Search Results (7,569)

Venous thromboembolism (VTE), including pulmonary embolism (PE) and deep vein thrombosis (DVT), remains a major cause of morbidity and mortality worldwide, with significant clinical challenges in diagnosis and risk stratification. Traditional diagnostic tools, including clinical prediction scores, D-dimer testing, and imaging, are limited by suboptimal specificity or sensitivity. In this context, proteomics-based approaches have emerged as powerful tools to elucidate the molecular mechanisms of VTE and to identify novel diagnostic and prognostic biomarkers. This review synthesizes recent advances in proteomic research relevant to VTE. We searched four databases (PubMed, ScienceDirect, Springer Nature, and Wiley) using the keywords “acute pulmonary embolism”, “acute venous thromboembolism”, and “proteomics”. Thirty proteomic studies investigating VTE were examined. Across these studies, proteomic profiling consistently revealed alterations in pathways related to coagulation, inflammation, platelet activation, endothelial dysfunction, and fibrin clot structure. Multiple protein classes, including acute-phase reactants, complement components, coagulation factors, and platelet-derived proteins, have demonstrated potential value in improving diagnostic accuracy and refining prognostic stratification. Proteomic analyses have also revealed distinct molecular signatures between isolated PE and isolated DVT, supporting the concept of biologically heterogeneous VTE phenotypes. Furthermore, emerging evidence from COVID-19–associated thrombosis, cancer-associated VTE, and non-invasive sources such as exhaled breath condensate underscores the expanding clinical relevance of proteomic approaches. Although technical limitations and heterogeneity across studies remain challenges, the integration of proteomic data with clinical and genetic information holds promise for advancing precision medicine in VTE. Full article

Background: Thrombotic thrombocytopenic purpura (TTP) is a rare but life-threatening thrombotic microangiopathy (TMA) caused by severe deficiency of the von Willebrand factor–cleaving protease ADAMTS13. Pregnancy is a recognized trigger for both immune-mediated and congenital TTP and is associated with increased maternal and fetal morbidity. Clinical overlap with other pregnancy-associated TMAs, including preeclampsia and Hemolysis, Elevated Liver enzymes, and Low Platelet count (HELLP) syndrome, often delays diagnosis. This review synthesizes current evidence on pathophysiology, diagnostic uncertainty, and gestation-specific management of pregnancy-associated TTP, highlighting differences between immune-mediated and congenital disease. Methods: This is a narrative review. We performed a targeted literature search of PubMed/MEDLINE (from inception to December 2025) to identify English-language publications. The study types included were case reports/series, observational studies, large database studies, randomized trials, reviews, and relevant guidelines addressing TMA in pregnancy, with emphasis on immune-mediated and congenital TTP. Search terms included “pregnancy”, “thrombotic thrombocytopenic purpura”, “hereditary TTP”, “acquired TTP”, “ADAMTS13,” “thrombotic microangiopathy,” “HELLP,” “postpartum”, and “complement-mediated TMA” alone or in combination. The search was supplemented by manual screening of reference lists and key guidelines. Articles were selected based on relevance to diagnosis and management of pregnancy-associated TTP. Conference abstracts and non-peer-reviewed sources were not routinely included and were considered only when peer-reviewed evidence was limited. Results: Pregnancy-associated TTP remains a major diagnostic challenge due to overlapping clinical and laboratory features with other obstetric thrombotic microangiopathies. Distinguishing immune-mediated from congenital TTP is essential, as management and prognosis differ substantially. Prompt recognition and early initiation of therapeutic plasma exchange, immunosuppression, or prophylactic plasma therapy markedly improve maternal outcomes. Rapid ADAMTS13 testing, structured risk stratification, and multidisciplinary care are central to optimal management. Fetal outcomes are closely linked to gestational age at onset and timeliness of therapy. Conclusions: Early differentiation of TTP from other pregnancy-associated TMAs is critical for maternal and fetal survival. Advances in rapid ADAMTS13 diagnostics and emerging targeted therapies, including caplacizumab and recombinant ADAMTS13, offer opportunities to improve precision management and outcomes in future pregnancies. Full article

