Journal of Thrombosis and Thrombolysis最新文献

{"title":"Clinical spectrum and mechanistic insights into cardiotoxicity from cancer therapies.","authors":"Richard C Becker","doi":"10.1007/s11239-026-03336-x","DOIUrl":"10.1007/s11239-026-03336-x","url":null,"abstract":"<p><p>Cardiotoxicity is a major concern in oncology, influencing both patient safety and therapeutic decision-making. Part 1 of a dedicated 3-part series provides a comprehensive overview of the fundamentals of cardiotoxicity associated with cancer therapeutics, beginning with a definition of cardiotoxicity and classifying its mechanisms into direct myocardial injury, indirect cardiovascular effects, and a combination of both. Clinical manifestations are examined across the spectrum of presentations, from asymptomatic cardiac biomarker elevations to overt heart failure, alongside current detection strategies including imaging and patient-reported outcomes. Timing and incidence patterns are analyzed to highlight early versus delayed toxicity and their implications for surveillance strategies used in clinical practice. Guideline-directed therapies are summarized and suggestions for drug development that concomitantly begins to frame cardiotoxic effects are introduced. Lastly, the impact of cardiotoxicity on cancer treatment decisions, including dose modifications, therapy discontinuation, multidisciplinary management, is considered to establish a clear context for optimal patient care.</p>","PeriodicalId":17546,"journal":{"name":"Journal of Thrombosis and Thrombolysis","volume":" ","pages":"1825-1834"},"PeriodicalIF":2.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13654869/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148143800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Time- and risk-dependent effects of dual antiplatelet therapy targeting the P2Y12 receptor after CABG: A network meta-analysis of graft permeability and clinical outcomes.","authors":"Yuan Zhou, Xiaoyu Zhang, Wenting Gui, Jiahui Xie, Jiaxiang Chen, Yi Song, Runwei Ma","doi":"10.1007/s11239-026-03330-3","DOIUrl":"10.1007/s11239-026-03330-3","url":null,"abstract":"<p><p>The optimal anticoagulation strategy following Coronary artery bypass grafting remains undetermined, particularly regarding the balance between graft patency, ischemic events, and bleeding across different follow-up periods and risk profiles. A systematic search was conducted in PubMed, Embase, Web of Science, and the Cochrane Database to identify randomized controlled trials comparing regimens of aspirin, DAPT (clopidogrel or ticagrelor), and rivaroxaban. The primary angiographic endpoints were saphenous vein graft(SVG) patency and the left internal mammary artery(LIMA) occlusion; clinical endpoints included myocardial infarction, major adverse cardiovascular events(MACE), major bleeding, and all-cause mortality. A random-effects network meta-analysis was conducted, reporting odds ratios (OR) and 95% CIs, with pre-specified 1-year follow-up stratification and multiple subgroup analyses.The primary analysis included 17 RCTs with 1-year follow-up (9,831 patients). SVG occlusion: Aspirin plus ticagrelor (OR = 0.41,95% CI:0.30-0.56) and aspirin plus clopidogrel (OR = 0.59, 95% CI: 0.44-0.78) were both significantly superior to aspirin monotherapy. MACE: Compared with aspirin monotherapy, no anticoagulation strategy showed a statistically significant difference. Major bleeding: Aspirin plus ticagrelor (OR = 2.53,95% CI:1.59-4.04) and rivaroxaban monotherapy (OR = 2.33, 95% CI: 1.01-5.37) significantly increased the risk. No strategy showed statistically significant differences in myocardial infarction or all-cause mortality. No clear conclusions could be drawn regarding LIMA occlusion due to the rarity of events. Subgroup analysis: In the subgroups of off-pump CABG (OR = 0.42, 95% CI: 0.19-0.90) and early initiation ≤ 48 h (OR = 0.47, 95% CI: 0.29-0.75), the combination of aspirin and ticagrelor significantly reduced MACE; however, the risk of bleeding increased with this regimen when initiation was delayed (> 48 h) (OR = 2.51, 95% CI: 1.52-4.16). Sensitivity analyses showed that the conclusions regarding SVG occlusion and major bleeding were highly robust (the direction and significance of ORs remained consistent across all sensitivity scenarios), whereas estimates for MACE and all-cause mortality were sensitive to specific studies. The net benefit of post-CABG antithrombotic therapy is time- and patient-specific. DAPT (particularly aspirin plus clopidogrel) offers the optimal balance between revascularization protection and bleeding risk; the ticagrelor regimen provides stronger ischemic protection but comes at a higher cost of bleeding; the rivaroxaban regimen is not suitable for routine use. An individualized antithrombotic strategy based on risk stratification is recommended.