Objective LncRNA HOXA11-AS was abnormally upregulated during heart failure, suggesting that it might be involved in the development of chronic heart failure (CHF). This study aims to explore the diagnostic value of HOXA11-AS in CHF and its mechanism of action in myocardial injury. Methods The level of HOXA11-AS in serum was detected by real-time quantitative polymerase chain reaction (RT-qPCR), and its diagnostic efficacy was evaluated by ROC curve. The model of CHF was established by treating AC16 cells with doxorubicin (DOX). Cell viability and apoptosis were detected by cell counting kit-8 (CCK-8) and flow cytometry. The levels of inflammatory factors and myocardial injury markers were detected by enzyme-linked immunosorbent assay (ELISA). The content of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD) were detected by kits. Dual-luciferase reporter assay was used to verify the targeting relationship between HOXA11-AS and miR-342-3p. Results The expression of HOXA11-AS in the serum of CHF patients was significantly increased. ROC analysis showed that HOXA11-AS had a high diagnostic value for CHF. In the DOX-induced cell model, knocking down HOXA11-AS could significantly enhance cell viability, inhibit cell apoptosis, and reduce the release of myocardial injury markers, pro-inflammatory factors, as well as the level of oxidative stress. miR-342-3p was the target gene of HOXA11-AS. Inhibition of miR-342-3p could reverse the myocardial protective effect produced by the knockout of HOXA11-AS. Conclusion HOXA11-AS, as a potential biomarker for diagnosing CHF, exacerbates myocardial injury, inflammatory response and oxidative stress by sponging miR-342-3p.
Background Acute coronary syndrome (ACS), a cardiovascular disease with high mortality, is closely associated with microRNA (miRNA) dysregulation, making miRNAs promising targets for diagnostic and therapeutic development. Aim This study evaluated the clinical value of miR-3615 in ACS and its pathological mechanism. Methods This study included 121 ACS patients and 72 controls; miR-3615 and DPF3 expression were quantified by qRT-PCR. The clinical diagnostic and prognostic value of miR-3615 was analyzed through the ROC curve, correlation analysis, multivariate regression analysis, and K-M survival analysis. In vitro, a cell model of human coronary artery smooth muscle cells (HCASMCs) was established by inducing oxidized low-density lipoprotein (ox-LDL). Inflammatory markers were analyzed using ELISA kits. CCK-8 and Transwell assays were used to evaluate cell proliferation and migration abilities. The targeting effect of miR-3615 on DPF3 was confirmed by dual luciferase assay. Results MiR-3615 expression was elevated in ACS patients, especially among those who experienced major adverse cardiovascular events (MACE). Furthermore, its levels showed a positive correlation with both the Gensini score (indicating coronary lesion severity) and cardiac troponin I (cTnI, a marker of myocardial injury). MiR-3615 has a high degree of accuracy in diagnosing ACS and predicting poor prognosis. In an ox-LDL-induced HCASMCs model, inhibition of miR-3615 effectively attenuated pathological cell proliferation, migration, and inflammatory responses. DPF3 was identified as a target of miR-3615. Conclusions MiR-3615 is expected to become a potential biomarker for the diagnosis and prognosis of ACS. Moreover, the upregulation of miR-3615 may induce damage to HCASMCs, thereby participating in the occurrence and development of ACS.