The incidence of cancer-associated thrombosis has increased in recent years. While the association between venous thromboembolism (VTE) and chemotherapy is well established, there is no clear link between immune checkpoint inhibitors (ICIs) and VTE risk. Many risk assessment models (RAMs) have been developed to identify high-risk patients who need prophylaxis. However, these models are validated in patients undergoing chemotherapy, while they are scarce in those receiving immunotherapy. Moreover, the mechanisms linking ICIs to thrombosis are still a matter of debate. They include the upregulation of pro-inflammatory intracellular pathways, the release of cytokines, the activation of innate immune cells, the release of tissue factors and platelet activation, and the increase in adhesion molecules, thus resulting in the recruitment of agents involved in coagulation. Promising biomarkers are emerging to identify patients undergoing ICIs who are at high risk of developing VTE and need prophylaxis. In this review we investigate the possible causation between cancer-associated thrombosis (CAT) and immunotherapy and the underlying pathophysiological mechanisms. Thus, we suggest the most appropriate therapeutic approaches based on currently available data. Full article

Aquaculture output, sustainability, and profitability can be enhanced by using functional feed additives. The effect of supplementation with two different dietary levels of propylene glycol (PG) and essential oils (EOs) was evaluated in Nile tilapia. A total of 150 juvenile fish were randomly allocated into five groups. Growth performance, feed utilization, serum biochemistry, hematology, and gene expression were assessed. PG supplementation significantly improved growth performance, feed conversion, protein efficiency, and energy utilization. Both additives significantly reduced cortisol and glucose levels and altered liver enzymes and lipid profiles. PG improved immunological indices, while hematological responses were dose-dependent; both EOs and PG increased hematocrit, mean corpuscular volume (MCV), and mean corpuscular hemoglobin (MCH). Moreover, the high PG dose significantly increased platelet counts, reduced hemoglobin (Hb), and elevated hematocrit. Additionally, EOs significantly upregulated antifreeze protein IV (AFPIV) and fat metabolism-related genes in a dose-dependent manner, indicating a potential role in lipid mobilization and stress tolerance. Expression analysis of the immunoglobulin H (IGMH) gene revealed a significant increase in PG-supplemented groups, suggesting its immunostimulatory potential. Overall, PG enhanced immunity and growth performance, while EOs promoted AFPIV and fat metabolism gene expression. Therefore, PG and EO supplementation could serve as an effective functional strategy to enhance O. niloticus growth, stress adaptation, and immune resilience. Full article

Cardiovascular diseases and metabolic dysfunction-associated steatotic liver disease (MASLD) are increasing sharply worldwide and share overlapping pathophysiological pathways, including oxidative stress, inflammation, hyperglycemia, obesity, dyslipidemia, and hypertension. Dark chocolate, rich in cocoa flavanols such as epicatechin and catechin, exhibits antioxidant and anti-inflammatory effects. Based on these properties, this narrative review uniquely integrates evidence on chocolate’s effects on both cardiovascular and hepatic health, exploring shared mechanisms and clinical implications. Evidence from clinical studies suggests that chocolate modulates nitric oxide bioavailability and NADPH oxidase activity. Clinical findings demonstrate improvements in flow-mediated dilation, decreased NT-proBNP, reduced intestinal permeability and endotoxemia, improved lipid profile (increased HDL-c and reduced total cholesterol, LDL-c, and triglycerides), increased plasma polyphenols, improved platelet function, and attenuated hepatocyte apoptosis. These findings suggest a potential role for cocoa flavanol-rich dark chocolate in cardiometabolic health; however, the evidence remains preliminary and is limited by heterogeneous study designs, small sample sizes, and short intervention durations. Despite these limitations, current evidence supports the inclusion of moderate dark chocolate consumption as a possible adjunct strategy to mitigate cardiometabolic and hepatic metabolic risks. Further large-scale, long-term trials are needed to confirm these beneficial effects and to standardize the dosage and formulation of cocoa flavanols. Full article

