Search Results (914)

Apparent diffusion coefficient (ADC) values, derived from diffusion-weighted magnetic resonance imaging (DW-MRI), increase with age, reflecting microstructural changes in white matter integrity. However, factors beyond chronological aging may influence cerebral diffusion characteristics. We investigated whether anticoagulant use is associated with favorable white matter ADC profiles, suggesting preserved microvascular health. ADC values were analyzed in cerebral white matter across four age-defined adult cohorts (20–59 years). Minimum, mean, and maximum ADC values were extracted. Patients at the lowest and highest ends of the ADC spectrum within each group were identified. The prevalence of anticoagulant use was compared between groups, and a logistic regression model adjusted for age was used to assess the independent association between anticoagulant use and lower ADC values. Across all cohorts (n = 892), anticoagulated patients (n = 89) were significantly overrepresented among individuals with low ADC values consistent with younger diffusion profiles. Of the anticoagulated patients, 93.3% had ADC values below the lower cut-off limit. In contrast, only 30% of non-anticoagulated patients exhibited such profiles. Anticoagulant use was independently associated with low ADC values after adjusting for age (OR = 4.89, p < 0.0001). Anticoagulation is strongly associated with lower, more favorable ADC values in cerebral white matter, independent of age. These findings support the potential neuroprotective role of anticoagulants and suggest that diffusion MRI may serve as a surrogate marker for early microvascular brain health. Full article

Background/Objectives: Chronic kidney disease (CKD) is a significant risk factor for thrombogenic and bleeding events in patients with atrial fibrillation (AF). Left atrial appendage occlusion (LAAO) is increasingly utilized as an alternative to oral anticoagulation. We aimed to compare LAAO against medical therapy in advanced CKD patients (A-CKD). Methods: We conducted a retrospective cohort study to compare patients with AF who had undergone LAAO (intervention group) or patients receiving oral anticoagulation (OAC) (control group). All of them had the diagnosis of A-CKD (estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m²). The primary endpoint was a composite of stroke, transient ischemic attack (TIA), systemic embolism (SE), and major bleeding. Secondary endpoints included: an efficacy combined endpoint (a composition of stroke, TIA, and SE); major bleedings (defined as Bleeding Academic Research Consortium (BARC) ≥ 3), and mortality at follow-up. A propensity score matching was used to balance the populations. Results: In total, 81 and 102 patients composed the LAAO and anticoagulation groups. Mean age was 78.27 ± 10.3 and 81.2 ± 9.07 (p = 0.069) and female sex was 38.3% and 44.1%, respectively. Patients who underwent LAAO had a higher HAS-BLED score: 3.46 ± 0.85 vs. 3.77 ± 1.06, p = 0.011. Median follow-up was 19.0 months [IQR: 10.9–33.5]. There were no differences in the primary combined endpoint at 3-years follow-up—22.2% vs. 34.2% (hazard ratio (HR) 0.63, CI-95%: 0.353–1.11, p = 0.102)—nor respecting the efficacy combined endpoint: 3.7% vs. 6.9% (HR 0.54, CI-95%: 0.14–2.09, p = 0.355). Patients under anticoagulation treatment did present major bleedings (BARC ≥ 3) more often than the intervention group: 38.3%vs50% (HR 0.52, CI-95%: 0.28–0.96, p = 0.031). A total of 15 patients (14.7%) from the control group underwent LAAO during follow-up. After a propensity score matching analysis, the primary combined endpoint was more frequent in the control group (HR 0.47, CI-95%: 0.25–0.90, p = 0.019). Conclusions: Compared with oral anticoagulation therapy, LAAO had no differences in efficacy, but fewer major bleeding rates were found. Full article