</p>","PeriodicalId":17546,"journal":{"name":"Journal of Thrombosis and Thrombolysis","volume":" ","pages":"1711-1727"},"PeriodicalIF":2.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148015641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systemic immune-inflammation index predicts left atrial thrombus in non-valvular atrial fibrillation: A retrospective study of 847 patients.","authors":"Yu Wang, Shaohua Zhou, Chunge Zhang, Hui Zhang","doi":"10.1007/s11239-026-03323-2","DOIUrl":"10.1007/s11239-026-03323-2","url":null,"abstract":"<p><p>Non-valvular atrial fibrillation (NVAF) serves as a primary cause of cardioembolic stroke, with left atrial thrombus (LAT) functioning as its major thrombotic substrate. The systemic immune-inflammation index (SII) has gained recognition as a dependable biomarker in cardiovascular disease. Nevertheless, its relationship with LAT in NVAF patients has not been thoroughly characterized in large-scale investigations. This retrospective study enrolled 847 NVAF patients who underwent transesophageal echocardiography (TEE). The primary outcome was TEE-detected left atrial thrombus (LAT). Patients were stratified into LAT-positive and LAT-negative groups. Univariable and multivariable logistic regression analyses identified independent predictors of LAT. Receiver operating characteristic (ROC) curve analysis evaluated the diagnostic performance of SII compared to the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and CHA₂DS₂-VASc score. Restricted cubic spline (RCS) analysis assessed the dose-response relationship between SII and LAT risk, and prespecified subgroup analyses examined whether this association remained consistent according to oral anticoagulant (OAC) use and other clinical strata. Of 847 patients, 142 (16.8%) were LAT-positive. Elevated SII was an independent predictor of LAT (OR = 1.13, 95% CI: 1.08-1.18 per 100-unit increase; P < 0.001) after adjusting for conventional risk factors. The optimal SII cutoff was 712.5 (AUC 0.786), showing slightly better discrimination than NLR, PLR, and CHA₂DS₂-VASc score. RCS analysis revealed a significant nonlinear dose-response relationship between SII and LAT risk, and the association remained consistent in both adequate-OAC and non-OAC subgroups. Elevated SII is independently associated with LAT in NVAF patients and offers useful discriminatory performance as an adjunct, rather than a standalone substitute, for established clinical assessment. As a readily accessible hematological parameter, SII may help identify patients with a low probability of LAT while supporting individualized decisions regarding TEE referral and anticoagulation management.</p>","PeriodicalId":17546,"journal":{"name":"Journal of Thrombosis and Thrombolysis","volume":" ","pages":"1792-1803"},"PeriodicalIF":2.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148005768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-cell transcriptomics reveals NDRG1/TGF‑β1 associated vascular smooth muscle cell phenotypic switching in chronic thromboembolic pulmonary hypertension.","authors":"Kai Zheng, Xia Zheng, Jie Li, Mingyuan Xu, Bin He, Xiaopeng Liu, Bo Ma, Jie Chen, Ran Miao, Zhidong Ye, Zhenguo Zhai, Peng Liu, Yanan Zhen","doi":"10.1007/s11239-026-03288-2","DOIUrl":"10.1007/s11239-026-03288-2","url":null,"abstract":"<p><p>Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by a unique combination of mechanical obstruction resulting from organized thrombi and a variable degree of secondary small-vessel remodeling, both of which contribute to increased pulmonary vascular resistance. In this process, pulmonary artery smooth muscle cell (SMC) phenotypic switching plays a critical role in the progression of