Background and Objectives: The risk of cardiovascular events rises when hypertensive patients fail to achieve sufficient blood pressure reduction during nighttime hours. This study examined the association between metabolic and inflammatory biomarkers and non-dipper patterns in patients with white-coat hypertension. Materials and Methods: A total of two hundred and forty-four (244) patients with newly diagnosed white-coat hypertension were included in the study. The study used ambulatory blood pressure monitoring to classify patients as dippers (n = 86) and non-dippers (n = 158). The study evaluated metabolic markers through triglyceride–glucose (TyG) index, atherogenic index of plasma (AIP) and uric acid measurements against inflammatory markers including neutrophil/lymphocyte ratio, platelet/lymphocyte ratio and monocyte/lymphocyte ratio. Results: The non-dipper group showed higher levels of uric acid (6.42 mg/dL vs. 5.65 mg/dL; p < 0.001), TyG index (8.82 vs. 8.51; p < 0.001), AIP (0.49 vs. 0.37 **; ** p < 0.001) and body mass index (26.0 kg/m² vs. 24.1 kg/m²; p < 0.001) when compared to the dipper group. The inflammatory markers showed no significant variation between the groups. Uric acid showed the highest discriminative ability (AUC = 0.722). The research showed that each one mg/dL increase in uric acid levels was associated with 89% higher odds of non-dipper status (OR = 1.892; p = 0.002). A one-unit increase in the TyG index was associated with approximately 2.5-fold-higher odds. Conclusions: Levels of TyG index, uric acid, BMI and AIP were higher in patients with the non-dipper pattern compared to the dipper patients. The TyG index, uric acid levels, and BMI were independently associated with the non-dipper pattern in white-coat hypertension patients. These findings suggest that metabolic biomarkers may help identify individuals at higher risk for circadian blood pressure dysregulation. Full article

Guided bone regeneration (GBR) relies on barrier membrane integrity to prevent soft-tissue ingrowth. Although collagen membranes are widely used, their limited longevity can compromise space maintenance, underscoring the need for strategies that enhance membrane stability without impairing the regenerative potential. We hypothesized that thermal denaturation of platelet-poor plasma (PPP), combined with heat-induced modifications of collagen fibrils, could generate a volume-stable, plasma-rich composite that preserves membrane structure and restricts cellular penetration. To test this proof-of-principle concept, collagen membranes were soaked in PPP and either kept at room temperature or subjected to thermal treatment (75 °C/10 min) prior to implantation in rat calvarial defects. Bone regeneration and membrane behavior were evaluated after three weeks using micro-computed tomography (micro-CT) and histology. Micro-CT suggested only minor numerical differences in mineralized tissue between groups; however, these data should not be overinterpreted because micro-CT cannot differentiate mineralization formed within the collagen membrane from mineralization adjacent to it. Consistent with this limitation, histology demonstrated that mineral deposition and early bone formation extended into the structure of room-temperature PPP membranes, whereas mineralized tissue in the thermally treated group was predominantly located outside the membrane, indicating reduced osteoconductive integration within the membrane. Together, these findings support that thermal denaturation of PPP shifts early composite membrane behavior toward barrier-dominant characteristics at the expense of intramembranous mineralization. Full article

Background: The extent to which bone marrow aspiration technique affects the biological quality of bone marrow aspirate and its clinical relevance in knee osteoarthritis remains uncertain. This study compares the efficacy of the traditional aspiration method and the Snap Back technique at two anatomical harvest sites, the posterior iliac crest and the proximal tibia. Methods: This ancillary post hoc analysis was conducted within a randomized trial comparing posterior iliac crest and proximal tibia harvest sites in 60 patients with unicompartmental knee OA. Aspiration technique (traditional vs. Snap Back) was selected intraoperatively and not randomized. BMA samples were analyzed for MSCs, mononuclear cells (MNCs), platelet concentration, and marrow purity. Clinical outcomes were assessed at baseline and six months using the Visual Analog Scale and the Western Ontario and McMaster Universities Osteoarthritis Index. Results: The posterior iliac crest yielded significantly higher MSC and MNC concentrations compared to the tibia, with superior purity and PLT counts observed using the Snap Back technique. Within each anatomical site, Snap Back aspiration provided improved cellular recovery over the traditional method. However, differences in clinical outcomes between groups were modest and did not consistently reach statistical significance. Conclusions: Both harvest site and aspiration technique were associated with substantial differences in the cellular composition of BMA. The withdrawal from posterior iliac crest combined with the Snap Back technique optimizes MSC yield and marrow purity, though clinical improvements appear independent of cellular concentration in the short term. These findings suggest that standardized aspiration protocols may be relevant for the biological efficacy of orthobiologic therapies in knee OA. Full article

