Hypoattenuated leaflet thickening (HALT), a subclinical form of valve thrombosis, is a common finding after transcatheter aortic valve replacement (TAVR). While anticoagulant therapy has been associated with HALT resolut...Hypoattenuated leaflet thickening (HALT), a subclinical form of valve thrombosis, is a common finding after transcatheter aortic valve replacement (TAVR). While anticoagulant therapy has been associated with HALT resolution, the efficacy and safety of this approach remain uncertain. To evaluate the effectiveness and safety of oral anticoagulant (OAC) therapy in resolving HALT after TAVR. A systematic review and meta-analysis was performed in accordance with PRISMA guidelines and registered in PROSPERO (CRD420251045514). Studies including adult TAVR patients with imaging-confirmed HALT treated with anticoagulants were included. Outcomes assessed included HALT resolution, valve dysfunction, and major bleeding. Risk of bias was assessed using the ROBINS-I tool, and certainty of evidence was evaluated via GRADE. Summary estimates were calculated using a random-effects model. Nine observational studies involving 369 patients were included, with a follow-up ranging from 78 to 217.6 days, and ranging from 5 days to 9.6 months of interval between TAVR and imaging. The overall pooled HALT resolution rate in imaging follow-up was 90% (95% CI: 0.84-0.95; I² = 15.0%). Otherwise, when discontinuation of OAC had a recurrence rate of 69% (95% CI: 0.49-0.84, I²=0). The bleeding event proportion was 0.05 (95% CI: 0.01-0.18, I² = 0.0%). Sensitivity analyses excluding influential studies suggest the robustness of findings. Anticoagulant therapy is associated with high rates of HALT resolution and appears superior to antiplatelet therapy. These findings support the role of anticoagulation in selected post-TAVR patients with HALT, though randomized trials are needed to confirm efficacy and assess bleeding risk.
Askarinejad A, Bucci T, Tartaglia E
… +8 more, Lam SHM, Rossi M, Zhao M, Tse HF, Haghjoo M, Boriani G, Chao TF, Lip GYH
J Thromb Thrombolysis
· 2026 Mar · PMID 41430514
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To evaluate the clinical course of patients with AF at high risk for both bleeding and stroke, according to OAC use. Data were analysed from three registries across the Middle East, Europe, and Asia-Pacific regions. The...To evaluate the clinical course of patients with AF at high risk for both bleeding and stroke, according to OAC use. Data were analysed from three registries across the Middle East, Europe, and Asia-Pacific regions. The study only included 'high risk' patients with AF and CHA₂DS₂-VASc scores ≥ 2 and HAS-BLED scores ≥ 3, who were divided into two groups based on OAC use: OAC users and OAC non-users. Of the 2,535 patients (41.7% female; mean age 75.4 ± 7.8 years), 80.3% (n = 2,037) received OAC therapy. OAC non‑users showed significantly higher crude 1‑year event rates of all‑cause death (116 [23.3%]), MACE (96 [19.3%]) and major bleeding (31 [6.2%]); after multivariable adjustment, they had higher odds of all‑cause death (adjusted odds ratio (aOR) 2.23, 95% CI 1.65-3.01), MACE (aOR 1.92, 95% CI 1.38-2.64) and major bleeding (aOR 2.38, 95% CI 1.42-3.92) compared to OAC users. Enrolment in a non-European setting was associated with a lower risk of all-cause death (aOR 0.61, 95%CI 0.44-0.85) and MACE (aOR 0.42, 95%CI 0.28-0.62). In patients with AF at high risk of both bleeding and stroke, OAC non-use was associated with higher risk of adverse events and bleeding. Decisions on discontinuation of OACs in this subset of patients with AF should be cautiously made and such patients require careful re-evaluation and follow-up.
