Search Results (1,068)

Extracorporeal membrane oxygenation (ECMO) provides critical support for patients with severe cardiopulmonary dysfunction. Unfractionated heparin (UFH) is used for anticoagulation to maintain circuit patency and avoid thrombotic complications, but it increases the risk of bleeding. Extracellular vesicles (EVs), nano-sized subcellular spheres with potential pro-coagulant properties, are released during cellular stress and may serve as potential targets for monitoring anticoagulation, particularly in thromboinflammation. We investigated the impact of UFH dose during ECMO therapy at the coagulation–inflammation interface level, focusing on complement activation and changes in circulating large EV (lEV) subsets. In a post hoc analysis of a multicenter randomized controlled trial comparing two anticoagulation management algorithms, we examined lEV levels and complement activation in 23 veno-venous-ECMO patients stratified by UFH dose. Blood samples were collected at different time points and grouped into three phases of ECMO therapy: initiation (day 1), mid (days 3–4), and late (days 6–7). Immunoassays detected complement activation, and flow cytometry analyzed lEV populations with an emphasis on mitochondria-carrying subsets. Patients receiving <15 IU/kg/h UFH exhibited higher levels of the complement activation product C5a and soluble terminal complement complex (sC5b-9). Lower UFH doses were linked to increased endothelial-derived lEVs, while higher doses were associated with elevated RBC-derived and mitochondria-positive lEVs. Our findings suggest the potential theranostic relevance of EV detection at the coagulation–inflammation interface. Further research is needed to standardize EV detection methods and validate these findings in larger ECMO patient cohorts. Full article

Hypoxia-inducible factor 1 (HIF-1) may play a role in mammary gland development, milk production and secretion in mammals. Due to the limited number of scientific reports on the expression of HIF genes in colostrum cells, it was decided to examine the expression of HIF1A, HIF3A and EPAS1 in the these cells, collected from 35 patients who voluntarily agreed to provide their biological material for research, were informed about the purpose of the study and signed a consent to participate in it. The expression of HIF genes was assessed using qPCR. Additionally, the influence of clinical parameters (method of delivery, occurrence of stillbirths in previous pregnancies, BMI level before pregnancy and at the moment of delivery, presence of hypertension during pregnancy, presence of Escherichia coli in vaginal culture, iron supplement and heparin intake during pregnancy) on the gene expression was assessed, revealing statistically significant correlations. The expression of HIF1A was 3.5-fold higher in the case of patients with the presence of E. coli in vaginal culture (p = 0.041) and 2.5 times higher (p = 0.031) in samples from women who used heparin during pregnancy. Approximately 1.7-fold higher expression of the EPAS1 was observed in women who did not supplement iron during pregnancy (p = 0.046). To our knowledge, these are the first studies showing the relationship between HIF expression in cells from breast milk and the method of delivery and health condition of women giving birth. The assessment of HIF expression requires deeper examination in a larger study group, and the results of further studies will allow to determine whether HIF can become biomarkers in pregnancy pathology states. Full article