Background: Deep vein thrombosis (DVT) is a common and potentially serious complication in elderly patients with hip fractures, as it may progress to pulmonary embolism. Despite advances in perioperative care, preoperative DVT remains an important clinical concern; therefore, in this study, we aimed to identify risk factors associated with preoperative DVT in elderly patients with hip fractures. Methods: A retrospective case–control study was conducted in patients aged > 60 years with hip fractures who had undergone preoperative Doppler ultrasonography between January 2015 and August 2024, while patients with prior or chronic DVT or incomplete medical records were excluded. Demographic, clinical, and laboratory data were collected, and uni- and multivariate logistic regression analyses were performed to identify independent predictors of preoperative DVT. Results: Of 669 eligible patients, 454 were included, and 23 (5.1%) were diagnosed with preoperative DVT. The mean age of the whole cohort was 79.5 years, and 70.7% were female. Univariate analysis revealed that thirteen predictors with p < 0.1 were associated with preoperative DVT, while through multivariate analysis, we identified four independent predictors: female sex (p = 0.02), active smoking (p = 0.01), Wells’ score ≥ 2 (p = 0.01), and elevated platelet-to-lymphocyte ratio (PLR) (p = 0.05). The model demonstrated good discriminative performance, with an AUC of 0.81. Conclusions: Preoperative DVT remains clinically significant in elderly patients with hip fractures. Female sex, active smoking, higher Wells’ score, and elevated PLR are independent predictors of this condition, so incorporating these factors into preoperative assessment may improve risk stratification and optimize Doppler ultrasonography use. Full article

Objective: To investigate the relationship between glycemic control and inflammation–nutrition indices in older adults with type 2 diabetes mellitus and to evaluate their prognostic value for 30-day mortality. Methods: This retrospective cohort study included 372 hospitalized patients aged ≥65 years with type 2 diabetes. Laboratory data were used to calculate the hemoglobin–albumin–lymphocyte–platelet (HALP) score, the endothelial activation and stress index (EASIX), and the uric acid-to-high-density lipoprotein cholesterol ratio (UHR). Cox regression analyses were performed to identify independent predictors of 30-day mortality, and combined stratification models using HALP, EASIX, and UHR were evaluated for risk discrimination. Results: Thirty-day mortality occurred in 57 patients (15.3%). HbA1c levels were not significantly associated with mortality (p = 0.615). Non-survivors had higher UHR, and EASIX, and lower HALP score levels (all p < 0.05). In multivariate Cox regression, age (HR 1.066, 95% CI 1.024–1.109, p = 0.002), length of hospital stay (HR 1.050, 95% CI 1.026–1.074, p < 0.001), ICU admission (HR 2.394, 95% CI 1.227–4.672, p = 0.010), and UHR (HR 1.028, 95% CI 1.013–1.042, p < 0.001) were independent predictors of mortality. Stratification by EASIX and UHR revealed that patients with both high EASIX or UHR and low HALP had the highest mortality risk, with adjusted HRs up to 4.206 (95% CI 1.930–9.166, p < 0.001). Conclusions: Among older adults with type 2 diabetes, short-term mortality is more strongly associated with inflammation, endothelial stress, and nutritional status than with glycemic control. Combined inflammation–nutrition indices (HALP, EASIX, UHR) provide superior risk stratification and help identify high-risk patients early. Full article