This systematic review and meta-analysis aims to investigate the effect of heparin full-dose anticoagulation on preventing COVID-19 disease progression in non-critically ill COVID-19 adult patients in accordance with the...This systematic review and meta-analysis aims to investigate the effect of heparin full-dose anticoagulation on preventing COVID-19 disease progression in non-critically ill COVID-19 adult patients in accordance with the Cochrane methodology and the Preferred Reporting for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched PubMed/Medline, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL) and Clinicaltrials.gov (from inception to September 2025). Multicenter randomized controlled trials (mRCTs) comparing full-dose heparin anticoagulation with no full-dose anticoagulation (including prophylactic or intermediate-dose anticoagulation with heparin). The primary outcome was the need for invasive mechanical ventilation. The protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) with the number CRD42022348993. We included 6 mRCTs in the analysis, randomizing a total of 5777 COVID-19 patients. The rate of need for invasive mechanical ventilation was lower in patients treated with full-dose heparin at 7.9% (226/2842) compared with 9.5% (279/2935) in those receiving prophylactic or intermediate-dose ([RR] = 0.81; 95% [CI] = 0.68–0.96; P = 0.01). The absolute risk (AR) of requiring invasive mechanical ventilation was 77 per 1.000 in patients treated with full-dose heparin, compared with 95 per 1.000 in patients treated with prophylactic or intermediate-dose heparin. According to our updated data analysis of high-quality mRCTs, full-dose anticoagulation with heparin can be considered an important strategy to prevent disease progression and the need for invasive organ support in hospitalized non-critically ill COVID-19 patients.
Lung cancer is one of the most common malignancies, characterized by a wide prognosis spectrum, different histological subtypes, and a high mortality rate. Hemostatic system imbalance in patients with lung cancer often l...Lung cancer is one of the most common malignancies, characterized by a wide prognosis spectrum, different histological subtypes, and a high mortality rate. Hemostatic system imbalance in patients with lung cancer often leads to increased mortality. Intracellular RNAs that share common miRNA binding sites create a competing endogenous RNA (ceRNA) network that plays an important role in gene expression regulation. The emerging role of ceRNAs in tumor development is increasingly being recognized; however, their connection to hemostatic system imbalance in lung squamous cell carcinoma (LUSC) remains unclear. In this study, RNA-seq data of LUSC and normal tissues were downloaded from the TCGA data portal. Differentially expressed mRNAs (DEmRNAs), miRNAs (DEmiRNAs), and lncRNAs (DElncRNAs) between LUSC and corresponding paracancerous tissues were analyzed using the DESeq2 package in R statistical software. Hemostasis-related genes linked to coagulation and complement cascades (hsa04610) and platelet activation (hsa04611) pathways were identified using the KEGGREST package. The ceRNA network associated with system hemostasis was constructed using differentially expressed RNAs (DERNAs), including mRNAs, lncRNAs, and miRNAs. The GO and KEGG enrichment analysis of DEmRNAs was conducted using the enrichR package. Hazard ratio (HR) and Kaplan-Meier curve were employed to assess the prognostic value of DERNAs using the survival and survminer packages. A ceRNA network comprising 100 hemostasis-related genes, 5 miRNAs, and 57 lncRNAs was constructed. Of these, 19 hemostasis genes, one miRNA (miR-23-3p), and 6 lncRNAs (LINC01615, LINC00707, LINC00702, FEZF1-AS1, DLX6-AS1, CLRN1-AS1) were significantly associated with prognosis in LUSC. Based on correlation analysis, MEF2C-AS1/miR-429/F8, RAP1A, GNAI2, C3AR1, F13A1, P2RY12, LCP2, C1QC axis and CASC11, CASC9, PVT1, BBOX1-AS1/ miR-23b-3p/ PLAU axis may represent key pathways involved in hemostatic system imbalance and the pathogenesis of LUSC. Our analysis revealed a complex ceRNA network associated with system hemostasis and the prognosis of LUSC. These findings may contribute to the development of personalized therapies and valuable prognostic biomarkers for LUSC patients.
