Association between frailty and acute kidney injury after cardiac surgery: unraveling the moderation effect of body fat through an international, retrospective, multi-cohort study.

BACKGROUND: Acute kidney injury (AKI) is a common and serious complication after cardiac surgery that significantly affects patient outcomes. Given the limited treatment options available, identifying modifiable risk factors is critical. Frailty and obesity, two heterogeneous physiological states, have significant implications for identifying and preventing AKI. Our study investigated the interplay among frailty, body composition, and AKI risk after cardiac surgery to inform patient management strategies. MATERIAL AND METHODS: This retrospective cohort study included three international cohorts. Primary analysis was conducted in adult patients who underwent cardiac surgery between 2014 and 2019 at Wuhan XX Hospital, China. We tested the generalizability of our findings with data from two independent international cohorts, the Medical Information Mart for Intensive Care IV (MIMIC-IV) and the eICU Collaborative Research Database. Frailty was assessed using a clinical lab-based frailty index (FI-LAB), while total body fat percentage (BF%) was calculated based on a formula accounting for BMI, sex, and age. Logistic regression models were used to analyze the associations between frailty, body fat, and AKI, adjusting for pertinent covariates. RESULTS: A total of 8785 patients across three international cohorts were included in the study. In the primary analysis of 3,569 patients from Wuhan XX Hospital, moderate and severe frailty were associated with an increased AKI risk after cardiac surgery. Moreover, a nonlinear relationship was observed between body fat percentage and AKI risk. When stratified by the degree of frailty, lower body fat correlated with a decreased incidence of AKI. Extended analyses using the MIMIC-IV and eICU cohorts (n=3,951 and n=1,265, respectively) validated these findings and demonstrated that a lower total BF% was associated with decreased AKI incidence. Moderation analysis revealed that the effect of frailty on AKI risk was moderated by the body fat percentage. Sensitivity analyses demonstrated results consistent with the main analyses. CONCLUSION: Higher degrees of frailty were associated with an elevated risk of AKI following cardiac surgery, and total BF% moderated this relationship. This research underscores the significance of integrating frailty and body fat assessments into routine cardiovascular care to identify high-risk patients for AKI and implement personalized interventions to improve patient outcomes.

Risk Factors and Short-Term Outcomes of Postoperative Pulmonary Complications in Elderly Patients After Cardiopulmonary Bypass.

Objective: The risk factors of postoperative pulmonary complications (PPCs) have been extensively investigated in non-cardiac surgery and non-elderly adult patients undergoing cardiac surgery. However, data on elderly patients after cardiopulmonary bypass (CPB) is limited. This study aimed to evaluate the risk factors and short-term outcomes for PPCs in elderly patients undergoing CPB procedures. Patients and Methods: Data from 660 patients who underwent CPB over a six-year period at a tertiary care hospital were collected. The primary outcome encompassed the incidence of PPCs, including re-intubation, postoperative mechanical ventilation exceeding 48 hours, pulmonary infection, pleural effusion requiring thoracic drainage, and acute respiratory distress syndrome. Missing data were managed using multiple imputation. Univariate analysis and the multiple logistic regression method were utilized to ascertain independent risk factors for PPCs. Results: Among the 660 patients, PPCs were observed in 375 individuals (56.82%). Multiple logistic regression identified serum albumin levels <40 g/L, type of surgery, CPB duration >150 minutes, blood transfusion, and intra-aortic balloon pump use before extubation as independent risk factors for PPCs. Patients experiencing PPCs had prolonged mechanical ventilation, extended hospitalization and ICU stays, elevated postoperative mortality, and higher tracheotomy rates compared to those without PPCs. Conclusion: Elderly patients following CPB displayed a substantially high incidence of PPCs, significantly impacting their prognosis. Additionally, this study identified five prominent risk factors associated with PPCs in this population. These findings enable clinicians to better recognize patients who may benefit from perioperative prevention strategies based on these risk factors.

Remote ischemic preconditioning reduces mitochondrial apoptosis mediated by calpain 1 activation in myocardial ischemia-reperfusion injury through calcium channel subunit Cacna2d3.