Osteoarthritis is associated with chronic inflammation, which contributes to a hypercoagulable state. Oxidative stress may further disrupt homeostatic balance, thereby promoting thrombotic events. This study evaluated the association between biomarkers of oxidative stress, inflammation, haemostasis, and bone metabolism in patients with spinal osteoarthritis. A total of 48 patients were included. The levels of inflammatory, bone turnover, haematological, and coagulation biomarkers were determined using standard laboratory methods. Redox status was assessed via prooxidant–antioxidant balance (PAB) and superoxide dismutase (SOD) activity. Patients with elevated PAB showed significantly higher erythrocyte sedimentation rate (ESR) (p = 0.005), alkaline phosphatase (ALP) (p = 0.003) and fibrinogen levels (p = 0.006) and platelet count (p = 0.040), along with lower 25-OH vitamin D levels (p = 0.045) and shortened PT (p = 0.008) and aPTT (p = 0.017). In low oxidative stress states (PAB < 100 U/L), significant correlations were observed among redox, coagulation, and bone turnover markers, whereas in high oxidative stress (PAB ≥ 100 U/L), it was characterised by predominant associations between redox and bone turnover biomarkers. Patients with grade V disc degeneration had a significantly higher probability of elevated D-dimer levels compared to those with grade IV (OR = 5.440; p = 0.009). In addition, elevated D-dimer levels were associated with increased ESR (p = 0.015), IL-6 (p = 0.016) and ALP levels (p = 0.034). The associations between biomarkers of redox status, inflammation, coagulation and bone turnover are influenced by the extent of oxidative stress. Our results suggest that PAB and D-dimer may serve as potential biomarkers for disease severity and thrombotic risk. Further studies are needed to confirm these preliminary findings. Full article

Background and Objectives: Early saphenous vein graft (SVG) failure remains a clinically significant limitation of contemporary coronary artery bypass grafting (CABG). Platelet function testing has been proposed to identify patients with an attenuated aspirin effect who may be at higher thrombotic risk. Therefore, this study aimed to determine whether preoperative aspirin non-responsiveness, assessed by the platelet function assay, is associated with early graft failure after CABG, as evaluated by CT coronary angiography. Materials and Methods: In this prospective observational study, consecutive patients undergoing elective, first-time isolated on-pump CABG with ≥1 SVG and preoperative aspirin therapy were enrolled. Platelet function was measured preoperatively using a point-of-care assay (ASPI, aspirin reaction units [ARU]), and patients were stratified as responders (<550 ARU) or non-responders (≥550 ARU). The primary endpoint was early SVG occlusion, detected by CT angiography performed before discharge after CABG. Secondary endpoints included postoperative cardiac and renal biomarkers, myocardial infarction, stroke, rehospitalization, and 30-day mortality. Results: Early CT-confirmed SVG occlusion occurred in 22/170 patients (12.9%) and did not differ between responders and non-responders (20/136 [14.7%] vs. 2/34 [5.9%]; p = 0.21). Cardiac biomarkers were similar between the groups for 4–24 h. Thirty-day mortality (1.5%), myocardial infarction (5.9% in each group), and stroke (2.2% vs. 5.9%) were infrequent and similar between groups. Rehospitalization was more common among non-responders, driven by deep wound infection (5.9% vs. 0%; p = 0.040). In exploratory analysis, females had a significantly higher early graft occlusion rate than males (27.3% vs. 8.6%; p = 0.004). Conclusions: Aspirin non-responsiveness, as assessed by ASPI testing, was not associated with early CT-confirmed SVG occlusion, and these data do not support intensifying antiplatelet therapy based solely on a single preoperative platelet-function measurement. Given the absence of serial postoperative platelet function measurements, future studies should prioritize postoperative platelet reactivity and different treatment strategies during the early window of graft vulnerability. Full article