microvascular disease. However, the underlying molecular mechanisms remain incompletely elucidated. Single-cell RNA sequencing (scRNA-seq) data from CTEPH patients and normal pulmonary artery tissues (GSE224143, GSE228644) were integrated. After data preprocessing, unsupervised clustering, and cell type annotation using Seurat, we focused on SMC subtype analysis and constructed functional landscapes via pseudobulk DESeq2, Gene Ontology (GO) enrichment analysis, Monocle3 pseudotime trajectory analysis, and high-dimensional weighted gene co-expression network analysis (hdWGCNA). Core findings were validated using bulk RNA-seq datasets (GSE84538) and experimental approaches, including Western blotting, immunofluorescence, EdU proliferation assay, and Transwell/scratch wound healing migration assay. scRNA-seq analysis identified 18 distinct cell clusters in pulmonary vascular tissues. Compared with controls, CTEPH tissues showed reduced fibroblasts and increased immune cells (T cells, monocytes/macrophages) and SMCs. Four SMC phenotypes were identified, with a marked expansion of fibroblast-like SMCs in CTEPH and a dynamic transition from contractile to fibroblast-like phenotype confirmed by pseudotime analysis. Upregulated genes in CTEPH SMCs were enriched in extracellular matrix organization and TGF-β signaling pathways (significantly activated). Cross-validation via hdWGCNA, pseudotime trajectory, and bulk RNA-seq data identified NDRG1 (a hypoxia-inducible gene) as a core gene. NDRG1 was significantly overexpressed in CTEPH SMCs and tissues, positively correlating with pulmonary vascular resistance (PVR). Functional experiments showed that NDRG1 knockdown inhibited hypoxia-induced migration/proliferation of human pulmonary artery smooth muscle cells (HPASMCs), suppressed TGF-β/SMAD pathway activation, and reduced fibroblast-like phenotype marker (Vimentin, COL1A1) expression. NDRG1 is associated with SMC phenotypic switching toward the fibroblast-like phenotype and promotes pulmonary vascular remodeling in CTEPH via the TGF-β/SMAD pathway. NDRG1 and related key gene axes may serve as potential therapeutic targets for CTEPH.</p>","PeriodicalId":17546,"journal":{"name":"Journal of Thrombosis and Thrombolysis","volume":" ","pages":"1944-1959"},"PeriodicalIF":2.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148055270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pulmonary embolism associated with CRBN-targeting immunomodulatory drugs: a FAERS-based pharmacovigilance and mechanistic analysis.","authors":"Bingda Li, Yi Xu, Yu Liu, Mingbin Hu, Shu Liao, Yun Tu","doi":"10.1007/s11239-026-03309-0","DOIUrl":"10.1007/s11239-026-03309-0","url":null,"abstract":"<p><p>CRBN-targeting immunomodulatory drugs (IMiDs), including lenalidomide and pomalidomide, are widely used in hematologic malignancies but are associated with an elevated risk of venous thromboembolism (VTE). However, real-world risk patterns and the potential biological mechanisms underlying pulmonary embolism (PE) remain incompletely characterized. We conducted a comprehensive pharmacovigilance analysis using the FDA Adverse Event Reporting System (FAERS) from 2004 to Q3 2025. Disproportionality analyses (ROR, PRR, BCPNN, MGPS) and Weibull distribution modeling were employed to assess signal strength and time-to-onset (TTO). Systems biology tools, including network pharmacology and enrichment analyses (GO, KEGG), were used to uncover shared and drug-specific pathogenic pathways. Bibliometric mapping of core literature further validated mechanistic insights and policy relevance. A total of 2,428 and 372 PE cases were identified for lenalidomide and pomalidomide, respectively. Both drugs exhibited an \"early failure\" risk profile (β < 1), with a shorter median TTO for lenalidomide (81.5 days) compared to pomalidomide (134 days). High-risk subgroups included males, elderly patients (65-85 years), and individuals with obesity (> 100 kg). The PI3K-Akt pathway emerged as a central mechanism for endothelial dysfunction and thrombogenesis. Pomalidomide showed additional enrichment in fluid shear stress and TNF signaling pathways. Literature analysis confirmed alignment with core topics such as thrombotic events, platelet function, and prophylactic anticoagulation. Our findings highlight an urgent need to shift from empirical anticoagulation to precision-based thromboprophylaxis in patients treated with CRBN-targeting IMiDs. Early-onset PE risk is mechanistically linked to vascular endothelial injury and inflammatory signaling, supporting the use of dynamic risk stratification tools (e.g., IMPEDE-VTE score) and early DOAC intervention. Public health policy should integrate molecular insights with real-world surveillance to optimize clinical safety frameworks for oncology patients.