(1) Background: Citrate is preferred in continuous renal replacement therapy (CRRT) for critically ill patients because it prolongs filter life and reduces bleeding risks compared to unfractionated heparin (UFH). However, regional citrate anticoagulation (RCA) can lead to acid–base disturbances, citrate accumulation, and overload. This study compares the safety and efficacy of citrate-based CRRT with UFH and no anticoagulation (NA) in acute kidney injury (AKI) patients. (2) Methods: A retrospective analysis was conducted on adult patients (≥18 years) who underwent CRRT from July 2010 to June 2021 in an intensive care unit. (3) Results: Among 829 AKI patients on CRRT: 552 received RCA, 232 UFH, and 45 NA. The RCA group had a longer filter lifespan compared to UFH and NA (56 h [IQR, 24–110] vs. 36.0 h [IQR, 17–63.5] vs. 22 h [IQR, 12–48]; all P_adj < 0.001). Bleeding complications were fewer in the RCA group than in the UFH group (median 3 units [IQR, 2–7 units] vs. median 5 units [IQR, 2–12 units]; P_adj < 0.001) and fewer in the NA group than in the UFH group (median 3 units [IQR, 1–5 units] vs. 5 units [IQR, 2–12 units]; P_adj = 0.03). Metabolic alkalosis was more common in the RCA group (32.5%) compared to the UFH (16.2%) and NA (13.5%) groups, while metabolic acidosis persisted more in the UFH group and NA group (29.1% and 34.6%) by the end of therapy vs. the citrate group (16.8%). ICU mortality was lower in the RCA group (52.7%) compared to the UFH group (63.4%; P_adj = 0.02) and NA group (77.8%; P_adj = 0.003). (4) Conclusions: Citrate anticoagulation outperforms heparin-based and no anticoagulation in filter patency, potentially leading to better outcomes through improved therapy effectiveness and reduced transfusion needs. However, careful monitoring is crucial to limit potential complications attributable to its use. Full article

Molecular hydrogen (H₂) has antioxidant, anti-inflammatory, and anti-fibrotic effects. In a rat model simulating pulmonary fibrotic changes induced by monocrotaline-induced pulmonary hypertension (MPH), we had previously explored the impact of inhaled H₂ on lung inflammation and blood pressure. In this study, we further focused the biological effects of H₂ on mast cells (MCs) and the parameters of the fibrotic phenotype of the local tissue microenvironment. MPH resulted in a significantly increased number of MCs in both the pneumatic and respiratory parts of the lungs, an increased number of tryptase-positive MCs with increased expression of TGF-β, activated interaction with immunocompetent cells (macrophages and plasma cells) and fibroblasts, and increased MC colocalization with a fibrous component of the extracellular matrix of connective tissue. The alteration in the properties of the MC population occurred together with intensified collagen fibrillogenesis and an increase in the integral volume of collagen and elastic fibers of the extracellular matrix of the pulmonary connective tissue. The exposure of H₂ together with monocrotaline (MCT), despite individual differences between animals, tended to decrease the intrapulmonary MC population and the severity of the fibrotic phenotype of the local tissue microenvironment compared to changes in animals exposed to the MCT effect alone. In addition, the activity of collagen fibrillogenesis associated with MCs and the expression of TGF-β and tryptase in MCs decreased, accompanied by a reduction in the absolute and relative content of reticular and elastic fibers in the lung stroma. Thus, with MCT exposure, inhaled H₂ has antifibrotic effects involving MCs in the lungs of rats. This reveals the unknown development mechanisms of the biological effects of H₂ on the remodeling features of the extracellular matrix under inflammatory background conditions of the tissue microenvironment. Full article

Heparin, a naturally occurring polysaccharide, has fascinated researchers and clinicians for nearly a century due to its versatile biological properties and has been used for various therapeutic purposes. Discovered in the early 20th century, heparin has been a key therapeutic anticoagulant ever since, and its use is now implemented as a life-saving pharmacological intervention in the management of thrombotic disorders and beyond. In addition to its known anticoagulant properties, heparin has been found to exhibit anti-inflammatory, antiviral, and anti-tumorigenic activities, which may lead to its widespread use in the future as an essential drug against infectious diseases such as COVID-19 and in various medical treatments. Furthermore, recent advancements in nanotechnology, including nano-drug delivery systems and nanomaterials, have significantly enhanced the intrinsic biofunctionalities of heparin. These breakthroughs have paved the way for innovative applications in medicine and therapy, expanding the potential of heparin research. Therefore, this review aims to provide a creation profile of heparin, space for its utilities in therapeutic complications, and future characteristics such as bioengineering and nanotechnology. It also discusses the challenges and opportunities in realizing the full potential of heparin to improve patient outcomes and elevate therapeutic interventions. Full article