Extracellular vesicles (EVs) have long been understood to be important mediators of cell-to-cell communication and may lead to the molecular aftermath and exacerbation of brain injuries such as stroke. This study explored how the source of the EVs influenced their characteristics and the effect these differences had on naïve brain tissue. EVs were isolated from mice post-stroke in the acute or chronic stages of recovery in animals with and without reperfusion (transient and permanent middle cerebral artery occlusion) and from a model of systemic inflammation (i.p. lipopolysaccharide). The data show that neither stroke nor inflammation significantly increases EV numbers compared to sham or naïve animals. Post-stroke EVs exhibited a panel of different platelet and inflammatory markers when compared to EVs derived from a model of inflammation, reflecting differences between stroke and systemic immune activation. When injected into the brain, both stroke-derived and inflammation-derived EVs induced pro-inflammatory cytokine gene expression (IL-1β and CXCL1), suggesting a potential role in neuroinflammation. However, no clear group-level differences in microglial or astrocytic reactivity were detected at the level of regional histological assessment, despite consistent increases in ICAM-1 reactivity. The findings here underscore the complexity of EVs’ roles in pathophysiology and highlight the need for improved EV isolation methods. With further longitudinal studies, we may be able to more accurately determine how the context of the injury (reperfusion vs. no reperfusion vs. inflammation) might contribute to the EV populations and their function. Understanding more about EVs in different contexts will improve our ability to use EVs as biomarkers but also our capacity to interfere with EV biology as a novel therapeutic approach. Full article

The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and systemic immune-inflammation index (SII) are derived hematological indices reflecting systemic inflammatory balance in dogs with different serological statuses for canine leishmaniosis (CanL). The aim of this study was to describe and compare hematological ratios (HRs) between dogs seropositive and seronegative for Leishmania infantum and to assess their distribution across LeishVet stages. A retrospective multicenter case–control study was conducted, including 305 seropositive dogs and 305 seronegative controls from referral hospitals in Spain. Hematological data were retrospectively reviewed and analyzed. Significant differences were observed in NLR and MLR between seronegative control dogs and dogs with leishmaniosis, whereas no differences were found for PLR or SII. Median NLR and MLR values were higher in dogs with leishmaniosis compared to controls. In addition, comparisons across LeishVet stages revealed statistically significant differences for all evaluated HRs. These findings indicate that NLR and MLR are increased in dogs with CanL and that HR varies across LeishVet stages, as these indices represent the relative proportions of neutrophils and monocytes in relation to lymphocytes; therefore, changes in their values reflect shifts in leukocyte distribution observed across clinical stages. Full article

Background: Pharmacological cardioversion (PC) with antiarrhythmic agents is a common initial rhythm control strategy in patients with new-onset atrial fibrillation (AF). However, predictive tools for estimating the likelihood of successful PC remain limited. The systemic immune-inflammation index (SII), a novel composite marker derived from neutrophil, lymphocyte, and platelet counts, may reflect atrial inflammatory burden and structural remodeling. This study aimed to investigate the prognostic value of SII in predicting pharmacological cardioversion success in patients with acute-onset symptomatic AF. Methods: This prospective observational study included patients with hemodynamically stable, new-onset symptomatic AF admitted since October 2025. All patients received intravenous amiodarone for pharmacological cardioversion. Baseline clinical, echocardiographic, and laboratory parameters were recorded. Patients were classified into cardioversion-success and non-response groups based on ECG-confirmed restoration of sinus rhythm. Logistic regression analyses were performed to identify independent predictors of rhythm control, and ROC curves were generated to determine predictive performance. Results: Among 95 patients (mean age 54.2 ± 9.8 years, 48.4% female), successful pharmacological cardioversion was achieved in 74.7%. Compared to the non-response group, the cardioversion-success group had significantly lower SII levels (p < 0.001) and left atrial volume index (LAVI, p < 0.001). Multivariate analysis identified both SII and LAVI as independent predictors of cardioversion success. Inverse correlations were observed between both SII (r = −0.419, p < 0.01) and LAVI (r = −0.567, p < 0.01) and rhythm control. The optimal SII cutoff of 645.16 predicted successful rhythm restoration with 75% sensitivity and 75% specificity (AUC: 0.803, 95% CI: 0.710–0.895). Conclusions: Higher SII levels were independently associated with lower rates of successful pharmacological cardioversion in patients with new-onset atrial fibrillation. Incorporating SII into routine assessment may enhance clinical decision-making and patient stratification for rhythm control strategies. Full article