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.

No abstract

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.

Statins exert atheroprotective effects through the induction of specific transcriptional factors in multiple organs. In endothelial cells, statin-dependent atheroprotective gene up-regulation is mediated by Kruppel-like factor (KLF) family transcription factors. To dissect the mechanism of gene regulation, we sought to determine molecular targets by performing microarray analyses of human umbilical vein endothelial cells (HUVECs) treated with pitavastatin, and KLF4 was determined to be the most highly induced gene. In addition, it was revealed that the atheroprotective genes induced with pitavastatin, such as nitric oxide synthase 3 (NOS3) and thrombomodulin (THBD), were suppressed by KLF4 knockdown. Myocyte enhancer factor-2 (MEF2) family activation is reported to be involved in pitavastatin-dependent KLF4 induction. We focused on MEF2C among the MEF2 family members and identified a novel functional MEF2C binding site 148 kb upstream of the KLF4 gene by chromatin immunoprecipitation along with deep sequencing (ChIP-seq) followed by luciferase assay. By applying whole genome and quantitative chromatin conformation analysis {chromatin interaction analysis with paired end tag sequencing (ChIA-PET), and real time chromosome conformation capture (3C) assay}, we observed that the MEF2C-bound enhancer and transcription start site (TSS) of KLF4 came into closer spatial proximity by pitavastatin treatment. 3D-Fluorescence in situ hybridization (FISH) imaging supported the conformational change in individual cells. Taken together, dynamic chromatin conformation change was shown to mediate pitavastatin-responsive gene induction in endothelial cells.

Background: Thrombosis is a characteristic complication in coronavirus disease 2019 (COVID-19). Since coagulopathy has been observed over the entire clinical course, thrombosis might be a clue to understanding the specific pathology in COVID-19. Currently, there is limited epidemiological data of COVID-19-associated thrombosis in the Japanese population and none regarding variant strains of SARS-CoV-2. Here, we elucidate the risk factors and the pattern of thrombosis in COVID-19 patients.Methods: The patients consecutively admitted to Tokyo Medical and Dental University Hospital with COVID-19 were retrospectively analyzed. SARS-CoV-2 variants of concern/interest (VOC/VOI) carrying the spike protein mutants E484K, N501Y, or L452R were identified by PCR-based analysis. All thrombotic events were diagnosed by clinical symptoms, ultrasonography, and/or radiological tests.Results: Among the 516 patients, 32 patients experienced 42 thromboembolic events. Advanced age, severe respiratory conditions, and several abnormal laboratory markers were associated with the development of thrombosis. While thrombotic events occurred in 13% of the patients with a severe respiratory condition, those events still occurred in 2.5% of the patients who did not require oxygen therapy. Elevated D-dimer and ferritin levels on admission were independent risk factors of thrombosis (adjusted odds ratio 9.39 and 3.11, 95% confidence interval 2.08–42.3, and 1.06–9.17, respectively). Of the thrombotic events, 22 were venous, whereas 20 were arterial. While patients with thrombosis received anticoagulation and antiinflammatory therapies with a higher proportion, the mortality rate, organ dysfunctions, and bleeding complications in these patients were higher than those without thrombosis. The incidence of thrombosis in COVID-19 became less frequent over time, such as during the replacement of the earlier strains of SARS-CoV-2 by VOC/VOI and during increased use of anticoagulatory therapeutics.Conclusion: This study elucidated that elevated D-dimer and ferritin levels are useful biomarkers of thrombosis in COVID-19 patients. The comparable incidence of arterial thrombosis with venous thrombosis and the development of thrombosis in less severe patients required further considerations for the management of Japanese patients with COVID-19. Further studies would be required to identify high-risk populations and establish appropriate interventions for thrombotic complications in COVID-19.

In this study, transfusion strategies with high plasma to red blood cell and platelet to red blood cell ratios did not have survival benefits, but were associated with an increase in adverse events.

We report a rare adult case of gallbladder agenesis with no other biliary tract abnormality. The patient was a 29-year-old man with pain in the right upper-quadrant of the abdomen, and vomiting. The gallbladder was not visualized by ultrasonography, computed tomography, or endoscopic retrograde cholangiography. The common bile duct was slightly dilated. No other abnormalities, including anomalous choledochopancreatic duct junction, were found. Based on these imaging findings and the patient's right hypochondrial pain, there was a high index of suspicion of chronic cholecystitis caused by incarcerated gallstones in the neck of the gallbladder. At operation, we carefully observed the gallbladder fossa, using laparoscopy, and found gallbladder to be absent. Although the operation involved only observation via a laparoscope, the patient has since remained well and asymptomatic. It is difficult to make a correct diagnosis of gallbladder agenesis preoperatively. We believe that, if the gallbladder is not visualized by imaging techniques, it may be better to perform laparoscopy for observation before performing laparotomy, in order to reduce surgical stress.

No abstract