Background Venous thromboembolism (VTE), the third leading cause of cardiovascular mortality, is a common but preventable complication in hospitalized patients. However, VTE prophylaxis remains underutilized. This study aims to explore physicians’ knowledge, attitudes, practices (KAP) regarding VTE prevention in Chinese public hospitals and their interrelationships to inform improvement strategies. Methods A cross-sectional, multicenter online survey was conducted using a KAP-based questionnaire distributed to physicians in Chinese public hospitals. Data analysis integrated descriptive statistics, Pearson correlations, and structural equation modeling (SEM). Results Among 787 valid responses, KAP scores were positive (Knowledge: 4.00 ± 0.81; Attitude: 4.38 ± 0.78; Practice: 4.38 ± 0.82). Scores on knowledge of intermittent pneumatic compression usage (3.40 ± 1.24) and VTE risk assessment tools (3.98 ± 1.08) were relatively low, while only 23% and 40% of physicians reported being very familiar with them, respectively. About half strongly agreed on performing dynamic VTE/bleeding risk assessments and tailoring prophylactic measures accordingly. Poor patient awareness and adherence also hindered VTE prevention. Positive correlations were observed among KAP domains ( r = 0.35 – 0.59, P < 0.001). SEM demonstrated knowledge directly influenced practice ( β = 0.50, P < 0.05), while attitude facilitated knowledge-to-practice translation ( β = 0.25, P < 0.05). Conclusions Knowledge is pivotal for VTE prophylaxis implementation. Future targeted training should focus on addressing physicians’ knowledge deficiencies, enhancing awareness of dynamic risk assessment and improving patient education to strengthen institutional VTE prevention capabilities. Given the predominance of tertiary public hospital respondents, the generalizability of these findings should be interpreted with caution.
Background Previous studies demonstrated the superiority of a genotype-guided warfarin dosing (GWD) method for warfarin initiation. International GWD models such as Gage et al model were validated in diverse populations but Arab patients were not well represented in these studies. Objective To derive and validate a GWD model in an Arab population and compare the outcomes to Gage et al model. Methods In this cross-sectional study, DNA was collected through saliva kits from a cohort of recruited Arab patients on warfarin . Clinical factors and demographics were recorded and genotyping for VKORC1 (−1639G > A) , CYP2C9*2 , CYP2C9*3 and CYP4F2*3 was performed. Subjects were randomly divided to derivation and validation cohorts. Simple and Multiple linear regression analyses were used to identify factors associated with warfarin dose and derive a warfarin dosing model. The warfarin dose was also calculated using Gage et al model. Accuracy of the 2 models were compared through the mean absolute error (MAE) and percentage of predicted warfarin doses within 20% of the actual warfarin dose Results The Arab cohort included 405 patients. In the derivation cohort (n = 270), multiple regression analysis showed a dosing model consisting of VKORC1 (−1639G > A) , CYP2C9*2 & CYP2C9*3 genotypes, along with other clinical factors (R 2 = 51.6%) (P < 0.05). When compared to Gage et al model, the Arab model had a significantly lower MAE of weekly warfarin dose (9.3 ± 7.6 mg/week vs 12.4 ± 10.4 mg/week, p = 0.03) Conclusion A model derived and validated in an Arab population had better prediction accuracy compared to an internationally validated one.
Background Oral anticoagulants (OACs) remain the standard strategy for stroke prevention in atrial fibrillation (AF) but are limited by bleeding risk, intolerance, and long-term adherence challenges. Left atrial appendage closure (LAAC) has emerged as a catheter-based alternative for thromboembolic prevention in non-valvular AF. This systematic review evaluated the comparative efficacy and safety of LAAC versus OAC therapy in patients with AF. Methods PubMed and Embase were systematically searched for randomized controlled trials (RCTs) comparing percutaneous LAAC with OACs, including direct oral anticoagulants (DOACs) and warfarin, in patients with AF. Results Four pivotal randomized trials (PROTECT AF, PREVAIL, PRAGUE-17, and OPTION) were included. Compared with DOAC therapy, LAAC demonstrated non-inferiority for the composite endpoint of all-cause death, stroke, or systemic embolism in OPTION and for the primary composite outcome in PRAGUE-17. LAAC was associated with significantly lower non-procedural bleeding compared with DOACs in OPTION and PRAGUE-17. Compared with warfarin, LAAC achieved non-inferiority for ischemic stroke or systemic embolism beyond 7 days after randomization in PREVAIL and reduced long-term cardiovascular mortality in PROTECT AF. Procedure-related complications declined with increasing operator experience. Conclusion LAAC provides non-inferior thromboembolic protection compared with OAC therapy while reducing long-term bleeding events in selected patients with AF. LAAC represents an important alternative for patients at elevated bleeding risk or with contraindications to long-term anticoagulation.