</p>","PeriodicalId":17546,"journal":{"name":"Journal of Thrombosis and Thrombolysis","volume":" ","pages":"1930-1943"},"PeriodicalIF":2.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148005776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Outcomes of Venous-Arterial Extracorporeal Membrane Oxygenation Therapy in Acute Pulmonary Embolism: A Single-Center Experience.","authors":"Caleb J Chiang, Laith Alhuneafat, Peter S Salama, Andrea M Elliott, Demetris Yannopoulos, Jason A Bartos, Alejandra Gutierrez Bernal","doi":"10.1007/s11239-026-03298-0","DOIUrl":"10.1007/s11239-026-03298-0","url":null,"abstract":"<p><p>Outcomes of venous-arterial extracorporeal membrane oxygenation (VA-ECMO) therapy in acute pulmonary embolism. High-risk pulmonary embolism (PE) has a high mortality risk. VA-ECMO provides essential cardiopulmonary support, although data outcomes remain limited. We sought to describe the characteristics and clinical outcomes of patients supported with VA-ECMO for the management of high-risk PE. We retrospectively analyzed outcomes of adult patients treated with VA-ECMO for high-risk PE at the University of Minnesota between January 2015 and May 2024. High-risk PE was defined by the European Society of Cardiology criteria. Clinical, demographic, procedural, and outcome data were analyzed. Mortality predictors were assessed using logistic regression. Of 1350 patients supported by VA-ECMO, 58 (4.3%) presented with high-risk PE (69% cardiac arrest, 31% shock). Mortality was significantly higher among patients cannulated for cardiac arrest than for shock (72.5% vs. 33.3%, P = 0.005). An independent predictor of mortality was out-of-hospital cardiac arrest (OR 6.67, 95% CI 1.15-38.7, P = 0.035). The duration of CPR was shorter among survivors (25.9 vs. 44.2 min, P = 0.02). Neither catheter-directed therapy nor systemic thrombolysis was associated with survival. Major bleeding occurred in 67% of patients and was not significantly associated with mortality. Neurologic injury was the leading cause of death in cardiac arrest patients; multiorgan failure predominated in the shock group. Despite the use of VA-ECMO, mortality in high-risk PE remains elevated, but differed by indication for cannulation. Survival was higher in patients presenting with shock, in-hospital cardiac arrest, shorter CPR duration, and sustained return of spontaneous circulation. Further research is needed to define the role of VA-ECMO and adjunctive therapies across varied clinical presentations.</p>","PeriodicalId":17546,"journal":{"name":"Journal of Thrombosis and Thrombolysis","volume":" ","pages":"1739-1748"},"PeriodicalIF":2.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13654874/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147973468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Temporal Trends and Future Projections of P ulmonary Embolism and Top Contributing Causes of death in the United States, 1968-2040: insights from the CDC WONDER database.","authors":"Saifullah Khan, Faizan Abbas, Muhammad Hassan, Muhammad Hussain, Muhammad Ahmed, Aiza Ahsan, Shaheer Qureshi, Nisha Khalid, Asim Sajjad, Maria Baig, Saad Ahmed Waqas, Gregg C Fonarow, Stephen J Greene, Faizan Ahmed","doi":"10.1007/s11239-026-03281-9","DOIUrl":"10.1007/s11239-026-03281-9","url":null,"abstract":"<p><p>Pulmonary embolism (PE) is a preventable yet often deadly cardiovascular event. We aimed to investigate PE mortality trends from 1968-2023 and forecast rates through 2040 in the U.S. We analyzed CDC WONDER death certificates for adults ≥ 25 years. Age-adjusted mortality rates (AAMRs), annual percent changes (APCs) were used to analyse trends and Auto-ARIMA/Prophet forecasting models were used for future projections, all stratified by sex, age, race, and