The Role of the Intestinal Flora and Its Derivatives in Neurocognitive Disorders: A Narrative Review from Surgical Perspective.

Perioperative neurocognitive dysfunction is a significant concern for population health, impacting postoperative recovery and increasing the financial burden on patients. With an increasing number of surgical procedures being performed, the prevention and management of perioperative neurocognitive dysfunction have garnered significant attention. While factors such as age, lifestyle, genetics, and education are known to influence the development of cognitive dysfunction, recent research has highlighted the role of the gut microbiota in neurological health. An increased abundance of pro-inflammatory gut microbiota can trigger and worsen neuroinflammation, neuronal cell damage, and impaired cellular autophagy. Moreover, the inflammation-promoting gut microbiota can disrupt immune function, impair neuroautophagy, and affect the production and circulation of extracellular vesicles and neurotransmitters. These factors collectively play a role in the onset and advancement of cognitive impairment. This narrative review delves into the molecular mechanisms through which gut microbiota and their derivatives contribute to cognitive impairment, focusing on the impact of anesthesia surgery, changes in gut microbial populations, and perioperative cognitive impairment associations. The study suggests that alterations in the abundance of various bacterial species and their metabolites pre- and post-surgery may be linked to postoperative cognitive impairment. Furthermore, the potential of probiotics or prebiotics in addressing cognitive impairment is discussed, offering a promising avenue for investigating the treatment of perioperative neurocognitive disorders.

Effects of different anesthetic regimens on postoperative cognitive function of elderly patients undergoing thoracic surgery: a double-blinded randomized controlled trial.

OBJECTIVE: Postoperative cognitive dysfunction (POCD) is a serious surgical complication. We assessed the different POCD incidences between anesthesia using sevoflurane and sevoflurane combined with dexmedetomidine, with propofol-based sedation in elderly patients who underwent a thoracic surgical procedure. METHODS: A total of 90 patients aged 65 to 80 years old who underwent a thoracic surgical procedure at our hospital and 15 nonsurgical participants as controls, were enrolled in this study. Patients were divided in a randomized 1:1:1 ratio into 3 groups. All participants were randomized into a trial with three anesthesia groups (P, PS, PSD) or a control group (C) of healthy matches. All trial groups received distinct anesthetic combinations during surgery, while controls mirrored patient criteria.Group P (propofol and remifentanil were maintained during the surgery), Group PS (propofol, remifentanil, and sevoflurane were maintained during the surgery), and Group PSD (propofol, remifentanil, sevoflurane, and dexmedetomidine were maintained during the surgery).All participants were rated using a series of cognitive assessment scales before and three days after surgery. All participants were interviewed over the telephone, 7 days, 30 days, and 90 days postoperatively. RESULTS: POCD incidences in the PSD (combined anesthetization with propofol, sevoflurane, and dexmedetomidine) group was significantly lower than that in the PS (combined anesthetization with propofol and sevoflurane) group, 1 day post-surgery (10.0% vs. 40.0%, P = 0.008), and the results were consistent at 3 days post-surgery. When the patients were assessed 7 days, 30 days, and 90 days postoperatively, there was no significant difference in POCD incidence among the three groups. Multivariate logistic regression analysis of POCD one day after surgery showed that education level was negatively correlated with incidence of POCD (P = 0.018) and single lung ventilation time was positively correlated with incidence of POCD (P = 0.001). CONCLUSION: For elderly patients who underwent a thoracic surgical procedure, dexmedetomidine sedation shows an obvious advantage on improving short-term POCD incidence, which is caused by sevoflurane.

Postoperative Cognitive Decline in Patients Undergoing Major Gynecologic Oncology Surgery: A Pilot Prospective Study.

OBJECTIVES: Postoperative cognitive decline (POCD) is characterised by deficits in attention, memory, executive function, and information processing that persist beyond the early postoperative period. Its incidence ranges from 10%-25% after noncardiac surgery. Limited literature exists on POCD after gynecologic oncology surgery. Our primary objective was to identify the incidence of POCD among patients 55 years or older undergoing major gynecologic oncology surgery. METHODS: This mixed-methods, prospective, observational cohort study followed patients 55 years or older who underwent surgery for gynecologic malignancies between February and July 2022. Semi-structured interviews and the Mini-Mental State Exam (MMSE) were administered before surgery as well as 1 and 3 months after. Assessments were delivered virtually and in-person in the context of the COVID-19 pandemic. POCD was defined as ≥2-point decline from baseline MMSE score. RESULTS: Twenty-four patients participated; 19 completed the 1-month follow-up, and 15 completed the 3-month follow-up. The average age was 64 (range: 56-90). The mean preoperative MMSE score was 16.6 out of 17 (virtual) and 12.9 out of 13 (in-person). Two patients had a 1-point decline in their 1-month MMSE score; both recovered by 3 months. One patient had a 1-point decline in their 3-month MMSE score. Semi-structured interviews revealed common themes of "brain fog" at the 1-month follow-up and mild, persistent attention and word-finding deficits at 3 months postoperatively. CONCLUSIONS: This study's qualitative component captured subtle subjective findings suggestive of potential POCD. Larger studies are required, and a more extensive neuropsychological test battery may be required to elicit subtle findings not clearly reflected by MMSE scores.