J Thromb Thrombolysis
· 2026 Mar · PMID 41405757
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Amyloid microclots have been implicated in thrombotic complications across various pathological conditions such as Long COVID symptoms, yet their resistance to enzymatic fibrinolysis causes a therapeutic challenge. In th...Amyloid microclots have been implicated in thrombotic complications across various pathological conditions such as Long COVID symptoms, yet their resistance to enzymatic fibrinolysis causes a therapeutic challenge. In this study we examine the effects of three fibrinolytic enzymes rtPA, Lumbrokinase, and Nattokinase on plasma-derived amyloid microclots, in combination with ultrasound-induced microstreaming and microbubbles. A lab-on-chip platform was used to expose the clots to ultrasound at 150, 300, and 500 kHz. Quantitative analysis revealed that ultrasound alone significantly disrupted clot structures, particularly at 150 kHz, where mean clot diameter was reduced by over 60% and large-clot count (> 30 μm) dropped by more than 80% compared to controls. The addition of fibrinolytic enzymes, however, did not produce statistically significant effects at 150-300 kHz which indicates that mechanical forces were the dominant contributors to clot disruption. At 500 kHz, where ultrasound alone was less effective, enzymatic treatment moderately enhanced the reduction in large-clot burden. These results show the potential of low-frequency ultrasound as a primary method of amyloid microclot breakdown, with enzyme co-treatment offering limited but measurable effect.
Thrombosis presents significant healthcare challenges due to its complex nature. Recent advancements in data-driven mathematical and computational models of blood clot formation offer promising insights. The integration...Thrombosis presents significant healthcare challenges due to its complex nature. Recent advancements in data-driven mathematical and computational models of blood clot formation offer promising insights. The integration of machine learning (ML) and computational methods in thrombosis research is still in its early stages, but it could leverage the strengths of both approaches. This systematic review followed the PRISMA methodology to assess studies that (i) utilized computational models, (ii) modeled blood clot formation or thrombin generation through the coagulation cascade, and (iii) incorporated ML algorithms. We identified 11 eligible studies that focused on platelet signaling, outcome prediction, thrombin threshold prediction, shear rate prediction, and multiscale modeling. Artificial neural networks and support vector machines were the most commonly used ML models. The hybrid approach combining ML and computational models is still nascent but shows significant promise for advancing thrombosis research. These models offer valuable insights for improving thrombosis diagnosis, prognosis, and treatment, particularly in the context of personalized medicine for hemostatic disorders. The integration of ML with computational models holds great potential for improving thrombosis management, but further research is needed. Future work should focus on enhancing the physiological realism of these models, incorporating patient-specific data, and addressing challenges related to data standardization and clinical implementation. The field is in its early stages but shows promising growth potential and is well positioned to advance precision medicine approaches in thrombosis and hemostatic disorders.
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired disorder characterized by complement-mediated hemolysis and a high thrombotic risk. The introduction of complement inhibitors has markedly reduced thromboembol...Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired disorder characterized by complement-mediated hemolysis and a high thrombotic risk. The introduction of complement inhibitors has markedly reduced thromboembolic events. Eculizumab, the first approved C5 inhibitor, requires biweekly infusions, while ravulizumab, with a prolonged half-life, allows administration every eight weeks. To compare their effects on coagulation dynamics, we retrospectively analyzed paired plasma samples from nine PNH patients sequentially treated with both agents using the Thrombin Generation Assay TGA. TGA parameters were largely comparable between treatments, with a significantly shorter start-tail time observed during ravulizumab therapy (p = 0.04). This data indicating a shorter duration of thrombin generation is consistent with the known more sustained complement inhibition during ravulizumab. No significant differences were found in hemolysis markers, PNH clone size, or blood counts. Despite the small sample size and retrospective design, this study provides the first evidence that ravulizumab and eculizumab exert similar effects on thrombin generation, supporting the equivalent efficacy of long-acting C5 inhibition in maintaining hemostatic balance in PNH.
