Effect of tocilizumab plus corticosteroid on clinical outcome in patients hospitalized with severe fever with thrombocytopenia syndrome: A randomized clinical trial.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging viral hemorrhagic fever with high fatality rates. The blockade of pro-inflammatory cytokines presents a promising therapeutic strategy. METHODS: We conducted a randomized clinical trial at the 154th hospital, Xinyang, Henan Province. Eligible patients with severe SFTS disease were randomly assigned in a 1:2 ratio to receive either a single intravenous infusion of tocilizumab plus usual care; or usual care only. The primary outcome was the clinical status of death/survival at day 14, while secondary outcomes included improvement from baseline in liver and kidney damage and time required for hospital discharge. The efficacy of tocilizumab plus corticosteroid was compared to those receiving corticosteroid alone. The trial is registered with the Chinese Clinical Trial Registry website (ChiCTR2300076317). RESULTS: 63 eligible patients were assigned to the tocilizumab group and 126 to the control group. The addition of tocilizumab to usual care was associated with a reduced death rate (9.5%) compared to those received only usual care (23.0%), with an adjusted hazard ratio (aHR) of 0.37 (95% confidence interval [CI], 0.15 to 0.91, P = 0.029). Combination therapy of tocilizumab and corticosteroids was associated with a significantly reduced fatality (aHR, 0.21; 95% CI, 0.08 to 0.56; P = 0.002) compared to those receiving corticosteroids alone. CONCLUSIONS: A significant benefit of reducing fatality in severe SFTS patients was observed by using tocilizumab. A combined therapy of tocilizumab plus corticosteroids was recommended for the therapy of severe SFTS.

Clinical efficacy of immunoglobulin on the treatment of severe fever with thrombocytopenia syndrome: a retrospective cohort study.

BACKGROUND: Optimal treatment strategy for severe fever with thrombocytopenia syndrome (SFTS) remained unknown. We aimed to evaluate the efficacy of intravenous immunoglobulin (IVIG) on SFTS. METHODS: A retrospective cohort study was conducted based on medical records of the laboratory-confirmed SFTS patients hospitalized during 2010-2020 in the 154th hospital, China. A 1:1 propensity score matching with age, sex, the interval from symptom onset to admission, presence of chronic viral hepatitis, diabetes and disease severity was performed between Non-IVIG group (supportive therapy) and IVIG group (IVIG plus supportive therapy). The matching variables were adjusted to compare the case fatality rates (CFRs), viral load and laboratory parameters between the two groups. Risk ratio (RR) and 95% confidence interval (CI) were reported. FINDINGS: Totally 2219 SFTS patients were recruited. CFRs were significantly higher in 1051 patients in IVIG group than 1168 patients in Non-IVIG group (19.0% vs. 4.6%, RR = 4.30, 95% CI 3.12-5.93). The difference remained significant after matching (17.2% vs. 5.1%, RR = 4.02, 95% CI 2.71-5.97). The CFR of IVIG group was significantly higher in all age groups, two IVIG therapy delay groups and two therapy duration groups compared to that of Non-IVIG group (all P < 0.05). IVIG therapy was related to higher viral loads and reduced counts of lymphocytes, T cells, CD4+ T cells and natural killer cells in the blood (all P < 0.05). INTERPRETATION: No obvious efficacy of IVIG in saving life or improving outcome of SFTS was observed. Caution is needed for clinical physicians to continue prescribing IVIG for SFTS patients. FUNDING: Natural Science Foundation of China.

Matrine derivate MASM protects murine MC3T3-E1 osteoblastic cells against dexamethasone-induced apoptosis via the regulation of USP14/p53.

Matrine derivative MASM (M19) is a quinolizine alkaloid with diverse pharmacological effects including preventing postmenopausal osteoporosis. In the current study, we observed that pretreatment with M19 inhibited cell apoptosis of murine osteoblastic MC3T3-E1 and primary osteoblasts induced by 1 µM dexamethasone in a dose-dependent manner. Our study also showed that pretreatment with M19 significantly prevented the upregulation of p53 that is caused by dexamethasone but had no effect on the p53 mRNA expression levels. Further immunoprecipitation (IP) experiments showed that M19 treatment increases the ubiquitination of p53 in dexamethasone-treated MC3T3-E1 cells. The expression of USP14, a deubiquitinating enzyme, increased with dexamethasone and decreased with M19 pretreatment. Co-IP experiments demonstrated the interaction between USP14 and p53, and the induced effect of a USP14 inhibitor (IU1) on p53 ubiquitination, which indicated that USP14 is a potential deubiquitinase for p53. Furthermore, pretreatment with IU1 or a p53 inhibitor (PFT-α) partially blocked dexamethasone-induced apoptosis of MC3T3-E1 cells. The overexpression of USP14 or p53 reversed the antiapoptotic effect of M19 in dexamethasone-treated MC3T3-E1 cells. In addition, PFT-α treatment remarkably blocked the effects of USP14 overexpression. In summary, our findings suggest that M19 exerts protective effects on dexamethasone-treated MC3T3-E1 cells by regulating USP14/p53.