Intraoperative Dexmedetomidine for Prevention of Postoperative Cognitive Dysfunction and Delirium in Elderly Patients with Lobectomy: A Propensity Score-Matched, Retrospective Study.

Purpose: This study aims to investigate whether dexmedetomidine could prevent postoperative cognitive dysfunction and delirium in patients with lobectomy. Patients and Methods: Patients with lung cancer who underwent thoracoscopic lobectomy under general anesthesia were enrolled in this study and divided into dexmedetomidine group or control group. Propensity-score match (PSM) was used to reduce the bias and imbalance of confounding variables. After PSM, 87 patients in each group were included. Primary outcomes were postoperative cognitive function and delirium. Secondary outcomes include plasma TNF-α, IL-6, and S100 ß protein concentrations. Adverse events were also collected. Results: There were no significant differences in the demographic characteristics and hemodynamic parameters between the two groups. Compared with the control group, the MoCA scores were significantly higher (P<0.01), while the incidence of delirium (P<0.01) and the plasma TNF-α (P<0.01), IL-6 (P<0.01), and S100 ß protein (P<0.01) concentrations were significantly lower in the dexmedetomidine group at 7 days post-operatively. The incidences of adverse events were similar between the two groups. Conclusion: Dexmedetomidine could prevent postoperative cognitive dysfunction and delirium in patients with lobectomy by decreasing neuroinflammation.

Risk Factors for Postoperative Cognitive Decline After Orthopedic Surgery in Elderly Chinese Patients: A Retrospective Cohort Study.

Purpose: We aimed to identify the risk factors for postoperative cognitive decline (POCD) by evaluating the outcomes from preoperative comprehensive geriatric assessment (CGA) and intraoperative anesthetic interventions. Patients and Methods: Data used in the study were obtained from the Aged Patient Perioperative Longitudinal Evaluation-Multidisciplinary Trial (APPLE-MDT) cohort recruited from the Department of Orthopedics in Xuanwu Hospital, Capital Medical University between March, 2019 and June, 2022. All patients accepted preoperative CGA by the multidisciplinary team using 13 common scales across 15 domains reflecting the multi-organ functions. The variables included demographic data, scales in CGA, comorbidities, laboratory tests and intraoperative anesthetic data. Cognitive function was assessed by Montreal Cognitive Assessment scale within 48 hours after admission and after surgery. Dropping of ≥1 point between the preoperative and postoperative scale was defined as POCD. Results: We enrolled 119 patients. The median age was 80.00 years [IQR, 77.00, 82.00] and 68 patients (57.1%) were female. Forty-two patients (35.3%) developed POCD. Three cognitive domains including calculation (P = 0.046), recall (P = 0.047) and attention (P = 0.007) were significantly worsened after surgery. Univariate analysis showed that disability of instrumental activity of daily living, incidence rate of postoperative respiratory failure (PRF) ≥4.2%, STOP-Bang scale score, Caprini risk scale score and Sufentanil for maintenance of anesthesia were different between the POCD and non-POCD patients. In the multivariable logistic regression analysis, PRF ≥ 4.2% (odds ratio [OR] = 2.343; 95% confidence interval [CI]: 1.028-5.551; P = 0.046) and Sufentanil for maintenance of anesthesia (OR = 0.260; 95% CI: 0.057-0.859; P = 0.044) was independently associated with POCD as risk and protective factors, respectively. Conclusion: Our study suggests that POCD is frequent among older patients undergoing elective orthopedic surgery, in which decline of calculation, recall and attention was predominant. Preoperative comprehensive geriatric assessments are important to identify the high-risk individuals of POCD.

Efficacy of Supplemental Ultrasound-Guided Pericapsular Nerve Group (PENG) Block Combined with Lateral Femoral Cutaneous Nerve Block in Patients Receiving Local Infiltration Analgesia after Hip Fracture Surgery: A Prospective Randomized Controlled Trial.

