Sodium acetate and sodium butyrate ameliorate postoperative cognitive dysfunction in aged rats by suppressing inflammation and ferroptosis via inhibition of the cGAS-STING signaling pathway.

Impact of surgical interventions on postoperative cognitive dysfunction: A focus on gene expression in the hippocampus and cerebral cortex and peripheral blood cells.

Enhanced meningeal lymphatic drainage alleviates cognitive dysfunction induced by anesthesia and surgery in aged mice.

Discovery of a novel mitophagy inducer attenuating postoperative cognitive dysfunction through structure-based virtual screening and biological validation.

IntroductionTotal knee arthroplasty (TKA) is a widely used treatment for advanced knee osteoarthritis. While cemented fixation is the standard technique, cementless fixation has demonstrated comparable long-term outcomes. However, the association between cement use and postoperative complications, including venous thromboembolism and surgical site infections, remains unclear, particularly in Japanese patients. This study aimed to investigate the incidence of postoperative complications in cemented and cementless TKA using a nationwide database.MethodsA nationwide cohort study was conducted using Japan’s DPC database from April 2016 to March 2023. Patients who underwent TKA were identified, and postoperative complications, including deep vein thrombosis, pulmonary embolism, pneumonia, cerebrovascular events, postoperative cognitive dysfunction, and surgical site infection, were analyzed. One-to-one propensity score (PS) matching was performed based on age, sex, body mass index, type of anesthesia, simultaneous bilateral surgery, Charlson comorbidity index, and comorbidities to ensure comparability. Statistical analyses included χ² tests, Student’s t-tests, and multivariate logistic regression analysis.ResultsA total of 228,595 patients met the eligibility criteria, with 21,906 matched pairs in the cemented and cementless groups after PS matching. The incidence of deep vein thrombosis (OR: 1.231, 95% CI: 1.151–1.316, p < 0.0001) and surgical site infection (OR: 1.716, 95% CI: 1.420–2.073, p < 0.0001) was significantly higher in the cemented group. No significant differences were observed in pulmonary embolism or other complications.ConclusionCement application was associated with an increased risk of deep vein thrombosis and surgical site infection. These findings suggest that careful perioperative management may be warranted in patients undergoing cemented TKA.

Near-infrared light improves postoperative cognitive dysfunction by alleviating Lcn2-dependent ferroptosis induced neuronal injury.

Comment on "The association between diabetes mellitus and postoperative cognitive dysfunction: a systematic review and meta-analysis".

Propofol exerted the neuroprotective effects by regulating renin-angiotensin system and mitochondria-associated endoplasmic reticulum membrane in the postoperative cognitive dysfunction.

Anesthesia in older patients is challenging and requires a range of skills in various techniques, both during surgery and in the post-operative period. Post-operative delirium is one of the most common cognitive dysfunctions after surgery, and elderly patients are at the highest risk. The pathophysiology of post-operative delirium remains incompletely understood. Several mechanisms (vascular, neurodegenerative, neuroimmune, neuroinflammation, drug-induced, stress-induced, and monoaminergic) have been considered to play a role. The type of anesthesia—general (gas, total intravenous), regional, or combined—was identified as a predictive factor. However, numerous prospective and retrospective studies have failed to determine which anesthetic technique is the best for preventing post-operative delirium. The type of surgery appears to be more critical than the type of anesthesia. However, the development of post-operative cognitive dysfunction could be linked to the depth of anesthesia. Dexmedetomidine displayed promising therapeutic potential for the efficient prevention or treatment of hyperactive post-operative delirium. The management of hypoactive post-operative delirium still requires further investigations, particularly in elderly patients.

