome, FIB-4 modeling approach, and effect measure, with odds ratios (ORs) and hazard ratios (HRs) analyzed separately. Prediction intervals were calculated for random-effects analyses containing at least three independent estimates.

Twenty-two studies, including 20 cohort studies and two cross-sectional studies, were included, of which 20 contributed to at least one quantitative synthesis. Elevated categorical FIB-4 was associated with greater odds of overall stroke (OR = 1.86, 95% CI: 1.63-2.14), ischemic stroke (OR = 2.03, 95% CI: 1.72-2.40), symptomatic intracranial hemorrhage (OR = 2.52, 95% CI: 1.79-3.53), poor functional outcome (OR = 2.88, 95% CI: 2.47-3.35), and all-cause mortality (OR = 2.98, 95% CI: 2.51-3.53). Continuous FIB-4 was also associated with overall stroke (HR = 1.08, 95% CI: 1.02-1.14), symptomatic intracranial hemorrhage (OR = 1.33, 95% CI: 1.20-1.48), poor functional outcome (OR = 1.26, 95% CI: 1.11-1.43), and all-cause mortality (HR = 1.08, 95% CI: 1.03-1.12). However, prediction intervals crossed the null for the continuous analyses of poor functional outcome and all-cause mortality, and the categorical overall-stroke analysis was exploratory.

Higher FIB-4 was associated with stroke and adverse stroke-related outcomes across several observational analyses. FIB-4 may provide adjunctive risk information, but prospective validation and formal assessment of its incremental clinical value are required before routine implementation.

https://www.crd.york.ac.uk/prospero/search, identifier: CRD420251207801.

Ischemic brain injury is a major contributor to global mortality and disability. Despite extensive pathological characterization, systematic integration of rodent transcriptomic data remains limited. This study investigates orthologous transcription factors (TFs) in cerebral ischemia models and their roles in regulating neuroinflammation to develop novel diagnostic and/or predictive biomarkers.

We employed an integrated bioinformatics approach to analyze RNA-seq data from ten public datasets. Robustly up- and down-regulated differentially expressed genes (DEGs) were first identified from integrated rat and mouse datasets, followed by functional enrichment analysis. Orthologous TFs co-expressed in both species were screened from these robust DEGs and functionally characterized. Using machine learning, a diagnostic biomarker panel comprising five TFs (Atf3, Maff, Cebpa, Myc, and Relb) was identified from these conserved TFs, and the model's clinical value and diagnostic efficacy were evaluated. CIBERSORT-based immune cell infiltration analysis was performed using public datasets and in-house samples (SD rat HIE model; C57BL/6 mouse MCAO model), revealing associations between biomarkers and macrophages. Spatial localization was further assessed via scRNA-seq data. Key findings were validated in vitro using qRT-PCR and immunofluorescence staining.

Robust DEGs common to rats and mice were primarily enriched in immune cell differentiation, immune responses, and synaptic signaling. Screening identified 51 orthologous TFs similarly enriched in leukocyte differentiation and development pathways. The machine learning-derived biomarker panel (Atf3, Maff, Cebpa, Myc, Relb) demonstrated high diagnostic performance. Immune infiltration analyses revealed significant associations among Atf3, Cebpa, Relb, and macrophages across datasets and models. scRNA-seq localized their predominant expression to microglial cells. In vitro validation confirmed that Cebpa and Relb are predominantly localized within microglia.

This study identifies Cebpa and Relb as orthologous TFs in rodent cerebral ischemic injury and reveals their functional association with neuroimmune dysregulation, suggesting their potential as novel biomarkers.

Ischemia-reperfusion injury (IRI) constitutes a common pathological basis for organ dysfunction across various critical clinical conditions, including ischemic stroke, myocardial infarction, and organ transplantation. This review focuses on the functions of unconventional T cells in IRI in the brain, liver, kidneys, heart, and mucosal barrier organs, highlighting their diverse regulatory mechanisms in various tissue injury patterns. It also examines the dual functions of these cells in IRI: instead of solely acting as consistent pro-inflammatory effectors, they demonstrate a context-dependent immunomodulatory profile influenced by the organ microenvironment and disease stage, capable of promoting inflammatory damage and facilitating anti-inflammatory repair. Their behavior is shaped by a common injury response program that integrates local antigen cues, the cytokine milieu, metabolic checkpoints, and signals from the repair stage. Expounding on the spatiotemporal heterogeneity, functional plasticity, and regulatory networks of unconventional T cells in IRI will enhance our understanding of the immunopathological mechanisms. It also offers a theoretical basis and potential targets for formulating precision immunomodulatory strategies tailored to specific time windows and cell subsets.

Cardiovascular (CV) diseases, particularly ischemic heart disease and stroke, remain the leading cause of mortality worldwide and constitute a major global health challenge. Primary hyperparathyroidism (PHPT), a prevalent endocrine disorder, has recently emerged as a potential contributor to CV risk, although its impact on vascular structure and function has yet to be fully elucidated.

This systematic review and meta-analysis aimed to provide an in-depth characterization of vascular involvement by assessing markers of vascular remodeling and function in PHPT, including carotid intima-media thickness (IMT), carotid plaque prevalence, brachial artery flow-mediated dilation (FMD) and nitroglycerin-mediated dilation (NMD), as well as the effects of parathyroidectomy (PTX) on these parameters.

A comprehensive literature search was conducted across four databases (PubMed, Embase, Web of Science and Scopus) until March 2026. Original studies written in English enrolling patients with PHPT and assessing the pre-specified vascular markers using ultrasound evaluation were included. Thirty-two studies were eligible for the qualitative synthesis, of which thirty were included in the meta-analysis.

Compared with controls, PHPT patients exhibited significantly increased carotid IMT and markedly reduced FMD, indicating early structural arterial changes and endothelial dysfunction. No significant differences were observed in carotid plaque prevalence or in NMD, the latter suggesting preserved endothelium-independent vascular function. PTX was associated with a modest short-term reduction in carotid IMT at 6 months, while improvements in endothelial function were inconsistent and did not reach statistical significance.

Overall, these findings support a model in which PHPT primarily affects vascular function through endothelial impairment, followed by mild structural remodeling, rather than advanced atherosclerotic plaque formation. These alterations may represent an early and potentially reversible stage of vascular disease. Although current guidelines do not include CV involvement as an indication for surgery, vascular markers may contribute to improved risk stratification and management decisions in PHPT. Further prospective studies employing standardized vascular assessment methodologies are needed to clarify the clinical significance of these findings.

A 63-year-old woman presented with intermittent palpitations. Transoesophageal echocardiography (TEE) identified a high-velocity shunt from a tortuous left circumflex artery into an enlarged coronary sinus, with a 5-mm fistulous orifice. Coronary CT angiography delineated the full course of a congenital coronary arteriovenous fistula (CAVF), associated circumflex aneurysm, and coronary sinus dilatation. Surgical closure was successfully performed, with intraoperative confirmation of shunt resolution. This case highlights the synergistic utility of multimodal imaging: echocardiography for real-time hemodynamic assessment and CT angiography for precise anatomical mapping-which enables accurate diagnosis, optimal surgical planning, and timely intervention in anatomically complex CAVF before irreversible myocardial damage ensues.