クラリスロマイシンはインフルエンザAウイルスに感染したマウスにおいて、monocyte chemoattractant protein-1とmatrix metalloproteinase-9の発現誘導を抑制し、肺と心臓における病理学的変化を改善する

The influenza A virus (IAV)–cytokine–trypsin/matrix metalloproteinase-9 (MMP-9) cycle is one of the important mechanisms of multiple organ failure in severe influenza. Clarithromycin, a macrolide antibiotic, has immune modulatory and anti-inflammatory effects. We analyzed the effects of clarithromycin on the induction of chemokines, cytokines, MMP-9, trypsin, vascular hyper-permeability and inflammatory aggravation in mice with IAV infection. IAV/Puerto Rico/8/34(H1N1) infection increased the levels of monocyte chemoattractant protein- 1 (MCP-1) and cytokines in serum, and MMP-9 and trypsin in serum and/or the lungs and heart. Clarithromycin significantly suppressed the induction of serum MCP-1 and MMP-9 and vascular hyperpermeability in these organs in the early phase of infection, but did not suppress the induction of trypsin, IL-6 or IFN-γ. Histopathological examination showed that clarithromycin tended to reduce inflammatory cell accumulation in the lungs and heart. These results suggest that clarithromycin suppresses infection-related inflammation and reduces vascular hyperpermeability by suppressing the induction of MCP-1 and MMP-9

Long-Term Survival after Stroke in 1.4 Million Japanese Population : Shiga Stroke and Heart Attack Registry.

Background and Purpose:Although numerous measures for stroke exist, stroke remains one of the leading causes of death in Japan. In this study, we aimed to determine the long-term survival rate after first-ever stroke using data from a large-scale population-based stroke registry study in Japan.Methods:Part of the Shiga Stroke and Heart Attack Registry, the Shiga Stroke Registry is an ongoing population-based registry study of stroke, which covers approximately 1.4 million residents of Shiga Prefecture in Japan. A total 1,880 patients with non-fatal first-ever stroke (among 29-day survivors after stroke onset) registered in 2011 were followed up until December 2016. Five-year cumulative survival rates were estimated using the Kaplan-Meier method, according to subtype of the index stroke. Cox proportional hazards models were used to assess predictors of subsequent all-cause death.Results:During an average 4.3-year follow-up period, 677 patients died. The 5-year cumulative survival rate after non-fatal first-ever stroke was 65.9%. Heterogeneity was present in 5-year cumulative survival according to stroke subtype: lacunar infarction, 75.1%; large-artery infarction, 61.5%; cardioembolic infarction, 44.9%; intracerebral hemorrhage, 69.1%; and subarachnoid hemorrhage, 77.9%. Age, male sex, Japan Coma Scale score on admission, and modified Rankin Scale score before stroke onset were associated with increased mortality during the chronic phase of ischemic and hemorrhagic stroke.Conclusions:In this study conducted in a real-world setting of Japan, the 5-year survival rate after non-fatal first-ever stroke remained low, particularly among patients with cardioembolic infarction and large-artery infarction in the present population-based stroke registry

Control of Diabetes Mellitus and Long-Term Prognosis in Stroke Patients : The Shiga Stroke and Heart Attack Registry.

Background:The relationship between diabetes control status and long-term prognosis after stroke incidence remains unclear. This study aimed to investigate the effect of diabetes status at admission on long-term survival in patients with first-ever stroke.Methods:A retrospective cohort study was conducted based on the Shiga Stroke and Heart Attack Registry in Japan. Patients were classified according to their diabetes status and glycated hemoglobin (HbA1c) value at hospital admission into the following: (1) free of diabetes (no history of diabetes and HbA1c <6.5%); (2) good control (history of diabetes and HbA1c <7%; free of history and 6.5% ≤HbA1c <7%); and (3) poor control (with or without a history of diabetes and HbA1c ≥7%). Multivariable Cox regression models were used to evaluate the association between diabetes status and long-term survival from stroke onset. Additionally, we also evaluated the association between diabetes status and conditional survival, beginning 29 days after stroke onset.Results:A total of 6,331 first-ever stroke patients were eligible for this study. Among study patients, the mean (±SD) age was 72.85 ± 13.19 years, and the mean (±SD) follow-up year was 2.76 ± 1.66 years; additionally, 42.09% of patients were women. Among patients with all strokes, considering the free-of-diabetes group as the reference group, the adjusted hazard ratio (95% confidence interval) for mortality was 1.26 (1.10, 1.44) in the good control group and 1.22 (1.05, 1.41) in the poor control group. Among patients with ischemic stroke, the adjusted hazard ratio was 1.24 (1.06, 1.46) in good control group and 1.27 (1.08, 1.50) in poor control group. After excluding patients who died within 28 days, the adjusted hazard ratio for conditional mortality in the poor control group was 1.31 (1.12, 1.54) among all stroke patients and 1.29 (1.08, 1.54) among ischemic stroke patients. No significant associations were observed between diabetic status and long-term mortality in intracerebral hemorrhage patients.Conclusions:The findings suggest that first-ever stroke patients with diabetes exhibited a higher risk of all-cause mortality than those without diabetes, particularly in the overall stroke and ischemic stroke populations. Additionally, in stroke populations after 28 days of onset, high risk of long-term mortality was stated in stroke patients with poor HbA1c control