Inflammation-induced coagulopathy is a common complication associated with coronavirus disease 2019 (COVID-19). We aim to evaluate the association of NETosis and complement markers with each other as well as their association with thrombogenicity and disease severity in COVID-19. The study included hospitalized patients with an acute respiratory infection: patients with SARS-CoV2 infection (COVpos, n = 47) or either pneumonia or infection-triggered acute exacerbated COPD (COVneg, n = 36). Our results show that NETosis, coagulation, and platelets, as well as complement markers, were significantly increased in COVpos patients, especially in severely ill COVpos patients. NETosis marker MPO/DNA complexes correlated with coagulation, platelet, and complement markers only in COVpos. Severely ill COVpos patients showed an association between complement C3 and SOFA (R = 0.48; p ≤ 0.028), C5 and SOFA (R = 0.46; p ≤ 0.038), and C5b-9 and SOFA (R = 0.44; p ≤ 0.046). This study provides further evidence that NETosis and the complement system are key players in COVID-19 inflammation and clinical severity. Unlike previous studies that found NETosis and complement markers to be elevated in COVID-19 patients compared to healthy controls, our findings show that this characteristic distinguishes COVID-19 from other pulmonary infectious diseases. Based on our results, we propose that COVID-19 patients at high risk for immunothrombosis could be identified via elevated complement markers such as C5.

Galectin-3 is a beta-galactoside-binding lectin involved in inflammation and lung fibrosis and postulated to enhance thrombosis. In COVID-19, it is considered to be a prognostic marker of severity. The aim of this study was to evaluate whether galectin-3 is associated with thrombogenicity in COVID-19. Patients with moderate-to-severe COVID-19 (COVpos; n = 55) and patients with acute respiratory diseases, but without COVID-19 (COVneg; n = 35), were included in the study. We measured the amount of galectin-3, as well as other platelet and coagulation markers, and correlated galectin-3 levels with these markers of thrombogenicity and with the SOFA Score values. We found that galectin-3 levels, as well as von Willebrand Factor (vWF), antithrombin and tissue plasminogen activator levels, were higher in the COVpos than they were in the COVneg cohort. Galectin-3 correlated positively with vWF, antithrombin and D-dimer in the COVpos cohort, but not in the COVneg cohort. Moreover, galactin-3 correlated also with clinical disease severity, as measured by the SOFA Score. In patients with acute respiratory diseases, galectin-3 can be considered as a marker not only for disease severity, but also for increased hypercoagulability. Whether galectin-3 might be a useful therapeutic target in COVID-19 needs to be assessed in future studies.

Patients with first-diagnosed atrial fibrillation (FDAF) exhibit major adverse cardiovascular events (MACEs) during follow-up. Preclinical models have demonstrated that thrombo-inflammation mediates adverse cardiac remodeling and atherothrombotic events. We have hypothesized that thrombin activity (FIIa) links coagulation with inflammation and cardiac fibrosis/dysfunction. Surrogate markers of the thrombo-inflammatory response in plasma have not been characterized in FDAF. In this prospective longitudinal study, patients presenting with FDAF (n = 80), and 20 matched controls, were included. FIIa generation and activity in plasma were increased in the patients with early AF compared to the patients with chronic cardiovascular disease without AF (controls; p < 0.0001). This increase was accompanied by elevated biomarkers (ELISA) of platelet and endothelial activation in plasma. Pro-inflammatory peripheral immune cells (TNF-α⁺ or IL-6⁺) that expressed FIIa-activated protease-activated receptor 1 (PAR1) (flow cytometry) circulated more frequently in patients with FDAF compared to the controls (p < 0.0001). FIIa activity correlated with cardiac fibrosis (collagen turnover) and cardiac dysfunction (NT-pro ANP/NT-pro BNP) surrogate markers. FIIa activity in plasma was higher in patients with FDAF who experienced MACE. Signaling via FIIa might be a presumed link between the coagulation system (tissue factor-FXa/FIIa-PAR1 axis), inflammation, and pro-fibrotic pathways (thrombo-inflammation) in FDAF.

