Background: and Purpose We aimed to evaluate whether early versus late initiation of direct oral anticoagulant (DOAC) after acute ischemic stroke (AIS) yields different safety and efficacy outcomes in Asian versus non-Asian patients. Methods: We analyzed Early versus Late initiation of direct oral Anticoagulants in post-ischaemic stroke patients with atrial fibrillatioN (ELAN) trial data from 2,013 AIS patients with atrial fibrillation (AF) randomized to early (≤48 hours for minor/moderate stroke, 6–7 days for major stroke) or late DOAC initiation (3–4 days for minor ischemic stroke, 6–7 days for moderate ischemic stroke, 12–14 days for major ischemic stroke). Patients were categorized by region as Asian (Japan and India) or non-Asian. The primary outcome was a composite of major extracranial bleeding, symptomatic uncerintracranial hemorrhage (SICH), recurrent ischemic stroke, systemic embolism (SE), or vascular death at 30 days (trial registration: ClinicalTrials.gov number, NCT03148457). Results: Among 1,975 patients, 245 were Asian (192 from Japan and 53 from India) and 1,730 were non-Asian. The primary outcome occurred in 6.5% of Asian patients (4.8% early vs. 8.3% late) and 3.1% of non-Asian patients (2.7% vs. 3.6%) (p<0.01). Higher rates of recurrent ischemic stroke (4.1% [2.4% vs. 5.8%] vs. 1.7% [1.3% vs. 2.1%], p=0.02) and SE (2.0% [0.8% vs. 3.3%] vs. 0.5% [0.4% vs. 0.6%], p=0.02) accounted for this difference. No significant differences were observed in major extracranial bleeding, SICH, recurrent ischemic stroke, SE, or vascular death. No significant interaction was observed between region and treatment allocation. Conclusions Although Asian patients had worse baseline profiles and outcomes, treatment effects did not differ by region, supporting the generalizability of early DOAC initiation in Asian AIS patients without region-specific timing modifications.

Background: and Purpose Carotid artery stenosis or occlusion (CASO) is a causative disease of vascular cognitive impairment (VCI) attributed to cerebral hypoperfusion, even without the development of symptomatic ischemic stroke. Preclinically, resveratrol has been demonstrated to play an important role in improving cognitive function in rodent CASO models. This study investigated the association between long-term resveratrol intake and improvements in cognitive and cerebral hemodynamic impairments in patients with CASO. Methods: A retrospective cohort study was conducted on patients with asymptomatic carotid artery stenosis of ≥50% or occlusion who underwent 15O-gas positron emission tomography (15O-gas PET) and neuropsychological tests such as Montreal Cognitive Assessment (MoCA) and Alzheimer’s Disease Assessment Scale-Cognitive Subscale 13 (ADAS-Cog) twice between July 2020 and March 2022 allowing >125-day interval. Patients were administered 30 mg/day resveratrol after the first 15O-gas PET and neuropsychological tests were compared with those who were not. Results: A total of 79 patients were enrolled in this study; 36 received resveratrol and 43 did not. Over a mean follow-up of 221.2 and 244.8 days, long-term resveratrol treatment significantly improved visuospatial/executive function (P=0.020) in MoCA, and memory domain (P=0.007) and total score (P=0.019) in ADAS-Cog. Cerebral blood flow demonstrated improvement in the right frontal lobe (P=0.027), left lenticular nucleus (P=0.009), right thalamus (P=0.035), and left thalamus (P=0.010) on 15O-gas PET. No adverse events were reported. Conclusion Long-term daily intake of oral resveratrol may prevent or treat VCI by improving the cerebral blood flow in asymptomatic patients with CASO.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common monogenic disorder of the cerebral small blood vessels. It is caused by mutations in the NOTCH3 gene on chromosome 19, and more than 280 distinct pathogenic mutations have been reported to date. CADASIL was once considered a very rare disease with an estimated prevalence of 1.3–4.1 per 100,000 adults. However, recent large-scale genomic studies have revealed a high prevalence of pathogenic NOTCH3 variants among the general population, with the highest risk being among Asians. The disease severity and age at onset vary significantly even among individuals who carry the same NOTCH3 mutations. It is still unclear whether a significant genotype–phenotype correlation is present in CADASIL. The accumulation of granular osmiophilic material in the vasculature is a characteristic feature of CADASIL. However, the exact pathogenesis of CADASIL remains largely unclear despite various laboratory and clinical observations being made. Major hypotheses proposed so far have included aberrant NOTCH3 signaling, toxic aggregation, and abnormal matrisomes. Several characteristic features have been observed in the brain magnetic resonance images of patients with CADASIL, including subcortical lacunar lesions and white matter hyperintensities in the anterior temporal lobe or external capsule, which were useful in differentiating CADASIL from sporadic stroke in patients. The number of lacunes and the degree of brain atrophy were useful in predicting the clinical outcomes of patients with CADASIL. Several promising blood biomarkers have also recently been discovered for CADASIL, which require further research for validation.

We report a rare case of gastric cancer presenting with a gastrocolic fistula during ramucirumab and paclitaxel combination therapy that was successfully managed with colonic stenting. A 75-year-old man was admitted to our hospital with the chief complaint of melena. Esophagogastroduodenoscopy revealed a large ulcerated tumor in the lower stomach, judged by laparoscopy as unresectable (sT4bN1M0). After four cycles of first-line chemotherapy with S-1 plus oxaliplatin, the patient showed disease progression, and second-line therapy with ramucirumab and paclitaxel was started. At the end of the third cycle, the patient had gastric antral stenosis, which necessitated the placement of a gastroduodenal stent. When the patient complained of diarrhea 10 days later, esophagogastroduodenoscopy revealed a fistula between the greater curvature of the stomach and the transverse colon. The fistula was covered by double colonic stenting, with a covered metal stent placed within an uncovered metal stent, after which leakage from the stomach to the colon stopped.