Risk assessment of vertebral artery injury in anterior controllable antedisplacement and fusion (ACAF) surgery: a cadaveric and radiologic study.

PURPOSE: We have introduced a novel surgery technique named anterior controllable antedisplacement and fusion (ACAF) for the treatment of ossification of the posterior longitudinal ligament. As reported, the satisfactory postoperative outcome can be attributed to the larger decompression width. However, it may associate with high prevalence of vertebral artery injury (VAI) theoretically. Thus, assessment of the vulnerability of vertebral artery in ACAF is of great importance. METHODS: Computed tomographic scan data of 28 patients were retrospectively studied. Seven radiographic parameters were evaluated: uncinate process (UP) tips distance, transverse foramen (TF)-UP tips distance, TF-LWL (the ipsilateral limited wedging line) distance, the limited distance of lateral decompression, the maximum oblique angle of LWL, TF-LWG (the lateral wall of groove) distance, and width of groove. Eleven fresh cadaveric spines undergoing ACAF surgery were also studied. Two anatomic parameters were evaluated: width of groove and LWG-TF distance. RESULTS: The UP tips distance increased from C3 to C6 and tended to be larger in males. The UP tip-TF distance and LWL-TF distance were smallest at C4, but both were larger than 2 mm. Maximum oblique angle decreased from C3 to C6. Postoperatively, both radiographic and cadaveric measurements showed the width of groove was larger than UP tips distance, but LWG-TF distance was larger than 2 mm in all levels. CONCLUSION: UP can be used as anatomical landmarks to avoid VAI during ACAF surgery. Radiographic and cadaveric measurements verified the safety of ACAF surgery, even for those cases with wedging and lateral slotting.

Surgical Outcomes After Anterior Controllable Antedisplacement and Fusion Compared with Single Open-Door Laminoplasty: Preliminary Analysis of Postoperative Changes of Spinal Cord Displacements on T2-Weighted Magnetic Resonance Imaging.

OBJECTIVE: This retrospective cohort study aimed to investigate the change of spinal cord displacements and the occurrence of C5 palsy between anterior controllable antedisplacement and fusion (ACAF) (group A) and single open-door laminoplasty (group L). METHODS: From January 2016 to December 2017, a total of 80 patients with cervical ossification of the posterior longitudinal ligament (OPLL) were enrolled. All patients underwent computed tomography and magnetic resonance imaging. The types and extent of OPLL, spinal cord rotation, deviation angle, and distance between the vertebral arteries line and spinal cord (DVS) were measured. Patients with postoperative C5 palsy were recorded. Neurologic function was evaluated by Japanese Orthopaedic Association (JOA) score. RESULTS: Three days after surgery, patients in group A had better recovery (6.7° ± 2.4°) of spinal cord rotation than group L (3.1° ± 0.8°; P < 0.05). Deviation angle showed similar changes to spinal cord rotation. At the final follow-up, patients in group A had decreased DVS (11.0 ± 0.7 mm), whereas patients in group L had increased DVS (15.1 ± 0.8 mm) compared with preoperation (P < 0.05). Five patients (1 in group A and 4 in group L) developed postoperative C5 palsy (P > 0.05). Patients in group A had a higher JOA score at the final follow-up than those in group L (P < 0.05). CONCLUSIONS: ACAF could achieve in situ decompression in terms of spinal cord rotation, deviation angle, and spinal cord shift with better clinical outcomes and relatively lower incidence of C5 palsy compared with single open-door laminoplasty.

Salvianolic acid B attenuates apoptosis and inflammation via SIRT1 activation in experimental stroke rats.

Silent information regulator 1 (SIRT1), a histone deacetylase, has been suggested to be effective in ischemic brain diseases. Salvianolic acid B (SalB) is a polyphenolic and one of the active components of Salvia miltiorrhiza Bunge. Previous studies suggested that SalB is protective against ischemic stroke. However, the role of SIRT1 in the protective effect of SalB against cerebral ischemia has not been explored. In this study, the rat brain was subjected to middle cerebral artery occlusion (MCAO). Before this surgery, rats were intraperitoneally administrated SalB with or without EX527, a specific SIRT1 inhibitor. The infarct volume, neurological score and brain water content were assessed. In addition, levels of TNF-α and IL-1ß in the brain tissues were detected by commercial ELISA kits. And the expression levels of SIRT, Ac-FOXO1, Bcl-2 and Bax were detected by Western blot. The results suggested that SalB exerted a cerebral-protective effect, as shown by reduced infarct volume, lowered brain edema and increased neurological scores. SalB also exerted anti-inflammatory effects as indicated by the decreased TNF-α and IL-1ß levels in the brain tissue. Moreover, SalB upregulated the expression of SIRT1 and Bcl-2 and downregulated the expression of Ac-FOXO1 and Bax. These effects of SalB were abolished by EX527 treatment. In summary, our results demonstrate that SalB treatment attenuates brain injury induced by ischemic stoke via reducing apoptosis and inflammation through the activation of SIRT1 signaling.