Background and Objectives: Local infiltration analgesia (LIA) represents a potential approach to reducing pain in patients undergoing total hip arthroplasty (THA). The pericapsular nerve group (PENG) block also provides adequate analgesia for fractures and THA. As most hip surgeries use a lateral incision, affecting the cutaneous supply by branches of the lateral femoral cutaneous nerve (LFCN), the LFCN block can contribute to postoperative analgesia. However, no studies have investigated the effectiveness of supplemental PENG block combined with LFCN block in patients undergoing LIA after hip fracture surgery. Our study aimed to assess the effectiveness of PENG combined with LFCN block following hip fracture surgery in patients who underwent LIA. Materials and Methods: Forty-six patients were randomly assigned to LIA or PENG + LFCN + LIA groups. The primary outcome was the pain score at rest and during movement at 2, 6, 12, 24, and 48 h postoperatively. The total opioid dose for postoperative analgesia was also measured at the same time points. Secondary outcomes included postoperative cognitive function assessment. Results: The median pain scores at rest and during movement were lower in the PENG + LFCN + LIA group throughout the study periods compared to the LIA group, except at 2 h (at rest) and 48 h (during movement) after surgery. The total fentanyl dose was lower in the PENG + LFCN + LIA group at all time points after surgery when compared to the LIA group. Postoperative delirium incidence and the median abbreviated mental test scores were not significantly different between the two groups. Conclusions: The combination of PENG and LFCN blocks may contribute to enhanced recovery for patients undergoing LIA after hip fracture surgery. However, further well-controlled research is necessary to determine the effectiveness of supplemental PENG combined with LFCN block in addressing cognitive deficits in these patients.

Comparing analog and digital neurocognitive tests with older adults: a study of the ISPOCD battery vs. a digital test battery from Mindmore.

BACKGROUND: Delayed neurocognitive recovery and neurocognitive disorder are common postoperative complications among older adults. The assessment of these complications traditionally relies on analog neurocognitive tests, predominantly using the test battery from the ISPOCD-study as the standard approach. However, analog tests are time-consuming and necessitate trained staff which poses limitations. The potential availability of a digital neurocognitive test as an alternative to the ISPOCD remains unknown. We conducted a comparative study between the analog test battery from ISPOCD and the self-administrated digital test battery developed by Mindmore. METHODS: We conducted a crossover study with 50 cognitively healthy older adults ≥ 60 years of age recruited in Stockholm Sweden, between February and April 2022. The primary outcome focused on measuring comparability between the two test batteries. Our secondary outcomes included assessing participants' perceptions and attitudes about the tests with qualitative interviews and their usability experiences. RESULTS: Fifty older adults, mean age 76, female 56%, with a university or college degree 48% participated in the study. The sub tests in two test batteries demonstrated a medium-large correlation (r = 0.3-0.5), except for one measure. For four out of six measures, significant differences were found with medium to large effect sizes, ranging from 0.57-1.43. Two categories were recognized in the qualitative analysis: self-competing in a safe environment, and experience with technology. Participants expressed feeling safe and at ease during the assessment, with some preferring the digital test over the analog. Participants reported a high level of usability with the digital test and a majority participants (n = 47) reported they would undergo the digital test for a potential future surgery. CONCLUSIONS: The digital test battery developed by Mindmore offers several advantages, including rapid access to test results, easy comprehension, and use for participants, thereby increased accessibility of cognitive screening. TRIAL REGISTRATION NUMBER: NCT05253612; ClinicalTrials.gov, 24/02/2022.

Preoperative mild cognitive impairment as a risk factor of postoperative cognitive dysfunction in elderly patients undergoing spine surgery.

Introduction: Any persistent degree of cognitive impairment in older adults is a concern as it can progress to dementia. This study aimed to determine the incidence and risk factors for early postoperative cognitive dysfunction (POCD) in elderly patients undergoing spine surgery. Methods: Patients were enrolled from a previous prospective observational study after screening for normal cognitive function using the Mini Mental State Examination (MMSE). Cognitive function was evaluated before surgery and at 1 week, month, and year post-surgery using MMSE and Montreal Cognitive Assessment scores (MoCA). Mild cognitive impairment (MCI) was determined using the MoCA scores adjusted for age. POCD was defined as a drop of three or more points on the MMSE 1 week post-surgery. Multivariate logistic analysis was performed to identify POCD risk factors. Results: A total of 427 patients were included. Eighty-five (20%) had pre-existing MCI. The MCI group showed lower MoCA scores at each time point (baseline, 1 week after surgery, 1 month after surgery, 1 year after surgery) compared to the non-MCI group. Those in the MCI group had a higher rate of admission to intensive care unit after surgery, postoperative delirium, and POCD 1 week post-surgery, than those in the non-MCI group (16.5% vs. 6.7%, p = 0.008; 27.1% vs. 15.8%, p = 0.024; and 18.8% vs. 8.2%, p < 0.001, respectively). Among them, 10.3% were assessed for POCD on postoperative day 7 and self-reported poor social roles and physical functioning 1 week postoperatively. Conclusion: Preoperative MCI was seen in ~20% of surgical patients aged >70 years. POCD was seen in ~20% of patients with pre-existing MCI, and ~ 10% of those without. Benzodiazepine use, significant comorbidities, pre-existing MCI, and depressive tendencies were risk factors for POCD.

Comparison of Volatile Anesthetics Versus Propofol on Postoperative Cognitive Function After Cardiac Surgery: A Systematic Review and Meta-analysis.

