Introduction: The ideal measures to prevent postoperative delirium remain unestablished. We conducted this systematic review and meta-analysis to clarify the significance of potential interventions. Methods: The PRISMA statement guidelines were followed. Two researchers searched MEDLINE, EMBASE, CINAHL and the Cochrane Library for articles published in English before August 2012. Additional sources included reference lists from reviews and related articles from 'Google Scholar'. Randomized clinical trials (RCTs) on interventions seeking to prevent postoperative delirium in adult patients were included. Data extraction and methodological quality assessment were performed using predefined data fields and scoring system. Meta-analysis was accomplished for studies that used similar strategies. The primary outcome measure was the incidence of postoperative delirium. We further tested whether interventions effective in preventing postoperative delirium shortened the length of hospital stay. Results: We identified 38 RCTs with interventions ranging from perioperative managements to pharmacological, psychological or multicomponent interventions. Meta-analysis showed dexmedetomidine sedation was associated with less delirium compared to sedation produced by other drugs (two RCTs with 415 patients, pooled risk ratio (RR) = 0.39; 95% confidence interval (CI) = 0.16 to 0.95). Both typical (three RCTs with 965 patients, RR = 0.71; 95% CI = 0.54 to 0.93) and atypical antipsychotics (three RCTs with 627 patients, RR = 0.36; 95% CI = 0.26 to 0.50) decreased delirium occurrence when compared to placebos. Multicomponent interventions (two RCTs with 325 patients, RR = 0.71; 95% CI = 0.58 to 0.86) were effective in preventing delirium. No difference in the incidences of delirium was found between: neuraxial and general anesthesia (four RCTs with 511 patients, RR = 0.99; 95% CI = 0.65 to 1.50); epidural and intravenous analgesia (three RCTs with 167 patients, RR = 0.93; 95% CI = 0.61 to 1.43) or acetylcholinesterase inhibitors and placebo (four RCTs with 242 patients, RR = 0.95; 95% CI = 0.63 to 1.44). Effective prevention of postoperative delirium did not shorten the length of hospital stay (10 RCTs with 1,636 patients, pooled SMD (standard mean difference) = -0.06; 95% CI = -0.16 to 0.04). Conclusions: The included studies showed great inconsistencies in definition, incidence, severity and duration of postoperative delirium. Meta-analysis supported dexmedetomidine sedation, multicomponent interventions and antipsychotics were useful in preventing postoperative delirium.

Corrigendum: Type 2 diabetes increases risk of unfavorable survival outcome for postoperative ischemic stroke in patients who underwent non-cardiac surgery: A retrospective cohort study

Neuroinflammation is a vital pathogenic mechanism for neurodegenerative diseases such as Alzheimer’s, schizophrenia, and age-related cognitive decline. Regulatory T cells (Tregs) exhibit potent anti-inflammatory properties and can modulate neurodegenerative diseases arising from central nervous system inflammatory responses. However, the role of Tregs in neuroinflammation-related cognitive dysfunction remains unclear. It is highly plausible that Htr7+ Tregs expressing unique genes associated with the nervous system, including the Htr7 gene encoding the serotonin receptor 5-HT7, play a pivotal role. Mice were given a tryptophan-rich diet (with a tryptophan content of 0.6%) or a normal diet (with a tryptophan content of 0.16%). The neuroinflammation-mediated cognitive dysfunction model was established by intracerebroventricular injection of lipopolysaccharide (LPS) in 8-week-old C57BL/6J mice. The activation and infiltration of Tregs were measured using flow cytometry. Primary Tregs were cocultured separately with primary CD8+ T cells and primary microglia for in vitro validation of the impact of 5-HT and 5-HT7 receptor on Tregs. Prior to their transfer into recombination activating gene 1 (Rag1−/−) mice, Tregs were ex vivo transfected with lentivirus to knock down the expression of Htr7. In this study, the tryptophan-rich diet was found to reverse LPS-induced cognitive impairment and reduce the levels of 5-HT in peripheral blood. The tryptophan-rich diet led to increased levels of 5-HT in peripheral blood, which in turn promoted the proliferation and activation of Htr7+ Tregs. Additionally, the tryptophan-rich diet was also shown to attenuate LPS-mediated neuroinflammation by activating Htr7+ Tregs. Furthermore, 5-HT and 5-HT7 receptor were found to enhance the immunosuppressive effect of Tregs on CD8+ T cells and microglia. In Rag1−/− mice, Htr7+ Tregs were shown to alleviate LPS-induced neuroinflammation and cognitive impairment. Our research revealed the ability of Htr7+ Tregs to mitigate neuroinflammation and prevent neuronal damage by suppressing the infiltration of CD8+ T cells into the brain and excessive activation of microglia, thereby ameliorating LPS-induced cognitive impairment. These insights may offer novel therapeutic targets involving Tregs for neuroinflammation and cognitive impairment.

