Livedoid vasculopathy (LV) is a rare, chronic vascular disorder marked by painful, recurrent ulcerations that primarily affect the lower extremities. It is frequently associated with hypercoagulable states, although its pathophysiology remains incompletely understood. We present the case of a 25-year-old woman with a longstanding history of LV, elevated factor VIII, increased lipoprotein(a), recurrent kidney stones, and iron deficiency anemia who presented with worsening lower-extremity ulcerations. An extensive workup excluded other hypercoagulable and connective-tissue conditions, leaving elevated factor VIII and lipoprotein(a) as the most likely contributors to her disease. Although her symptoms initially resolved with treatment, they recurred over time, and management was further complicated by her desire for future pregnancy, which precluded the use of several standard anticoagulant therapies. Her regimen was ultimately centered on pentoxifylline and low-dose aspirin to control symptoms while minimizing risk to a future pregnancy. This case illustrates the importance of individualized treatment planning in LV, particularly when hypercoagulable risk factors intersect with reproductive goals.

Thromboembolic complications remain among the most serious complications of childhood idiopathic nephrotic syndrome (INS). Although their incidence is considerably lower than in adults, venous thromboembolism continues to cause substantial morbidity and occasional mortality, including pulmonary embolism, cerebral venous sinus thrombosis, and extensive deep venous thrombosis. Preventive management remains controversial because most affected children may not develop thrombosis, whereas pharmacological prophylaxis exposes many low-risk patients to potential overtreatment. Current recommendations are largely based on retrospective studies, expert opinions, and extrapolation from adult nephrotic syndrome, while prospective pediatric evidence remains scarce. This review examines the contemporary understanding of thrombogenesis in childhood INS, emphasizing that hypercoagulability extends beyond urinary antithrombin loss to involve hepatic overproduction of procoagulant factors, impaired fibrinolysis, platelet activation, endothelial dysfunction, and hemoconcentration. We also discuss the possibility that historical thrombotic risk may have been amplified by prolonged corticosteroid exposure and consider whether the widespread adoption of steroid-sparing immunosuppressive therapies and earlier relapse detection may have modified the epidemiology of thromboembolism in the modern therapeutic era. Current preventive strategies-including no routine prophylaxis, biomarker-guided individualized approaches, aspirin, and prophylactic low-molecular-weight heparin (LMWH)-are critically reviewed. We argue that increasingly complex biomarker-based algorithms have not demonstrated clear clinical superiority over simple, pragmatic decision-making. Severe hypoalbuminemia provides a pragmatic surrogate of nephrotic severity and may therefore help identify children in whom the overall prothrombotic state is likely to be substantial. We are not proposing albumin <20 g/L as a validated predictor of thrombosis. We are proposing it as a pragmatic clinical trigger for considering prophylaxis in a disease in which no validated predictive model currently exists. We propose a pragmatic risk-stratified approach in which routine pharmacological prophylaxis is unnecessary for early biochemical relapses with minimal clinical manifestations but should be strongly considered in children and adolescents with clinically significant active nephrotic syndrome associated with severe hypoalbuminemia (approximately <20 g/L), provided no major contraindications exist. Where feasible, LMWH appears to be the most appropriate prophylactic agent. Until prospective pediatric studies better define thrombotic risk and validate prediction models, practical consistency based on clinically meaningful risk thresholds may provide a more rational framework than theoretical precision for thromboprophylaxis in childhood INS.

Summary: Background: Cardiovascular physiology exhibits circadian rhythms, including a morning surge in platelet reactivity and cardiovascular events. Aligning the timing of antiplatelet therapy with these rhythms may be a simple, cost-effective approach to improve clinical efficacy. This systematic review evaluates the diurnal variability in platelet reactivity among individuals receiving aspirin, clopidogrel, ticagrelor, and prasugrel and explores the potential for timed administration to optimise platelet inhibition and other surrogate cardiovascular markers. Patients and methods: PubMed, Embase, Cochrane Central Register of Controlled Trials, and trial registries (e.g., ClinicalTrials.gov) were searched from 1980 to August 2025 for randomised controlled trials and observational studies in adults investigating morning versus evening dosing or diurnal efficacy. Results: Of 2,340 records, 25 studies were included (17 on aspirin, seven on clopidogrel, one on ticagrelor, and three overlapping with prasugrel). For aspirin, the data showed a tendency that evening administration achieved greater reductions in morning Cyclooxygenase-1 (COX-1)-dependent platelet reactivity in healthy volunteers and cardiovascular disease patients, although there were mixed effects on ambulatory blood pressure. Clopidogrel exhibited diurnal variability, with peaks in Adenosine Diphosphate (ADP)-induced aggregation occurring in the morning, while prasugrel provided more consistent inhibition than clopidogrel or ticagrelor. No studies directly compared evening versus morning dosing for P2Y12-Inhibitors, and clinical outcomes such as major adverse cardiac events were only assessed in one included study. Conclusions: While evening aspirin may enhance chronopharmacological efficacy, the available evidence is limited due to heterogeneity and variable quality. The limited number of studies on agents beyond aspirin highlights a critical research gap, with robust Randomised Controlled Trials needed to evaluate clinical benefits and inform chronotherapeutic strategies.