OBJECTIVE: To compare the effects of volatile anesthetics and propofol on neurocognitive function after cardiac surgery. DESIGN: A systematic review and meta-analysis of randomized controlled trials. SETTING: A literature search of PubMed, EMBASE, CENTRAL, CINAHL, Scopus, and Web of Science databases was conducted. PARTICIPANTS: A total of 10 randomized controlled trials comparing volatile anesthetics and propofol in cardiac surgery were included in the study. INTERVENTIONS: The standardized mean difference and risk ratio were calculated to estimate pooled effect sizes. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the postoperative neurocognitive function score, and the secondary outcome was the incidence of delirium after cardiac surgery. The analysis did not show significant differences in postoperative neurocognitive function scores (standardized mean difference -0.06, 95% CI -0.81-0.69; p = 0.879). The incidences of delirium (risk ratio 1.10, 95% CI 0.81-1.50) between the volatile anesthetics and propofol groups were not significant (p = 0.533). CONCLUSIONS: Unlike noncardiac surgery, there are no differences between volatile anesthetics and propofol regarding postoperative neurocognitive dysfunction after cardiac surgery.

The Effect of Dexmedetomidine on the Mini-Cog Score and High-Mobility Group Box 1 Levels in Elderly Patients with Postoperative Neurocognitive Disorders Undergoing Orthopedic Surgery.

Dexmedetomidine prevents postoperative cognitive dysfunction by inhibiting high-mobility group box 1 (HMGB1), which acts as an inflammatory marker. This study investigated the HMGB1 levels and the cognitive function using a Mini-Cog© score in elderly patients undergoing orthopedic surgery with dexmedetomidine infusion. In total, 128 patients aged ≥ 65 years were analyzed. The patients received saline in the control group and dexmedetomidine in the dexmedetomidine group until the end of surgery. Blood sampling and the Mini-Cog© test were performed before the surgery and on postoperative days 1 and 3. The primary outcomes were the effect of dexmedetomidine on the HMGB1 levels and the Mini-Cog© score in terms of postoperative cognitive function. The Mini-Cog© score over time differed significantly between the groups (p = 0.008), with an increase in the dexmedetomidine group. The postoperative HMGB1 levels increased over time in both groups; however, there was no significant difference between the groups (p = 0.969). The probability of perioperative neurocognitive disorders decreased by 0.48 times as the Mini-Cog© score on postoperative day 3 increased by 1 point. Intraoperative dexmedetomidine has shown an increase in the postoperative Mini-Cog© score. Thus, the Mini-Cog© score is a potential tool for evaluating cognitive function in elderly patients.

Association between Preoperative Hand Grip Strength and Postoperative Delirium after Cardiovascular Surgery: A Retrospective Study.

The association of frailty with postoperative delirium has not been fully investigated in patients undergoing cardiovascular surgery. Therefore, this study aimed to investigate whether preoperative hand grip strength is associated with postoperative delirium. This retrospective study included patients aged >65 years who had undergone elective cardiovascular surgery using cardiopulmonary bypass at a Japanese university hospital between April 2020 and February 2022. We defined low hand grip strength as hand grip values of <275 n and <177 n for men and women, respectively. Postoperative delirium was assessed using the confusion assessment method during patients' intensive care unit stay. The odds ratio of low hand grip strength for postoperative delirium was estimated using multiple logistic analysis, which was adjusted for prominent clinical factors. Ninety-five patients with a median age of 74 years were included in the final analysis, and 31.5% of them had low hand grip strength. Postoperative delirium occurred in 37% of patients, and the odds ratio of low preoperative hand grip strength for postoperative delirium was 4.58 (95% confidence interval: 1.57-13.2). Thirty-seven patients experienced postoperative delirium after cardiovascular surgery using cardiopulmonary bypass, and low preoperative hand grip strength was positively associated with its occurrence.

Effectiveness of cognitive interventions for adult surgical patients after general anaesthesia to improve cognitive functioning: A systematic review.

AIMS AND OBJECTIVES: To examine the effectiveness of cognitive interventions after general anaesthesia to improve cognitive functioning. BACKGROUND: The number of surgical procedures performed worldwide is large and growing. Postoperative cognitive dysfunction is a common complication associated with poor postoperative outcomes. A variety of cognitive interventions have been developed to maintain or improve cognitive function in one or more cognitive domains. Cognitive interventions have shown to be effective in healthy older populations, those with mild cognitive impairment, and those with heart failure. The impact of cognitive interventions in surgical patients after general anaesthesia is a relatively new focus of research and is therefore less well established. METHODS: Seven bibliographic databases were searched in relation to 'surgery' and 'cognitive interventions'; no date or language limits were imposed. Studies including adult patients who were scheduled for, or who had undergone surgery under general anaesthesia, had a baseline cognitive assessment using a validated measurement, and had engaged with any cognition-based intervention were included. Full-text review for inclusion, quality assessment and data extraction were undertaken independently by two authors. This study is reported in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. RESULTS: A total of 550 papers were identified for possible inclusion, of which nine met the inclusion criteria and were included in the review. The majority were randomised controlled trials (RCTs) (n = 6 [66.7%]). Four studies used computerised cognitive interventions, while five used traditional cognitive interventions. Most of the studies used multi-domain cognitive training focusing on two or more domains (n = 7 [77.8%]) while two studies used single-domain cognitive training. Memory (n = 7 [77.8%]) and attention (n = 5 [55.6%]) were the cognitive domains most often targeted during the intervention. CONCLUSIONS: The use of cognitive interventions demonstrated some efficacy in improving cognitive function after general anaesthesia, particularly those targeting memory. RELEVANCE FOR CLINICAL PRACTICE: The findings of this review suggest that cognitive interventions show promise at improving cognitive performance in patients with POCD and could be usefully implemented in clinical practice to improve patient outcomes.