Background: Large vessel occlusion (LVO) strokes account for a significant proportion of ischemic strokes and are often cardioembolic in origin, particularly following atrial fibrillation (AF) with thrombus formation in the left atrial appendage (LAA). Although direct oral anticoagulation (DOAC) therapy reduces stroke risk in AF, anatomical and flow-related factors may still allow thrombi to form and persist, revealing the limitations of anticoagulation in high-risk patients. Examining structural and hemodynamic factors contributing to thrombus persistence is essential for optimizing patient management. Methods: We retrospectively analyzed 169 AF patients with LVO stroke who underwent cardiac CT (cCT) during acute stroke assessment. Patients were categorized based on the presence or absence of persistent LAA thrombi and further stratified by DOAC status. LAA volume, blood stasis and left ventricular (LV) diameter were measured. Thrombi were assessed using Hounsfield Unit (HU) analysis to evaluate potential differences in thrombus composition. Logistic regression analysis was performed to identify independent predictors of thrombus persistence with adjustment for DOAC therapy. Results: Persistent LAA thrombi were identified in 23 patients (13.6%). Patients with thrombi had significantly higher rates of stasis (p = 0.004), larger left ventricular diameters (p = 0.0019) and higher LAA volumes (p = 0.004). When adjusted for DOAC therapy, larger LAA volume (OR 1.05, p = 0.011), presence of LAA stasis (OR 6.14, p = 0.013) and increased LV diameter (OR 1.06, p = 0.006) were independent predictors of thrombus persistence. Thrombus size and HU values did not differ significantly between DOAC and non-DOAC groups. Notably, 30.4% of patients with persistent thrombi were on adequate DOAC therapy. Conclusions: LAA volume, stasis and LV enlargement predict thrombus persistence in the LAA of AF patients with LVO stroke, even under adequate DOAC therapy. These findings highlight the potential need for alternative antithrombotic strategies, including interventional LAA occlusion, and warrant further investigation into individualized stroke prevention in high-risk AF populations. Full article

Age-related macular degeneration (AMD) is a leading cause of irreversible blindness worldwide, primarily due to pathological choroidal neovascularization (CNV). Our study investigates a chemically modified heparin derivative as a novel strategy to selectively modulate angiogenic signaling, offering a reduced anticoagulant risk and preclinical support for AMD treatment. We explored the therapeutic potential of 6-O-desulfated heparin (Hep-6Od) as an antiangiogenic agent with diminished anticoagulant activity. Synthesized via selective 6-O-desulfation and characterized using nuclear magnetic resonance (NMR), Hep-6Od demonstrated safety in retinal pigment epithelial cells with no cytotoxic effects at various concentrations. In vitro, the compound significantly inhibited endothelial cell proliferation, migration, and capillary tube formation. Differential scanning fluorimetry (DSF) assays confirmed molecular interaction between Hep-6Od and fibroblast growth factor 2 (FGF-2), suggesting interference with pro-angiogenic signaling pathways. In vivo, a laser-induced CNV model in lean Zucker rats showed a dose-dependent reduction in neovascular lesion areas after an intravitreal Hep-6Od injection. Compared to unfractionated heparin, Hep-6Od exhibited reduced anticoagulant effects in PT and aPTT assays while maintaining robust antiangiogenic properties. These findings support Hep-6Od as a promising alternative to anti-vascular endothelial growth factor (VEGF) therapies for AMD treatment, potentially expanding current retinal vascular disease interventions. The results underscore its potential to transform AMD management, pending further clinical validation and awaiting confirmation in further studies. Full article

In patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI), antiplatelet therapy is the cornerstone of treatment for secondary prevention. Although dual antiplatelet therapy (DAPT) consisting of aspirin and a P2Y₁₂ inhibitor is the current standard of care, being, respectively, recommended for 6 and 12 months in patients with chronic and acute coronary syndrome without a need for oral anticoagulation, the continuous improvement in PCI technology and pharmacology have significantly reduced the need for long-term DAPT. Mounting evidence supports the administration of P2Y₁₂ inhibitor monotherapy, particularly ticagrelor, after a short period of DAPT following PCI as a strategy to reduce bleeding without a trade-off in ischemic events compared to standard DAPT. In addition, there is a growing literature supporting P2Y₁₂ inhibitor monotherapy also for long-term secondary prevention of ischemic events. However, the data to this extent are not as robust as compared to the first-year post-PCI period, with aspirin monotherapy still remaining the mainstay of treatment for most patients. This review aims to summarize the rationale for long-term antiplatelet therapy, the pharmacology of current antiplatelet drugs tested for long-term administration as monotherapy, and current evidence on the available comparisons between different long-term antiplatelet monotherapies in patients with CAD. Full article