contributing cause of death. From 1968-2023, 516,187 PE deaths occurred, with a mean AAMR of 6.06 per 100,000 (AAPC -1.85). Mean AAMRs were 6.76 in men and 5.57 in women. By age, rates averaged 0.98 for adults 25-44 years, 3.96 for 45-64 years, and 21.73 for ≥ 65 years. Black adults had a mean AAMR of 10.87 versus 5.76 in White adults. From 1999-2023, PE death linked to Coronary Artery Disease, COPD, infection, and diabetes declined, while PE death linked to hypertension rose and heart failure related PE plateaued. Forecasts project an overall AAMR of 3.63 by 2040 (2.32 in men, 3.25 in women), with the highest predicted rate of 9.24 among adults ≥ 65 years. Projected racial AAMRs are 3.70 in White and 7.71 in Black individuals. Hypertension and heart failure linked rates are expected to rise further. Despite a sustained decline in PE death since 1968, persistent racial gaps, aging populations, and rising hypertension and heart-failure related PE threaten progress, highlighting the need for targeted prevention and equitable cardiovascular risk management.</p>","PeriodicalId":17546,"journal":{"name":"Journal of Thrombosis and Thrombolysis","volume":" ","pages":"1985-1995"},"PeriodicalIF":2.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13654879/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148005732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Methodological Approaches in the Evaluation of Platelet Structure and Function: An Instrumental Perspective.","authors":"Samir Kumar Beura, Paresh P Kulkarni, Sunil Kumar Singh","doi":"10.1007/s11239-026-03401-5","DOIUrl":"https://doi.org/10.1007/s11239-026-03401-5","url":null,"abstract":"<p><p>Platelets are anucleate yet metabolically active cells that play essential roles in hemostasis, thrombosis, and inflammation by rapidly responding to vascular injury and maintaining vascular integrity. Alteration of platelets can lead to bleeding disorders or thrombotic complications. Therefore, studying their structural and functional properties is essential for understanding their roles in both physiological and pathological processes. Recent advances in experimental techniques have revolutionized platelet research. It has allowed high-resolution structural visualization, precise functional assessment, and detailed mapping of interplatelet interactions. Recently, platelet count and structure have been assessed using specialized techniques. For example, automated hematology analyzers provide accurate platelet counts, while light and electron microscopy reveal platelet morphology and ultrastructure. Flow cytometry evaluates platelet size, granularity, and surface markers. In addition, the platelet function is assessed through different instruments and assays. For example, adhesion is studied using microscopy-based assays, aggregation by light transmission aggregometry. Similarly, activation, and secretion are measured by fluorescence microscopy or flow cytometry. The clot retraction is evaluated using Sonoclot or thromboelastography. Although, several studies have described techniques for assessing the platelet count, structure and function, a single comprehensive narrative review is lacking. Therefore, in this review, we summarize current techniques for assessing platelet structure and function. We also cover both classical and newly developed methods. We highlight recent technical advances and analytical challenges. In addition, we discuss innovations such as artificial intelligence-assisted data analysis. This review aims to help researchers select appropriate methods for studying platelet biology and its role in health and disease.</p>","PeriodicalId":17546,"journal":{"name":"Journal of Thrombosis and Thrombolysis","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149069898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting RUNX3 alleviates abdominal aortic aneurysm by ameliorating oxidative stress via mitophagy.","authors":"Zhongxiao Zhou, Xiaowei Wang, Guangxin Shao, Haimeng Zhou","doi":"10.1007/s11239-026-03399-w","DOIUrl":"https://doi.org/10.1007/s11239-026-03399-w","url":null,"abstract":"<p><p>This study aims to investigate the role of RUNX3 in the pathogenesis and progression of abdominal aortic aneurysm (AAA). AAA is a critical vascular disease characterized by