Dose-dependent relationship between intra-procedural hypoxaemia or hypocapnia and postoperative delirium in older patients.

BACKGROUND: Previous studies indicated an association between impaired cerebral perfusion and post-procedural neurological disorders. We investigated whether intra-procedural hypoxaemia or hypocapnia are associated with delirium after surgery. METHODS: Inpatients ≥60 yr of age undergoing anaesthesia for surgical or interventional procedures between 2009 and 2020 at an academic healthcare network in the USA (Massachusetts) were included in this hospital registry study. The primary exposure was intra-procedural hypoxaemia, defined as peripheral oxygen saturation <90% for >2 cohering min. The co-primary exposure was hypocapnia during general anaesthesia, defined as end-tidal carbon dioxide pressure ≤25 mm Hg for >5 cohering min. The primary outcome was delirium within 7 days after surgery. RESULTS: Of 71 717 included patients, 1702 (2.4%) developed postoperative delirium, and hypoxaemia was detected in 2532 (3.5%). Of 42 894 patients undergoing general anaesthesia, 532 (1.2%) experienced hypocapnia. The occurrence of either hypoxaemia (adjusted odds ratio [ORadj]=1.71; 95% confidence interval [CI], 1.40-2.07; P<0.001) or hypocapnia (ORadj=1.77; 95% CI, 1.30-2.41; P<0.001) was associated with a higher risk of delirium within 7 days. Both associations were dependent on the magnitude, and increased with event duration (ORadj=1.03; 95% CI, 1.02-1.04; P<0.001 and ORadj=1.01; 95% CI, 1.00-1.01; P=0.005, for each minute increase in the longest continuous episode, respectively). There was no association between occurrence of hypercapnia and postoperative delirium (ORadj=1.24; 95% CI, 0.90-1.71; P=0.181). CONCLUSIONS: Intra-procedural hypoxaemia and hypocapnia were dose-dependently associated with a higher risk of postoperative delirium. These findings support maintaining normal gas exchange to avoid postoperative neurological disorders.

Role of PI3K/Akt/mTOR signaling pathway in edaravone-induced reduction of postoperative cognitive dysfunction in aged rats / 中华麻醉学杂志

Objective:To evaluate the role of phosphatidylinositol 3-kinase (PI3K)/serine threonine protein kinase (Akt)/mammalian rapamycin target protein (mTOR) signaling pathway in edaravone-induced reduction of postoperative cognitive dysfunction in aged rats.Methods:Sixty healthy male Sprague-Dawley rats, aged 20 months, weighing 600-700 g, were divided into 4 groups ( n=15 each) using a random number table method: control group (group C), operation group (group O), edaravone group (group E) and PI3K inhibitor LY294002 group (group LY). The rats received laparotomy under 3% sevoflurane anesthesia in O, E and LY groups. Edaravone 3 mg/kg was intraperitoneally injected at 30 min before operation in E and LY groups, and LY294002 0.3 mg/kg was simultaneously injected via the tail vein in group LY. Open field test was performed at 3 days after surgery to evaluate the spontaneous activity of rats, then Morris water maze test was performed to evaluate the cognitive function of rats. The rats were sacrificed after the end of behavioral experiment to isolate hippocampal tissues for determination of the expression of phosphorylated PI3K (p-PI3K), phosphorylated Akt (p-Akt), phosphorylated mTOR (p-mTOR), synaptophysin (SYP) and postsynaptic density protein 95 (PSD 95) (by Western blot ) and dendrite length in hippocampal CA1 area (using Golgi staining). The density of dendrites was calculated. Results:There were no statistically significant differences in exercise speed, distance, and time of staying at the center between the four groups ( P>0.05). Compared with group C, the escape latency was significantly prolonged, the number of crossing the original platform was reduced, the expression of p-PI3K, p-Akt, p-mTOR, SYP and PSD-95 was down-regulated, the dendritic length of neurons in hippocampal CA1 region was shortened, and the density of neurons in hippocampal CA1 region was decreased in group O ( P<0.05). Compared with group O, the escape latency was significantly shortened, the number of crossing the original platform was increased, the expression of p-PI3K, p-Akt, p-mTOR, SYP and PSD-95 was up-regulated, the dendritic length of neurons in hippocampal CA1 region was prolonged, and the density of neurons in hippocampal CA1 region was increased in group E ( P<0.05). Compared with group E, the escape latency was significantly prolonged, the number of crossing the original platform was reduced, the expression of p-PI3K, p-Akt, p-mTOR, SYP and PSD-95 was down-regulated, and the dendritic length of neurons in hippocampal CA1 region was shortened, and the density of neurons in hippocampal CA1 region was decreased in group LY ( P<0.05). Conclusions:The mechanism by which edaravone reduces postoperative cognitive dysfunction is related to activating PI3K/Akt/mTOR signaling pathway and improving synaptic plasticity in aged rats.