Clinical practice guidelines on the optimal thromboprophylaxis duration following total hip and knee arthroplasty (THA and TKA) and hip fracture surgery are inconsistent. The aim of this meta-analysis is to investigate t...Clinical practice guidelines on the optimal thromboprophylaxis duration following total hip and knee arthroplasty (THA and TKA) and hip fracture surgery are inconsistent. The aim of this meta-analysis is to investigate the effect of pharmacological prophylaxis duration on postoperative venous thromboembolism (VTE) in these patients. The primary outcome was the incidence of symptomatic and confirmed VTE at three months following surgery. A systematic search was performed in MEDLINE Complete (EBSCO), Embase, CINAHL complete (EBSCO), Web of Science and in CENTRAL databases, for randomised controlled trials comparing extended (minimum 28 days for THA and 10 days for TKA) vs. shorter duration thromboprophylaxis or placebo following these operations. Fifteen trials with a total of 26,580 participants were identified. Compared to shorter prophylaxis, extended thromboprophylaxis reduced 90-day symptomatic and confirmed VTE (OR: 0.43; 95% CI: 0.26-0.72; P = 0.001, I = 0%; P = 0.75, respectively), significant only in the THA subgroup (P = 0.002). Beneficial effects were also observed with 30-day deep venous thrombosis (DVT) (OR: 0.32; 95% CI: 0.20-0.50; P < 0.001) and proximal DVT incidence (OR: 0.22; 95% CI: 0.12-0.41; P < 0.001) following THA. There were insufficient data to support extended prophylaxis for hip fracture surgery or TKA. Extending thromboprophylaxis up to 25-35 days appeared to reduce the incidence of 90-day symptomatic and confirmed VTE, particularly after THA. However, contemporary perioperative protocols, including early mobilisation and risk stratification, must be considered in determining optimal prophylaxis duration.
Left ventricular thrombus (LVT) is a significant complication following acute myocardial infarction (AMI), posing substantial risks of stroke and systemic embolism. Warfarin remains the traditional standard for anticoagu...Left ventricular thrombus (LVT) is a significant complication following acute myocardial infarction (AMI), posing substantial risks of stroke and systemic embolism. Warfarin remains the traditional standard for anticoagulation, but direct oral anticoagulants (DOACs) have emerged as practical alternatives despite limited comparative evidence. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to compare the efficacy and safety of DOACs versus warfarin in patients with LVT. We systematically searched PubMed, Embase, and Cochrane databases for RCTs comparing DOACs and warfarin in patients with LVT. Outcomes of interest included thrombus resolution rates at 1- and 3-month follow-up and safety outcomes, including major bleeding, stroke/systemic embolism, and all-cause mortality. We included 7 RCTs comprising 554 patients, of whom 319 received DOACs. No significant differences were found between DOACs and warfarin regarding LVT resolution at 1 month (OR: 1.69; 95% CI: 0.62–4.60; p = 0.31; I²=69%) or 3 months (OR: 1.39; 95% CI: 0.82–2.37; p = 0.22; I²=0%). Secondary outcomes, including major bleeding (OR: 0.51; 95% CI: 0.12–2.12), stroke/systemic embolism (OR: 0.69; 95% CI: 0.10–4.64), and all-cause mortality (OR: 0.86; 95% CI: 0.31–2.40), were also similar between groups. In patients with LVT, DOACs demonstrated comparable efficacy and safety to warfarin, offering practical advantages such as simplified management. These findings support DOACs as a reasonable alternative to warfarin for treating LVT. However, further large-scale trials using advanced imaging and standardized anticoagulation protocols are warranted.
Oral factor Xa inhibitors are preferred treatments for venous thromboembolism (VTE). While apixaban and rivaroxaban require an initial lead-in period, clinicians may reduce the period if patients have received prior ther...Oral factor Xa inhibitors are preferred treatments for venous thromboembolism (VTE). While apixaban and rivaroxaban require an initial lead-in period, clinicians may reduce the period if patients have received prior therapeutic parenteral anticoagulation, although supporting evidence is limited. The purpose of this study is to evaluate bleeding and thrombotic events associated with reducing factor Xa inhibitor lead-in duration in patients who have received prior parenteral anticoagulation. This multicenter retrospective cohort study was conducted across 29 hospitals and included adult patients hospitalized with a new diagnosis of VTE who received at least 24 h of therapeutic parenteral anticoagulation before starting apixaban or rivaroxaban. Patients with active bleeding on admission, anticoagulation prior to admission, antiphospholipid syndrome, severe liver disease, or contraindicated medications were excluded. The primary outcome was time to VTE recurrence within six months. Cox proportional hazard model was used to control for potential confounding factors and a sensitivity analysis was performed using propensity matching. Among 1,424 patients included, 1,068 received a full lead-in and 356 a reduced lead-in regimen. No significant difference in time to recurrent VTE (HR 0.53; 95% CI, 0.20-1.37;p = 0.19) or major bleeding (HR 0.69; 95% CI, 0.31-1.56;p = 0.45) was observed after controlling for confounding factors. No difference in recurrent VTE and major bleeding persisted after propensity matching. Among patients transitioning from parenteral anticoagulation to oral factor Xa inhibitors, a reduced lead-in duration was not associated with increased VTE recurrence or major bleeding.