The association between COVID-19 vaccination and thromboembolic events has garnered significant research attention, particularly with the advent of vaccines based on adenoviral vectors, including AstraZeneca’s and Johnson & Johnson’s vaccines. This review underscores the uncommon occurrence of venous thromboembolism (VTE), arterial thromboembolism (ATE), and vaccine-induced thrombotic thrombocytopenia (VITT) following COVID-19 vaccination. Although these complications are extremely rare compared to the heightened risk of thrombosis from COVID-19 infection, elements like age, biological sex, type of vaccine and underlying health conditions may contribute to their development. In addition, rare renal complications such as acute kidney injury and thrombotic microangiopathy have been documented, broadening the spectrum of potential vaccine-associated thrombotic manifestations. Current guidelines emphasize early detection, individualized risk assessment, and use of anticoagulation therapy to mitigate risks. Despite these events, the overwhelming majority of evidence supports the continued use of COVID-19 vaccines, given their proven efficacy in reducing severe illness and mortality. In addition, recent comparative data confirm that mRNA-based vaccines are associated with a significantly lower risk of serious thrombotic events compared to adenoviral vector platforms. Ongoing research is essential to further refine preventive and therapeutic strategies, particularly for at-risk populations. Full article

Background/Objectives: Direct oral anticoagulants (DOACs) are now the guideline-recommended alternative to vitamin K antagonists (VKAs) for long-term anticoagulation in patients with non-valvular atrial fibrillation. However, accurately assessing their impact on ischemic stroke outcomes remains challenging, primarily due to uncertainty regarding anticoagulation status at the time of hospital admission. This preliminary study addresses this gap by using point-of-care testing (POCT) to confirm DOAC activity at bedside, allowing for a more accurate comparison of 90-day functional outcomes between anticoagulated and non-anticoagulated stroke patients. Methods: We conducted a retrospective cohort study of 786 ischemic stroke patients admitted to the University of Pécs between February 2023 and February 2025. Active DOAC therapy was confirmed using the ClotPro^® viscoelastic testing platform, with ecarin Clotting Time (ECT) employed for thrombin inhibitors and Russell’s Viper Venom (RVV) assays for factor Xa inhibitors. Patients were categorized as non-anticoagulated (n = 767) or DOAC-treated with confirmed activity (n = 19). Mahalanobis distance-based matching was applied to account for confounding variables including age, sex, pre-stroke modified Rankin Scale (mRS), and National Institutes of Health Stroke Scale (NIHSS) scores at admission and 72 h post-stroke. The primary outcome was the change in mRS from baseline to 90 days. Statistical analysis included ordinary least squares (OLS) regression and principal component analysis (PCA). Results: After matching, 90-day functional outcomes were comparable between groups (mean mRS-shift: 2.00 in DOAC-treated vs. 1.78 in non-anticoagulated; p = 0.745). OLS regression showed no significant association between DOAC status and recovery (p = 0.599). In contrast, NIHSS score at 72 h (p = 0.004) and age (p = 0.015) were significant predictors of outcome. PCA supported these findings, identifying stroke severity as the primary driver of outcome. Conclusions: This preliminary analysis suggests that ischemic stroke patients with confirmed active DOAC therapy at admission may achieve 90-day functional outcomes comparable to those of non-anticoagulated patients. The integration of bedside POCT enhances the reliability of anticoagulation assessment and underscores its clinical value for real-time management in acute stroke care. Larger prospective studies are needed to validate these findings and to further refine treatment strategies. Full article