Risk factors for postoperative cognitive dysfunction and the predictive model in elderly patients undergoing lumbar surgery under general anesthesia / 中华麻醉学杂志

Objective:To identify the risk factors for postoperative cognitive dysfunction (POCD) and develop the prediction model in elderly patients undergoing lumbar surgery under general anesthesia.Methods:The elderly patients undergoing elective lumbar surgery under general anesthesia in our hospital from July 2021 to July 2022 were enrolled. Cognitive function was assessed at 7 days after surgery using Mini-Mental State Examination and Montreal Cognitive Assessment. When the decrease in both scales≥ 1 standard deviation, the patients were considered as having POCD. The patients were divided into POCD group and non-POCD group according to whether POCD developed. The propensity score matching was used to balance the confounding bias between two groups. The multivariate logistic regression analysis was used to identify the risk factors for POCD. The prediction model was constructed, and a nomogram was drawn for visualization of the model. The receiver operating characteristic curve, calibration plot and decision curve analysis (DCA) were drawn to evaluate the differentiation, consistency and clinical validity of the model, respectively.Results:A total of 159 patients were enrolled in this study, and the incidence of POCD was 31.4%. There were statistically significant differences in the ratio of intraoperative blood transfusion, cumulative time of hypotension, total infusion volume and operation time between two groups ( n=32 each) after propensity score matching ( P<0.05). The results of multivariate logistic regression showed that age, educational levels, diabetes mellitus, previous two or more operations under general anesthesia, APTT and cumulative time of hypotension were independent risk factors for POCD in elderly patients undergoing lumbar surgery under general anesthesia ( P<0.05). A model was developed based on the risk factors mentioned above: LogitP=-15.878+ 0.263 × Age (years) - 0.122 × Educational Level (years)+ 1.601 × Diabetes Mellitus+ 1.468 × History of General Anesthesia for 2 or more times+ 0.608 × Cumulative Time of Hypotension(min) - 0.140 × APTT (s). The area under the receiver operating characteristic curve was 0.930 (95% CI 0.887-0.973), the sensitivity was 0.920, specificity was 0.798 and Youden index was 0.718. After visualizing the model via nomogram, the model was verified by Hosmer-Lemeshow test, P=0.403, C index was 0.930, and corrected C index was 0.914. Conclusions:Age, educational levels, diabetes mellitus, previous multiple operations under general anesthesia, APTT and cumulative time of hypotension are independent risk factors for POCD in elderly patients undergoing lumbar surgery under general anesthesia, and the established risk prediction model can effectively predict the occurrence of POCD in elderly patients undergoing lumbar surgery under general anesthesia.

Effect of exosomes derived from bone mesenchymal stem cells on postoperative cognitive function and SIRT1/NF-κB signaling pathway in aged mice / 中华麻醉学杂志

Objective:To evaluate the effect of exosomes derived from bone mesenchymal stem cells (BMSCs-EXO) on the postoperative cognitive function and silent infomation regulator 1 (SIRT1)/ nuclear factor kappa B (NF-κB) signaling pathway in aged mice.Methods:BMSCs-EXO were isolated by differential centrifugation method and then identified. Twenty healthy male C57BL/6 aged mice, aged 18 months, weighing 35-40 g, were divided into 4 groups ( n=5 each) using a random number table method: sham operation group (Sham group), operation group (O group), BMSCs-EXO group and EX527 (SIRT1 inhibitor)group. The abdomen regions were shaved for sterilization without exploratory laparotomy in Sham group. Exploratory laparotomy was performed in O group. BMSCs-EXO 50 μg was injected through the tail vein at 1 h before surgery in BMSCs-EXO group. EX527 5 mg/kg was intraperitoneally injected daily at 1-3 days before surgery, and BMSCs-EXO 50 μg was injected through the tail vein at 1 h before surgery in EX527 group. Morris water maze test was used to evaluate the learning and memory ability for 5 consecutive days staring from the 1st day after surgery. Mice were sacrificed at 1 h after the end of Morris water maze test on day 5 after surgery, and the hippocampal tissues were collected for observation of the pathological changes of hippocampal CA1 region and for determination of the expression of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and IL-1β mRNA (quantitative real-time polymerase chain reaction) and SIRT1 and NF-κB p65 (by Western blot). Results:Compared with Sham group, the escape latency was significantly prolonged, the times of original platform crossing were decreased, the swimming time spent in the original platform quadrant was shortened, the expression of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and IL-1β mRNA was up-regulated, the SIRT1 expression was down-regulated, the NF-κB p65 expression was up-regulated ( P<0.05), and the pathological changes of hippocampal tissues in CA1 region were found in O group. Compared with O group, the escape latency was significantly shortened, the times of original platform crossing were increased, the swimming time spent in the original platform quadrant was prolonged, the expression of TNF-α, IL-6 and IL-1β mRNA was down-regulated, the expression of SIRT1 was up-regulated, the expression of NF-κB p65 was down-regulated ( P<0.05), and the pathological changes of hippocampal tissues in CA1 region were significantly attenuated in BMSCs-EXO group ( P<0.05). Compared with BMSCs-EXO group, the escape latency was significantly prolonged, the times of original platform crossing were decreased, the swimming time spent in the original platform quadrant was shortened, the expression of TNF-α, IL-6 and IL-1β mRNA was up-regulated, the SIRT1 expression was down-regulated, the NF-κB p65 expression was up-regulated ( P<0.05), and the pathological changes of hippocampal tissues in CA1 region were accentuated in EX527 group. Conclusions:BMSCs-EXO can improve the postoperative cognitive function in aged mice, and the mechanism may be associated with the activation of SIRT1/NF-κB signaling pathway.

