Corticosteroids are often administered prophylactically to attenuate the inflammatory response associated with cardiac surgery using cardiopulmonary bypass (CPB). However, the efficacy and safety profile of corticosteroids remain uncertain. The primary aim of this systematic review and meta-analysis was to investigate the effect of corticosteroids on mortality in adult cardiac surgery using CPB. Secondary aims were to examine the effect of corticosteroids on myocardial adverse events, pulmonary adverse events, atrial fibrillation, surgical site infection, gastrointestinal bleeding and duration of stay in the intensive care unit and hospital. Randomized controlled trials (RCTs) were systematically searched in electronic databases (MEDLINE, EMBASE, CINAHL, CENTRAL and Web of Science) from their inception until March 2019. Observational studies, case reports, case series and literature reviews were excluded. Sixty-two studies (n = 16 457 patients) were included in this meta-analysis. There was no significant difference in mortality between the corticosteroid and placebo groups [odds ratio (OR) 0.96, 95% confidence interval (CI) 0.81–1.14; P = 0.65, participants = 14 693, studies = 24, evidence of certainty: moderate]. Compared to those receiving a placebo, patients who were given corticosteroids had a significantly higher incidence of myocardial adverse events (OR 1.17, 95% CI 1.03–1.33; P = 0.01, participants = 14 512, studies = 23) and a lower incidence of pulmonary adverse events (OR 0.86, 95% CI 0.75–0.98; P = 0.02, participants = 13 426, studies = 17). The incidences of atrial fibrillation (OR 0.87, 95% CI 0.81–0.94; P < 0.001, participants = 14 148, studies = 24) and surgical site infection (OR 0.81, 95% CI 0.73–0.90; P < 0.001, participants = 13 946; studies = 22) were all lower in patients who were given corticosteroids. In the present meta-analysis of 62 RCTs (16 457 patients), including the 2 major RCTs (SIRS and DECS trials: 12 001 patients), we found that prophylactic corticosteroids in cardiac surgery did not reduce mortality. The clinical significance of an increase in myocardial adverse events remains unclear as the definition of a relevant myocardial end point following cardiac surgery varied greatly between RCTs.

IntroductionVariably protease sensitive prionopathy (VPSPr) is a recently described, sporadic human prion disease that is pathologically and biochemically distinct from the currently recognised sporadic Creutzfeldt-Jakob disease (sCJD) subtypes. The defining biochemical features of the abnormal form of the prion protein (PrPSc) in VPSPr are increased sensitivity to proteolysis and the presence of an N- and C-terminally cleaved ~8 kDa protease resistant PrPSc (PrPres) fragment. The biochemical and neuropathological profile of VPSPr has been proposed to resemble either Gerstmann–Sträussler–Scheinker syndrome (GSS) or familial CJD with the PRNP-V180I mutation. However, in some cases of VPSPr two protease resistant bands have been observed in Western blots that co-migrate with those of type 2 PrPres, suggesting that a proportion of the PrPSc present in VPSPr has properties similar to those of sCJD.ResultsHere, we have used conformation dependent immunoassay to confirm the presence of PrPSc in VPSPr that is more protease sensitive compared with sCJD. However, CDI also shows that a proportion of PrPSc in VPSPr resists PK digestion of its C-terminus, distinguishing it from GSS associated with ~8 kDa PrPres, and showing similarity to sCJD. Intensive investigation of a single VPSPr case with frozen tissue from multiple brain regions shows a broad, region-specific spectrum of protease sensitivity and differential stability of PrPSc in the absence of PK treatment. Finally, using protein misfolding cyclic amplification and real-time quaking induced conversion, we show that VPSPr PrPSc has the potential to seed conversion in vitro and that seeding activity is dispersed through a broad range of aggregate sizes. We further propose that seeding activity is associated with the ~19 and ~23 kDa PrPres rather than the ~8 kDa fragment.ConclusionsTherefore, PrPSc in VPSPr is heterogeneous in terms of protease sensitivity and stability to denaturation with the chaotrope GdnHCl and includes a proportion with similar properties to that found in sCJD.Electronic supplementary materialThe online version of this article (doi:10.1186/s40478-014-0152-4) contains supplementary material, which is available to authorized users.

Delirium is an acute and usually transient severe neuropsychiatric syndrome associated with significant long-term physical morbidity. However, its chronic psychiatric sequelae remain poorly characterized. To investigate the prevalence of psychiatric symptoms, namely anxiety, depressive, and post-traumatic stress disorder (PTSD) symptoms after delirium, a systematic literature search of MEDLINE, EMBASE and PsycINFO databases was performed independently by two authors in March 2016. Bibliographies were hand-searched, and a forward- and backward-citation search using Web of Science was performed for all included studies. Of 6411 titles, we included eight prospective cohort studies, including 370 patients with delirium and 1073 without delirium. Studies were heterogeneous and mostly included older people from a range of clinical groups. Consideration of confounders was variable. The prevalence of depressive symptoms was almost three times higher in patients with delirium than in patients without delirium (22.2% vs 8.0%, risk ratio = 2.79; 95% confidence interval = 1.36-5.73). There was no statistically significant difference between the prevalence of anxiety symptoms between patients with and without delirium. The prevalence of PTSD symptoms after delirium was inconclusive: only one study investigated this and no association between PTSD symptoms after delirium was reported. There is limited published evidence of the prevalence of psychiatric symptoms after non-ICU delirium and the strongest evidence is for depressive symptoms. Further longitudinal studies are warranted to investigate the prevalence of anxiety and PTSD symptoms.

Background: Ketamine is believed to reduce the incidence of emergence agitation in children undergoing surgery or procedure. However, recent randomized controlled trials reported conflicting findings. Aims:To investigate the effect of ketamine on emergence agitation in children. Methods: Databases of MEDLINE, EMBASE, and CENTRAL were systematically searched from their start date until February 2019. Randomized controlled trials comparing intravenous ketamine and placebo in children were sought. The primary outcome was the incidence of emergence agitation. Secondary outcomes included postoperative pain score, duration of discharge time, and the adverse effects associated with the use of ketamine, namely postoperative nausea and vomiting, desaturation, and laryngospasm.Results: Thirteen studies (1125 patients) were included in the quantitative metaanalysis. The incidence of emergence agitation was 14.7% in the ketamine group and 33.3% in the placebo group. Children receiving ketamine had a lower incidence of emergence agitation, with an odds ratio being 0.23 (95% confidence interval: 0.11 to 0.46), certainty of evidence: low. In comparison with the placebo, ketamine group achieved a lower postoperative pain score (odds ratio: −2.42, 95% confidence interval: −4.23 to −0.62, certainty of evidence: very low) and lower pediatric anesthesia emergence delirium scale at 5 minutes after operation (odds ratio: −3.99, 95% confidence interval: −5.03 to −2.95; certainty of evidence: moderate). However, no evidence was observed in terms of incidence of postoperative nausea and vomiting, desaturation, and laryngospasm. Conclusion:In this meta-analysis of 13 randomized controlled trials, high degree of heterogeneity and low certainty of evidence limit the recommendations of ketamine for the prevention of emergence agitation in children undergoing surgery or imaging procedures. However, the use of ketamine is well-tolerated without any notable adverse effects across all the included trials.PROSPERO registration: CRD42019131865. K E Y W O R D Semergence agitation, emergence delirium, ketamine, meta-analysis, pain, systematic review