progressive dilation of the aortic wall, and as the aneurysm grows, the risk of rupture significantly increases, leading to sharply elevated mortality. Recent studies have indicated that mitochondrial dysfunction plays a key role in the pathological process of AAA. This study focuses on RUNX3 and explores whether it participates in AAA progression by regulating mitophagy. AAA was induced in male C57BL/6 mice by pancreatic elastase and calcium chloride. Aortic morphology and pathology were assessed by H&E and EVG staining. Oxidative stress was measured by MDA and SOD levels. RUNX3 and mitophagy-related proteins were analyzed by Western blot. AAV2/9-mediated RUNX3 knockdown in vascular smooth muscle cells was combined with Mdivi-1 (a mitochondrial fission inhibitor, used to suppress mitophagy) for rescue experiments. Mice in the AAA model group showed significant local dilation of the abdominal aorta. H&E and EVG staining revealed disorganized aortic wall structure and elastic fiber fragmentation, and tissue oxidative stress levels were elevated. Western blot analysis showed that RUNX3 expression was significantly higher in the AAA group than in the sham group, while mitophagy-related protein expression was decreased. AAV2/9-mediated knockdown of RUNX3 significantly ameliorated AAA-related pathological damage, promoted mitophagy, and reduced oxidative stress; however, combined application of Mdivi-1 reversed the protective effects conferred by RUNX3 knockdown. This study suggested that RUNX3 expression is upregulated during AAA development and may promote disease progression by inhibiting mitophagy and exacerbating oxidative stress. Targeting RUNX3 may represent a potential strategy for alleviating AAA.</p>","PeriodicalId":17546,"journal":{"name":"Journal of Thrombosis and Thrombolysis","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149069855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Major bleeding modifiers in anticoagulated patients with atrial fibrillation and heart failure: a systematic review.","authors":"Jumpei Yamamoto, Keijiro Nakamura, Hidehiko Hara","doi":"10.1007/s11239-026-03400-6","DOIUrl":"https://doi.org/10.1007/s11239-026-03400-6","url":null,"abstract":"<p><p>Patients with atrial fibrillation (AF) and heart failure (HF) often require oral anticoagulation (OAC) but have renal dysfunction, anaemia, and polypharmacy. Evidence on bleeding-risk modifiers in patients with both AF and HF has not been synthesised specifically.We conducted a systematic review of studies reporting major bleeding modifiers in anticoagulated patients with atrial fibrillation and heart failure. Modifier domains, outcome definitions, study design features, and antithrombotic-treatment contexts were extracted. Structured narrative synthesis was the primary approach; only contrasts meeting the prespecified pooling criteria, with sufficiently comparable adjusted estimates, were evaluated in exploratory random-effects meta-analyses.Twenty-three studies provided 93 effect rows. Prominent clinically monitorable domains reported across the included studies were severe renal dysfunction (Cockcroft-Gault-based renal function <30 vs ≥80 mL/min: hazard ratio [HR] 5.77, 95% confidence interval [CI] 3.16-10.52), prior bleeding (HR 2.48, 1.44-4.28), inappropriate or unrevised anticoagulant dosing, anaemia, and concomitant antiplatelet therapy, with more limited evidence for nonsteroidal anti-inflammatory drug exposure. In a separate exploratory random-effects meta-analysis of the antithrombotic-treatment context, any direct oral anticoagulant (DOAC) versus warfarin or other non-DOAC oral anticoagulation was associated with lower major bleeding (pooled HR 0.69, 95% CI 0.55-0.87; k=6; I2=75%; τ2=0.05552). This was contextual safety evidence rather than a clinical modifier.This systematic review identifies clinically monitorable major bleeding modifier domains in anticoagulated patients with atrial fibrillation and heart failure. Quantitative synthesis was limited to a small number of comparable comparisons and should be interpreted as exploratory.</p>","PeriodicalId":17546,"journal":{"name":"Journal of Thrombosis and Thrombolysis","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149062201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}