Tryptophan-rich diet and its effects on Htr7+ Tregs in alleviating neuroinflammation and cognitive impairment induced by lipopolysaccharide.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Effect of intranasal insulin on perioperative cognitive function in older adults: a randomized, placebo-controlled, double-blind clinical trial.

BACKGROUND: Postoperative cognitive impairment are common neural complications in older surgical patients and exacerbate the burden of medical care on families and society. METHODS: A total of 140 older patients who were scheduled for elective orthopaedic surgery or pancreatic surgery with general anaesthesia were randomly assigned to Group S or Group I with a 1:1 allocation. Patients in Group S and Group I received intranasal administration of 400 µL of normal saline or 40 IU/400 µL of insulin, respectively, once daily from 5 minutes before anaesthesia induction until 3 days postoperatively. Perioperative cognitive function was assessed using the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment-Basic (MoCA-B) at 1 day before and 3 days after surgery and postoperative delirium (POD) incidence was assessed using the 3-minute Diagnostic Interview for CAM (3D-CAM) on postoperative days 1-3. Serum levels of interleukin-6 (IL-6), tumour necrosis factor α (TNF-α), S100-ß and C-reactive protein (CRP) were measured on the first day after surgery. RESULTS: Insulin treatment significantly increased postoperative MMSE and MoCA-B scores in group I than in group S (P < 0.001, P = 0.001, respectively), decreased the incidence of POD within the 3-day postoperative period in Group I than in Group S (10.9% vs 26.6%, P = 0.024), and inhibited postoperative IL-6 and S100-ß levels in Group I compared to Group S (P = 0.034, P = 0.044, respectively). CONCLUSIONS: Intranasal insulin administration is thus suggested as a potential therapy to improve postoperative cognition in older patients undergoing surgery. However, a more standardized multi-centre, large-sample study is needed to further validate these results.

Public Knowledge and Awareness of Anesthesiology and Anesthesiologists in China: A Cross-Sectional National Survey of 1 Million Participants.

BACKGROUND: In the past 20 years, anesthesiology has become one of the most advanced specialties and has undergone rapid development. However, public awareness regarding anesthesiology and anesthesiologists is limited, especially in developing countries. It is important for anesthesiologists to make the public aware of their role during surgery. Therefore, a nationwide survey was set up to investigate public awareness of anesthesiology and anesthesiologists in China. METHOD: A cross-sectional nationwide survey was performed from June 2018 to June 2019 in 34 provinces, municipalities, and autonomous regions across China and an overseas region. The questionnaires of the survey were divided into 2 main parts: general items and research items. General items included the demographic characteristics of the participants; research items consisted of 10 questions about the public's awareness of anesthesiologists and anesthesiology. Data quality control was undertaken by the investigation committee throughout the survey process. RESULTS: The nationwide survey enrolled 1,001,279 participants (male, 40.7%). We found that most of the participants regarded anesthesiologists as doctors. However, public knowledge of anesthesiologists' work and duties during surgery was quite low, with correct response rate ranging from 16.5% to 52.9%, and anesthesiologist responsibilities were often mistakenly attributed to surgeons or nurses. It is disappointing that more than half of participants still thought that, once the patient fell asleep after receiving anesthetics, the anesthesiologist could leave the operating room. Finally, the correct response rate was positively correlated with the economic levels of the regions. CONCLUSIONS: Public awareness regarding anesthesiology and anesthesiologists in China remains inadequate. Due to the biases and characteristics of the participants, the actual situation of the general Chinese public is likely even worse than reflected here. Therefore, extensive measures should be undertaken to improve public knowledge of anesthesiology and anesthesiologists.

Triglyceride-glucose index predicts postoperative delirium in elderly patients with type 2 diabetes mellitus: a retrospective cohort study.