Several risk assessment models (RAMs) guide standardized prophylaxis to prevent venous thromboembolism (VTE) in trauma patients. The Caprini, Trauma Embolic Scoring System (TESS), and Greenfield Risk Assessment Profile (...Several risk assessment models (RAMs) guide standardized prophylaxis to prevent venous thromboembolism (VTE) in trauma patients. The Caprini, Trauma Embolic Scoring System (TESS), and Greenfield Risk Assessment Profile (RAP) have been validated individually, but their predictive powers have not been directly compared in the general trauma population. This study evaluated the discriminatory ability of these three RAMs in trauma patients at an ACS-verified Level I Trauma Center. A retrospective review was performed of adult trauma patients in a single institution over one year. Demographic and clinical data were used to calculate Caprini, TESS, and RAP scores. The primary outcome was inpatient VTE. Logistic regression models - both combined and separate - generated receiver operating characteristic (ROC) curves for each score. Caprini served as the reference for comparing discriminatory ability. Among 1,276 patients, 33 (2.6%) developed inpatient VTE. Caprini, TESS, and RAP scores predicted VTE with odds ratios of 1.07 (95% CI 1.04-1.10), 1.39 (95% CI 1.23-1.56), and 1.20 (95% CI 1.12-1.29), respectively. ROC c-statistics were similar: Caprini 0.75 (95% CI 0.68-0.82), TESS 0.73 (95% CI 0.64-0.83), and RAP 0.70 (95% CI 0.60-0.79). Caprini, TESS, and RAP RAMs showed comparable moderate discriminatory ability (c-statistic > 0.70) in predicting inpatient VTE among trauma patients. No model was superior, suggesting any of these RAMs may guide standardized VTE prophylaxis in this population.
This study aimed to assess the prognostic value of the THRIVE scale in patients aged ≥ 60 years with acute ischemic stroke (AIS) after intravenous thrombolysis with the non-immunogenic staphylokinase compared with altepl...This study aimed to assess the prognostic value of the THRIVE scale in patients aged ≥ 60 years with acute ischemic stroke (AIS) after intravenous thrombolysis with the non-immunogenic staphylokinase compared with alteplase. The post-hoc analysis of FRIDA trial results was performed and enrolled patients aged ≥ 60 years were divided into two groups in accordance with the modified Rankin scale (mRS) score on day 90: good-outcome (mRS 0-2) and poor-outcome (mRS 3-6) groups. The receiver operating characteristic (ROC) curves were compared using Delong test. For all-cause mortality on day 90 the predicted AUC value by the THRIVE scale was 0.8 (0.71-0.9) in the non-immunogenic staphylokinase group and 0.76 (0.66-0.87) in the alteplase group (p = 0.57). For poor outcome, AUC value was 0.73 (0.64-0.82) in the non-immunogenic staphylokinase group and 0.79 (0.71-0.87) in alteplase group (p = 0.36). Thus, our study confirmed the prognostic value of the THRIVE scale to predict the outcomes of the patients aged ≥ 60 years treated with the non-immunogenic staphylokinase.