Objectives To develop a machine learning (ML)-based prognostic model for predicting the risk of lower extremity deep vein thrombosis (DVT) after acute stroke, with an emphasis on limb functional assessments. Methods We conducted a retrospective analysis of 225 acute stroke patients admitted within 15 days of onset between December 1, 2015, and April 30, 2025. Predictor variables were selected using collinearity diagnostics and Least Absolute Shrinkage and Selection Operator (LASSO) regression. Three machine learning survival models—Gradient Boosting Machine (GBM), Random Survival Forest (RSF), and Generalized Linear Model (GLM)—were employed to identify the most effective model. The performance of the optimal ML model was compared with that of the traditional Cox proportional hazards model using the concordance index (C-index), cumulative/dynamic area under the curve (C/D AUC), and integrated Brier score (IBS). The optimal model was further interpreted using SurvSHAP(t). Results Six variables were selected for the model: age, stroke type, gender, tension of the muscle, Brunnstrom stage (lower limb), and sitting balance. The RSF model, implemented using the Ranger algorithm, demonstrated superior performance, with an integrated Brier score (IBS) of 0.081 and a C-index of 0.841. Age and Brunnstrom stage (lower limb) were identified as the most influential predictors. Conclusion We developed an ML-based prognostic model for predicting the risk of lower limb DVT after acute stroke. Age and Brunnstrom stage (lower limb) were the most significant predictors. This model shows promise for risk stratification in clinical practice.
Objectives This study aimed to evaluate the efficacy and safety of AngioJet rheolytic thrombectomy with the adjunctive use of glycoprotein IIb/IIIa inhibitors (GPI) in the setting of ST-segment elevation myocardial infarction (STEMI). Methods We conducted a retrospective cohort study of 877 consecutive patients with STEMI. Propensity score matching (PSM) was employed to balance the baseline characteristics between the group receiving AngioJet rheolytic thrombectomy plus GPI (the AT + GPI group) and those receiving routine treatment (the RT group). The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE) at 1 year. Safety endpoints comprised any bleeding and major bleeding events. Results Ninety-seven patients received AngioJet rheolytic thrombectomy and GPI. No significant differences were observed between the two groups regarding in-hospital mortality, reinfarction, stent thrombosis, stroke, or bleeding. After propensity-score matching, the cumulative incidence of MACCE at 1 year did not differ significantly between the AT + GPI group and the RT group (8.2% vs 9.3%; hazard ratio, 0.894; 95% CI, 0.345 to 2.318; p = 0.818). The incidence rates of all individual safety endpoints—including stroke and bleeding—showed no significant differences between the two groups. Conclusions In this observational cohort of STEMI patients, the strategy of combining AngioJet rheolytic thrombectomy with GPI was not associated with improved 1-year outcomes compared to routine treatment, though it did not increase bleeding or stroke risk.
Background To investigate the risk factors for malignant cerebral edema (MCE) following mechanical thrombectomy (MT) in patients with large vessel occlusion (LVO) stroke, construct a risk prediction model, and provide evidence for early intervention. Methods A retrospective study was conducted on 248 patients with LVO who underwent MT between January 2021 to December 2024 (60 cases in the MCE group and 188 cases in the non-MCE group). Independent predictive factors were identified through univariate analysis, LASSO regression, and multivariate logistic regression. A nomogram model was constructed and validated internally using the Bootstrap method (1,000 resampling). Results Independent predictive factors for MCE after MT in LVO patients were identified, including high baseline NIHSS score ( OR = 1.805), infarct core volume ( OR = 1.235), good collateral circulation was a protective factor (OR = 0.287, indicating that each one-point increase in the collateral score reduced the risk of MCE by 71.3%), high (neutrophil-to-lymphocyte ratio) NLR (OR = 5.312), and hyperglycemia ( OR = 15.445) were significant risk factors, while successful reperfusion (mTICI ≥ 2b grade, OR = 0.068) was a key protective factor. The nomogram prediction model constructed based on the above six factors demonstrated excellent discriminative ability ( AUC = 0.902, 95%CI : 0.844 - 0.959) and good calibration ( Hosmer-Lemeshow test, P = 0.906). Conclusion NIHSS score, infarct core volume, collateral circulation, NLR, and blood glucose are independent risk factors for MCE after MT, while successful reperfusion is a key protective factor. The constructed nomogram model can effectively identify high-risk patients and guide individualized interventions.