BACKGROUND: Postoperative delirium (POD) is more prevalent among elderly patients with type 2 diabetes mellitus (T2DM). Insulin resistance (IR) can be assessed using the triglyceride-glucose (TyG) index, a novel biomarker. This study aims to investigate the predictive potential of the TyG index for POD in elderly patients with T2DM. MATERIALS AND METHODS: Elderly patients (≥ 65) with T2DM who underwent non-neurosurgery and non-cardiac surgery were enrolled. Univariate and multivariate logistic regression analyses were conducted to assess the association between the TyG index and POD. Additionally, subgroup analyses were performed to compare the sex-specific differences in the predictive ability of the TyG index for POD. RESULTS: A total of 4566 patients were included in this retrospective cohort. The receiver operating characteristic (ROC) curve analysis determined the optimal cut-off value for the TyG index to be 8.678. In the univariate model, a TyG index > 8.678 exhibited an odds ratio (OR) of 1.668 (95% CI: 1.210-2.324, P = 0.002) for predicting POD. In the multivariate regression models, the ORs were 1.590 (95% CI: 1.133-2.252, P < 0.008), 1.661 (95% CI: 1.199-2.325, P < 0.003), and 1.603 (95% CI: 1.137-2.283, P = 0.008) for different models. Subgroup analyses demonstrated that the predictive ability of the TyG index was more pronounced in females compared to males. CONCLUSION: The TyG index shows promise as a novel biomarker for predicting the occurrence of POD in elderly surgical patients with T2DM.

The relationship between trajectories of renal oxygen saturation and acute kidney injury: a prospective cohort study with a secondary analysis.

BACKGROUND: Acute kidney injury (AKI) is a major postoperative consequence, affecting prognosis of older patients. Effective prediction or intervention to predict or prevent the incidence of AKI is currently unavailable. AIMS: Dynamic changes of renal tissue oxygen saturation (RSO2) during surgery process are understudied and we intended to explore the distinct trajectories and associations with postoperative AKI. METHODS: This was a secondary analysis including data for older patients who underwent open hepatectomy surgery with informed consent. Latent class mixed models (LCMM) method was conducted to generate trajectories of intraoperative renal tissue RSO2 through different time points. The primary outcome was postoperative 7-day AKI. The univariate and multivariate regression analysis were performed to identify the relationship between distinct trajectories of renal tissue RSO2 and the risk of AKI. Meanwhile, the prediction efficacy of renal tissue RSO2 at different time points was compared to find potential intervention timing. RESULTS: Postoperative AKI occurred in 14 (15.2%) of 92 patients. There are two distinct renal tissue RSO2 trajectories, with 44.6% generating "high-downwards" trajectory and 55.4% generating "consistently-high" trajectory. Patients with "high-downwards" trajectory had significantly higher risk of postoperative AKI than another group (Unadjusted OR [Odds Ratio] = 3.790, 95% CI [Confidence Interval]: 1.091-13.164, p = 0.036; Adjusted OR = 3.973, 95% CI 1.020-15.478, p = 0.047, respectively). Predictive performance was 71.4% sensitivity and 60.3% specificity for "high-downwards" trajectory of renal tissue RSO2 to identify AKI. Furthermore, the renal tissue RSO2 exhibited the lowest level and the best results in terms of the sensitivity during the hepatic occlusion period, may be considered as a "time of concern". CONCLUSIONS: Older patients undergoing hepatectomy may show high-downwards trajectory of renal tissue RSO2, indicating a higher risk of AKI, and the lowest level was identified during the hepatic occlusion period. These findings may help to provide potential candidates for future early recognition of deterioration of kidney function and guide interventions.

Development and validation of a nomogram for predicting pulmonary complications in elderly patients undergoing thoracic surgery.

BACKGROUND: Postoperative pulmonary complications (PPCs) remain a prevalent concern among elderly patients undergoing surgery, with a notably higher incidence observed in elderly patients undergoing thoracic surgery. This study aimed to develop a nomogram to predict the risk of PPCs in this population. METHODS: A total of 2963 elderly patients who underwent thoracic surgery were enrolled and randomly divided into a training cohort (80%, n = 2369) or a validation cohort (20%, n = 593). Univariate and multivariate logistic regression analyses were conducted to identify risk factors for PPCs, and a nomogram was developed based on the findings from the training cohort. The validation cohort was used to validate the model. The predictive accuracy of the model was evaluated by receiver operating characteristic (ROC) curve, area under ROC (AUC), calibration curve, and decision curve analysis (DCA). RESULTS: A total of 918 (31.0%) patients reported PPCs. Nine independent risk factors for PPCs were identified: preoperative presence of chronic obstructive pulmonary disease (COPD), elevated leukocyte count, higher partial pressure of arterial carbon dioxide (PaCO2) level, surgical site, thoracotomy, intraoperative hypotension, blood loss > 100 mL, surgery duration > 180 min, and malignant tumor. The AUC value for the training cohort was 0.739 (95% CI: 0.719-0.762), and it was 0.703 for the validation cohort (95% CI: 0.657-0.749). The P-values for the Hosmer-Lemeshow test were 0.633 and 0.144 for the training and validation cohorts, respectively, indicating a notable calibration curve fit. The DCA curve indicated that the nomogram could be applied clinically if the risk threshold was between 12% and 84%, which was found to be between 8% and 82% in the validation cohort. CONCLUSION: This study highlighted the pressing need for early detection of PPCs in elderly patients undergoing thoracic surgery. The nomogram exhibited promising predictive efficacy for PPCs in elderly patients undergoing thoracic surgery, enabling the identification of high-risk patients and consequently aiding in the implementation of preventive interventions.

