Search Results (2,696)

This review examines the clinical data and basic science research to evaluate the potential of the Selective Cytopheretic Device (SCD) in mitigating Extracorporeal Membrane Oxygenation (ECMO)-associated inflammation. In brief, SCD is an immunomodulatory device used within extracorporeal blood circuits along with the use of citrate anticoagulation. SCD has been shown to be a novel, first-in-its-class device (being marketed as QUELimmune by SeaStar Medical), which is capable of the autologous processing of hyper-inflamed leukocytes to reduce systemic inflammation. Strong preclinical data gathered for SCD in the context of both Cardio-Pulmonary Bypass (CPB) as well as ECMO set the stage for SCD to be used in these life support circuits. ECMO played a crucial role during the COVID-19 pandemic, during a time period when SCD therapy was being evaluated in clinical trials, generating initial clinical data in this setting. SCD has also been utilized in the setting of pediatric acute kidney injury (AKI) and multiorgan dysfunction (MOD), where ECMO can be common. Full article

Activated protein C (APC) exerts anticoagulant and cytoprotective cell signaling activities. APC’s cell signaling requires protease-activated receptor (PAR) PAR1 and PAR3, and APC’s PAR cleavages generate peptides capable of agonizing biased G-protein coupled receptor (GPCR) cytoprotective signaling, resulting in anti-inflammatory and anti-apoptotic activities and endothelial barrier stabilization. The PAR-sequence-derived 34-residue “G10 peptide” comprising PAR1 residues 47–55 covalently attached by a 10-glycine linker to PAR3 residues 51–65 is an orthosteric/allosteric bivalent GPCR agonist that potently mimics APC’s anti-inflammatory activity and endothelial barrier stabilization activity. The objective of this study was to determine whether the G10 peptide mimics APC’s anti-apoptotic activity using cultured murine neurons challenged by N-methyl-d-aspartate that provokes neuronal apoptosis. In these new studies, the G10 peptide mimicked APC’s anti-apoptotic activity. Thus, the PAR-derived 34-residue G10 peptide mimics APC’s three major cytoprotective activities, namely anti-inflammatory and anti-apoptotic activities and endothelial barrier stabilization. Peptides that agonize GPCRs provide promising and currently approved drugs; e.g., semaglutide and tirzepatide that contain 31 and 39 amino acid residues, respectively. Thus, this new study adds to the rationale for pursuing further studies of the G10 peptide for potential therapeutic value for multiple pathologies where APC or signaling-selective APC variants are therapeutic in preclinical animal studies. Full article

Background/Objectives: Platelet counts can be affected by storage conditions, potentially leading to pseudothrombocytopenia. The present study aimed to investigate temperature-dependent changes in platelet counts and morphology in whole blood samples anticoagulated with heparin or EDTA. We also examined the molecular mechanism of cold-induced aggregation via integrin GPIIb/IIIa–fibrinogen interaction using established bioinformatics technologies (docking simulation). Methods: Peripheral blood was collected from healthy volunteers (n = 6) and treated with either heparin or EDTA. The samples were stored at 4 °C, room temperature, or incubated at 37 °C. Platelet counts were measured using an automated hematology analyzer. The morphology of various blood cells in smears was assessed using the May-Grünwald Giemsa staining method. Docking simulations using an available software (HADDOCK 2.4) were performed to evaluate integrin–fibrinogen binding at different temperatures. Results: In automated blood cell counting, platelet counts in heparinized blood were significantly decreased under low-temperature conditions (4 °C), but this decrease was restored to levels comparable to those at room temperature upon warming to 37 °C (p < 0.05). No significant changes were observed in EDTA-treated samples. Microscopical findings showed platelet aggregation only in heparinized samples at 4 °C, with normal morphology restored upon warming (37 °C). Docking simulations estimated stronger integrin GPIIb/IIIa–fibrinogen binding at 4 °C than at 37 °C (p = 0.0286), suggesting temperature-dependent enhancement of molecular interactions. Conclusions: These findings indicate that heparin can induce reversible platelet aggregation at low temperatures in whole blood samples, leading to pseudothrombocytopenia. This phenomenon may be mediated by increased integrin GPIIb/IIIa–fibrinogen binding. Full article