Background This study aimed to compare the efficacy of mechanical thrombus clearance combined with stenting versus direct stenting alone in patients with iliofemoral venous disease,, and to analyze the characteristics of different diagnostic subgroups among non-thrombotic patients. Methods A retrospective analysis was conducted on 137 patients who underwent iliac vein stent implantation between January 2020 and March 2025. Based on the presence of acute/subacute thrombosis and surgical strategy, patients were divided into a Thrombus Treatment Group (Angiojet thrombus aspiration + stenting, n=87) and a Non-Thrombotic Treatment Group (direct stenting, n=50). Within the Non-Thrombotic Group, further stratification yielded Subgroup A (pure iliac vein compression syndrome, n=29) and Subgroup B (associated thrombotic disease, e.g., post-thrombotic syndrome, n=21). Baseline characteristics, perioperative data, and 3-6 month follow-up outcomes were compared. Results Patients in the Thrombus Treatment Group were older (70.2±11.4 vs. 62.1±7.2 years, P<0.001), required fewer stents (1.3±0.6 vs. 1.8±0.9, P<0.001), but had longer procedure times (122.7±38.3 vs. 87.8±51.3 minutes, P<0.001). No significant differences were found between the two main groups in post-operative ultrasound patency rates (69.1% vs. 59.1%, P=0.243) or adverse event rates (2.5% vs. 6.8%, P=0.224). Subgroup analysis revealed that compared to Subgroup A, Subgroup B had a higher prevalence of prior DVT history (47.6% vs. 0%, P<0.001) and pre-operative swelling symptoms (81.0% vs. 6.9%, P<0.001), and required more complex procedures (stent use: 2.3±1.0 vs. 1.5±0.7, P<0.001). However, short-term follow-up outcomes were similar between the subgroups. Conclusion For iliofemoral venous disease with concomitant thrombosis, a strategy of thrombus clearance combined with selective stenting can reduce stent usage while achieving short-term efficacy comparable to direct stenting alone in its respective clinical context. Among non-thrombotic patients, the subgroup with thrombosis-related disease presents distinct clinical features and higher procedural complexity, yet still benefits from endovascular reconstruction.
Background Emerging evidence suggests that various types of immune cells are associated with venous thromboembolism (VTE). However, the roles of distinct immune cell phenotypes in VTE remain largely unclear. Methods By analyzing 731 distinct immune traits identified through genome-wide association studies (GWAS) and publicly available genetic data from patients with VTE in the FinnGen database, we applied rigorous quality control steps to identify instrumental variables (IVs) associated with exposure. We performed two-sample Mendelian randomization (MR) using inverse-variance weighting to assess causal associations between 731 immune traits and VTE, including deep vein thrombosis (DVT) and pulmonary embolism (PE). To assess the robustness of the findings, sensitivity analyses such as leave-one-out cross-validation and additional Mendelian randomization approaches were performed. Subsequently, Bayesian colocalization analysis (COLOC) was employed to identify potential colocalized genetic signals, thereby providing additional support for the MR findings. Results At an FDR-adjusted significance threshold, three immune phenotypes, including CD4 on CD39+CD4+T cell, naive CD4+ T cell absolute cell counts (ACs), and CD4-CD8-natural killer (NK) T% T cell were negatively associated with the risk of VTE. CD45RA+ CD8+ T cell AC was negatively linked to the onset of DVT. Additionally, five immune phenotypes, including human leukocyte antigen (HLA) DR+ NK%CD3-lymphocyte, HLA DR+ NK%NK, side scatter area (SSC)-A on HLA DR+ NK, PDL-1 on CD14-CD16+ monocyte and CD16 on CD14+CD16+ monocyte were negatively associated with the risk of PE. CD86+ myeloid dendritic cell (DC) ACs and CD86+ myeloid DC% DC were positively correlated with PE. COLOC analysis revealed that naive CD4+ T cell AC variants (rs3104369) colocalized with VTE. Conclusion Our findings reveal that different immune phenotypes exhibit either protective or risk-increasing effects on VTE, improving our understanding of VTE risk factors and offering valuable insights for advancing future research and clinical implementation.
