Background: Posttraumatic stress disorder (PTSD) and depression are highly comorbid. Psilocybin exerts substantial therapeutic effects on depression by promoting neuroplasticity. Fear extinction is a key process in the mechanism of first-line exposure-based therapies for PTSD. We hypothesized that psilocybin would facilitate fear extinction by promoting hippocampal neuroplasticity. Methods: First, we assessed the effects of psilocybin on percentage of freezing time in an auditory cued fear conditioning (FC) and fear extinction paradigm in mice. Psilocybin was administered 30 min before extinction training. Fear extinction testing was performed on the first day; fear extinction retrieval and fear renewal were tested on the sixth and seventh days, respectively. Furthermore, we verified the effect of psilocybin on hippocampal neuroplasticity using Golgi staining for the dendritic complexity and spine density, Western blotting for the protein levels of brain derived neurotrophic factor (BDNF) and mechanistic target of rapamycin (mTOR), and immunofluorescence staining for the numbers of doublecortin (DCX)- and bromodeoxyuridine (BrdU)-positive cells. Results: A single dose of psilocybin (2.5 mg/kg, i.p.) reduced the increase in the percentage of freezing time induced by FC at 24 h, 6th day and 7th day after administration. In terms of structural neuroplasticity, psilocybin rescued the decrease in hippocampal dendritic complexity and spine density induced by FC; in terms of neuroplasticity related proteins, psilocybin rescued the decrease in the protein levels of hippocampal BDNF and mTOR induced by FC; in terms of neurogenesis, psilocybin rescued the decrease in the numbers of DCX- and BrdU-positive cells in the hippocampal dentate gyrus induced by FC. Conclusions: A single dose of psilocybin facilitated rapid and sustained fear extinction; this effect might be partially mediated by the promotion of hippocampal neuroplasticity. This study indicates that psilocybin may be a useful adjunct to exposure-based therapies for PTSD and other mental disorders characterized by failure of fear extinction.

BACKGROUND: Bleeding and the need for allogeneic transfusions are still problems after off-pump coronary artery bypass grafting (OPCAB) surgery. We therefore evaluated the effects of an antifibrinolytic, tranexamic acid, on postoperative bleeding and transfusion requirements in patients undergoing OPCAB surgery. METHODS: Two hundred thirty-one consecutive patients scheduled for elective OPCAB were enrolled in the study. Using a double-blind method, the patients were randomly assigned to receive either tranexamic acid (bolus 1 g before surgical incision followed by an infusion of 400 mg/h during surgery; n = 116) or a placebo (infusion equivalent volume of saline solution; n = 115). The primary outcome was 24-hour postoperative chest tube drainage. Allogeneic transfusion, mortality, major morbidities, and resource utilization were also recorded. RESULTS: In comparison with the placebo group, the patients receiving tranexamic acid had a significant reduction in chest tube drainage at 6 hours (270 ± 118 mL vs 416 ± 179 mL, P < 0.001) and 24 hours (654 ± 224 mL vs 891 ± 295 mL, P < 0.001). There was also a significant reduction in allogeneic red blood cell transfusions (47 vs 31.9%, P = 0.019) and fresh frozen plasma (29.6% vs 17.2%, P = 0.027) transfusions. There were no differences in mortality, morbidity, and resource utilization between the 2 groups. CONCLUSIONS: Tranexamic acid reduces postoperative chest tube drainage and the requirement for allogeneic transfusion in off-pump coronary surgery.

The goal was to investigate the prevalence of acute kidney injury (AKI) after total arch replacement with frozen elephant trunk procedure, which was achieved by antegrade cerebral perfusion and moderate hypothermic circulatory arrest (MHCA) or deep hypothermic circulatory arrest (DHCA) among patients with type A aortic dissection. Overall, 627 adult type A aortic dissection patients who underwent total arch replacement with frozen elephant trunk from January 2013 until December 2016 at Fuwai Hospital were divided into the DHCA (14.1–20.0°C) and MHCA (20.1–28.0°C) groups. Postoperative AKI as the primary outcome was compared using propensity-matched scoring. Overall, 340 (54.2%) and 287 (45.8%) patients underwent DHCA and MHCA, respectively. The overall incidence of AKI was 75.4%. Age [odds ratio (OR) 1.02, 95% confidence interval (CI) 1.00–1.04; P = 0.022], body mass index (OR 1.06, 95% CI 1.01–1.12; P = 0.016), cardiopulmonary bypass duration (OR 1.01, 95% CI 1.00–1.01; P = 0.003) and hypertension history (OR 1.76, 95% CI 1.14–2.70; P = 0.010) were identified as independent risk factors for AKI onset with multivariable analysis. Postoperative AKI was not significantly different between the DHCA and MHCA groups regardless of the overall or propensity-matched cohort (overall data: P = 0.17; propensity score data: P = 0.88). Patients with MHCA experienced higher rates of postoperative stroke after propensity score analysis (DHCA 0.9% vs MHCA 3.7%; P = 0.034). MHCA was not superior to DHCA in decreasing postoperative AKI. Thus, MHCA should not definitively replace DHCA.

Background: The prognostic nutritional index (PNI) is a nutritional indicator and predictor of various diseases. However it is unclear whether PNI can be a predictor of perioperative ischemic stroke. This study aims to evaluate the association of the preoperative PNI and ischemic stroke in patients undergoing non-cardiac surgery. Methods: The retrospective cohort study included patients who underwent noncardiac surgery between January 2008 and August 2019. The patients were divided into PNI ≥ 38.8 and PNI < 38.8 groups according to the cut-off value of PNI. Univariate and multivariate logistic regression analyses were performed to explore the association between PNI and perioperative ischemic stroke. Subsequently, propensity score matching (PSM) analysis was performed to eliminate the confounding factors of covariates and further validate the results. Subgroup analyses were completed to assess the predictive utility of PNI for perioperative ischemic stroke in different groups. Results: Amongst 221,542 hospitalized patients enrolled, 485 (0.22%) experienced an ischemic stroke within 30 days of the surgery, 22.1% of patients were malnourished according to PNI < 38.8, and the occurrence of perioperative ischemic stroke was 0.34% (169/49055) in the PNI < 38.8 group. PNI < 38.8 was significantly associated with an increased incidence of perioperative ischemic stroke whether in univariate logistic regression analysis (OR = 1.884, 95% CI: 1.559—2.267, P < 0.001) or multivariate logistic regression analysis (OR = 1.306, 95% CI: 1.061—1.602, P = 0.011). After PSM analysis, the ORs of PNI < 38.8 group were 1.250 (95% CI: 1.000–1.556, P = 0.050) and 1.357 (95% CI: 1.077–1.704, P = 0.009) in univariate logistic regression analysis and multivariate logistic regression analysis respectively. The subgroup analysis indicated that reduced PNI was significantly associated to an increased risk of perioperative ischemic stroke in patients over 65 years old, ASA II, not taking aspirin before surgery, without a history of stroke, who had neurosurgery, non-emergency surgery, and were admitted to ICU after surgery. Conclusions: Our study indicates that low preoperative PNI is significantly associated with a higher incidence of ischemic stroke in patients undergoing non-cardiac surgery. Preoperative PNI, as a preoperative nutritional status evaluation index, is an independent risk factor useful to predict perioperative ischemic stroke risk, which could be used as an intervenable preoperative clinical biochemical index to reduce the incidence of perioperative ischemic stroke.