Relationship between hippocampal miR-3065-5p and IGF-1/PI3K/Akt signaling pathway in a mouse model of perioperative neurocognitive disorder / 中华麻醉学杂志

Objective:To evaluate the relationship between hippocampal miR-3065-5p and insulin-like growth factor-1/phosphatidylinositol 3-kinase/protein kinase B(IGF-1/PI3K/Akt)signaling pathway in a mouse model of perioperative neurocognitive disorder (PND).Methods:Eighty clean-grade healthy male C75BL/6 mice, aged 12-14 weeks, weighing 20-30 g, were divided them into 4 groups ( n=20 each) using the random number table method: control group (C group), PND group, miR-3065-5p agonist group (Ag group) and miR-3065-5p agonist negative control group (Ag-NC group). PND model was prepared by internal fixation of tibial fracture under anesthesia with 1.5% isoflurane. Two days before developing the model, miR-3065-5p agomir 2 μl was injected into the lateral ventricle in Ag group, miR-3065-5p agomir negative control 2 μl was injected into the lateral ventricle in Ag-NC group. Morris water maze test and open field test were performed at 7 days after surgery. The mice were sacrificed after the end of test, and hippocampal tissues were obtained for determination of the expression of miR-3065-5p, IGF-1 mRNA and Bcl-2 mRNA (by quantitative real-time polymerase chain reaction) and expression of IGF-1, phosphorylated Akt (p-Akt), phosphorylated glycogen synthase kinase-3β (p-GSK3β) and Bcl-2 (by Western blot). Results:There was no significant difference in each parameter in the open field test among the four groups ( P>0.05). Compared with group C, the postoperative escape latency was significantly prolonged, the percentage of time of stay at the target quadrant was decreased, the number of crossing the original platform was reduced, the expression of miR-3065-5p was up-regulated, and the expression of IGF-1 mRNA, Bcl-2 mRNA, IGF-1, p-Akt, p-GSK3β and Bcl-2 was down-regulated in the other three groups ( P<0.05). Compared with PND group and Ag-NC group, the postoperative escape latency was significantly prolonged, the percentage of time of stay at the target quadrant was decreased, the number of crossing the original platform was reduced, the expression of miR-3065-5p was up-regulated, and the expression of IGF-1 mRNA, Bcl-2 mRNA, IGF-1, p-Akt, p-GSK3β and Bcl-2 was down-regulated in Ag group ( P<0.05). Conclusions:Up-regulation of miR-3065-5p can inhibit the activation of IGF-1/PI3K/Akt signaling pathway, which might be one of the mechanisms of PND developed in mice.

Effect of Mongolian medicine Eerdun Wurile on postoperative cognitive function in elderly patients undergoing thoracoscopic lobectomy / 中华麻醉学杂志

Objective:To evaluate the effect of Mongolian medicine Eerdun Wurile on postoperative cognitive function in elderly patients undergoing thoracoscopic lobectomy.Methods:Sixty elderly patients of either gender, aged ≥60 yr, of American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ, with body mass index≤28 kg/m 2, with preoperative Mini-Mental State Examination (MMSE) score ≥27 points, undergoing thoracoscopic lobectomy under general anesthesia, were divided into 2 groups ( n=30 each) using the random number table method: control group (group C) and Eerdun Wurile group (group E). Eerdun Wurile 15 capsules per day were taken for 7 consecutive days starting from 3 days before surgery in group E, and placebo was given instead in group C. The peripheral venous blood samples were collected before medication at 3 days before surgery (T 1) and 24 and 72 h after surgery (T 2, 3) for determination of the concentrations of serum brain-derived neurotrophic factor (BDNF), interleukin-1beta (IL-1β), tumor necrosis factor-alpha (TNF-α) and Tau proteins by enzyme-linked immunosorbent assay. The patients′ cognitive function was assessed by MMSE at T 1 and 5 days after surgery (T 4), and the occurrence of cognitive decline (MMSE score < 27) was recorded. Results:Compared with group C, the serum BDNF concentration was significantly increased at T 2 and T 3, and the concentrations of IL-1β, TNF-α and Tau protein were decreased, the MMSE score was increased at T 4, and the incidence of cognitive decline was decreased in group E ( P<0.05). Conclusions:Mongolian medicine Eerdun Wurile can improve postoperative cognitive function in elderly patients undergoing thoracoscopic surgery, and the mechanism may be related to reduction of systemic inflammatory responses and promotion of nerve cell repair and regeneration.