Background and Clinical Significance: Hemophagocytic lymphohistiocytosis (HLH) and autoimmune hemolytic anemia (AIHA) are both life-threatening hematologic syndromes that rarely present together outside of malignancy. Advanced acquired immunodeficiency syndrome (AIDS) creates a milieu of profound immune dysregulation and hyperinflammation, predisposing patients to atypical overlaps of these disorders. Case Presentation: A 30-year-old woman with poorly controlled AIDS presented with three weeks of jaundice, fever, and fatigue. Initial labs revealed pancytopenia, hyperbilirubinemia, and elevated ferritin level. Direct anti-globulin testing confirmed warm AIHA (IgG⁺/C3d⁺) with transient cold agglutinins. Despite intravenous immunoglobulin (IVIG), rituximab, and transfusions, she developed hepatosplenomegaly, extreme hyperferritinemia, and sIL-2R > 10,000 pg/mL, meeting HLH-2004 criteria. Bone marrow biopsy excluded malignancy; further work-up revealed Epstein–Barr virus (EBV) viremia and cytomegalovirus (CMV) reactivation. Dexamethasone plus reduced-dose etoposide transiently reduced soluble interleukin-2 receptor (sIL-2R) but precipitated profound pancytopenia, Acute respiratory distress syndrome (ARDS) from CMV/parainfluenza pneumonia, bilateral deep vein thrombosis (DVT), and an ST-elevation myocardial infarction (STEMI). She ultimately died of hemorrhagic shock after anticoagulation despite maximal supportive measures. Conclusions: This case underscores the diagnostic challenges of HLH-AIHA overlap in AIDS, where cytopenias and hyperferritinemia mask the underlying cytokine storm. Pathogenesis likely involved IL-6/IFN-γ overproduction, impaired cytotoxic T-cell function, and molecular mimicry. While etoposide remains a cornerstone of HLH therapy, its myelotoxicity proved catastrophic in this immunocompromised host, highlighting the urgent need for cytokine-targeted agents to mitigate treatment-related mortality. Full article

Background/Objectives: Most snakebite incidents in Latin America are caused by species of the Bothrops genus. Their venom induces severe local effects, against which antivenom therapy has limited efficacy. Metabolites derived from Coffea arabica have demonstrated anti-inflammatory and anticoagulant properties, suggesting their potential as therapeutic agents to inhibit the local effects induced by B. asper venom. Methods: Three enzymatic assays were performed: inhibition of the procoagulant and amidolytic activities of snake venom serine proteinases (SVSPs); inhibition of the proteolytic activity of snake venom metalloproteinases (SVMPs); and inhibition of the catalytic activity of snake venom phospholipases A₂ (PLA_2s). Additionally, molecular docking studies were conducted to propose potential inhibitory mechanisms of the metabolites chlorogenic acid, caffeine, and caffeic acid. Results: Green and roasted coffee extracts partially inhibited the enzymatic activity of SVSPs and SVMPs. Notably, the green coffee extract, at a 1:20 ratio, effectively inhibited PLA₂ activity. Among the individual metabolites tested, partial inhibition of SVSP and PLA₂ activities was observed, whereas no significant inhibition of SVMP proteolytic activity was detected. Chlorogenic acid was the most effective metabolite, significantly prolonging plasma coagulation time and achieving up to 82% inhibition at a concentration of 62.5 μM. Molecular docking analysis revealed interactions between chlorogenic acid and key active site residues of SVSP and PLA₂ enzymes from B. asper venom. Conclusions: The roasted coffee extract demonstrated the highest inhibitory effect on venom toxins, potentially due to the formation of bioactive compounds during the Maillard reaction. Molecular modeling suggests that the tested inhibitors may bind to and occupy the substrate-binding clefts of the target enzymes. These findings support further in vivo research to explore the use of plant-derived polyphenols as adjuvant therapies in the treatment of snakebite envenoming. Full article

Background: Risk assessment in hyperthyroidism remains challenging. The aim of the present study is to determine the influence of hyperthyroid metabolic status on blood clotting and an increased risk of thrombosis. Methods: This prospective study included 50 patients after radical thyroidectomy and ablative radioiodine therapy because of thyroid carcinoma who were compared with 50 control subjects in a euthyroid metabolic state. Latent hyperthyroid patients with basal thyroid-stimulating hormone (TSH) ≤ 0.15 mU/L on levothyroxine hormone therapy were included. The control group was selected to match the patient group based on age and sex. The evaluation data were collected using laboratory coagulation tests and patient questionnaires. A bleeding and a thrombosis score were determined. Results: The coagulation parameters between the patient and control groups showed statistically significant differences. In particular, the patients’ group showed a significantly shortened activated partial thromboplastin time (aPTT/p = 0.009) and a significantly higher plasminogen activator inhibitor 1 (PAI-1/p < 0.001) compared to the control group. Age, sex, and medication use were not found to influence the patients’ laboratory results. Only body mass index was higher in the patient group than in the control group. Conclusions: Our results support a shift in the coagulation system in latent hyperthyroid metabolism towards increased coagulability and reduced fibrinolysis. A latent hyperthyroid metabolic state appears to be associated with an increased risk of thrombosis. Further prospective cohort studies with large patient populations are needed to verify the association between (latent) hyperthyroidism and thromboembolic events as well as to determine therapeutic anticoagulation or to adjust the indication for exogenous administration of thyroid hormone. Full article