BACKGROUNDTo investigate whether seasonal differences in ambient temperature affect the incidence of early postoperative cognitive dysfunction (POCD) among elderly patients undergoing laparoscopic surgery in tropical regions. Additionally, it explored the perioperative risk factors associated with early POCD following abdominal laparoscopic surgery.AIMTo investigate the influence of seasonal differences in ambient temperature on POCD of elderly patientsMETHODSA total of 125 patients aged ≥ 65 years from Hainan Province, China, who underwent laparoscopic surgery under general anesthesia with tracheal intubation, were enrolled. All patients completed the Mini-Mental State Examination one day before surgery and on postoperative days 1, 3, and 7. A decline of ≥ 2 points from baseline was considered indicative of cognitive dysfunction. Serum levels of S100 calcium binding protein B and neuron-specific enolase were measured using enzyme-linked immunosorbent assay at three time points: Preoperatively, immediately after extubation, and 24 hours postoperatively. Perioperative clinical data were collected to identify potential risk factors for POCD. Propensity score matching (PSM) was performed (1:1, caliper = 0.03), resulting in 41 matched patient pairs between winter and summer groups.RESULTSAfter PSM, baseline characteristics including age, gender, body mass index, education level, comorbidities, and surgical variables were well balanced between groups. There were no significant differences in the incidence of POCD on postoperative days 1, 3, and 7 between patients undergoing laparoscopic surgery in winter vs summer. However, multivariable logistic regression revealed that surgical duration (day 1, P value = 0.049), advanced age and elevated creatinine (day 3, P value = 0.044, P value = 0.008), and hypoalbuminemia (day 3, P value = 0.042; day 7, P value = 0.015) were independently associated with early POCD.CONCLUSIONAmbient temperature differences between winter and summer in tropical regions did not significantly affect the incidence of early POCD in elderly patients undergoing laparoscopic surgery. Nonetheless, age, longer surgical duration, elevated creatinine, and hypoalbuminemia emerged as key risk factors. These findings underscore the importance of perioperative optimization to reduce the risk of POCD in elderly patients, regardless of seasonal temperature variations.

Background and Objective: Postoperative delirium (POD) is a common complication of surgery, associated with significant morbidity and additional health care costs. Postoperative cognitive dysfunction (POCD) overlaps with postoperative delirium, but is considered to occur in the months following hospital discharge. The primary aim of this narrative review was to assess the effect of the use of depth of anesthesia (DoA) monitoring on the incidence of postoperative delirium. Secondary aims were to examine the effect of using DoA monitoring on postoperative cognitive dysfunction and the total dosage of anesthetics used. Methods: An extensive search of PubMed and Embase databases was conducted until April 2025. Inclusion criteria were randomized controlled trials and articles published in English, and studies including adult patients under general anesthesia, where anesthetics were titrated using a depth of anesthesia monitor, to determine the incidence of POD or POCD. The quality of relevant articles was assessed using the Cochrane risk-of-bias tool. Results: After full-text evaluation and quality assessment, ten articles were included in this narrative review. Six out of eight articles found a significant decline in POD when using a depth of anesthesia monitor. In comparison, only one of five studies found a significant decline in POCD. Seven study groups concluded that using a DoA monitoring system led to a decrease in the total dose of anesthetic administered. Conclusion: Based on the reviewed literature, there may be a beneficial effect on the incidence of POD when a DoA monitor is used during general anesthesia. The effect on POCD seems to be much less significant. DoA monitoring also seems to be useful in lowering anesthetic dosages. However, this subject needs further study in large-scale prospective studies.

Identifying peripheral proteins having therapeutic effects on cognitive impairment could provide beneficial insights into the prevention and treatment of cognition-related disorders, including postoperative cognitive dysfunction (POCD) that is a common postoperative cognitive impairment mainly caused by anesthesia/surgery. Here, proteomic and transcriptomic analyses in multiple organs from humans and POCD mice are conducted to identify potential peripheral targets for anesthesia/surgery-induced cognitive impairment. The results show that anesthesia/surgery can disrupt the blood-brain barrier (BBB) and promote the release of hepatogenous C3 protein into the blood. This surgical dual factors ultimately drove C3 to cross the damaged BBB and selectively colocalize with C3aR in the hippocampus. Anesthesia/surgery-induced C3 upregulation in the liver is associated with hypomethylation of C3 promoter. Inhibiting hepatogenous C3 is demonstrated to salvage the anesthesia/surgery-induced cognitive impairment, structural and functional injury of synapse, and C3aR-mediated microglial phagocytosis. Perioperative alterations in serum C3 protein in surgical patients are related to POCD, showing potential for predicting this disorder. This study emphasizes that peripheral C3 is a promising target for the prevention and therapy, and a potential biomarker for predicting cognitive impairment, and confirms that the liver mediates anesthesia/surgery-induced cognitive impairment.