Introduction Dysregulation of the coagulation and fibrinolytic systems has been closely linked to cancer progression and metastasis. This study investigated whether the coagulation- and fibrinolysis-related biomarkers, TAT, PIC, TM, and tPAIC, are correlated with cancer metastasis. Methods Plasma levels of TAT, PIC, TM, and tPAIC were measured in 240 treatment-naive patients with lung, ovarian, breast, or colorectal cancer and 120 healthy individuals. Participants were categorized into metastasis, non-metastasis and healthy groups based on clinical evaluation and imaging results. Statistical analysis and ROC curves were used to assess the performance of individual and combined biomarkers in detecting metastasis. Results All four biomarkers were significantly elevated in patients with metastasis ( P < .001). In multivariate logistic regression analysis, PIC demonstrated the strongest association with metastasis. ROC curve analysis revealed that in lung cancer patients, a parallel test of TAT and PIC achieved a sensitivity of 93.33% and an NPV of 88.24%. In ovarian cancer, a serial test of TAT, PIC, and TM achieved a specificity of 80.00% and a PPV of 75.00%. In breast cancer, a parallel test of TAT, PIC, and tPAIC yielded a sensitivity of 93.33% and an NPV of 89.47%. In colorectal cancer, a parallel test of all four markers achieved a sensitivity of 96.67% and an NPV of 93.75%. Conclusion Distinct combinations of coagulation and fibrinolysis biomarkers demonstrate high diagnostic performance for detecting metastasis across different cancer types. Tailoring biomarker panels according to cancer type may provide significant clinical value in monitoring and predicting cancer metastasis.
BackgroundSodium-glucose cotransporter 2 (SGLT2) inhibitors are widely used antidiabetic agents with established cardiorenal benefits, yet their genetic causal association with venous thromboembolism (VTE) remains uncertain.MethodsWe employed a multifaceted approach to investigate the causal relationship between SGLT2 inhibition and VTE, as well as deep vein thrombosis (DVT) and pulmonary embolism (PE). Drug-target Mendelian randomization (MR) and summary-data-based MR (SMR) analyses were conducted using genetic variants proxying SGLT2 inhibition, derived from SLC5A2 expression quantitative trait loci and glycemic traits. Positive control analyses confirmed validity using type 2 diabetes outcomes. Meta-analyses were performed across multiple independent genome-wide association study datasets. Complementary pharmacovigilance analysis was conducted using the FDA Adverse Event Reporting System (FAERS) to assess disproportionality of SGLT2 inhibitor-related VTE reports.ResultsGenetically proxied SGLT2 inhibition was significantly associated with reduced risk of type 2 diabetes (P < 0.05), validating its robustness. Most MR analyses showed no consistent causal association with VTE, DVT, or PE across datasets, and meta-analyses yielded non-significant pooled estimates (all P > 0.05). SMR analyses revealed no association between SLC5A2 expression and VTE-related outcomes (all P_SMR > 0.05). FAERS disproportionality analysis also identified no safety signals for PE (reporting odds ratio [ROR] = 0.51; 95% CI: 0.42-0.64) or DVT (ROR = 0.54; 95% CI: 0.45-0.64).ConclusionsThis integrative study provides consistent evidence that SGLT2 inhibition is not causally associated with VTE, DVT, or PE, supporting its thrombotic safety. However, generalizability to non-European populations requires future validation in diverse cohorts.