Oral anticoagulants, including warfarin, a vitamin K antagonist, have been used for anticoagulation therapy, but their limitations, such as drug interactions and complex dosing, have prompted the development of direct oral anticoagulants (DOACs) like rivaroxaban, apixaban, dabigatran, and edoxaban. This study reviews the interactions of both warfarin and DOACs, particularly those influenced by cytochrome P450 enzymes and P-glycoprotein. Warfarin is metabolized by various cytochrome P450 isoforms, making it vulnerable to interactions with medications and herbs that modulate these enzymes. In contrast, DOACs, while having fewer interactions, are still affected by strong inducers or inhibitors of cytochrome 3A4 and P-glycoprotein, depending on the specific drug. Some herbs may also interfere with these pathways. Continuous monitoring of these interactions is crucial to ensure the safe use of oral anticoagulants. The findings underscore the importance of identifying and understanding these interactions to improve patient safety and guide appropriate anticoagulant therapy. Full article

Background: Atrial fibrillation (AF) is one of the most common heart rhythm disorders encountered in clinical practice. Emerging evidence suggests a significant role of inflammation in the pathogenesis of AF, but certain questions still remain unanswered, in particular whether AF-related inflammation is a cause or a consequence of the arrhythmia, and whether inflammation reflects underlying disease or AF itself. At the current state of the art, scientific evidence on the role of oral anticoagulants (OAC) in modulating pro-inflammatory cytokines implicated in the pathogenesis of AF remains scarce. The aim of our study was to evaluate, in a population of AF patients undergoing OAC, the different roles of anticoagulant therapy [Vitamin K antagonists (VKAs) and direct oral anti-coagulants (DOACs)] in modulating the levels of inflammatory biomarkers in AF. Methods: The Strat-AF study is an observational, prospective, single center, hospital-based study enrolling elderly patients with AF. Results refer to 170 subjects with complete clinical and biohumoral assessment. Results: At multivariate logistic regression analysis, adjusted for several covariates, VKA treatment was an independent protective predictor for having a high grade of inflammation not balanced by anti-inflammatory cytokine levels [OR = 0.26 (0.10–0.69), p = 0.007]. Conclusions: These results from the Strat-AF study are “generators of hypotheses” and provide preliminary evidence for the differential effects of VKAs and DOACs on inflammatory biomarkers (e.g., IL-6, TNF-α) in AF patients. These findings suggest that inflammatory biomarkers could enhance stroke risk prediction models, potentially improving a tailored AF management. Full article

Background and Aims: Sodium-glucose cotransporter-2 (SGLT2) inhibitors have shown promise in metabolic dysfunction-associated steatotic liver disease (MASLD). This large real-world study aimed to evaluate the effects of SGLT2 inhibitors on MASLD patients’ clinical outcomes and liver-related complications over extended follow-up. Patients and Method: Data were sourced from TriNetX, a global health research platform with de-identified electronic medical records spanning 135 million patients across 112 healthcare organizations worldwide. We included MASLD adults diagnosed according to ICD9/10 criteria. Following propensity score matching based on 34 variables (demographics, comorbidities, laboratory tests and medication history), SGLT2 inhibitor-treated (n = 19,922) patients were compared with non-SGLT2 inhibitor (n = 19,922) cases. Exclusion criteria included baseline improved alanine aminotransferase (ALT) and alkaline phosphatase (ALP) levels > 4 upper normal limit (UNL), baseline advanced liver disease, liver transplant and cancer, past anticoagulation and non-MASLD etiologies. Assessed outcomes included survival, biochemical, hematologic, AFP, metabolic and cardiovascular parameters, progression to advanced liver disease (ALD), synthetic function, and metabolic markers over 1, 5, and 10 years. Results: Following matching, both cohorts were well-balanced across baseline characteristics. After one year, the SGLT2 inhibitor group demonstrated significantly reduced BMI (33.2 ± 6.2 vs. 34.1 ± 6.5 kg/m², p < 0.001), improved ALT (40.3 ± 31.5 vs. 48.3 ± 41.2 U/L, p < 0.001), and better glycemic control (HbA1c 7.35 ± 1.51% vs. 7.93 ± 1.72%, p < 0.001). The SGLT2 inhibitor group showed higher 10-year survival rates (95.00% vs. 88.69%, p < 0.001), fewer cardiovascular events (10.19% vs. 11.80%, p < 0.001), and markedly reduced progression to advanced liver disease (6.90% vs. 14.15%, p < 0.001). These benefits were consistent across clinical, laboratory, and medication-defined ALD categories. Notably, rates of hepatic decompensation events were significantly lower with SGLT2 inhibitor therapy. Conclusions: In this large real-world cohort, SGLT2 inhibitor use in MASLD patients was associated with significantly improved long-term survival, cardiovascular, and liver-related outcomes over 10 years of follow-up. These benefits likely result from combined metabolic improvements, anti-inflammatory effects, and direct hepatoprotective mechanisms. SGLT2 inhibitors represent a promising therapeutic strategy for improving outcomes in MASLD. Full article