Vaccination strategies are used to manage Salmonella in chickens. Salmonella-killed vaccines are considered safer since they are inactivated. However, little is known regarding the cellular immune activities at the site of vaccine administration of Salmonella-killed vaccines. The growing feather (GF) cutaneous test has been shown to be an effective bioassay to monitor local tissue/cellular responses. We assessed local and systemic antibody responses initiated by intradermal injection of Salmonella-killed vaccines into GF-pulps of 14–15-week-old pullets. Treatments consisted of two autogenous Salmonella-killed vaccines (SV1 and SV2), S. Enteritidis (SE) lipopolysaccharide (SE-LPS), and the water-oil-water (WOW) emulsion vehicle. GF-pulps were collected before (0 h) and at 6, 24, 48, and 72 h post-GF-pulp injection for leukocyte population analysis, while heparinized blood samples were collected before (0 d) and at 3, 5, 7, 10, 14, 21, and 28 d after GF-pulp injections to assess plasma levels (a.u.) of SE-specific IgM, avian IgY (IgG), and IgA antibodies using an ELISA. Injection of GF-pulps with SV1, SV2, or SE-LPS, all in a WOW vehicle, initiated inflammatory responses characterized by the recruitment of heterophils, monocytes/macrophages, and a few lymphocytes. The WOW vehicle emulsion alone recruited more lymphocytes than vaccines or SE-LPS. The SV1 and SV2 vaccines stimulated Salmonella-specific IgM and IgA early, while IgG levels were greatly elevated later during the primary response. Overall, SV1 and SV2 stimulated a heterophil and macrophage-dominated local inflammatory- and SE-specific humoral response with an isotype switch from IgM to IgG, characteristic of a T-dependent primary antibody response. This study provides comprehensive information on innate and adaptive immune responses to autogenous Salmonella-killed vaccines and their components that will find application in the management of Salmonella in poultry. Full article

Introduction: Trans-radial access for coronary angiography and percutaneous coronary intervention (PCI) has gained popularity due to its advantages over the traditional transfemoral approach. However, radial artery occlusion (RAO) remains a common complication following trans-radial procedures. This study aimed to investigate the incidence of early and late RAO along with their risk factors. Methods: Six databases, Medline (Ovid), National Library of Medicine (MeSH), Cochrane Database of Systematic Reviews (Wiley), Embase, Scopus, and Global Index Medicus, were searched. The systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data were extracted and analyzed. Using a random-effect model, the primary endpoint was the overall incidence of RAO after invasive coronary procedures. Subgroup analysis and meta-regression were also performed to identify possible predictors of RAO. Results: A total of 41 studies with 30,020 patients were included. The overall incidence of RAO was 13% (95% CI = 0.09–0.16). The incidence of early RAO (within 24 h) was 14% (95% CI = 0.10–0.18) in 26 studies, while the incidence of late RAO (after 24 h) was 10% (95% CI = 0.04–0.16) in 22 studies. The average incidence rates of early RAO in studies with catheter sizes of <6 Fr, 6 Fr, and >6 Fr were 9.8%, 9.4%, and 8.8%. The overall effect size of female gender as a predictor was 0.22 with a 95% CI of 0.00–0.44. Age was a potential predictor of early RAO (B = 0.000357; 95% CI = −0.015–0.0027, p: 0.006). Conclusions: This meta-analysis provides essential information on the incidence of early (14%) and late (10%) RAO following angiographic procedures. Additionally, our findings suggest that female sex and age are possible predictors of RAO. A larger catheter, especially (6 Fr) and hemostatic compression time <90 min post-procedure, substantially reduced the incidence of RAO. The use of oral anticoagulation and the appropriate dosage of low-molecular-weight heparin (LMWH) does reduce RAO, but a comparison between them showed no statistical significance. Full article