Background The incidence of thromboembolism (TE) is lower in prostate cancer than in other malignancies, but its sequelae are associated with increased mortality. This study investigated the incidence, risk factors, and survival impact of TE in Asian population with localized prostate cancer undergoing surgical management. Methods This was a single-center retrospective cohort study of 4,880 localized prostate cancer patients who underwent surgical resection between March 1, 2002, and December 31, 2019. TE, venous thromboembolism (VTE), survival outcome, and related clinical variables were analyzed. Results The 3-month TE cumulative incidence was 0.33% and the 3-month VTE incidence was 0.16%. The 2-year TE and VTE incidence were 0.81% and 0.29%, respectively. Older age (≥75) (Subdistribution Hazard Ratio (SHR) 2.16, P = 0.0155) and an elevated C-reactive protein levels (≥0.35 mg/dL) (SHR 2.91, P = 0.0001) were significant risk factors for an increased incidence of TE. Older age (SHR 3.67, P = 0.0113) and pathological venous invasion (SHR 5.13, P = 0.0195) were significant risk factors for an increased incidence of VTE. The occurrence of VTE, older age, a history of diabetes, and high Gleason scores (≥8) were independently associated with poor survival. Conclusions The incidence of TE was low in this East Asian cohort of surgically treated patients with localized prostate cancer, however, VTE was an independent predictor of worse overall survival. These findings suggest that pharmacological thromboprophylaxis should be reserved for patients identified as being at high-risk for TE, whereas mechanical measures appear sufficient for the general low-risk cohort.
Background Approximately 50% of venous thromboembolism (VTE) are unprovoked, and 30% recur, leading to significant patient morbidity. Clonal hematopoiesis (CH) are acquired hematopoietic mutations that increase the risk of cardiovascular disease and myeloid neoplasms. CH may be associated with VTE and/or a predictive risk factor for recurrent VTE. Methods We conducted the first prospective pilot single-center study for patients with VTE to assess rate of CH, VTE recurrence rate, and clinical outcomes. Subjects with prior VTE underwent blood sample collection and detailed history collection during routine clinic visits. Next generation sequencing of samples was performed with Ion Torrent instrument using a custom Ampliseq 25 gene panel. CH was defined as variant allele frequency (VAF) of 2.0% or greater (CH≥2%). CH with VAF detected between 0.1% to 2.0% were confirmed by random sampling via digital droplet polymerase chain reaction. Statistical analysis on VTE outcomes for CH≥2% and on micro-CH, (defined as CH with VAF of ≥ 0.1%), was performed. Results/Conclusions 167 subjects were enrolled with median follow up of 400 days. Approximately half (45.5%) had history of recurrent VTE and 80% had unprovoked VTE at study enrollment. The CH≥2% rate detected was 13.2% in the study population. There were 9.5 recurrent VTE events per 100 person-years and 40.1 bleeding events per 100 person-years in this study. There were no significant associations between CH and VTE in this pilot study. Larger clinical studies are needed.
Introduction Collateral circulation is a critical determinant of outcomes in acute ischemic stroke (AIS). This bibliometric analysis evaluates research trends and future directions on this topic. Methods A systematic search was conducted in the Web of Science Core Collection to identify publications on AIS and collateral circulation between 1981 and 2025. Bibliometric analysis and visualization were performed using VOSviewer, CiteSpace, and the R package “bibliometric.” Results The analysis included 482 publications. China was the most productive countries, leading in publication volume (642). The University of California System emerged as top contributing institutions. Stroke was the most influential journals in terms of H-index (33), TP (53), and TC (3796). David S. Liebeskind and Gregory W. Albers were identified as leading authors. Keyword co-occurrence and cluster analysis revealed four main thematic areas: imaging and diagnostic assessment, treatment strategies, prognosis and outcome prediction, and pathophysiological mechanisms and hemodynamics. In addition, burst keyword analysis showed that terms like “large vessel occlusion”, “score”, “management”, and “endovascular thrombectomy” remained active through 2025. Conclusion Research on collateral circulation in AIS has evolved from exploring basic mechanisms to focusing on clinical applications. The current landscape integrates imaging-based collateral assessment with treatment decisions and prognosis to guide precise endovascular therapy. Future research will likely concentrate on collateral-guided precision treatment, imaging scores, and strategies for extending the therapeutic window. This study provides a comprehensive overview and valuable insights for researchers.