Background: Antithrombotic therapy plays an important role in acute coronary syndrome (ACS). The combination of anticoagulant and antiplatelet therapy resulted in fewer complications and stronger potency compared to traditional monotherapy. Our net meta-analysis aimed to compare and rank the safety of different treatments used in patients with ACS. Method: We conducted a search for trials in three prominent databases. The main objective of our investigation was to assess hemorrhage. Additional outcomes included mortality, myocardial infarction, stroke, and embolism. We used a frequentist network meta-analysis with a random-effects model to, directly and indirectly, compare safety across different antithrombotic strategies. Result: A total of 30 randomized clinical trials were included in this net meta-analysis with 135,471 ACS patients. In these eight different antithrombotic therapies, SAPT (single-agent platelet inhibitor therapy) showed the lowest risk of bleeding (SUCRA = 0.5%). The highest risk of bleeding was observed in VKA (vitamin K antagonists) + DAPT (dual antiplatelet therapy) (SUCRA = 99.8%). Bleeding among NOAC (non-vitamin K antagonist oral anticoagulants) + DAPT was found to be higher than DAPT (OR = 1.94, 95% CI = 1.42–2.65). NOAC + SAPT significantly reduced the embolism (OR = 1.50, 95% CI = 1.16–1.94) and myocardial infarction (OR = 1.22, 95% CI = 1.08–1.37) events compared with SAPT. In addition, VKA significantly reduced the rate of stroke compared with SAPT (OR = 3.45, 95% CI = 1.17–10.18). However, no significant difference was observed in death events among these eight antithrombotic therapies. Conclusions: We advise against the use of SAPT in ACS due to its elevated risk of embolism, myocardial infarction, and stroke. It is important to mention that the combination of NOAC and SAPT has a lower incidence of myocardial infarction, bleeding and embolism problems. Therefore, the combination of NOAC and SAPT may be the optimal approach to achieve a balance between the risks of bleeding and embolism. This meta-analysis was registered in PROSPERO with the registration number CRD42024542826. Full article

Background: Non-variceal upper gastrointestinal bleeding (NVUGIB) remains a critical medical–surgical emergency associated with significant morbidity, mortality, and healthcare burden worldwide. Despite advances in diagnostic and therapeutic modalities, NVUGIB continues to pose complex clinical challenges, particularly in resource-limited settings. Methods: This retrospective observational study analyzed 364 consecutive adult patients diagnosed with NVUGIB and hospitalized at the First Surgical Clinic of the County Emergency Clinical Hospital Craiova between January 2009 and December 2014. Inclusion criteria required a confirmed diagnosis based on clinical presentation, laboratory findings, and upper gastrointestinal endoscopy (UGIE). Demographic variables, etiology, comorbidities, drug-induced triggers, laboratory parameters, onset-to-admission and onset-to-surgery intervals, endoscopic findings, therapeutic interventions (medical, endoscopic, surgical), rebleeding rates, and mortality were recorded and analyzed. Results were descriptively compared with historical data from the national and international literature. Due to the retrospective and aggregate nature of the data, survival analysis (Kaplan–Meier) was not applicable. Results: Peptic ulcers, erosive gastritis, Mallory–Weiss syndrome, and gastric neoplasms were the predominant etiologies. NSAID use, oral anticoagulation, and alcohol consumption emerged as major risk factors. Endoscopic hemostasis was achieved in the majority of cases; surgical intervention was required in 11.5% of patients, mainly for refractory or recurrent bleeding. The overall mortality rate was 10.9%, consistent with historical benchmarks. Comparative analysis revealed trends in etiology and management reflecting evolving clinical practice standards. Conclusions: NVUGIB remains a significant clinical challenge with persistent mortality and rebleeding risks. This cohort highlights the need for timely diagnosis, risk stratification, and an evidence-based therapeutic strategy integrating modern endoscopic and surgical options. An updated diagnostic and management algorithm is proposed to guide practical decision-making and optimize outcomes in similar tertiary care settings. Full article

