Chronic kidney disease (CKD) is associated with an increased risk of severe urinary tract infections (UTIs), particularly those caused by antimicrobial-resistant bacteria. Although urinary microbiota and bacterial membrane vesicles (BMVs) are thought to contribute to UTI pathogenesis, their roles in CKD remain insufficiently understood. In this exploratory study, urine samples were collected from 10 male patients with CKD (eGFR <45 mL/min/1.73 m²) and 10 male non-CKD controls (eGFR ≥60 mL/min/1.73 m²). Urinary microbiota and BMV fractions were isolated and analyzed to compare microbial composition and antimicrobial resistance gene (ARG) profiles, and to evaluate their potential involvement in UTI development and the emergence of antimicrobial resistance in CKD. Both fractions were subjected to shotgun metagenomic sequencing; metagenomic analysis of BMVs was performed using pooled samples within each group. In addition, BMV fractions were characterized by transmission electron microscopy and 16S rRNA gene PCR. Urinary microbiota α-diversity was significantly lower in patients with CKD than in controls (ACE index, p = 0.04). Vesicle-like structures consistent with BMVs, with diameters of 20-200 nm, were detected in urine samples from both controls and patients with CKD. Principal coordinate analysis demonstrated that BMV fractions clustered within the corresponding urinary microbiota profiles. Furthermore, multiple antimicrobial resistance genes (ARGs), including ftsI and adeF, were identified in both urinary microbiota and BMV fractions. This study provides exploratory evidence of reduced urinary microbiota α-diversity in patients with CKD and the presence of ARGs in both urinary microbiota and BMV fractions from controls and patients with CKD. These findings suggest microbiological factors that may contribute to the high incidence of antimicrobial-resistant UTIs in this population. Future validation in larger cohorts with individual-level BMV profiling will be required to determine whether analyses focusing on urinary microbiota and BMVs can contribute to a better understanding of antimicrobial-resistant UTIs and to improved infection risk assessment in patients with CKD.
BACKGROUND:Antithrombotic agents are essential for preventing cerebrovascular and cardiovascular diseases; however, bleeding complications remain a major concern, particularly among elderly patients and those receiving combination therapy. AIMS:We designed the Bleeding with Antithrombotic Therapy 2 (BAT2) Study, a prospective multicenter registry involving hospitals from a clinical research network in Japan, to clarify the risk of bleeding events in patients taking antithrombotic agents for cerebrovascular and cardiovascular diseases in recent clinical settings. METHODS:This prospective, multicenter, observational study followed bleeding and ischemic events for up to 2 years in patients with cerebrovascular and cardiovascular diseases. The primary outcome was major bleeding, and secondary outcomes included intracranial hemorrhage (ICH). RESULTS:The 5250 patients enrolled comprised 3134 (70 ± 11 years; male, 66.6%; HASBLED ⩾ 3, 32.8%) treated with single antiplatelet therapy (SAPT), 551 (71 ± 11 years; 25.8%; 40.8%, respectively) with dual antiplatelet therapy (DAPT), 870 (75 ± 10 years; 37.1%; 39.8%, respectively) with direct oral anticoagulant (DOAC) alone, 433 (72 ± 12 years; 34.2%; 41.4%, respectively) with warfarin alone, 143 (76 ± 8 years; 16.8%; 42.7%, respectively) with DOAC plus antiplatelet agents (AP), and 119 (73 ± 12 years; 18.5%; 47.5%, respectively) with warfarin plus AP. During follow-up (median, 1.98 years), 93 patients experienced major bleeding, and 55 developed ICH. Compared with the SAPT group (37 events, 0.63%/year), the DOAC (18 events, 1.12%/year; adjusted hazard ratio (aHR) = 1.94, 95% confidence interval (CI) = 1.09-3.46), warfarin (16 events, 2.02%/year; 3.44, 1.90-6.23), and DOAC plus AP groups (six events, 2.24%/year; 3.07, 1.28-7.35) exhibited significantly higher risks of major bleeding after multivariable adjustment. DAPT (aHR 2.47, 95% CI = 1.11-5.48), warfarin (5.38, 2.65-10.92), and DOAC plus AP (3.86, 1.30-11.47) had significantly higher risks of ICH than SAPT. The DAPT (2.28, 95% CI = 1.65-3.14), DOAC plus AP (1.96, 1.08-3.56), and warfarin plus AP (2.83, 1.62-4.92) groups showed significantly higher risks of ischemic events than the SAPT group. CONCLUSION:Oral anticoagulant alone and DOAC with antiplatelet therapy were associated with higher risks of major bleeding events than SAPT in long-term follow-up for patients with stroke and cardiovascular disease.