Background: Metabolic dysregulation and disruption of immune homeostasis have been widely associated with perioperative complications including perioperative ischemic stroke. Although immunometabolite S-2-hydroxyglutarate (S-2HG) is an emerging regulator of immune cells and thus triggers the immune response, it is unclear whether and how S-2HG elicits perioperative ischemic brain injury and exacerbates post-stroke cognitive dysfunction. Methods: Perioperative ischemic stroke was induced by transient middle cerebral artery occlusion for 60 min in C57BL/6 mice 1 day after ileocecal resection. CD8⁺ T lymphocyte activation and invasion of the cerebrovascular compartment were measured using flow cytometry. Untargeted metabolomic profiling was performed to detect metabolic changes in sorted CD8⁺ T lymphocytes after ischemia. CD8⁺ T lymphocytes were transfected with lentivirus ex vivo to mobilize cell proliferation and differentiation before being transferred into recombination activating gene 1 (Rag1^−/−) stroke mice. Results: The perioperative stroke mice exhibit more severe cerebral ischemic injury and neurological dysfunction than the stroke-only mice. CD8⁺ T lymphocyte invasion of brain parenchyma and neurotoxicity augment cerebral ischemic injury in the perioperative stroke mice. CD8⁺ T lymphocyte depletion reverses exacerbated immune-mediated cerebral ischemic brain injury in perioperative stroke mice. Perioperative ischemic stroke triggers aberrant metabolic alterations in peripheral CD8⁺ T cells, in which S-2HG is more abundant. S-2HG alters CD8⁺ T lymphocyte proliferation and differentiation ex vivo and modulates the immune-mediated ischemic brain injury and post-stroke cognitive dysfunction by enhancing CD8⁺ T lymphocyte-mediated neurotoxicity. Conclusion: Our study establishes that S-2HG signaling-mediated activation and neurotoxicity of CD8⁺ T lymphocytes might exacerbate perioperative ischemic brain injury and may represent a promising immunotherapy target in perioperative ischemic stroke.

Among the elderly, depression is one of the most common mental disorders, which seriously affects their physical and mental health and quality of life, and their suicide rate is particularly high. Depression in the elderly is strongly associated with surgery. In this study, we aimed to explore the risk factors and establish a predictive model of depressive symptoms 1 month after video-assisted thoracoscopic surgery (VATS) in elderly patients. The study participants included 272 elderly patients (age > 65 years) undergoing VATS from April 2020 to May 2021 at 1 of 18 medical centers in China. The patients were divided into a depression group and a nondepression group according to the Chinese version of the nine-item Patient Health Questionnaire (PHQ-9). The patients’ pre- and postoperative characteristics and questionnaires were collected and compared. Then, binary logistic regression was used to determine the risk factors that affect postoperative depressive symptoms, and the predictive model was constructed. The prediction efficiency of the model was evaluated by drawing the receiver operating characteristic curve (ROC), and the area under the curve (AUC) was calculated to evaluate the value of the predictive model. Among all of the included patients, 16.54% (45/272) suffered from depressive symptoms after VATS. The results of the univariate analysis showed that body mass index (BMI), chronic pain, leukocyte count, fibrinogen levels, prothrombin time, ASA physical status, infusion volume, anxiety, sleep quality, and postoperative pain were related to postoperative depressive symptoms (all p < 0.05). The results of multivariate logistic regression analysis showed that a high fibrinogen level (OR = 2.42), postoperative anxiety (OR = 12.05), poor sleep quality (OR = 0.61), and pain (OR = 2.85) were risk factors of postoperative depressive symptoms. A predictive model was constructed according to the regression coefficient of each variable, the ROC curve was drawn, and the AUC value was calculated to be 0.889. The prediction model may help medical personnel identify older patients at risk of developing depressive disorders associated with VATS and may be useful for clinical purposes.

Objective: Diabetes mellitus (DM) has been critically associated with unfavorable outcomes in the general population. We aimed to investigate the association between type 2 DM and long-term survival outcomes for postoperative ischemic stroke in patients who underwent non-cardiac surgery.Research Design and Methods: This was a retrospective cohort study of patients with non-cardiac surgery who had suffered from postoperative ischemic stroke between January 2008 and August 2019. Diabetic individuals were included in postoperative ischemic stroke patients with the DM group. The outcome of interest was long-term overall survival (OS). We conducted propensity score matching (PSM) and inverse probability treatment weighting (IPTW) to adjust for baseline characteristic differences between groups. Multivariate Cox regression analysis with stepwise selection was used to calculate the adjusted hazard ratio (HR) of OS and type 2 DM.Results: During a median follow-up of 46.2 month [interquartile range (IQR), 21.1, 84.2], 200 of 408 patients (49.0%) died. The OS rates at 3, 5, and 10 years were significantly lower for postoperative ischemic stroke patients with DM than those without DM (3 years OS: 52.2 vs. 69.5%, p < 0.001; 5 years OS: 41.6 vs. 62.4%, p < 0.001; 10 years OS: 37.2 vs. 56.6%, p < 0.001). All covariates were between-group balanced after using PSM or IPTW. The postoperative ischemic stroke patients with type 2 DM had a shortened OS in primary analysis (HR: 1.947; 95% CI: 1.397–2.713; p < 0.001), PSM analysis (HR: 2.190; 95% CI: 1.354–3.540; p = 0.001), and IPTW analysis (HR: 2.551; 95% CI: 1.769–3.679; p < 0.001).Conclusion: Type 2 DM was associated with an unfavorable survival outcome for postoperative ischemic stroke in patients who underwent non-cardiac surgery. When postoperative ischemic stroke co-occurred with type 2 DM, the potential synergies would have multiplicative mortality risk. Further research to assess the adverse effects of type 2 DM on long-term survival may be warranted.