Association of sleep quality on the night of operative day with postoperative delirium in elderly patients: A prospective cohort study.

BACKGROUND: Sleep disturbances in the peri-operative period have been associated with adverse outcomes, including postoperative delirium (POD). However, research on sleep quality during the immediate postoperative period is limited. OBJECTIVES: This study aimed to investigate the association between sleep quality on the night of the operative day assessed using the Sleep Quality Numeric Rating Scale (SQ-NRS), and the incidence of POD in a large cohort of surgical patients. DESIGN: A prospective cohort study. SETTING: A tertiary hospital in China. PATIENTS: This study enrolled patients aged 65 years or older undergoing elective surgery under general anaesthesia. The participants were categorised into the sleep disturbance and no sleep disturbance groups according to their operative night SQ-NRS. MAIN OUTCOME MEASURES: The primary outcome was delirium incidence, whereas the secondary outcomes included acute kidney injury, stroke, pulmonary infection, cardiovascular complications and all-cause mortality within 1 year postoperatively. RESULTS: In total, 3072 patients were included in the analysis of this study. Among them, 791 (25.72%) experienced sleep disturbances on the night of operative day. Patients in the sleep disturbance group had a significantly higher risk of developing POD (adjusted OR 1.43, 95% CI 1.11 to 1.82, P  = 0.005). Subgroup analysis revealed that age 65-75 years; male sex; ASA III and IV; haemoglobin more than 12 g l -1 ; intra-operative hypotension; surgical duration more than 120 min; and education 9 years or less were significantly associated with POD. No interaction was observed between the subgroups. No significant differences were observed in the secondary outcomes, such as acute kidney injury, stroke, pulmonary infection, cardiovascular complications and all-cause mortality within 1 year postoperatively. CONCLUSIONS: The poor subjective sleep quality on the night of operative day was independently associated with increased POD risk, especially in certain subpopulations. Optimising peri-operative sleep may reduce POD. Further research should investigate potential mechanisms and causal relationships. TRIAL REGISTRY: chictr.org.cn: ChiCTR1900028545.

Preoperative Frailty Assessment Predicts Postoperative Mortality, Delirium and Pneumonia in Elderly Lung Cancer Patients: A Retrospective Cohort Study.

BACKGROUND: The purpose of this study was to investigate the predictive value of the 5-factor modified frailty index (mFI-5) for postoperative mortality, delirium and pneumonia in patients over 65 years of age undergoing elective lung cancer surgery. METHODS: Data were collected from a single-center retrospective cohort study conducted in a general tertiary hospital from January 2017 to August 2019. In total, the study included 1372 elderly patients aged over 65 who underwent elective lung cancer surgery. They were divided into frail group (mFI-5, 2-5), prefrail group (mFI-5, 1) and robust group (mFI-5, 0) on the basis of mFI-5 classification. The primary outcome was postoperative 1-year all-cause mortality. Secondary outcomes were postoperative pneumonia and postoperative delirium. RESULTS: Frailty group had the highest incidence of postoperative delirium (frailty 31.2% versus prefrailty 1.6% versus robust 1.5%, p < 0.001), postoperative pneumonia (frailty 23.5% versus prefrailty 7.2% versus robust 7.7%, p < 0.001), and postoperative 1-year mortality (frailty 7.0% versus prefrailty 2.2% versus robust 1.9%. p < 0.001). Frail patients have significantly longer length of hospitalization than those in the robust group and prefrail patients (p < 0.001). Multivariate analysis showed a clear link between frailty and increased risk of postoperative delirium (aOR 2.775, 95% CI 1.776-5.417, p < 0.001), postoperative pneumonia (aOR 3.291, 95% CI 2.169-4.993, p < 0.001) and postoperative 1-year mortality (aOR 3.364, 95% CI, 1.516-7.464, p = 0.003). CONCLUSIONS: mFI-5 has potential clinical utility in predicting postoperative death, delirium and pneumonia incidence in elderly patients undergoing radical lung cancer surgery. Frailty screening of patients (mFI-5) may provide benefits in risk stratification, targeted intervention efforts, and assist physicians in clinical decision-making.