BACKGROUND:Introduction of guideline-directed medical therapy (GDMT) has transformed the care of heart failure (HF) with reduced ejection fraction, establishing four foundational drug classes. Yet, in clinical practice, many patients cannot initiate or maintain all four, and clinicians must pragmatically prioritise agents such as angiotensin receptor-neprilysin inhibitor and sodium-glucose cotransporter-2 inhibitor, whose comparative impacts are still explored. Moreover, the optimal loop diuretic to pair with modern GDMT, which enhances natriuresis, remains uncertain. METHODS:Between January 2022 and February 2024, we conducted a multicentre, open-label, randomised, 2×2 factorial design trial for ambulatory patients with symptomatic HF, elevated natriuretic peptide levels and left ventricular ejection fraction (LVEF) <50%, despite conventional therapies (eg, renin-angiotensin-aldosterone system inhibitors and beta-blockers). The patients were assigned to receive either sacubitril/valsartan or dapagliflozin, and torsemide or furosemide. The primary endpoint was the change in the Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OSS) over 6 months; a prespecified secondary endpoint was a hierarchical clinical outcome. RESULTS:Of 231 randomised patients (median age 73 years; median LVEF 36%; 84.0% New York Heart Association class II), changes in KCCQ-OSS did not differ between sacubitril/valsartan and dapagliflozin (adjusted mean difference 2.53 points; 95% confidence interval (CI) -1.81 to 6.88; p=0.25) or between torsemide and furosemide (0.25 points; 95% CI -4.10 to 4.59; p=0.91). Hierarchical composite outcome analyses also showed no significant differences between sacubitril/valsartan and dapagliflozin (win ratio, 1.15; 95% CI 0.71 to 1.88), or between torsemide and furosemide (win ratio, 1.15; 95% CI 0.70 to 1.85). CONCLUSIONS:This trial found no evidence of benefit of one treatment over another for health status over 6 months. Given the sample size and predefined power, modest differences between treatments cannot be excluded. TRIAL REGISTRATION NUMBER:UMIN000045229.
Bird-beak configuration (BBC) is a common finding after thoracic endovascular aortic repair (TEVAR) and a risk factor for type Ia endoleaks. Although cerebral infarction due to stent graft collapse associated with BBC has been reported, thrombus formation within the BBC serving as an embolic source is rare. We report the case of an 81-year-old male who underwent TEVAR for a ruptured distal aortic arch aneurysm and subsequently developed multiple recurrent cerebral infarctions. Imaging revealed thrombus formation at the proximal edge of the stent graft in the BBC region. Despite intensive antithrombotic therapy, cerebral infarctions recurred, necessitating ascending aortic arch replacement with a frozen elephant trunk procedure. Intraoperative findings confirmed the presence of a thrombus at the BBC site, and transesophageal echocardiography revealed turbulence. Computational fluid dynamics (CFD) analysis allowed visualization of flow stagnation within the BBC, supporting its role in thrombus formation. This case demonstrates that progressive BBC after TEVAR can cause recurrent cerebral embolism through thrombus formation and highlights the utility of CFD analysis in clinical decision-making.