Background and Objectives: Deep venous thrombosis (DVT) is associated with pulmonary embolism and long-term complications such as post-thrombotic syndrome (PTS). Anticoagulation prevents thrombus extension but does not actively remove clot. Interventional techniques, including catheter-directed thrombolysis, mechanical and pharmacomechanical thrombectomy, and venous stenting, have been introduced to restore venous patency and reduce complications. This systematic review summarizes current evidence on outcomes, safety, and patient selection for these procedures. Materials and Methods: A systematic search of PubMed, EMBASE, Cochrane Library, and Web of Science was conducted for studies published between January 2000 and February 2024. Eligible studies included randomized controlled trials, systematic reviews, meta-analyses, and observational studies with ≥20 patients. Extracted outcomes were technical success, thrombus clearance, venous patency, PTS, quality of life, and complications. Risk of bias was assessed using the Cochrane Risk of Bias Tool, Newcastle–Ottawa Scale, and AMSTAR-2. Results: Of 456 records screened, 35 studies were included. Randomized trials (CaVenT, ATTRACT, CAVA) showed that catheter-directed and pharmacomechanical approaches improved venous patency and reduced moderate-to-severe PTS in selected patients with iliofemoral DVT, though overall benefit was variable. Mechanical thrombectomy devices (e.g., AngioJet, ClotTriever, FlowTriever) achieved high thrombus clearance and shorter procedural times, with device-specific complication profiles. Observational data demonstrated venous stenting patency rates of 74–89% at 12 months. Study heterogeneity limited direct comparisons. Conclusions: Interventional procedures can reduce PTS and improve outcomes in carefully selected patients, particularly those with acute iliofemoral DVT. Modern mechanical and pharmacomechanical techniques enhance efficiency and safety, while venous stenting addresses underlying obstructions. Further high-quality trials with long-term follow-up are needed to define optimal patient selection and comparative effectiveness. Full article

Systemic or localized infections increase the risk of venous thromboembolism (VTE). All types of infection can elevate the risk of VTE thrombosis, although some appear to increase risk more than others. In the current narrative review, we seek to overview the available evidence related to the epidemiology of VTE caused by infections. We focused on patients with infection in community setting or hospitalized, on patients with COVID-19, HIV infection, tuberculosis, HCV infection, and CMV infection, as well as on individuals with other types of infection that might increase the risk of VTE. Moreover, we tried to evaluate how the risk of VTE in person with different types of infections could be addressed in clinical practice with the use of anticoagulants. Extended VTE prophylaxis may not be warranted for all infections, but may be very helpful for some, such as those with intra-abdominal infection, systemic bloodstream infection, lower respiratory infection, and symptomatic urinary tract infection. Full article

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

(1) Background: Atrial fibrillation (AF) is the most common arrhythmia and poses a clinical dilemma in the very elderly due to increased thromboembolic and bleeding risks. This study aimed to evaluate clinical outcomes—including thromboembolic events, major bleeding, and all-cause mortality—by age group in elderly East Asian patients with non-valvular AF receiving oral anticoagulants. (2) Methods: This retrospective single-center study included 502 patients aged ≥70 years treated with direct oral anticoagulants (DOACs: dabigatran, rivaroxaban, edoxaban, or apixaban) or warfarin between 2016 and 2024. Patients were stratified into two age groups: 70–79 and ≥80 years. The primary outcomes were ischemic stroke, systemic thromboembolism, and major bleeding. (3) Results: Although patients aged ≥80 years showed a numerically higher incidence of bleeding in both the DOAC and warfarin groups, these differences were not statistically significant after multivariable adjustment (DOAC group: HR 0.832; 95% CI, 0.456–1.518; p = 0.549; warfarin group: HR 3.617; 95% CI, 0.600–21.804; p = 0.161). Ischemic and thromboembolic event rates were also comparable between age groups. (4) Conclusions: Despite a numerically higher bleeding risk in the very elderly, DOACs remained safe and effective when appropriately managed. These findings support individualized anticoagulation decisions based on clinical factors rather than age alone in elderly East Asian patients with AF. Full article