Remote Ischemic Preconditioning (RIPC) can reduce myocardial ischemia-reperfusion injury, but its mechanism is not clear. In order to explore the mechanism of RIPC in myocardial protection, we collected myocardial specimens during cardiac surgery in children with tetralogy of Fallot for sequencing. Our study found RIPC reduces the expression of the calcium channel subunit cacna2d3, thereby impacting the function of calcium channels. As a result, calcium overload during ischemia-reperfusion is reduced, and the activation of calpain 1 is inhibited. This ultimately leads to a decrease in calpain 1 cleavage of Bax, consequently inhibiting increased mitochondrial permeability-mediated apoptosis. Notably, in both murine and human models of myocardial ischemia-reperfusion injury, RIPC inhibiting the expression of the calcium channel subunit cacna2d3 and the activation of calpain 1, improving cardiac function and histological outcomes. Overall, our findings put forth a proposed mechanism that elucidates how RIPC reduces myocardial ischemia-reperfusion injury, ultimately providing a solid theoretical foundation for the widespread clinic application of RIPC.

Sugammadex Reduced the Incidence of Postoperative Pulmonary Complications in Susceptible Patients Identified by ARISCAT Risk Index: Systematic Review and Meta-analysis.

INTRODUCTION: The efficacy of sugammadex on postoperative pulmonary complications (PPCs) in susceptible patients, compared with neostigmine, remains indeterminate. The Assess Respiratory Risk in Surgical Patients in Catalonia (ARISCAT) Group Investigators proposed a risk index for the early identification of susceptible patients, with excellent externally validated discrimination ability. Meta-analytical techniques were applied to evaluate the efficacy of sugammadex on PPCs in patients with ARISCAT-defined risk factors. METHODS: The study is registered on PROSPERO, number CRD42021261156. We searched PubMed, Scopus, Embase, Cochrane library, GreyNet, and OpenGrey for eligible randomized controlled trials (RCTs) without restricting the language or year of publication. RESULTS: Twelve RCTs consisting of 1182 patients susceptible to PPCs were included. A robust reduction was observed on the incidence of PPCs in susceptible patients who received sugammadex [RR 0.66; 95% CI (0.54, 0.80), p < 0.01], with a low level of between-study heterogeneity (I2 = 45.98%; H2 = 1.85). Similar protective effects were also proved in avoiding residual neuromuscular block (NMB) [RR 0.25; 95% CI (0.11, 0.56); p < 0.01], atelectasis [RR 0.74; 95% CI (0.59, 0.95); p = 0.02], pneumonia [RR 0.49; 95% CI (0.28, 0.88); p = 0.02], and respiratory failure [RR 0.61; 95% CI (0.39, 0.96); p = 0.03]. No difference was observed regarding adverse events [RR 0.85; 95% CI (0.72, 1.01); p = 0.06]. CONCLUSION: Low to moderate quality of evidence demonstrated the edge of sugammadex over neostigmine for NMB reversal in reducing the likelihood of PPCs and residual NMB in patients with ARISCAT-defined risk factors. Clinicians may reassess the type of reversal agent when treating patients susceptible to PPCs.

Lasso-Based Machine Learning Algorithm for Predicting Postoperative Lung Complications in Elderly: A Single-Center Retrospective Study from China.

Background: The predictive effect of systemic inflammatory factors on postoperative pulmonary complications in elderly patients remains unclear. In addition, machine learning models are rarely used in prediction models for elderly patients. Patients and Methods: We retrospectively evaluated elderly patients who underwent general anesthesia during a 6-year period. Eligible patients were randomly assigned in a 7:3 ratio to the development group and validation group. The Least logistic absolute shrinkage and selection operator (LASSO) regression model and multiple logistic regression analysis were used to select the optimal feature. The discrimination, calibration and net reclassification improvement (NRI) of the final model were compared with "the Assess Respiratory Risk in Surgical Patients in Catalonia" (ARISCAT) model. Results: Of the 9775 patients analyzed, 8.31% developed PPCs. The final model included age, preoperative SpO2, ANS (the Albumin/NLR Score), operation time, and red blood cells (RBC) transfusion. The concordance index (C-index) values of the model for the development cohort and the validation cohort were 0.740 and 0.748, respectively. The P values of the Hosmer-Lemeshow test in two cohorts were insignificant. Our model outperformed ARISCAT model, with C-index (0.740 VS 0.717, P = 0.003) and NRI (0.117, P < 0.001). Conclusion: Based on LASSO machine learning algorithm, we constructed a prediction model superior to ARISCAT model in predicting the risk of PPCs. Clinicians could utilize these predictors to optimize prospective and preventive interventions in this patient population.

Early identification of delayed extubation following cardiac surgery: Development and validation of a risk prediction model.

