BACKGROUND:Patients with noncardioembolic ischemic stroke or transient ischemic attack (TIA) are at risk for recurrent stroke. Low factor XI levels are associated with a reduced risk of ischemic stroke. Asundexian inhibits activated factor XI. Whether the addition of asundexian to antiplatelet therapy would be superior to antiplatelet therapy alone for the secondary prevention of ischemic stroke is unclear. METHODS:In this phase 3, double-blind trial, we randomly assigned patients within 72 hours after the onset of a noncardioembolic ischemic stroke or high-risk TIA to receive asundexian (50 mg once daily) or placebo, in addition to planned dual or single antiplatelet therapy. Patients had at least one of the following: a nonlacunar infarct on imaging, a history of atherosclerosis, or evidence of atherosclerotic plaque at any location on cerebrovascular imaging. The primary efficacy outcome was ischemic stroke. The composite of death from cardiovascular causes, myocardial infarction, or stroke was a key secondary outcome. The primary safety outcome was major bleeding. RESULTS:Among 12,327 patients who underwent randomization (6162 to the asundexian group and 6165 to the placebo group), the incidence of ischemic stroke was lower in the asundexian group than in the placebo group (6.2% vs. 8.4%; cause-specific hazard ratio, 0.74; 95% confidence interval [CI], 0.65 to 0.84; P<0.001). The incidence of the composite of death from cardiovascular causes, myocardial infarction, or stroke was lower in the asundexian group than in the placebo group. The incidence of major bleeding was similar in the asundexian group and the placebo group (1.9% and 1.7%, respectively; cause-specific hazard ratio, 1.10; 95% CI, 0.85 to 1.44). The incidence of adverse events was 69.3% in the asundexian group and 70.1% in the placebo group; the incidence of serious adverse events was 19.2% and 19.5%, respectively. CONCLUSIONS:Among patients with noncardioembolic ischemic stroke or high-risk TIA treated with antiplatelet therapy, asundexian at a daily dose of 50 mg resulted in lower risks of ischemic stroke and major cardiovascular events than placebo, without a higher risk of major bleeding. (Funded by Bayer; OCEANIC-STROKE ClinicalTrials.gov number, NCT05686070.).
Fascioliasis is a zoonosis caused by the trematodes Fasciola hepatica or Fasciola gigantica, acquired through ingestion of contaminated water or aquatic plants. Clinically, it presents with an acute phase characterized by fever, abdominal pain, and hepatomegaly, and a chronic phase, which is usually asymptomatic. Portal vein thrombosis (PVT) is a rare complication, not previously described among the approximately 30 cases of fascioliasis reported in Portugal. We describe a 48-year-old man who had been on a recent trip to Cape Verde and consumed unpackaged watercress. He was admitted with fever and right upper quadrant pain; laboratory results showed eosinophilia and recurrence of a hepatic abscess associated with PVT. Positive Fasciola hepatica serology and immunoblot confirmed the diagnosis. Treatment with triclabendazole led to a significant reduction of the abscess after three months. Fascioliasis should be considered in the differential diagnosis of hepatic abscesses in patients with epidemiological risk factors and poor response to conventional antibiotic therapy, to prevent possible complications.
Abstract Background Peak circulatory power (PCP), a CPET-derived index obtained by the product of peak oxygen consumption and peak systolic arterial pressure, has been proposed as a prognostic marker in several heart-failure phenotypes. Whether PCP predicts mortality across the full left-ventricular ejection–fraction (LVEF) spectrum remains insufficiently defined. Aim To investigate the ability of PCP to predict mortality in an unselected population entering a phase II cardiac rehabilitation (CR) program. Methods We retrospectively analyzed patients enrolled in a phase II CR program from 2015 to 2025 who completed CPET prior to initiation. ROC analysis was used to evaluate the discriminative ability of peak PCP and identify an optimal cutoff for mortality prediction. Survival was assessed using Kaplan–Meier curves and Cox proportional-hazards models. Results A total of 479 patients were included (mean age 61 years; 80% male; mean LVEF 50%). Over a mean follow-up of 2.5 years, 20 deaths occurred. Peak PCP demonstrated fair discriminatory power for mortality (AUC 0.64), with an optimal threshold of <2300 mL/kg/min·mmHg, yielding 68% sensitivity and 63% specificity. Patients below this cutoff exhibited significantly higher mortality (log-rank p=0.006). PCP <2300 mL/kg/min·mmHg was associated with increased mortality on univariate analysis (HR 3.350, 95% CI 1.335–8.404, p=0.01) and remained an independent predictor after adjustment age, sex and LVEF (HR 2.985, 95% CI 1.040–8.567, p=0.042). Conclusions In our cohort, PCP is a predictor of all-cause mortality, regardless of LVEF. A low PCP (<2300 mL/kg/min·mmHg) identifies individuals at substantially elevated risk, reinforcing its role as a simple, noninvasive CPET-derived metric for prognostic assessment. Larger, prospective studies are warranted to validate these observations and clarify its potential integration into routine risk stratification.For image description, please refer to the figure legend and surrounding text.