Background/Objectives: The question of whether the benefits of anticoagulation outweigh the risks of bleeding in patients with dementia and atrial fibrillation (AF) remains unresolved. This study aimed to evaluate the effectiveness of oral anticoagulation (OAC) and to compare the safety and effectiveness of direct oral anticoagulants (DOACs) with vitamin K antagonists (VKAs) within this at-risk population. Methods: This meta-analysis was conducted following the PRISMA guidelines and was registered in PROSPERO. Data were extracted from MEDLINE, Web of Science, and Cochrane Library. The Newcastle–Ottawa Scale was used to assess the risk of bias. The outcomes were analyzed using the Comprehensive Meta-Analysis software, with odds ratios (ORs) and 95% confidence intervals (CIs) calculated for dichotomous variables. Results: Eight retrospective studies were included, with sample sizes of up to 40,350 participants. The primary outcome was mortality incidence, while secondary outcomes included ischemic stroke, major bleeding, and intracranial hemorrhage (ICH). DOACs significantly reduced ICH events compared to VKAs (OR 0.38, 95% CI 0.17–0.84; I² = 87.3%) but showed no significant difference in major bleeding (OR 0.48, 95% CI 0.22–1.03; I² = 88%). Mortality and ischemic stroke rates were similar between the DOAC and VKA groups. OAC use reduced mortality by 29% compared to no OAC (OR 0.71, 95% CI 0.57–0.88; I² = 81.3%) but increased major bleeding risk (OR 1.19, 95% CI 1.08–1.3; I² = 0%). Conclusions: DOACs offer a safer profile regarding ICH in dementia patients with AF compared to VKAs, with no significant differences in mortality or ischemic stroke rates. This study highlights the need for careful anticoagulant selection in this vulnerable population. Full article

Acanthophis antarcticus, commonly known as the death adder, is a venomous Australian snake and a member of the Elapidae family. Due to its robust body and triangular head, it was historically misclassified as a viper. Its venom is known for neurotoxic, hemorrhagic, and hemolytic effects but displays low anticoagulant activity. Although key toxins such as three-finger toxins (3FTxs) and phospholipase A₂ (PLA₂) have been previously described, no study has integrated proteomic and functional analyses to date. In this study, we conducted a comprehensive characterization of A. antarcticus venom. Reverse-phase high-performance liquid chromatography (RP-HPLC) followed by LC-MS/MS enabled the identification of nine toxin families, with 3FTxs and PLA₂ as the most abundant. Less abundant but functionally relevant toxins included Kunitz-type inhibitors, CRISP, SVMP, LAAO, NGF, natriuretic peptides, and nucleotidases, the latter being reported here for the first time based on proteomic evidence. Hydrophilic interaction chromatography (HILIC) coupled with MALDI-TOF was used to analyze polar, non-retained venom components, revealing the presence of low-molecular-weight peptides (2–4 kDa). Functional assays confirmed the enzymatic activity of HYAL, PLA₂, and LAAO and, for the first time, demonstrated inhibitory activity on serine peptidases and fibrinogenolytic activity in the venom of this species. These findings expand our understanding of the biochemical and functional diversity of this venom. Full article