Correlation between the expression level of serum exosome miR-29C and postoperative cognitive dysfunction in elderly patients undergoing surgery / 中国医师杂志

Objective:To investigate the correlation between the expression level of serum exosome miR-29C and postoperative cognitive dysfunction (POCD) in elderly patients undergoing surgery.Methods:A total of 119 elderly patients who underwent elective spinal surgery in the Second Hospital of Shanxi Medical University from January 2021 to January 2022 were selected and scored on the Montreal Cognitive Assessment (MoCA) Scale 1 day before surgery and 1, 7 and 21 days after surgery. The selected patients were divided into POCD group (51 cases) and non-POCD group (68 cases) according to whether the MoCA Scale score decreased ≥2 points 1 day before surgery and 1 day after surgery. S100-β, neuron-specific enolase (NSE) levels and serum exosome miR-29C expression levels were detected and analyzed in all patients 1 day before and 1 day after surgery. Pearson correlation analysis showed the correlation between MoCA Scale score and S100-β, NSE and miR-29C. Receiver operating characteristic (ROC) curve was used to evaluate the predictive value of S100-β, NSE and miR-29C for POCD occurrence in elderly patients undergoing surgery.Results:The score of MoCA Scale in POCD group were significantly decreased 1, 7 and 21 days after surgery compared with 1 day before surgery (all P<0.05), while the score of MoCA Scale in non-POCD group were significantly decreased only 1 day after surgery compared with 1 day before surgery ( P<0.05). The levels of S100-β and NSE and the expression level of serum exosome miR-29C in 2 groups were significantly increased 1 day after surgery compared with 1 day before surgery (all P<0.05). Moreover, the levels of S100-β and NSE and the expression level of serum exosome miR-29C in POCD group were significantly higher than those in non-POCD group 1 day after surgery (all P<0.05). There was a negative correlation between the MoCA Scale score and the expression level of serum exosome miR-29C 1 day after surgery in the POCD group ( P<0.05). ROC curve analysis showed that the expression levels of NSE, S100-β and exosome miR-29C 1 day after surgery predicted the risk of POCD in elderly surgical patients with area under the curve (AUC) of 0.891, 0.908 and 0.918, respectively. Conclusions:The occurrence of POCD in elderly patients with surgery is related to the increase of the expression level of serum exosome miR-29C, and the expression level of serum exosome miR-29C is negatively correlated with MoCA Scale score. Early monitoring of the miR-29C expression level can provide a basis for the occurrence and development of postoperative POCD in elderly patients, disease diagnosis and clinical intervention.

The effect of type 2 diabetes mellitus on perioperative neurocognitive disorders in patients undergoing elective noncardiac surgery under general anesthesia. A prospective cohort study.

Background and Aims: Preliminary evidence suggests a possible relationship between type 2 diabetes mellitus (T2DM) and perioperative neurocognitive disorders (NCD). We sought to investigate whether patients with T2DM, undergoing elective noncardiac surgery under general anesthesia, are at increased risk of perioperative NCD. Material and Methods: A prospective cohort study was designed. One-hundred and forty-four patients with T2DM and 144 healthy controls were recruited. Controls were matched for sex, age, type of operation, and educational background. Postoperative delirium (POD), delayed neurocognitive recovery and postoperative NCD were evaluated. Results: Two hundred twenty-eight patients were analyzed. Compared to controls, patients with T2DM were diagnosed with higher rates of NCD preoperatively (n = 96 vs. n = 26, P < 0.05) and higher POD up to 4 days postoperatively (n = 204 vs. n = 68, P < 0.05). Increased rates of delayed neurocognitive recovery and postoperative NCD were recorded in patients with T2DM up to 9 months postoperatively (n = 473 vs. n = 192, P < 0.05). Insulin-dependent patients had higher rates of POD on the second (n = 38 vs. n = 24, P < 0.05) and third day (n = 27 vs. n = 16, P < 0.05) when compared to noninsulin-dependent patients. Logistic multivariable analysis revealed that patients with T2DM are at increased risk for postoperative cognitive disorders. Conclusion: Patients with type 2 diabetes mellitus appear to be at a higher risk of perioperative NCDs up to 9 months after elective noncardiac surgery under general anesthesia.