BACKGROUND: OCEANIC-STROKE (XXX) showed that asundexian added to antiplatelet therapy reduced ischemic stroke without significantly increasing bleeding in patients with noncardioembolic ischemic stroke or high-risk transient ischemic attack. We characterized bleeding categories, sites, and key subgroups. METHODS: In the safety population, 12 254 participants received at least 1 dose of asundexian (n=6124) or placebo (n=6130). Bleeding was categorized by International Society on Thrombosis and Haemostasis criteria as major, clinically relevant nonmajor (CRNM), or minor. While-on-treatment analyses included events through 2 days after the last dose, with death and permanent discontinuation as competing risks. RESULTS: Major bleeding occurred in 117 (1.9%) participants with asundexian and 107 (1.7%) with placebo (cause-specific hazard ratio [csHR], 1.10 [95% CI, 0.85–1.44]; P =0.46). Major or CRNM bleeding occurred in 339 (5.5%) and 307 (5.0%), respectively (csHR, 1.12 [95% CI, 0.96–1.30]; P =0.16), and any bleeding in 763 (12.5%) and 752 (12.3%) (csHR, 1.02 [95% CI, 0.93–1.13]; P =0.65). Treatment effects for major and major or CRNM bleeding were consistent across prespecified subgroups, including planned dual antiplatelet therapy. Symptomatic intracranial hemorrhage occurred in 41 (0.7%) and 36 (0.6%) participants. Any gastrointestinal bleeding occurred in 186 (3.0%) and 147 (2.4%) (csHR, 1.28 [95% CI, 1.03–1.59]), and lower gastrointestinal bleeding in 102 (1.7%) and 59 (1.0%) (csHR, 1.75 [95% CI, 1.27–2.41]), primarily rectal bleeding. Any procedure-related bleeding and any mucosal bleeding did not differ significantly. CONCLUSIONS: Asundexian added to antiplatelet therapy reduced ischemic stroke without significantly increasing major, major or CRNM, or any bleeding. Lower gastrointestinal bleeding was more frequent with asundexian, whereas treatment effects on major and major or CRNM bleeding were consistent across prespecified subgroups. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique Identifier: NCT05686070.
Abstract Introduction Timely therapy is central in acute heart failure, but the real-world impact of delays in intravenous (IV) diuretics remains unclear. This study examined whether time from emergency department (ED) arrival to first IV furosemide was associated with admission, in-hospital mortality, and 1-year outcomes. Methods We performed a retrospective single-center study of patients that went to the ED in 2023 with acute heart failure and received IV furosemide. Demographic, clinical, laboratory, and treatment variables were extracted from electronic records. Outcomes included admission, length of stay, in-hospital mortality, and 1-year mortality. Group comparisons used Mann–Whitney U or χ² tests; logistic regression assessed associations between delay and outcomes. ROC analysis identified an optimal delay threshold, applied in Kaplan–Meier and Cox models. Results Among 305 patients (mean age 81 ± 11 years; 63% female), comorbidities were common: hypertension in 82%, atrial fibrillation in 45%, ischemic heart disease in 22% and diabetes in 38%. Median NT-proBNP was 12,683 pg/mL; mean estimated glomerular filtration rate, 47 ± 22 mL/min; mean LVEF, 51±13%. First furosemide dose averaged 46 ± 20 mg, with a mean administration delay of 10 ± 14 hours. Overall, 166 patients (55%) were admitted (median stay 9 days); 30 (10%) died in-hospital and 71 (23%) died within one year. Admitted patients had longer delays than discharged patients (6.8 vs 5.0 h; p = 0.021), and each additional hour increased odds of admission by 2.3% (OR 1.023; p = 0.029). In-hospital deaths had substantially longer delays (9.7 vs 5.3 h; p = 0.029); each hour increased odds of death by 3.4% (OR 1.034; p < 0.001). ROC analysis identified 10 hours as the optimal cut-off for predicting early mortality. Patients treated after ≥10 hours had higher early mortality (HR 2.38; 95% CI 1.16–4.87; p = 0.017), with early and persistent Kaplan–Meier separation. Delay was initially linked to 1-year mortality (OR 1.022; p = 0.012), but this association disappeared after excluding in-hospital deaths, indicating the long-term effect was driven by early mortality. Conclusion Delayed IV furosemide, especially beyond 10 hours, was associated with increased admission and markedly higher in-hospital and short-term mortality. The effect did not persist after discharge, suggesting the harm of delayed treatment occurs early. Timely furosemide administration in the ED is critical to improve outcomes.For image description, please refer to the figure legend and surrounding text.