Background: Direct oral anticoagulants (DOACs) are generally preferred over warfarin for preventing arterial and venous thromboembolism. However, the efficacy and safety of DOACs in patients with extremely low body weight (BW) are uncertain. This study investigates anti-factor Xa (anti-FXa) activity of apixaban and compares it between patients with normal BW (>50 kg) and underweight (≤50 kg). Methods: We enrolled 150 patients on branded generic apixaban (Apixan^TM) for atrial fibrillation (AF), venous thromboembolism, and intracardiac thrombus. Anti-FXa activity of apixaban was measured at peak concentration (C_peak) and trough concentration (C_trough) after at least one week of therapy. Results: Mean age was 64.0 ± 12.7 years, with 53.3% being male. Mean BW was 61.3 ± 15.3 kg. Of the 150 patients, 132 (88%) had AF, and 43 (28.7%) had low BW. Overall, 87.3% and 84.7% of patients had C_trough and C_peak within the expected range. Underweight patients had significantly higher mean C_trough and C_peak than normal BW patients. A higher proportion of low-BW patients exceeded the expected C_peak range compared to normal-BW patients (25.6% vs. 3.7%, p < 0.001). Low BW was the only independent predictor of exceeding C_peak specified range (adjusted OR 4.87, 95% CI 1.31–18.15, p = 0.018). Conclusions: Most patients maintained apixaban levels within expected ranges, but those with low BW were more likely to exceed the specified range of C_peak. Full article

Background/Objectives: Atrial fibrillation (AF) is the most significant modifying risk factor for the development of cardioembolic stroke, which is associated with worse outcomes and higher intrahospital mortality compared to other types of ischemic stroke. Antithrombotic medications are administered as prophylactic treatment in patients with a risk of stroke. The aim of this study was to determine outcome measures in patients with first-ever ischemic stroke and AF regarding prior antithrombotic therapy. Methods: We collected data on stroke risk factors, CHADS₂ score, and international normalized ratio (INR) value in the context of warfarin therapy, as well as data related to localization, stroke severity, and functional outcome at discharge. Results: A total of 754 subjects with first-ever ischemic stroke and AF were included in this cross-sectional study (122 on warfarin, 210 on acetylsalicylic acid, and 422 without prior antithrombotic therapy). The diagnosis of AF was previously unknown in 31% of the subjects. Stroke risk factors (arterial hypertension, hyperlipidemia, diabetes mellitus, and cardiomyopathy) were significantly lower in the group without prior antithrombotic therapy. The anticoagulant group was significantly younger (p = 0.001). Overall, 45.4% of subjects with a previously known AF event and a high risk of developing stroke received anticoagulant therapy. Participants on warfarin had a significantly better functional outcome than those on antiplatelet therapy or without prior antithrombotic therapy (median mRS 4 vs. 5 vs. 5; p = 0.025) and lower NIHSS scores, although the difference was not statistically significant (median 10 vs. 12 vs. 12; p = 0.09). There was no difference between stroke localization among groups (p = 0.116). Conclusions: Our study showed that, in our cohort, first-ever ischemic stroke due to AF was more common in women. Subjects on prior anticoagulant therapy had more favorable outcomes at discharge. Full article