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.

Six 1-month-old piglets were intravenously injected with deoxynivalenol (DON) at the concentration of 1 mg/kg body weight, with three pigs each necropsied at 6 and 24 h post-injection (PI) for investigation of hepatotoxicity and immunotoxicity with special attention to apoptotic changes and cytokine mRNA expression. Histopathological examination of the DON-injected pigs revealed systemic apoptosis of lymphocytes in lymphoid tissues and hepatocytes. Apoptosis of lymphocytes and hepatocytes was confirmed by the TdT-mediated dUTP-biotin nick end-labeling (TUNEL) method and immunohistochemical staining against single-stranded DNA and cleaved caspase-3. The number of TUNEL-positive cells in the thymus and Peyer's patches of the ileum was increased at 24 h PI compared to 6 h PI, but the peak was at 6 h PI in the liver. The mRNA expression of interleukin (IL)-1beta, IL-6, IL-18, and tumor necrosis factor (TNF)-alpha in the spleen, thymus and mesenteric lymph nodes were determined by semi-quantitative RT-PCR, and elevated expression of IL-1beta mRNA at 6 h PI and a decrease of IL-18 mRNA at 24 h PI were observed in the spleen. IL-1beta and IL-6 mRNA expressions increased significantly at 6 h PI in the thymus, but TNF-alpha decreased at 6 h PI in the mesenteric lymph nodes. These results show the apoptosis of hepatocytes suggesting the hepatotoxic potential of DON, in addition to an immunotoxic effect on the modulation of proinflammatory cytokine genes in lymphoid organs with extensive apoptosis of lymphocytes induced by acute exposure to DON in pigs.
Animals ; Apoptosis/*drug effects/immunology ; Cytokines/*biosynthesis/genetics ; Gene Expression Regulation/drug effects ; Histocytochemistry/veterinary ; In Situ Nick-End Labeling/veterinary ; Liver/*drug effects/immunology ; Lymphoid Tissue/*drug effects/immunology ; RNA, Messenger/*biosynthesis/genetics/immunology ; Reverse Transcriptase Polymerase Chain Reaction/veterinary ; Specific Pathogen-Free Organisms ; Swine/*immunology ; Trichothecenes/*toxicity

Complementary medicine aimed at improving patients’ QOL by complementing modern medicine has recently become the focus of attention. These alternative supplements or functional foods are commonly biologically based. Contained within food itself, these specialized components serve a tertiary function regarding biological regulation and defense. Further, in vivo mechanisms are considered to be closely linked to mucosal immunity of the intestine. As the mechanism of innate immunity is further elucidated, the significant role of certain food components in relation to mucosal immunity of the intestine has become a focus of interest.
In this paper, I would like to describe the experimental and clinical applications of complementary medicine in cases of chronic and/or intractable inflammatory bowel disease.