A significant population of patients undergoing total knee arthroplasty (TKA) concomitantly have atrial fibrillation (AF). Previous studies have examined acute postoperative complications; however, the long-term impact of pre-existing AF on surgical outcomes after TKA remains underexplored. This study aimed to evaluate 2-, 5-, and 10-year risk and indications for revision among patients with AF undergoing TKA. The TriNetX database was utilized for this retrospective cohort study. The primary outcome was 2-, 5-, and 10-year risk of revision following primary TKA among patients with and without pre-existing AF. The AF and control cohorts were 1:1 propensity matched by age, sex, race, clinical comorbidities, and anticoagulant and aspirin use. Covariate balance after matching was assessed using standardized mean differences (SMDs). Cox proportional hazards models and Kaplan-Meier survival estimates were used to evaluate all-cause revision and specific complications. Results were reported as hazard ratios (HRs) with 95% confidence intervals (CIs), survival probabilities, and p-values. A p-value of < 0.05 was considered statistically significant. Patients with pre-existing AF (n = 24,671) had a significantly higher risk of all-cause revision at 2 years (HR 1.27, 95% CI: 1.13-1.43, p < 0.0001), 5 years (HR 1.23, 95% CI: 1.11-1.37, p < 0.0001), and 10 years (HR 1.23, 95% CI: 1.12-1.35, p < 0.0001) post-TKA compared to matched controls (n = 24,671). The AF cohort demonstrated increased risk of periprosthetic joint infection (PJI) (HR 1.33, 95% CI: 1.22-1.44, p < 0.0001) while showing decreased incidence of arthrofibrosis (HR 0.85, 95% CI: 0.80-0.91, p < 0.0001). No significant difference in periprosthetic fracture, mechanical loosening, osteolysis, or articular wear was observed. Pre-existing AF is associated with increased long-term risk of revision following TKA up to 10 years postoperatively compared to matched controls, even after matching for comorbidity burden and anticoagulant use. These findings should be interpreted cautiously in the context of modest effect sizes and limitations inherent within the TriNetX database. Future studies should examine whether perioperative anticoagulation management strategies influence long-term postoperative complications in patients with AF undergoing TKA.

Hematoma expansion (HE), an increase in bleeding into the brain, is a modifiable cause of disability and death after intracerebral hemorrhage (ICH). Some specialized hemostatic biomarkers are associated with HE. Widely available hemostatic biomarkers could improve our understanding of HE and lead to targeted treatments.

Redox imbalance contributes significantly to the initiation and progression of inflammatory responses. Although conventional anti-inflammatory drugs are widely used, their prolonged administration is associated with a number of adverse effects. Lawsone methyl ether (LME) and lawsone are plant-derived, redox-active naphthoquinones, exhibiting diverse pharmacological activities; however, their cyclooxygenase (COX)-inhibitory effects, redox-modulatory properties, and oral toxicity profiles remain insufficiently characterized. Therefore, this study investigated the COX-inhibitory activity, redox-modulatory effects, and oral toxicity profiles of LME and lawsone using integrated computational, enzyme-inhibitory, and in vivo approaches. Molecular docking analysis revealed favorable binding scores/interactions of LME against COX-1 (-5.9 kcal/mol), lipoxygenase (LOX; -6.6 kcal/mol), NAD(P)H oxidase (-5.6 kcal/mol), and myeloperoxidase (MPO; -4.7 kcal/mol), surpassing lawsone and reference inhibitors (aspirin, and zileuton). These results were further validated by molecular dynamics (MD) simulations. Additionally, LME exhibited higher in vitro inhibition of COX-1 (IC50: 8.1 µM) and COX-2 (IC50: 4.2 µM) than lawsone. Furthermore, acute (50/300 mg/kg) and subacute (50 mg/kg) oral administration of LME in Wistar rats significantly ameliorated glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and thiobarbituric acid-reactive substance (TBARS) levels, more effectively than lawsone. Following Karber's method, oral LD50 values calculated for LME and lawsone were 542 and 175 mg/kg, respectively. However, in a 28-day repeated oral toxicity study, a no-observed-adverse-effect level (NOAEL) of at least 50 mg/kg was established for both the compounds, with no toxicity observed across various rat parameters. Overall, LME was better tolerated than lawsone, exhibiting COX inhibitory and redox-modulatory effects, but its therapeutic significance requires further validation.

[This corrects the article DOI: 10.3389/fphar.2026.1821883.].

Inflammation is an important component of protective immunity in the lower female genital tract but must be tightly regulated to limit host tissue damage. In this study, we evaluated the in vivo potential of the anti-inflammatory drug Acetylsalicylic Acid (ASA) to lower proinflammatory cytokine production, restore vaginal barrier integrity and reduce the frequency of activated T cells that serve as targets for HIV infection. Daily intraperitoneal administration of ASA in mice had no effect on epithelial layer structure and CD4[+] T cell activation status at homeostasis but significantly reduced barrier disruption in response to inflammatory bacteria Mobiluncus mulieris (M. muleiris). ASA treatment lowered the frequency of activated CXCR6[+] TH17 subsets in the vaginal mucosa in response to M. muleiris and Gardnerella vaginalis challenge, also reducing the number of CCR5[+] T cells in the latter. RNAseq analysis of the draining lymph nodes indicate that ASA treatment modulates immunologic and metabolic pathways associated with inflammation, cytokine signaling and cell-cell junction proteins. Our data indicate that ASA administration may reduce inflammation and help restore vaginal homeostasis in mice and aligns with human cohort studies evaluating the potential for oral ASA to reduce HIV transmission.