So called “sticky platelet syndrome” (SPS) is an inherited thrombophilic thrombocytopathy characterized by platelet hyperaggregability to low concentrations of adenosine diphosphate and/or epinephrine using light transmission aggregometry and is a recognized cause of otherwise unexplained venous thromboembolism (VTE). Variants within the ARHGEF3 gene have previously been implicated in platelet-related traits, suggesting its potential role in thrombosis associated with SPS. We investigated the association between eight selected single nucleotide polymorphisms (SNPs) within the ARHGEF3 gene and the risk of VTE in 49 patients with SPS and VTE compared with 70 healthy controls. Genetic associations were evaluated using allelic, genotype-based (dominant and recessive models), and haplotype analyses, with stratification according to SPS subtype. In the overall SPS cohort, the minor allele of rs9851853 was significantly more frequent in patients with SPS and VTE compared to controls. SNP rs4681767 showed a borderline allelic association in the overall cohort but reached statistical significance in patients with SPS type II. Genotype-based analyses revealed significant associations for rs9851853 under the dominant model and for rs4681767 and rs1354034 under the recessive model, predominantly in the SPS type II subgroup. Haplotype analysis identified distinct risk- and protective haplotypes within the ARHGEF3 locus. The TAT haplotype was associated with an increased risk of VTE, whereas the CAC haplotype conferred a protective effect, more significantly in SPS type II patients. Our findings indicate that genetic variability within the ARHGEF3 gene, particularly rs9851853, rs4681767, and rs1354034, may modulate thrombotic susceptibility in patients with SPS, especially in the epinephrine-sensitive SPS type II.
BackgroundPatients with pulmonary embolism (PE) and chronic kidney disease (CKD) have a fragile hemostatic balance, yet evidence comparing bleeding risk between direct oral anticoagulants (DOACs) and warfarin in critically ill patients remains limited. We compared overall and major bleeding risks associated with DOACs versus warfarin in ICU patients with PE and CKD.MethodsWe conducted a retrospective cohort study using the MIMIC-IV (v3.1) database. Adult ICU patients with PE and an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 treated with DOACs or warfarin were included. Propensity score matching (PSM) was used as the primary adjustment strategy, with stabilized inverse probability of treatment weighting (IPTW) as sensitivity analysis. Cox proportional hazards models were applied. The primary outcome was any bleeding, and the secondary outcome was major bleeding.ResultsAmong 1,363 patients, 832 received warfarin and 531 received DOACs. After PSM, 1,038 patients were well balanced. In IPTW-weighted analyses, DOAC use was associated with a higher risk of any bleeding compared with warfarin (HR 1.37, 95% CI 1.13-1.66; P = 0.001), while no significant difference was observed for major bleeding (HR 0.97, 95% CI 0.74-1.28; P = 0.84). Results were consistent in the PSM cohort. Renal function did not significantly modify the relative bleeding risk.ConclusionsIn critically ill patients with PE and CKD, DOACs were associated with increased overall bleeding but not major bleeding compared with warfarin. Differentiating non-major from major bleeding is essential when selecting anticoagulant therapy in this population.