With the development of comfortable medical care, the application of intravenous anesthesia in painless gastroscopy is becoming increasingly widespread. However, anesthetic drugs may have adverse effects on postoperative cognitive function, and the risk of postoperative cognitive dysfunction (POCD) is particularly worthy of attention in the elderly population. Our aim is to evaluate the effect of intravenous anesthesia on postoperative cognitive function (POCF) in patients undergoing painless gastroscopy, with a focus on identifying potential risks of POCD and guiding clinical anesthesia practices. Analyzing randomized controlled trials (RCTs) published in English that assessed the impact of intravenous anesthesia on POCF in patients over 60 years old undergoing elective gastrointestinal endoscopy. The literature search spanned databases including PubMed、Embase、Web of Science、Scopus、Cochrane, and Clinical Key. Study inclusion and exclusion criteria were rigorously defined, and the Cochrane bias risk assessment tool was utilized to evaluate study quality. Meta-analyses were performed using RevMan 5.3, with heterogeneity assessed via I-square statistics. From a total of 432 articles identified, 7 studies involving 219 patients met the inclusion criteria. The meta-analysis revealed no significant difference in the incidence rates of POCD on Day 1 and Day 3 postoperatively between patients undergoing intravenous versus inhalation anesthesia. However, on Day 7, the incidence of POCD was significantly lower in the intravenous anesthesia group, with a combined Odds Ratio (OR) of 0.96 (95% Confidence Interval (CI): 0.73-1.26, I^2 = 34%, n = 7, P < 0.00001). Furthermore, plasma levels of S-100β protein, a marker for neural injury, were significantly lower in the intravenous anesthesia group, with a Mean Difference (MD) of 0.34 (95% CI: 0.23-0.48, I^2 = 0%, n = 5, P < 0.00001). Intravenous anesthesia for painless gastroscopy appears to be associated with a lower incidence of POCD on Day 7 postoperatively, suggesting a potentially reduced risk of early postoperative cognitive decline compared to inhalation anesthesia. The findings indicate that intravenous anesthesia may be preferable in minimizing the risk of POCD, particularly in older adults undergoing painless gastroscopy. However, further high-quality, large-scale RCTs are warranted to validate these results and explore the effects across different patient demographics.

Deep neuromuscular blockade (NMB) optimizes surgical conditions, particularly during laparoscopic procedures. However, its effects on systemic cytokines associated with anesthesia-related complications, including postoperative delirium and cognitive dysfunction, remain unclear. In this review, we quantified the impact of deep NMB on serum cytokine levels. PubMed, EMBASE, CENTRAL, CINAHL, Scopus, Web of Science, and Google Scholar databases were searched to identify randomized controlled trials (RCTs) evaluating serum cytokine levels in surgical patients under deep or moderate NMB. Eight RCTs, including 661 patients undergoing laparoscopic and orthopedic surgeries, met the inclusion criteria. Immediately postoperatively, meta-analysis suggested a potential reduction in tumor necrosis factor-α (TNF-α, standardized mean difference -0.48; 95% confidence interval [95% CI] -0.90 to -0.06; P = 0.03), with no significant differences in interleukin-1β (IL-1β) or interleukin-6 (IL-6) levels. At 24-h and 48-h postoperatively, no significant differences were observed in IL-1β, IL-6, TNF-α, or C-reactive protein levels. Meta-regression analysis indicated that inhalational anesthesia was associated with high IL-1β (estimate = 1.2135; 95% CI, 0.5107-1.9162; P < 0.01) and TNF-α levels (estimate = 0.6271; 95% CI, 0.0544-1.1997; P = 0.032) immediately postoperatively; however, younger patients exhibited elevated IL-1β levels under moderate NMB at 24-h postoperatively (estimate = 0.0242; 95% CI, 0.0065-0.0419; P < 0.01). Deep NMB may be associated with reduced TNF-α levels immediately postoperatively. Inhalational anesthesia and younger age may contribute more to higher serum cytokine levels compared with total intravenous anesthesia and older age, respectively, suggesting a potential immunomodulatory effect of deep NMB. Further studies should clarify its clinical relevance.

Sugammadex is a relatively new therapeutic agent that reverses neuromuscular blockade. Compared to neostigmine, it is hypothesised that sugammadex could have a beneficial effect on postoperative cognitive function, benefitting postoperative recovery. To compare the effects of both sugammadex and neostigmine on delirium and postoperative cognitive dysfunction. A systematic search of all relevant randomised controlled trials and observational cohort studies was performed in October 2024, utilising the following inclusion criteria: incidence of delirium and postoperative cognitive dysfunction following administration of neostigmine or sugammadex, adult patients, patients given rocuronium or vecuronium, English language studies, papers since the introduction of sugammadex (2008). CASP and Cochrane risk-of-bias tools were utilised for study appraisal, with a narrative synthesis of the results. Five studies, reporting interventions in 49,910 patients, met the review criteria and were included. Of these, four showed no difference in cognitive function between sugammadex and neostigmine. One cohort study of 21 patients showed favourable outcomes postoperatively in the sugammadex group. This systematic review suggests the possibility of a very limited neurological protective role of sugammadex compared to neostigmine, but no clinical significance was reported. Only a limited number of studies were available, suggesting the need for further research.

