Background: Emerging data suggest that direct oral anticoagulants may be a suitable choice for anticoagulation for cerebral venous thrombosis (CVT). However, conducting high-quality trials in CVT is challenging as it is a rare disease with low rates of adverse outcomes such as major bleeding and functional dependence. To facilitate the design of future CVT trials, SECRET (Study of Rivaroxaban for Cerebral Venous Thrombosis) assessed (1) the feasibility of recruitment, (2) the safety of rivaroxaban compared with standard-of-care anticoagulation, and (3) patient-centered functional outcomes. Methods: This was a phase II, prospective, open-label blinded-end point 1:1 randomized trial conducted at 12 Canadian centers. Participants were aged ≥18 years, within 14 days of a new diagnosis of symptomatic CVT, and suitable for oral anticoagulation; they were randomized to receive rivaroxaban 20 mg daily, or standard-of-care anticoagulation (warfarin, target international normalized ratio, 2.0–3.0, or low-molecular-weight heparin) for 180 days, with optional extension up to 365 days. Primary outcomes were annual rate of recruitment (feasibility); and a composite of symptomatic intracranial hemorrhage, major extracranial hemorrhage, or mortality at 180 days (safety). Secondary outcomes included recurrent venous thromboembolism, recanalization, clinically relevant nonmajor bleeding, and functional and patient-reported outcomes (modified Rankin Scale, quality of life, headache, mood, fatigue, and cognition) at days 180 and 365. Results: Fifty-five participants were randomized. The rate of recruitment was 21.3 participants/year; 57% of eligible candidates consented. Median age was 48.0 years (interquartile range, 38.5–73.2); 66% were female. There was 1 primary event (symptomatic intracranial hemorrhage), 2 clinically relevant nonmajor bleeding events, and 1 recurrent CVT by day 180, all in the rivaroxaban group. All participants in both arms had at least partial recanalization by day 180. At enrollment, both groups on average reported reduced quality of life, low mood, fatigue, and headache with impaired cognitive performance. All metrics improved markedly by day 180. Conclusions: Recruitment targets were reached, but many eligible participants declined randomization. There were numerically more bleeding events in patients taking rivaroxaban compared with control, but rates of bleeding and recurrent venous thromboembolism were low overall and in keeping with previous studies. Participants had symptoms affecting their well-being at enrollment but improved over time. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03178864.

We investigated the role of IL-17A in sevoflurane-inducedneurocognitive impairment in neonatal mice. Seventy-two wild-type (WT) and 42 IL-17A knockout (KO) neonatal mice were randomly divided into WT ( n = 36), IL-17A −/− ( n = 6), sevoflurane (Sev, n = 36), and IL-17A −/− + sevoflurane (IL-17A −/− + Sev, n = 36) groups. The latter two groups were given 3% sevoflurane for 2 h per day on postnatal days (P) 6–8. Behavioral experiments were performed on P30–36. At P37, RNA sequencing and qRT-PCR of the hippocampus was performed, neurons were detected by Nissl staining, and neuropathological changes were evaluated by HE staining. NF-κB pathway-related proteins were evaluated by western blot and immunofluorescence analyses, IL-1β and IL-6 levels were assessed by ELISA. RNA sequencing identified 131 differentially expressed genes, highlighting several enriched biological processes (chemokine activity, immune response, extracellular region, extracellular space, inflammatory response) and signaling pathways (IL-17 signaling pathway, chemokine signaling pathway, cytokine–cytokine receptor interaction, ECM–receptor interaction and influenza A). Repeated sevoflurane exposures induced long-term cognitive impairment in WT mice. The cognitive impairment was comparatively less severe in IL-17A KO mice. In addition, the increased levels of NF-κB p65, iNOS, COX-2, IL-17A, IL-6 and IL-1β, reduced neuronal numbers and neuropathological changes were ameliorated in neonatal mice in the IL-17A −/− + Sev group compared with neonatal mice in Sev group. IL-17A deletion protects against long-term cognitive impairment induced by repeated sevoflurane exposure in neonatal mice. The underlying mechanism may relate to inhibiting NF-κB signaling pathway as well as the reducing neuroinflammation.

Introduction Single nerve block provides excellent analgesia, but rebound pain after the nerve block disappears has gradually attracted people’s attention. Perineural dexamethasone has been shown to extend the duration of a single nerve block and reduce rebound pain. However, no studies have compared the effect of reducing rebound pain between the two. The hypothesis was tested that perineural or intravenous would have an equivalent effect on prevent the rebound pain after nerve block. Methods We recruited 135 patients with ankle fractures scheduled for open reduction and internal fixation (ORIF), each of whom received a single sciatic-popliteal nerve block in combination with a single nerve block. Patients were randomized into three group: 40ml ropivacaine 0.375% (C); 40ml ropivacaine 0.375% with perineural dexamethasone 10mg(PN); 40ml ropivacaine 0.375% with intravenous dexamethasone (IV). The primary outcome was the incidence of rebound pain. Results The incidence of rebound pain was significantly lower in group PN (11%)and group IV(17.8%), compared with group C(42.2%). Both Groups PN and IV had reduced pain score, reduced postoperative consumption of analgesics and improved the quality of sleep on the night of surgery compared with Group C.Conclusions Dexamethasone 10mg can prevent the rebound pain after combined femoral nerve and sciatic nerve blocks nerve block, which has nothing to do with the way of dexamethasone. Trial registration number www.chictr.org.cn/index.aspx ChiCTR2100049075

Purpose A single-injection nerve block provides excellent analgesia in a short time, but rebound pain after the nerve block disappears has attracted researchers’ attention. The aim of this study is to evaluate the effect of intravenous dexamethasone on rebound pain after adductor canal block (ACB) and popliteal sciatic nerve block in patients with ankle fracture. Methods We recruited 130 patients with ankle fractures scheduled for open reduction and internal fixation (ORIF), each of whom received ACB and popliteal sciatic nerve block. Patients were divided into two groups: C (ropivacaine only) and IV (ropivacaine with intravenous dexamethasone). The primary outcome was the incidence of rebound pain. Secondary outcomes included the following: pain scores at 6 h (T 1 ), 12 h (T 2 ), 18 h (T 3 ), 24 h (T 4 ), and 48 h (T 5 ) after operation; duration of the nerve block; number of presses of the analgesia pump and rescue analgesic consumption in the three-day postoperative period; quality of recovery scale (QoR-15 score); postoperative sleep quality; satisfaction of patients; and levels of serum inflammatory markers (IL-1β, IL-6, and TNF-α) six hours after surgery. Results Compared with group C, the incidence of rebound pain in group IV was significantly reduced, and the duration of nerve block was extended by approximately nine hours ( P <0.05). Moreover, patients in group IV had significantly lower pain scores at T 2 -T 4 , lower levels of serum inflammatory markers (IL-1β, IL-6, and TNF-α), higher QoR-15 score two days after the operation, and satisfactory sleep quality the night after surgery ( P <0.05). Conclusion Intravenous dexamethasone can reduce the rebound pain after adductor block and sciatic popliteal nerve block in patients with ankle fracture surgery, prolong the duration of nerve block, and improve the quality of early postoperative recovery.