Background Women with atrial fibrillation (AF) have historically been considered to have higher thromboembolic risk than men. The CHA 2 DS 2 -VASc score treated female sex as an independent risk factor. Recent guidelines recommend CHA 2 DS 2 -VA score, redefining female sex as a risk modifier. Aims This study aimed to assess the prevalence of left atrial appendage thrombus (LAAT) by sex and identify independent predictive factors for LAAT. Methods This analysis used data from the multicenter, prospective Left Atrial Thrombus on Transesophageal Echocardiography (LATTEE) registry, including 3,109 patients with AF. All patients underwent preprocedural transesophageal echocardiography to assess LAAT. Results Women constituted 36.5% of the study population. They were older, had more comorbidities, higher CHA 2 DS 2 -VA scores compared with men (median 3 vs. 2, p < 0.001). Among 3034 patients, LAAT was detected in 7.7% of cases, without significant difference between sexes (8% vs. 7.2%, p = 0.42). In multivariable logistic regression, paroxysmal AF was associated with lower odds of LAAT (OR 0.35), smoking (OR 1.71), reduced left ventricular ejection fraction (LVEF) <50% (OR 1.94), DOAC use (OR 0.42), and LAAV (per 1 cm/s increase; OR 0.92) were independent predictors of LAAT in men. In women only LAAV (per 1 cm/s increase; OR 0.91) remained significant ( p < 0.001). No sex-related effect modification was observed ( p > 0.05). Conclusions Although women with AF present a more adverse clinical profile, sex itself was not an independent predictor of LAAT.
Background Vascular inflammation has an important role in the development and progression of coronavirus disease 2019 (COVID-19). Also, a high cytokine level predicts a poor prognosis for COVID-19. In this study, we aimed to investigate the effect of salusin-α and salusin-β peptides in determining the severity of the disease in the acute period of COVID-19. Method The investigation involved studying a group of 74 hospitalized individuals who had tested positive for SARS-CoV-2 through polymerase chain reaction (PCR) tests. The patients were divided into two groups: those who did not reach the primary endpoint and were discharged without complications and those who reached the primary endpoint (a composite of ICU admission and/or mortality). Salusin-α and salusin-β levels of serum samples taken at the time of application were statistically compared. Outcome There was no statistically significant difference in salusin-α levels between the groups (p=0.279). However, salusin-β levels were found to be significantly higher in patients who reached the primary endpoint compared to those who did not reach the primary endpoint and the healthy control group. Conclusion The results of the analysis showed that a salusin-β level of 12.45 ng/mL predicts the risk of complications such as intensive care unit admission or mortality, with a sensitivity of 83.8% and a specificity of 40.5% for the estimation of the primary endpoint. The obtained data support our hypothesis, but observational studies with larger sample sizes are needed to evaluate salusins’ determination of COVID-19 prognosis.
Background Sepsis and its complications pose a major global health burden. Mendelian randomization (MR) provides a genetic approach to assess causality. Methods We conducted a two-sample Mendelian randomization (MR) study using data from large-scale genome-wide association studies (GWAS). This study aimed to assess the causal effects of six key biomarkers (D-dimer, Galectin-3, activated protein C, tumor necrosis factor receptor 2, interleukin-6 receptor subunit alpha, and thrombomodulin) on six sepsis-related complications, including acute respiratory distress syndrome (ARDS) and acute renal failure. The primary analysis utilized the inverse-variance weighted (IVW) method, with comprehensive sensitivity analyses to assess for heterogeneity and pleiotropy. A False Discovery Rate (FDR) was applied to correct for multiple testing. Results The primary IVW analysis suggested several potential causal associations. Genetically predicted D-dimer was associated with a lower risk of ARDS (OR = 0.63, P = 0.025), IL-6Rα with a reduced risk of acute renal failure (OR = 0.85, P = 0.035), and Galectin-3 with a lower risk of streptococcal septicaemia (OR = 0.95, P = 0.039). Reverse MR analysis suggested that genetic liability to sepsis (critical care) was associated with lower D-dimer levels. However, after FDR correction, none of these associations remained statistically significant. Sensitivity analyses did not indicate the presence of significant horizontal pleiotropy. Conclusion This study did not find robust genetic evidence to support a causal relationship between the six selected biomarkers and the risk of sepsis-related complications after correction for multiple testing. The suggestive associations observed prior to correction warrant further investigation.