HMGB1 promotes LPS-induced M1 polarization and apoptosis in microglia by mediating the expression of immune and inflammation-related genes.

Postoperative cognitive dysfunction (POCD) occurs in 20% to 80% of patients following cardiac surgical interventions. The incidence of delirium is from 20% to 50%. Impaired cerebral autoregulation (CA) during cardiopulmonary bypass (CPB) contributes to these issues. We investigated a novel method for real-time monitoring of CA during CPB. The study aimed to obtain real-time CA impairment data to demonstrate the timely arterial blood pressure (ABP) management for immediate restoration of intact CA and, potentially, to reduce the incidences of POCD and delirium. An observational pilot clinical trial involved 108 elective on-pump surgery patients of whom 78 were included in the final analysis. All patients were evaluated for cognitive function on the 7th to 10th postoperative day. A rectangular blood flow modulation technique was proposed and applied to facilitate real-time detection of CA status impairment by using CA(t) transient response analysis. A single CA impairment event lasting longer than 241 seconds was statistically significantly associated with POCD (P=0.0178), while impairments exceeding 262 seconds were related to delirium (P=0.0315). It was demonstrated that CA impairment events and patient-specific lower and upper limits of CA can be identified with sub-minute delays during cardiac surgery. The study demonstrated the feasibility of a novel heart and lung machine operation mode with rectangular blood flow modulation. Precise personal ABP(t) management can be performed during CPB to restore patient-specific optimal brain perfusion with sub-minute time resolution and, potentially, to reduce incidences of POCD and delirium.

Propofol induces mitochondrial dysfunction in hippocampal neurons and postoperative cognitive dysfunction in male 3xTg-AD mice by blocking ESRRG-mediated HSD11B2 transcription.

Effects of different doses of glucocorticoids on postoperative neurocognitive function and mood disorders: A systematic Review and network meta-analysis.

BackgroundIntraoperative hypotension (IOH) is a common complication in non-cardiac surgeries, with significant impacts on postoperative outcomes such as acute kidney injury (AKI), myocardial injury after non-cardiac surgery (MINS), and postoperative cognitive dysfunction (delirium). Traditional non-invasive blood pressure monitoring often results in blind gaps through the discontinuous measurement, potentially missing critical hypotensive events. This study investigates the efficacy of a non-invasive, continuous AI-supported technology using the Hypotension Prediction Index (HPI) system, designed to predict and mitigate IOH, in reducing the incidence and severity of IOH and related complications in major orthopedic and trauma surgeries.Methods/designThis monocentric, randomized, prospective interventional trial will be conducted at the University Hospital Giessen. The study will include patients aged 45 years and older undergoing major orthopedic or trauma surgeries. Participants will be randomized into two groups: an intervention group receiving hemodynamic management using the ClearSight system in combination with a HPI-based treatment algorithm and a control group receiving standard care. The patients from the standard group also receive continuous cardiac output monitoring; however, this will be blinded to the anesthesiologist, to ensure the comparability of the measured hemodynamic parameters. The primary endpoint is the incidence, duration and severity of IOH, which is defined as MAP < 65 mmHg for at least one minute and which is calculated as the area under MAP < 65 mmHg and the time-weighted average (TWA) of MAP < 65 mmHg. Secondary endpoints include the occurrence of postoperative AKI (measured by KDIGO criteria), MINS (measured by high-sensitivity troponin I assays), and postoperative delirium. The study aims to recruit 150 patients, accounting for potential dropouts, to provide sufficient power to detect differences in the primary and secondary endpoints.ConclusionThis study aims to demonstrate improved intraoperative hemodynamic stability, with a reduction of hypotension and a reduced incidence of postoperative complications, potentially setting a new standard for non-invasive continuous monitoring in orthopedic and trauma patients.Trial registrationClinicalTrials.gov NCT06291714. Registered on 4 March 2024.Supplementary InformationThe online version contains supplementary material available at 10.1186/s13063-025-09194-x.