Association between intraoperative mean arterial pressure variability and postoperative delirium after hip fracture surgery: a retrospective cohort study.

BACKGROUND: Postoperative delirium (POD) is a common complication in elderly patients after hip fracture surgery. Our study was to investigate whether intraoperative mean arterial pressure variability (MAPV) was associated with POD in elderly patients after hip fracture surgery. METHODS: In this retrospective cohort study, patients aged 65 years and older undergoing hip fracture surgery were included. The correlation between MAPV and POD was investigated using univariate and multivariate logistic regression. Covariate-related confounding effects were eliminated with propensity score matching (PSM) analysis. Then, a subgroup analysis was conducted to further examine the associations between MAPV and POD. RESULTS: Nine hundred sixty-three patients with a median age of 80 years (IQR: 73-84) were enrolled. POD occurred in 115/963 (11.9%) patients within 7 days after surgery. According to multivariate regression analysis, MAPV > 2.17 was associated with an increased risk of POD (OR: 2.379, 95% CI: 1.496-3.771, P < 0.001). All covariates between the two groups were well balanced after PSM adjustment. A significant correlation between MAPV and POD was found in the PSM analysis (OR: 2.851, 95% CI: 1.710-4.746, P < 0.001). CONCLUSIONS: An increased intraoperative MAPV may be a predictor for POD.

The modified lymphocyte C-reactive protein score is a promising indicator for predicting 3-year mortality in elderly patients with intertrochanteric fractures.

BACKGROUND: Hip fractures are common in elderly patients, and almost all the patients undergo surgery. This study aimed to develop a novel modified lymphocyte C-reactive protein (CRP) score (mLCS) to simply and conveniently predict 3-year mortality in elderly patients undergoing intertrochanteric fracture surgery. METHODS: A retrospective study was conducted on elderly patients who underwent intertrochanteric fracture surgery between January 2014 and December 2017. The mLCS was developed according to the value of CRP and lymphocyte counts. Univariate and multivariate Cox regression analyses were used to identify independent risk factors for 3-year mortality after surgery. The performances of the lymphocyte CRP score (LCS) and mLCS to predict 3-year mortality were then compared using C-statistics, decision curve analysis (DCA), net reclassification index (NRI) and integrated discrimination improvement (IDI). RESULTS: A total of 291 patients were enrolled, of whom 52 (17.9%) died within 3 years after surgery. In the multivariate Cox regression analysis, mLCS (hazard ratio (HR), 5.415; 95% confidence interval (CI), 1.743-16.822; P = 0.003) was significantly associated with postoperative 3-year mortality. The C-statistics of LCS and mLCS for predicting 3-year mortality were 0.644 and 0.686, respectively. The NRI (mLCS vs. LCS, 0.018) and IDI (mLCS vs. LCS, 0.017) indicated that the mLCS performed better than the LCS. DCA also showed that mLCS had a higher clinical net benefit. CONCLUSIONS: mLCS is a promising predictor that can simply and conveniently predict 3-year mortality in elderly patients undergoing intertrochanteric fracture surgery.

Prognostic Nutritional Index (PNI) as a potential predictor and intervention target for perioperative ischemic stroke: a retrospective cohort study.

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.

The complexity analysis of cerebral oxygen saturation during pneumoperitoneum and Trendelenburg position: a retrospective cohort study.