Background: The optimal timing of surgical treatment for ankle fractures remains a topic that is associated with clinical uncertainty. While delayed surgery is often necessary for safe wound closure, prolonged immobilization, impaired functional outcomes, protracted hospitalization, and an increased risk of infection are potential disadvantages. This study was aimed at investigating the interval between trauma, surgical fixation, and postoperative infections among patients with closed ankle fractures. Methods: We conducted a retrospective cohort study involving 224 patients treated surgically for fractures of the upper ankle joint between January 2020 and December 2023. The patients were stratified into two groups based on surgical timing: within 24 h of hospital admission (early surgery) or after 24 h (delayed surgery). The primary outcome was the incidence of postoperative infections. A multivariate logistic regression model was constructed to assess independent risk factors. Results: Of the 224 patients, 30 (13.4%) developed postoperative infections. Infection occurred in 11.1% of patients who underwent early surgery and 13.7% of those subjected to delayed surgery. This difference was not statistically significant in the unadjusted analysis (p = 0.747). However, an additional day of surgical delay was associated with an 11% increase in the odds of postoperative infection (OR = 1.11; 95% CI: 1.01–1.22; p = 0.034). Female patients had over threefold higher odds of infection than males (OR = 3.20; 95% CI: 1.32–8.09; p = 0.011), and diabetes was a significant risk factor, with diabetic individuals showing more than fivefold increased odds (OR = 5.56; 95% CI: 1.30–25.00; p = 0.019). Patients with delayed surgery had significantly longer hospital stays (+2.83 days, p < 0.05). Conclusions: Early surgical intervention appears to lower the risk of postoperative infections, is associated with hospitalization duration, and should be considered when clinically appropriate.

Background: Aortic regurgitation (AR) frequently remains asymptomatic for prolonged periods, with guideline recommendations for intervention largely guided by imaging-based assessment of left ventricular remodeling. While renal dysfunction has been linked to adverse outcomes in AR, prior studies have predominantly focused on advanced disease stages and post-interventional outcomes, with limited data on pre-interventional progression, offering limited insight into pre-interventional disease progression or biologically informed approaches to risk stratification. Methods: We investigated renal biomarkers in individuals with AR from the UK Biobank ( n = 2,493) and assessed associations with time to aortic valve replacement (AVR) using Cox proportional hazards models. Associations with cardiovascular imaging and hemodynamic phenotypes were examined via logistic regression. To place clinical findings in a biological context, we performed genome-wide colocalization analyses between AR phenotypes, blood pressure, and renal traits, followed by regulatory annotation, single-cell RNA sequencing (Kidney Cell Atlas), and phenome-wide association analyses. Results: Among patients with AR, higher circulating UMOD levels were independently associated with a lower risk of subsequent AVR (adjusted HR per SD 0.57, 95% CI 0.34–0.98; p = 0.041), whereas conventional renal markers (creatinine, urea, microalbumin) showed no association. UMOD levels were strongly associated with lower arterial stiffness ( β = −5.32 ± 0.27; p < 0.001 and lower systolic blood pressure ( β = −0.91 ± 0.13; p < 0.001), both associated with disease progression, but not with left ventricular volumes. Genome-wide colocalization identified a shared genetic signal at the UMOD locus linking AR, blood pressure, and kidney function. Regulatory annotation and single-cell data localized UMOD expression to the thick ascending limb of Henle's loop, supporting a tubular-specific mechanism. Phenome-wide analyses further implicated UMOD variants in renal tubular and hemodynamic traits. Conclusions: These findings identify uromodulin as a genetically anchored, kidney-specific biomarker associated with pre-interventional progression and timing of valve intervention in AR. Our study shifts the renal–AR paradigm from post-operative risk modification toward a mechanistically grounded model of tubular-driven disease progression, with implications for earlier risk stratification and surgical referral.