The liver possesses a high regenerative capacity. Liver regeneration is a compensatory response overcoming disturbances of whole-body homeostasis provoked by organ defects. Here we show that a vagus-macrophage-hepatocyte link regulates acute liver regeneration after liver injury and that this system is critical for promoting survival. Hepatic Foxm1 is rapidly upregulated after partial hepatectomy (PHx). Hepatic branch vagotomy (HV) suppresses this upregulation and hepatocyte proliferation, thereby increasing mortality. In addition, hepatic FoxM1 supplementation in vagotomized mice reverses the suppression of liver regeneration and blocks the increase in post-PHx mortality. Hepatic macrophage depletion suppresses both post-PHx Foxm1 upregulation and remnant liver regeneration, and increases mortality. Hepatic Il-6 rises rapidly after PHx and this is suppressed by HV, muscarinic blockade or resident macrophage depletion. Furthermore, IL-6 neutralization suppresses post-PHx Foxm1 upregulation and remnant liver regeneration. Collectively, vagal signal-mediated IL-6 production in hepatic macrophages upregulates hepatocyte FoxM1, leading to liver regeneration and assures survival.

Background and Purpose— Although several clinical studies suggested the beneficial effects of edaravone in acute ischemic stroke, most were performed under settings that differ from those in the current treatment strategy, which has dramatically changed with progress in reperfusion therapies. This study aimed to evaluate the efficacy of edaravone in patients with acute ischemic stroke treated by emergent endovascular reperfusion therapy. Methods— We conducted a retrospective observational study using a national administrative database. Patients with acute ischemic stroke treated by emergent endovascular reperfusion therapy were identified and dichotomized by whether edaravone was used within 2 days of admission. We compared the functional independence at hospital discharge, in-hospital mortality, and intracranial hemorrhage after admission between groups, adjusted by a well-validated case-mix adjustment model, in multivariate mixed-effect regression and propensity score matching analyses. Results— Of 11 508 patients eligible for analysis, 10 281 (89.3%) received edaravone therapy. The established risk adjustment model had good predictability for functional independence at hospital discharge, with an area under the receiver operating characteristic curve of 0.74. In the mixed-effect regression analysis, edaravone use was significantly associated with greater functional independence at hospital discharge (32.3% in the edaravone group versus 25.9% in the control group; adjusted odds ratio, 1.21; 95% confidence interval, 1.03–1.41), lower in-hospital mortality (9.9% in the edaravone group versus 17.4% in the control group; adjusted odds ratio, 0.52; 95% confidence interval, 0.43–0.62), and reduced intracranial hemorrhage after admission (1.4% in the edaravone group versus 2.7% in the control group; adjusted odds ratio, 0.55; 95% confidence interval, 0.37–0.82). Results of the propensity score matching analysis corroborated these results. Conclusions— This retrospective analysis of a Japanese nationwide administrative database suggested that combination therapy with edaravone and endovascular reperfusion therapy could be a promising therapeutic strategy in acute ischemic stroke. Further randomized control trials are warranted.

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BackgroundRecent studies have implicated the differences in the ABO blood system as a potential risk for various diseases, including hemostatic disorders and hemorrhage. In this study, we evaluated the impact of the difference in the ABO blood type on mortality in patients with severe trauma.MethodsA retrospective observational study was conducted in two tertiary emergency critical care medical centers in Japan. Patients with trauma with an Injury Severity Score (ISS) > 15 were included. The association between the different blood types (type O versus other blood types) and the outcomes of all-cause mortality, cause-specific mortalities (exsanguination, traumatic brain injury, and others), ventilator-free days (VFD), and total transfusion volume were evaluated using univariate and multivariate competing-risk regression models. Moreover, the impact of blood type O on the outcomes was assessed using regression coefficients in the multivariate analysis adjusted for age, ISS, and the Revised Trauma Score (RTS).ResultsA total of 901 patients were included in this study. The study population was divided based on the ABO blood type: type O, 284 (32%); type A, 285 (32%); type B, 209 (23%); and type AB, 123 (13%). Blood type O was associated with high mortality (28% in patients with blood type O versus 11% in patients with other blood types; p <  0.001). Moreover, this association was observed in a multivariate model (adjusted odds ratio = 2.86, 95% confidence interval 1.84–4.46; p <  0.001). The impact of blood type O on all-cause in-hospital mortality was comparable to 12 increases in the ISS, 1.5 decreases in the RTS, and 26 increases in age. Furthermore, blood type O was significantly associated with higher cause-specific mortalities and shorter VFD compared with the other blood types; however, a significant difference was not observed in the transfusion volume between the two groups.ConclusionsBlood type O was significantly associated with high mortality in severe trauma patients and might have a great impact on outcomes. Further studies elucidating the mechanism underlying this association are warranted to develop the appropriate intervention.Electronic supplementary materialThe online version of this article (10.1186/s13054-018-2022-0) contains supplementary material, which is available to authorized users.

Background Outcomes after sirolimus-eluting stent (SES: Cypher ® ) implantation remained to be elucidated in Japan. Methods and Results Among 1,070 consecutive angiographic follow-up lesions, 99 lesions underwent target lesion revascularization (TLR) with in-stent restenosis (ISR). Retrospective estimation by multivariate analysis including 50 variables showed that the ostiums of right coronary and left circumflex arteries, hemodialysis, calcification, non-direct stenting, ISR of SES, and non-eccentric lesion were the predictors of TLR. There was no documented late stent thrombosis (LST) among 2,166 lesions and very LST (VLST) among 1,423 lesions. Conclusion Further revises are needed to implant SES to these predictive lesions. LST and VLST were very rare. (Circ J 2007; 71: 1328 -1331