Background: Successful weaning and extubation after cardiac surgery is an important step of postoperative recovery. Delayed extubation is associated with poor prognosis and high mortality, thereby contributing to a substantial economic burden. The aim of this study was to develop and validate a prediction model estimate the risk of delayed extubation after cardiac surgery based on perioperative risk factors. Methods: We performed a retrospective cohort study of adult patients undergoing cardiac surgery from 2014 to 2019. Eligible participants were randomly assigned into the development and validation cohorts, with a ratio of 7:3. Variables were selected using least absolute shrinkage and selection operator (LASSO) logistic regression model with 10-fold cross-validation. Multivariable logistic regression was applied to develop a predictive model by introducing the predictors selected from the LASSO regression. Receiver operating characteristic (ROC) curve, calibration plot, decision curve analysis (DCA) and clinical impact curve were used to evaluate the performance of the predictive risk score model. Results: Among the 3,919 adults included in our study, 533 patients (13.6%) experienced delayed extubation. The median ventilation time was 68 h in the group with delayed extubation and 21 h in the group without delayed extubation. A predictive scoring system was derived based on 10 identified risk factors based on 10 identified risk factors including age, BMI ≥ 28 kg/m2, EF < 50%, history of cardiac surgery, type of operation, emergency surgery, CPB ≥ 120 min, duration of surgery, IABP and eGFR < 60 mL/min/1.73 m2. According to the scoring system, the patients were classified into three risk intervals: low, medium and high risk. The model performed well in the validation set with AUC of 0.782 and a non-significant p-value of 0.901 in the Hosmer-Lemeshow test. The DCA curve and clinical impact curve showed a good clinical utility of this model. Conclusions: We developed and validated a prediction score model to predict the risk of delayed extubation after cardiac surgery, which may help identify high-risk patients to target with potential preventive measures.

Long-term sevoflurane exposure reduces the differentiation potential and hypoxia tolerance potential of neural stem cells.

PURPOSE: To investigate the effect of prolonged sevoflurane (SEV) exposure on differentiation potential and hypoxia tolerance of neural stem cells (NSCs). MATERIALS AND METHODS: NSCs were extracted from 15-day fetal mice. After sub-culture, SEV exposure treatment was performed. Cell cycle were detected by flow cytometry. Western blot and immunofluorescence assay were used to detect the expression and spatial distribution of Nestin, NSE, GFAP, Oct4, and SOX2; CCK-8 detected cell viability. Cell growth morphology was observed under a microscope. TUNEL detected cell apoptosis; the concentration of extracel-lular lactate dehydrogenase (LDH) was determined by ELISA. RESULTS: Compared with the control group, the proportion of NSCs in the G2/M phase increased in the SEV exposure group; our results also suggested the sphere-formation rate decreased significantly, increased apoptosis and decreased cell viability. Besides, the level of LDH release increased. CONCLUSION: Long-term exposure to SEV (>8 h) promoted the premature differentiation of NSCs and reduced their pluripotency, reserves, and hypoxia tolerance. This study reveals the reasons underlying damage to the nervous system of young children induced by long-term exposure to SEV from the perspective of CNS reserve cells.

Dexmedetomidine attenuates one-lung ventilation associated lung injury by suppressing inflammatory responses: A systematic review and meta-analysis.

One-lung ventilation (OLV), a common ventilation technique, is associated with perioperative lung injury, tightly connected with inflammatory responses. Dexmedetomidine has shown positive anti-inflammatory effects in lung tissues in pre-clinical models. This study investigated the efficacy of dexmedetomidine for suppressing inflammatory responses in patients requiring OLV. We searched PubMed, MEDLINE, Embase, Scopus, Ovid, and Cochrane Library for randomized controlled trials focusing on dexmedetomidine's anti-inflammatory effects on patients requiring OLV without any limitation on the year of publication or languages. 20 clinical trials were assessed with 870 patients in the dexmedetomidine group and 844 in the control group. Our meta-analysis investigated the anti-inflammatory property of dexmedetomidine perioperatively [T1 (30-min OLV), T2 (90-min OLV), T3 (end of surgery) and T4 (postoperative day 1)], demonstrating that dexmedetomidine's intraoperative administration resulted in a significant reduction in serum concentration of interleukin-6, tumor necrosis factor-α and other inflammatory cytokines perioperatively. By calculating specific I2 index, significant heterogeneity was observed on all occasions, with I2 index ranging from 95% to 99%. For IL-6 changes, sensitivity analysis showed that the exclusion of a single study led to a significant decrease of heterogeneity (96%-0%; p < 0.00001). Besides, pulmonary oxygenation was ameliorated in the dexmedetomidine group comparing with the control group. In conclusion, perioperative administration of dexmedetomidine can attenuate OLV induced inflammation, ameliorate pulmonary oxygenation, and may be conducive to a decreased occurrence of postoperative complications and better prognosis. However, the results should be prudently interpreted due to the evidence of heterogeneity and the limited number of studies.