BACKGROUND: The human brain is a highly complex and nonlinear system, nonlinear complexity measures such as approximate entropy (ApEn) and sample entropy (SampEn) can better reveal characteristics of brain dynamics. However, no studies report complexity of perioperative physiological signals to reveal how brain complexity associates with age, varies along with the development of surgery and postoperative neurological complications. AIM: This study examined the complexity of intraoperative regional cerebral oxygen saturation (rSO2), aiming to reveal brain dynamics during surgery. METHODS: This retrospective cohort study enrolled patients who scheduled for robot-assisted urological surgery. Intraoperative rSO2 was continuously monitored throughout the surgery. Postoperative delirium (POD) was diagnosed by the Confusion Assessment Method. ApEn and SampEn were used to characterize the complexity of rSO2. Pearson correlation coefficients were used to measure the correlation between complexity of rSO2 and age. The association between complexity of rSO2 and POD was examined using T tests. RESULTS: A total of 68 patients (mean [SD] age, 63.0 (12.0) years; 47 (69.1%) males) were include in this analysis. There was a significant reverse relationship between the complexity of rSO2 and age (The correlation coefficients range between - 0.32 and - 0.28, all p < 0.05). Patients ≥ 75 years showed significantly lower complexity of rSO2 than the other two groups. Older age remained an independent factor influencing complexity of rSO2 after adjusting for a number of covariates. Six patients (8.8%) developed POD, and POD patients had lower complexity of rSO2 compared with non-POD patients. CONCLUSIONS: The complexity of rSO2 may serve as a new candidate marker of aging and POD prediction.

Individualised positive end-expiratory pressure titrated intra-operatively by electrical impedance tomography optimises pulmonary mechanics and reduces postoperative atelectasis: A randomised controlled trial.

BACKGROUND: A protective intra-operative lung ventilation strategy has been widely recommended for laparoscopic surgery. However, there is no consensus regarding the optimal level of positive end-expiratory pressure (PEEP) and its effects during pneumoperitoneum. Electrical impedance tomography (EIT) has recently been introduced as a bedside tool to monitor lung ventilation in real-time. OBJECTIVE: We hypothesised that individually titrated EIT-PEEP adjusted to the surgical intervention would improve respiratory mechanics during and after surgery. DESIGN: Randomised controlled trial. SETTING: First Medical Centre of Chinese PLA General Hospital, Beijing. PATIENTS: Seventy-five patients undergoing robotic-assisted laparoscopic hepatobiliary and pancreatic surgery under general anaesthesia. INTERVENTIONS: Patients were randomly assigned 2 : 1 to individualised EIT-titrated PEEP (PEEPEIT; n = 50) or traditional PEEP 5 cmH2O (PEEP5 cmH2O; n = 25). The PEEPEIT group received individually titrated EIT-PEEP during pneumoperitoneum. The PEEP5 cmH2O group received PEEP of 5 cmH2O during pneumoperitoneum. MAIN OUTCOME MEASURES: The primary outcome was respiratory system compliance during laparoscopic surgery. Secondary outcomes were individualised PEEP levels, oxygenation, respiratory and haemodynamic status, and occurrence of postoperative pulmonary complications (PPCs) within 7 days. RESULTS: Compared with PEEP5 cmH2O, patients who received PEEPEIT had higher respiratory system compliance (mean values during surgery of 44.3 ±â€Š11.3 vs. 31.9 ±â€Š6.6, ml cmH2O-1; P < 0.001), lower driving pressure (11.5 ±â€Š2.1 vs. 14.0 ±â€Š2.4 cmH2O; P < 0.001), better oxygenation (mean PaO2/FiO2 427.5 ±â€Š28.6 vs. 366.8 ±â€Š36.4; P = 0.003), and less postoperative atelectasis (19.4 ±â€Š1.6 vs. 46.3 ±â€Š14.8 g of lung tissue mass; P = 0.003). Haemodynamic values did not differ significantly between the groups. No adverse effects were observed during surgery. CONCLUSION: Individualised PEEP by EIT may improve intra-operative pulmonary mechanics and oxygenation without impairing haemodynamic stability, and decrease postoperative atelectasis. TRIAL REGISTRATION: Chinese Clinical Trial Registry (www.chictr.org.cn) identifier: ChiCTR2100045166.

The immunometabolite S-2-hydroxyglutarate exacerbates perioperative ischemic brain injury and cognitive dysfunction by enhancing CD8+ T lymphocyte-mediated neurotoxicity.

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.

Preoperative Anxiety in Chinese Adult Patients Undergoing Elective Surgeries: A Multicenter Cross-Sectional Study.