Due to their very wide range of indications, anticoagulants are one of the most commonly used drug groups. Although these drugs are characterized by different mechanisms of action, the most common complication of their use is still bleeding episodes, the frequency of which depends largely on the clinical condition of the patient using such therapy. For this reason, to this day, the best method of preventing bleeding complications remains the assessment of bleeding risk using scales such as HAS-BLED. There are many reports in the literature assessing the occurrence of this type of complication after the use of drugs affecting the coagulation process, as well as many reports comparing individual groups of drugs with different mechanisms of action. However, there are still no clear guidelines that would indicate which group of anticoagulants should be preferred in particular groups of patients. The aim of our article is to summarize the data collected so far regarding the safety of using specific groups of anticoagulants and the frequency of bleeding complications after their use. Full article

Fucosylated chondroitin sulfate (FCS) was prepared from Bohadschia ocellata using protease hydrolysis. The structural characteristics of FCS were confirmed through chemical composition analysis using FTIR spectroscopy, ¹H NMR, and ¹³C NMR. FCS from B. ocellata (FCS-Bo) exhibited an average molecular weight of approximately 122 kDa. The biological activities of FCS-Bo, including anticoagulant, anti-cancer, and Protein Tyrosine Phosphatase 1B (PTP1B) inhibition, were evaluated. FCS-Bo displayed potent anticoagulant properties, markedly extending activated partial thromboplastin time, prothrombin time, and thrombin time when compared to the heparin control. In anti-cancer bioactivity research, FCS-Bo efficiently inhibited colony formation in the colon cancer cell lines HCT-116, HT-29, and DLD-1, achieving inhibition rates of up to 65%. Additionally, FCS-Bo exhibited significant inhibition of PTP1B, with an IC₅₀ as low as 0.0326 µg/mL, suggesting its potential for improving insulin sensitivity and managing conditions such as type 2 diabetes and obesity. Full article

The integration of unmanned aerial vehicles or uncrewed aerial vehicles (UAVs)—commonly known as drones—into medical logistics offers transformative potential for the transportation of sensitive medical materials, such as blood samples. Traditional car transportation is often hindered by traffic delays, road conditions, and geographic barriers, which can compromise timely delivery. This study provides a comprehensive analysis comparing high-speed drone transportation with traditional car transportation. Blood samples, including EDTA whole blood, serum, lithium-heparin plasma, and citrate plasma tubes, were transported via both methods across temperatures ranging from 4 to 20 degrees Celsius. The integrity of the samples was assessed using a wide array of analytes and statistical analyses, including Passing–Bablok regression and Bland–Altman plots. The results demonstrated that drone transportation maintains blood sample integrity comparable to traditional car transportation. For serum samples, the correlation coefficients (r) ranged from 0.830 to 1.000, and the slopes varied from 0.913 to 1.111, with minor discrepancies in five analytes (total bilirubin, calcium, ferritin, potassium, and sodium). Similar patterns were observed for EDTA, lithium-heparin, and citrate samples, indicating no significant differences between transportation methods. Conclusions: These findings highlight the potential of drones to enhance the efficiency and reliability of medical sample transport, particularly in scenarios requiring rapid and reliable delivery. Drones could significantly improve logistical operations in healthcare by overcoming traditional transportation challenges. Full article

In contrast to other common anticoagulants such as citrate and low-molecular-weight heparin (LMWH), high-molecular-weight heparin (HMWH) induces the expression of matrix metalloproteinase (MMP)-9, which is also measured as a biomarker for stroke in blood samples. Mechanistically, HMWH-stimulated T cells produce cytokines that induce monocytic MMP-9 expression. Here, the influence of further anticoagulants (Fondaparinux, Hirudin, and Alteplase) and the heparin-contaminating glycosaminoglycans (GAG) hyaluronic acid (HA), dermatan sulfate (DS), chondroitin sulfate (CS), and over-sulfated CS (OSCS) on MMP-9 was analyzed to assess its suitability as a biomarker under various conditions. Therefore, starved Jurkat T cells were stimulated with anticoagulants/contaminants. Subsequently, starved monocytic THP-1 cells were incubated with the conditioned Jurkat supernatant, and MMP-9 mRNA levels were monitored (quantitative (q)PCR). Jurkat-derived mediators secreted in response to anticoagulants/contaminants were also assessed (proteome profiler array). The supernatants of HMWH-, Hirudin-, CS-, and OSCS-treated Jurkat cells comprised combinations of activating mediators and led to a significant (in the case of OSCS, dramatic) MMP-9 induction in THP-1. HA induced MMP-9 only in high concentrations, while LMWH, Fondaparinux, Alteplase, and DS had no effect. This indicates that depending on molecular weight and charge (but independent of anticoagulant activity), anticoagulants/contaminants provoke the expression of T-cell-derived cytokines/chemokines that induce monocytic MMP-9 expression, thus potentially impairing the diagnostic validity of MMP-9. Full article