Piccolo R, Laino A, Vitale AP
… +15 more, Canonico ME, Avvedimento M, Simonetti F, Paolillo R, Piaz FD, Charlier B, Spinelli A, Cristiano S, Serafino LD, Cirillo P, Gargiulo G, Franzone A, Filippelli A, Conti V, Esposito G
J Thromb Thrombolysis
· 2026 Mar · PMID 41243071
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No sex-based data are available on the pharmacodynamic and pharmacokinetic profile of ticagrelor 60 mg twice daily as alternative to its standard dose during the early phase after acute coronary syndrome (ACS). This post...No sex-based data are available on the pharmacodynamic and pharmacokinetic profile of ticagrelor 60 mg twice daily as alternative to its standard dose during the early phase after acute coronary syndrome (ACS). This post-hoc study is a sex-based secondary analysis of the PLINY THE ELDER randomized, crossover trial (NCT04739384), which compared ticagrelor 60 vs. 90 mg in elderly patients with ACS undergoing percutaneous coronary intervention (PCI). The primary endpoint was the pre-dose P2Y reaction units (PRU) using the VerifyNow-P2Y (Accumetrics, San Diego, CA, USA) at 14 days after treatment with ticagrelor 60 or 90 mg twice daily. A total of 50 elderly patients with ACS was included in the study. Of these patients, 28 (56%) were males and 22 (44%) females. The two doses of ticagrelor had a comparable PRU in both males (pre-dose: LSM difference -7.00, 95%CI -25.3 to 11.3, p = 0.44; post-dose: LSM difference 3.90, 95%CI -10.6 to 18.5, p = 0.59) and females (pre-dose: LSM difference -0.89, 95%CI -20.3 to 18.5, p = 0.93; post-dose: LSM difference -1.10, 95%CI -16.6 to 14.3, p = 0.88), with no evidence of sex-based interaction (pre-dose: p for interaction = 0.88; post-dose: p for interaction = 0.65). Consistently, transmittance aggregometry and multiple electrode aggregometry showed a similar pharmacodynamic profile between the two doses of ticagrelor in both male and female patients. Plasma levels of ticagrelor were significantly lower using the reduced dose of ticagrelor as compared with the standard dose in both males (pre-dose: LSM difference -212, 95%CI -391 to -33.0, p < 0.002; post-dose: LSM difference -308, 95%CI -510 to -105, p = 0.004) and females (pre-dose: LSM difference -131, 95%CI -332 to 69.1, p = 0.19; post-dose: LSM difference -670, 95%CI -898 to -442, p < 0.001). Ticagrelor 60 mg and ticagrelor 90 twice daily yielded the same magnitude of platelet inhibition among elderly patients with ACS irrespective of sex.
J Thromb Thrombolysis
· 2026 Mar · PMID 41222888
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Reactive oxygen species (ROS) play a pivotal role in myocardial infarction (MI), contributing to oxidative stress, inflammation, and tissue remodeling. However, ROS-related gene signatures with diagnostic and mechanistic...Reactive oxygen species (ROS) play a pivotal role in myocardial infarction (MI), contributing to oxidative stress, inflammation, and tissue remodeling. However, ROS-related gene signatures with diagnostic and mechanistic relevance in MI remain insufficiently defined. Transcriptomic data from six MI cohorts were integrated, with GSE66360 as the training set and five datasets as external validation. Batch correction was performed using ComBat. ROS pathway activity was assessed by single-sample gene set enrichment analysis (ssGSEA). Differentially expressed genes (DEGs) shared across datasets were intersected with ROS-related genes to construct an elastic net logistic regression model. Model performance was evaluated using ROC, calibration, and decision curve analysis. SHAP analysis was conducted for interpretability. Upstream transcription factor and miRNA interactions were predicted, and single-gene GSEA was used to explore biological pathways. Immune infiltration and checkpoint expression were analyzed using multiple deconvolution algorithms. Human AC16 cardiomyocytes were used to explore the functions of ADAM9 in MI. To validate our findings in vivo, we established the mice MI model and performed histology, immunostaining, and qRT-PCR to examine the six signature genes. ROS pathway activity was consistently elevated in MI samples across all cohorts. A six-gene signature (MMP9, ADAM9, BST1, TLR4, CLEC7A, CYP1B1) showed strong diagnostic performance. SHAP analysis identified MMP9 as the top contributor. Regulatory network analysis highlighted NFKB1, STAT1, and miR-21-5p as upstream regulators. Functional enrichment revealed an association with inflammatory and immune pathways. Software algorithm predictions from patient blood cell samples showed that the MI sample exhibited increased infiltration of macrophages, dendritic cells, and fibroblasts, along with upregulation of immune and inflammatory genes. Several model genes correlated positively with endothelial cell infiltration. Function studies in human AC16 cardiomyocytes suggested that ADAM9 inhibited cardiomyocyte survival and enhanced oxidative stress. Experimental validation confirmed that all six genes were significantly upregulated at both mRNA and protein levels in infarcted mouse hearts. We identified a ROS-related six-gene diagnostic signature for MI, with strong performance and mechanistic links to immune activation and vascular remodeling. This model may aid early diagnosis and provide insight into redox-immune interplay in MI.