Background/Objectives: The role of direct oral anticoagulants (DOACs) vs. vitamin K antagonists (VKAs) in preventing recurrent thrombosis in patients with antiphospholipid syndrome (APS) remains uncertain. Using real-world data, we aimed to evaluate the effectiveness and internal validity of a digital twin (DT) approach for modeling thrombotic recurrence risk in APS patients treated with DOACs or VKAs. Methods: We conducted a multicenter observational study that included thrombotic APS patients treated with DOACs or VKAs. Clinical data were used to generate DT via conditional generative adversarial networks (CGANs), incorporating a directed acyclic graph (DAG) to preserve causal relationships. Validation metrics included absolute standardized mean differences (ASMD), mean ASMD (MASMD), and Spearman correlation matrices to assess structural fidelity. Treatment effects were estimated in a CGAN-conditioned cohort matched on key covariates. Results: Eighty-nine thrombotic APS patients were included: 70 (78.7%) received VKAs and 19 (21.3%) received DOACs. Thrombotic recurrences occurred in 5 DOAC patients (26.3%) and 17 AVK patients (24.3%). The CGAN-generated synthetic cohort closely mirrored the original data (MASMD = 0.073 ± 0.041), with 85.4% of pairwise correlations differing by <0.1 in absolute value. In the conditioned DT cohort, predicted recurrence was 24.2% for DOACs and 19.9% for VKAs. Recurrence risk increased with antibody burden, reaching 41.3% in triple-positive patients and 46.8% in those with index arterial thrombosis treated with DOACs. Conclusions: DT technology accurately replicated the clinical structure of APS patients, supporting its application for simulating counterfactual scenarios and estimating individualized treatment effects. Full article

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

Background: Spontaneous intracerebral hemorrhage (ICH) has the highest case fatality of all stroke types, yet recent epidemiological and outcome data from Central and Eastern Europe remain limited. Methods: We retrospectively analyzed prospectively collected data for 601 consecutive adults with primary ICH admitted to Sibiu County Clinical Emergency Hospital, Romania (2017–2023). Demographics, Glasgow Coma Scale (GCS), CT-derived hematoma volume (ABC/2), anatomical site, intraventricular extension (IVH), treatment, comorbidities, and in-hospital death were reported with exact counts and percentages; no imputation was performed. Results: Mean age was 68.4 ± 12.9 years, and 59.7% were male. Mean hematoma volume was 30.4 mL, and 23.0% exceeded 30 mL. IVH occurred in 40.1% and doubled mortality (50.6% vs. 16.7%). Overall case fatality was 29.6% and climbed to 74.5% for brain-stem bleeds. Men, although younger than women (66.0 vs. 71.9 years), died more often (35.4% vs. 21.1%; risk ratio 1.67, 95% CI 1.26–2.21). Systemic hazards amplified death risk: Oral anticoagulation, 44.2%; chronic alcohol misuse, 51.4%; thrombocytopenia, 41.0%; chronic kidney disease, 42.3%. Conservative management (74.9%) yielded 27.8% mortality overall and ≤15 for small-to-mid lobar or capsulo-lenticular bleeds; lobar surgery matched this (13.4%) only in large clots. Thalamic evacuation was futile (82.3% mortality), and cerebellar decompression performed late still carried 54.5% mortality versus 16.6% medically. Multivariable analysis confirmed that low GCS, IVH, large hematoma volume, thrombocytopenia, and chronic alcohol use independently predicted in-hospital mortality. Limitations: This retrospective study lacked post-discharge functional outcome data (e.g., mRS at 90 days). Conclusions: This study presents the largest Romanian single-center ICH cohort, establishing national benchmarks and underscoring modifiable risk factors. Early ICH lethality aligns with Western data but is amplified by exposures such as alcohol misuse, anticoagulation, thrombocytopenia, and CKD. Priorities include preventive strategies, timely surgical access, wider adoption of minimally invasive techniques, and development of a prospective regional registry. Full article