BACKGROUND: Preoperative anxiety is associated with increased use of anesthetics and poorer postoperative outcomes. However, the prevalence of preoperative anxiety has not been characterized in Chinese patients. In this study, we aimed to estimate the overall prevalence of preoperative anxiety in Chinese adult patients and to explore the sociodemographic and clinical factors associated with preoperative anxiety in China. METHODS: This study was a multicenter cross-sectional study conducted at 32 tertiary referral centers in China from September 1 to October 31, 2020. Adult patients scheduled for elective surgery were evaluated by the 7-item Perioperative Anxiety Scale (PAS-7) for preoperative anxiety after entrance to the operating zone. RESULTS: A total of 5191 patients were recruited, and 5018 of them were analyzed. The prevalence of preoperative anxiety measured by PAS-7 was 15.8% (95% CI 14.8 to 16.9%). Multivariable analyses showed female sex, younger age, non-retired, first in a lifetime surgery, surgery of higher risk, and poorer preoperative sleep were associated with higher prevalence of preoperative anxiety. CONCLUSIONS: Preoperative anxiety was relatively common (prevalence of 15.8%) among adult Chinese patients undergoing elective surgeries. Further studies are needed using suitable assessment tools to better characterize preoperative anxiety, and additional focus should be placed on perioperative education and intervention, especially in primary hospitals. TRIAL REGISTRATION: This study was registered prospectively at www.chictr.org.cn (ChiCTR1900027639) on November 22, 2019.

Systemic immune-inflammation index predicts postoperative delirium in elderly patients after surgery: a retrospective cohort study.

BACKGROUND: Postoperative delirium (POD) is a common complication among elderly patients after surgery. It is unclear whether the systemic immune-inflammation index (SII) can be a predictor of POD. We explored the prognostic value of the SII in predicting POD in elderly patients undergoing non-neurosurgery and non-cardiac surgery in a large retrospective cohort. METHODS: We enrolled elderly patients undergoing non-neurosurgery and non-cardiac surgery between January 2014 and August 2019. Univariate and multivariate logistic regression analyses were performed to explore the correlation between POD and the SII value as both a continuous and categorical variable. Then, propensity score matching (PSM) analysis was applied to eliminate the confounding effect of covariates and prove our results. Subgroup analyses were then performed to discover the association between the SII and POD in different subgroups. RESULTS: A total of 29,608 patients with a median age of 70 years (IQR: 67-74) were enrolled in the retrospective cohort. The cut-off value of the SII was 650, which was determined by the receiver operating characteristic (ROC) curve. The ORs of an SII value > 650 was 2.709 (95% CI:2.373-3.092, P < 0.001), 1.615 (95% CI:1.384-1.882, P < 0.001), 1.855 (95% CI:1.602-2.146, P < 0.001), and 1.302 (95% CI:1.106-1.531, P = 0.001) for prediction of POD in univariate model and three multivariate regression models. After PSM, the OR of an SII value > 650 was 1.301 (95% CI: 1.062-1.598, P = 0.011). The subgroup analysis indicated that the SII indicates a significantly increased risk of POD in patients with Hb < 130 g/L, 4*109/L < WBC ≤ 10*109/L, albumin < 39 g/L, or duration of MAP < 60 mmHg ≥ 5 min. The SII was found to be a useful prognostic predictor of POD for patients of different ages, sexes, and ASA classifications. CONCLUSIONS: The SII had a predictive value for POD in patients undergoing non-neurosurgery and non-cardiac surgery. As an index generated from routine blood tests, the SII has advantages regarding cost and time. After further validation, the SII may provide a new option for POD prediction.

Comparison of propofol-nalbuphine and propofol-fentanyl sedation for patients undergoing endoscopic retrograde cholangiopancreatography: a double-blind, randomized controlled trial.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) has been increasingly used to treat patients with biliary/pancreatic duct obstruction or stricture outside the operating room. Effective and safe sedation techniques are needed because of painful stimuli and the long duration of the ERCP procedure.Nalbuphine has been shown to cause less respiratory depression during sedation than similar cases without nalbuphine. This study compared the effects of propofol-nalbuphine (PN) and propofol-fentanyl (PF) sedation in patients undergoing ERCP. METHODS: Four hundred patients scheduled for ERCP procedures were divided into two groups: the PF group (receiving PF sedation,n = 199) and the PN group (receiving PN sedation,n = 201). Vital signs, adverse events during surgery, patient movement scores, pain scores, and adverse events one day post-ERCP were recorded. RESULTS: Stable haemodynamics were observed in both groups.Compared to the PF group, the PN group showed significantly decreased respiratory depression (P < 0.0001) and surgical interruptions (P = 0.048).Nalbuphine decreased patient movement by reducing pain from ERCP. CONCLUSION: Nalbuphine, instead of fentanyl, precipitated less respiratory depression while permitting adequate/equivalent sedation for ERCP and therefore provides more efficient and safer sedation. Trial registration ChiCTR, ChiCTR1800016018, Registered 7 May 2018, http://www.chictr.org.cn/showproj.aspx?proj=27085.