Chaudhri M, Mahrizi ADA, Nadeem SA
… +10 more, Canal A, Rajendran P, Rapelli VR, Gill H, Haroon B, Shahzad A, Acquah F, Kaunzinger C, Albert C, Raza MR
J Thromb Thrombolysis
· 2026 Apr · PMID 41222886
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The optimal postaortic valve replacement (AVR) anticoagulation strategy remains poorly defined, particularly when comparing nonvitamin K antagonist oral anticoagulants (NOACs) versus warfarin. This systematic review and...The optimal postaortic valve replacement (AVR) anticoagulation strategy remains poorly defined, particularly when comparing nonvitamin K antagonist oral anticoagulants (NOACs) versus warfarin. This systematic review and meta-analysis aimed to evaluate the safety and efficacy of NOACs compared with warfarin in these patients. Our study was registered on PROSPERO (ID CRD420251028998). A search of the PubMed, EMBASE, and Cochrane databases was conducted on April 9, 2025, for studies published between 2015 and 2025 that compared NOACs to warfarin after aortic bioprosthetic valve replacement. Inclusion criteria included randomized controlled trials (RCTs) and observational studies reporting thromboembolic events, major bleeding, and mortality with at least 6 months of follow-up. Studies on mechanical valves, case reports, and publications that could not be translated into English were excluded. Data extraction was conducted based on study design, patient demographics, clinical outcomes, and effect sizes, expressed as hazard ratios (HRs) with 95% confidence intervals (CIs) using a random effects model. Risk of bias was assessed using the ROBINS-I tool. Seventeen studies (n = 93,510 participants) were included. NOACs were associated with an HR of 0.91 for thromboembolic events (95% CI: 0.76-1.09) and a pooled HR of 1.22 for major bleeding (95% CI: 0.88-1.68). Several studies have suggested a trend toward lower all-cause mortality and major bleeding with NOACs, particularly in patients with lower bleeding risk. In patients undergoing aortic bioprosthetic valve replacement, NOACs show similar efficacy and safety to warfarin for preventing thromboembolic events and major bleeding. However, anticoagulation decisions should be individualized, and larger RCTs are needed to determine the optimal approach.
Deep vein thrombosis (DVT) is a prevalent thrombotic condition affecting a wide range of patients, including post-partum women, immobilized individuals, and those who have undergone surgery, suffered heavy trauma, or had...Deep vein thrombosis (DVT) is a prevalent thrombotic condition affecting a wide range of patients, including post-partum women, immobilized individuals, and those who have undergone surgery, suffered heavy trauma, or had malignancies. Given the high incidence of the disease, identifying molecular and genetic tools that can predict, indicate prognosis, and serve as therapeutic targets would be a significant advancement in clinical practice for a broad spectrum of patients. However, traditional treatments often face challenges, leading to post-thrombotic syndrome (PTS) development in complex cases. Non-coding RNAs (ncRNAs), such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), have demonstrated essential regulatory roles in cellular pathways and have been found to be dysregulated in DVT patients and animal models. This knowledge provides new insights into the pathophysiology of DVT and paves the way for utilizing ncRNAs as diagnostic, predictive, and prognostic indicators, as well as therapeutic targets. Recent advancements have led to significant recanalization of thrombosed veins in animal models. In this review, we delve into the current literature on ncRNAs in DVT to highlight their potential for understanding disease mechanisms and improving patient outcomes.