Background: Thrombosis is the abnormal formation of blood clots within blood vessels; it results from an imbalance between fibrinolytic, pro-coagulant, and anticoagulant systems. Pediatric arterial thrombosis, especially related to catheter usage, is an emerging issue with limited evidence. This study evaluates the efficacy of enoxaparin in treating arterial thrombosis in pediatric patients at a single center. Methods: A retrospective single-center study included children under 14 years old diagnosed with catheter-related arterial thrombosis (CAT) and treated with low-molecular-weight heparin (LMWH) at King Abdulaziz Medical City between 2016 and 2021. Patients without follow-up at our institution or those using other anticoagulants were excluded. Data collected included age, sex, weight, catheter type, location and degree of thrombosis, ultrasonographic results, treatment duration, hemoglobin and platelet levels, and missed refills. Radiologic confirmation of CAT was required for inclusion. Results: This study included 111 children treated with enoxaparin for non-cerebral arterial thrombosis. The median age at diagnosis was 3 months, with 58% being male patients. Most cases (87%) involved cardiac catheterization, and all were confirmed using ultrasonography. Complete thrombus resolution was achieved in 90% of patients, partial resolution in 8.1%, and 1.8% had no resolution. The median duration of enoxaparin therapy was 20 days. Multivariate analysis indicated that higher age and lower body weight were associated with a higher risk of non-resolution. Indwelling catheters also posed a greater risk of non-resolution compared to cardiac catheters. Conclusions: Enoxaparin proved effective in treating catheter-related arterial thrombosis in children, with high resolution rates and few side effects. This study helps inform treatment strategies in pediatric thrombosis management and highlights the need for further research to refine treatment durations and address patient risk factors. Full article

Background: Valve-in-Valve (ViV) transcatheter aortic valve implantation (TAVI) has emerged as a viable therapeutic option for structural valve degeneration following surgical aortic valve replacement (SAVR) or prior TAVI. However, the understanding of long-term complications and their management remains limited. Case presentation: We present the case of a 69-year-old male with a history of ViV-TAVI, who presented with symptoms of non-ST elevation myocardial infarction (NSTEMI) and transient ischemic attack (TIA). Computed tomography (CT) revealed thrombosis of the ascending aortic graft and aortic valve prosthesis. Transthoracic echocardiography (TTE) further confirmed new valve dysfunction, indicated by an increase in the aortic valve mean gradient. Treatment with low-molecular-weight heparin (LMWH) resulted in partial thrombus resolution. The multidisciplinary Heart Team opted against coronary angiography and recommended the long-term administration of vitamin K antagonists (VKAs). Follow-up CT showed the complete resolution of the thrombus. Conclusions: Thrombosis of the aortic graft and aortic valve following ViV-TAVI may be attributed to alterations in blood flow or mechanical manipulations during the TAVI procedure, yet it can be effectively managed with VKA therapy. CT is a valuable tool in coronary assessment in patients with NSTEMI and aortic valve and/or aortic graft thrombosis. Full article