Development and validation of a risk nomogram for postoperative acute kidney injury in older patients undergoing liver resection: a pilot study.

BACKGROUND: Postoperative acute kidney injury (AKI) is associated with poor clinical outcomes. Early identification of high-risk patients of developing postoperative AKI can optimize perioperative renal management and facilitate patient survival. The present study aims to develop and validate a nomogram to predict postoperative AKI after liver resection in older patients. METHODS: A retrospective observational study was conducted involving data from 843 older patients scheduled for liver resection at a single tertiary high caseload general hospital between 2012 and 2019. The data were randomly divided into training (70%, n = 599) and validation (30%, n = 244) datasets. The training cohort was used to construct a predictive nomogram for postoperative AKI with the logistic regression model which was confirmed by a validation cohort. The model was evaluated by receiver operating characteristic (ROC) curve, calibration plot, and decision curve analysis in the validation cohort. A summary risk score was also constructed for identifying postoperative AKI patients. RESULTS: Postoperative AKI occurred in 155 (18.4%) patients and was highly associated with in-hospital mortality (5.2% vs. 0.7%, P <  0.001). The six predictors selected and assembled into the nomogram included age, preexisting chronic kidney disease (CKD), non-steroidal anti-inflammatory drugs (NSAIDs) usage, intraoperative hepatic inflow occlusion, blood loss, and transfusion. The predictive nomogram performed well in terms of discrimination with area under ROC curve (AUC) in training (0.73, 95% confidence interval (CI): 0.68-0.78) and validation (0.71, 95% CI: 0.63-0.80) datasets. The nomogram was well-calibrated with the Hosmer-Lemeshow chi-square value of 9.68 (P = 0.47). Decision curve analysis demonstrated a significant clinical benefit. The summary risk score calculated as the sum of points from the six variables (one point for each variable) performed as well as the nomogram in identifying the risk of AKI (AUC 0.71, 95% CI: 0.66-0.76). CONCLUSION: This nomogram and summary risk score accurately predicted postoperative AKI using six clinically accessible variables, with potential application in facilitating the optimized perioperative renal management in older patients undergoing liver resection. TRIAL REGISTRATION: NCT04922866 , retrospectively registered on clinicaltrials.gov on June 11, 2021.

Does propofol definitely improve postoperative cognitive dysfunction?-a review of propofol-related cognitive impairment.

Postoperative cognitive dysfunction (POCD) is a common brain function-related complication after surgery. In addition to old age being an independent risk factor, anesthetics are also important predisposing factors. Among them, propofol is the most commonly used intravenous anesthetic in clinical practice. It has a rapid onset, short half-life, and high recovery quality. Many studies report that propofol can attenuate surgery-induced cognitive impairment, however, some other studies reveal that propofol also induces cognitive dysfunction. Therefore, this review summarizes the effects of propofol on the cognition, and discusses possible related mechanisms, which aims to provide some evidence for the follow-up studies.

Rapid determination and continuous monitoring of propofol in microliter whole blood sample during anesthesia by paper spray ionization-mass spectrometry.

Propofol is a widely used intravenous anesthetic agent in sedation and general anesthesia. To improve the safety and maintain the depth of anesthesia, it is important to develop a rapid, sensitive, and reliable method to monitor the concentration of propofol in blood during anesthesia continuously. Here, we present a novel strategy based on paper spray ionization-mass spectrometry (PSI-MS) to detect propofol. Samples (in 10 µL) were mixed with methanol as protein precipitation solvent and 2,6-dimethylphenol as internal standard. Protein micro-precipitation was achieved with methanol by vortexing and centrifuging for 5 s each, and propofol was extracted to the supernatant. PSI-MS was performed in negative ionization mode, and MS signal lasted for 1 min. The analysis of a single sample was completed within 2 min. The area ratios of propofol to internal standard were calculated for quantification. Limit of detection of 5.5 ng mL-1 and limit of quantification of 18.2 ng mL-1 were achieved for propofol in whole blood. Calibration curve was linear in the range of 0.02-10 µg mL-1. The developed method was used successfully in monitoring the propofol concentration in 3 patients' whole blood during anesthesia, showing its further application in controlling and feeding-back target concentration infusion. Graphical abstract.