Clinical effect and antiviral mechanism of T-705 in treating severe fever with thrombocytopenia syndrome

Severe fever with thrombocytopenia syndrome(SFTS)virus(SFTSV)is an emerging tick-borne virus with high fatality and an expanding endemic.Currently,effective anti-SFTSV intervention remains unavailable.Favipiravir(T-705)was recently reported to show in vitro and in animal model antiviral efficacy against SFTSV.Here,we conducted a single-blind,randomized controlled trial to assess the efficacy and safety of T-705 in treating SFTS(Chinese Clinical Trial Registry website,number ChiCTR1900023350).From May to August 2018,laboratory-confirmed SFTS patients were recruited from a designated hospital and randomly assigned to receive oral T-705 in combination with supportive care or supportive care only.Fatal outcome occurred in 9.5%(7/74)of T-705 treated patients and 18.3%(13/71)of controls(odds ratio,0.466,95%Cl,0.174-1.247).Cox regression showed a significant reduction in case fatality rate(CFR)with an adjusted hazard ratio of 0.366(95%Cl,0.142-0.944).Among the low-viral load subgroup(RT-PCR cycle threshold>26),T-705 treatment significantly reduced CFR from 11.5 to 1.6%(P=0.029),while no between-arm difference was observed in the high-viral load subgroup(RT-PCR cycle threshold<26).The T-705-treated group showed shorter viral clearance,lower incidence of hemorrhagic signs,and faster recovery of laboratory abnormities compared with the controls.The in vitro and animal experiments demonstrated that the antiviral efficacies of T-705 were proportionally induced by SFTSV mutation rates,particularly from two transition mutation types.The mutation analyses on T-705-treated serum samples disclosed a partially consistent mutagenesis pattern as those of the in vitro or animal experiments in reducing the SFTSV viral loads,further supporting the anti-SFTSV effect of T-705,especially for the low-viral loads.

Multimodal image fusion-assisted endoscopic evacuation of spontaneous intracerebral hemorrhage

Purpose:Although traditional craniotomy(TC)surgery has failed to show benefits for the functional outcome of intracerebral hemorrhage(ICH).However,a minimally invasive hematoma removal plan to avoid white matter fiber damage may be a safer and more feasible surgical approach,which may improve the prognosis of ICH.We conducted a historical cohort study on the use of multimodal image fusion-assisted neuroendoscopic surgery(MINS)for the treatment of ICH,and compared its safety and effectiveness with traditional methods.Methods:This is a historical cohort study involving 241 patients with cerebral hemorrhage.Divided into MINS group and TC group based on surgical methods.Multimodal images(CT skull,CT angiography,and white matter fiber of MRI diffusion-tensor imaging)were fused into 3 dimensional images for preoperative planning and intraoperative guidance of endoscopic hematoma removal in the MINS group.Clinical features,operative efficiency,perioperative complications,and prognoses between 2 groups were compared.Normally distributed data were analyzed usingt-test of 2 independent samples,Nonnormally distributed data were compared using the Kruskal-Wallis test.Meanwhile categorical data were analyzed via the Chi-square test or Fisher’s exact test.All statistical tests were two-sided,andp<0.05 was considered statistically significant.Results:A total of 42 patients with ICH were enrolled,who underwent TC surgery or MINS.Patients who underwent MINS had shorter operative time(p<0.001),less blood loss(p<0.001),better hematoma evacuation(p=0.003),and a shorter stay in the intensive care unit(p=0.002)than patients who underwent TC.Based on clinical characteristics and analysis of perioperative complications,there is no significant difference between the 2 surgical methods.Modified Rankin scale scores at 180 days were better in the MINS than in the TC group(p=0.014).Conclusions:Compared with TC for the treatment of ICH,MINS is safer and more efficient in cleaning ICH,which improved the prognosis of the patients.In the future,a larger sample size clinical trial will be needed to evaluate its efficacy.