Background: Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare but severe complication following vaccination with adenovirus vector-based COVID-19 vaccines. Antibodies directed against platelet factor 4 (PF4) are thought to be responsible for platelet activation and subsequent thromboembolic events in these patients. Since a single vaccination does not lead to sufficient immunization, subsequent vaccinations against COVID-19 have been recommended. However, concerns exist regarding the possible development of a new thromboembolic episode after subsequent vaccinations in VITT patients. Methods: We prospectively analyzed follow-up data from four VITT patients (three women and one man; median age, 44 years [range, 22 to 62 years]) who subsequently received additional COVID-19 vaccines. Platelet counts, anti-PF4/heparin antibody level measurements, and a functional platelet activation assay were performed at each follow-up visit. Additionally, we conducted a literature review and summarized similar reports on the outcome of subsequent vaccinations in patients with VITT. Results: The patients had developed thrombocytopenia and thrombosis 4 to 17 days after the first vaccination with ChAdOx1 nCoV-19. The optical densities (ODs) of anti-PF4/heparin antibodies decreased with time, and three out of four patients tested negative within 4 months. One patient remained positive even after 10 months post first vaccination. All four patients received an mRNA-based vaccine as a second vaccination against SARS-CoV-2. No significant drop in platelet count or new thromboembolic complications were observed during follow-up. We identified seven publications reporting subsequent COVID-19 vaccination in VITT patients. None of the patients developed thrombocytopenia or thrombosis after the subsequent vaccination. Conclusion: Subsequent vaccination with an mRNA vaccine appears to be safe in VITT patients. Full article

Background and Objectives: Pulmonary embolism (PE) incidence has been increasing in the last 10 years. Computed thoracic pulmonary angiography (CTPA) had a major role in PE diagnosis and prognosis. The main purpose of this study was as follows: the prognostic value of a CTPA parameter, pulmonary artery obstruction index (PAOI), in PE risk assessment and the predictive accuracy of biomarkers, D-dimer and cardiac Troponin T (c-TnT), in 7-day mortality. A second objective of the research was to investigate the relationship between imaging by PAOI and these biomarkers in different etiologies of PE. Materials and Methods: This study comprised 109 patients with PE, hospitalized and treated between February 2021 and August 2022. They had different etiologies of PE: deep vein thrombosis (DVT); persistent atrial fibrillation (AF); chronic obstructive pulmonary disease (COPD) exacerbation; COVID-19; and cancers. The investigations were as follows: clinical examination; D-dimer testing, as a mandatory method for PE suspicion (values ≥500 µg/L were highly suggestive for PE); c-TnT, as a marker of myocardial injury (values ≥14 ng/L were abnormal); CTPA, with right ventricle dysfunction (RVD) signs and PAOI. Treatments were according to PE risk: systemic thrombolysis in high-risk PE; low weight molecular heparins (LWMH) in high-risk PE, after systemic thrombolysis or from the beginning, when systemic thrombolysis was contraindicated; and direct oral anticoagulants (DOAC) in low- and intermediate-risk PE. Results: PAOI had a high predictive accuracy for high-risk PE (area under curve, AUC = 0.993). D-dimer and cTnT had a statistically significant relationship with 7-day mortality for the entire sample, p < 0.001, and for AF, p = 0.0036; COVID-19, p = 0.003; and cancer patients, p = 0.005. PAOI had statistical significance for 7-day mortality only in COVID-19, p = 0.045, and cancer patients, p = 0.038. The relationship PAOI–D-dimer and PAOI–c-TnT had very strong statistical correlation for the entire sample and for DVT, AF, COPD, and COVID-19 subgroups (Rho = 0.815–0.982). Conclusions: PAOI was an important tool for PE risk assessment. D-dimer and c-TnT were valuable predictors for 7-day mortality in PE. PAOI (imaging parameter for PE extent) and D-dimer (biomarker for PE severity) as well as PAOI and c-TnT (biomarker for myocardial injury) were strongly correlated for the entire PE sample and for DVT, AF, COPD, and COVID-19 patients. Full article