Objective: The mortality rate of critically ill patients in ICUs is relatively high. In order to evaluate patients’ mortality risk, different scoring systems are used to help clinicians assess prognosis in ICUs, such as the Acute Physiology and Chronic Health Evaluation III (APACHE III) and the Logistic Organ Dysfunction Score (LODS). In this research, we aimed to establish and compare multiple machine learning models with physiology subscores of APACHE III—namely, the Acute Physiology Score III (APS III)—and LODS scoring systems in order to obtain better performance for ICU mortality prediction. Methods: A total number of 67,748 patients from the Medical Information Database for Intensive Care (MIMIC-IV) were enrolled, including 7055 deceased patients, and the same number of surviving patients were selected by the random downsampling technique, for a total of 14,110 patients included in the study. The enrolled patients were randomly divided into a training dataset (n = 9877) and a validation dataset (n = 4233). Fivefold cross-validation and grid search procedures were used to find and evaluate the best hyperparameters in different machine learning models. Taking the subscores of LODS and the physiology subscores that are part of the APACHE III scoring systems as input variables, four machine learning methods of XGBoost, logistic regression, support vector machine, and decision tree were used to establish ICU mortality prediction models, with AUCs as metrics. AUCs, specificity, sensitivity, positive predictive value, negative predictive value, and calibration curves were used to find the best model. Results: For the prediction of mortality risk in ICU patients, the AUC of the XGBoost model was 0.918 (95%CI, 0.915–0.922), and the AUCs of logistic regression, SVM, and decision tree were 0.872 (95%CI, 0.867–0.877), 0.872 (95%CI, 0.867–0.877), and 0.852 (95%CI, 0.847–0.857), respectively. The calibration curves of logistic regression and support vector machine performed better than the other two models in the ranges 0–40% and 70%–100%, respectively, while XGBoost performed better in the range of 40–70%. Conclusions: The mortality risk of ICU patients can be better predicted by the characteristics of the Acute Physiology Score III and the Logistic Organ Dysfunction Score with XGBoost in terms of ROC curve, sensitivity, and specificity. The XGBoost model could assist clinicians in judging in-hospital outcome of critically ill patients, especially in patients with a more uncertain survival outcome.

Background: The brain contains the highest level of cholesterol in the body, and the total amount of serum cholesterol in the blood has a huge impact on brain aging and cognitive performance. However, the association of total serum cholesterol with cognitive function remains uncertain. This study determines whether there is an association between the total amount of cholesterol in the blood and cognitive performance in elderly females without a history of stroke. Methods: This population-based cross-sectional study was conducted on elderly (over 60 years old) females and males without a history of stroke from 2011 to 2014 in the US National Health and Nutrition Examination Survey (NHANES). The primary exposure was total blood cholesterol, and the main outcome was cognitive performance; this association was assessed with logistic regression analysis and restricted cubic splines. Results: 1309 female and 1272 male participants were included. In females, higher total cholesterol was significantly associated with higher cognitive scores, particularly in the digit symbol substitution test (OR 0.51, 95% CI (0.36–0.72)) and the animal fluency test (OR 0.64, 95% CI (0.45–0.91)). This association remained significant in models adjusted for age, race, smoking status, education level, and chronic conditions (OR 0.40, 95% CI (0.25–0.63)). This association was not significant in males, however. Conclusions: A higher concentration of total cholesterol measured in later life may be a protective factor for cognitive performance among females over 60 years old without a history of stroke. Further, this association was more pronounced among women with higher levels of education than women with lower or no education.

Impaired Ca2+ handling is involved in diabetic cardiomyopathy (DCM) progression. The activation of acid sphingomyelinase (ASMase) stimulated cardiomyocytes apoptosis and caused DCM. Here, we aimed to investigate whether ASMase regulates mitochondrial Ca2+ homeostasis by acting on mitochondrial calcium uptake 1 (MICU1) and mitochondria-associated endoplasmic reticulum membranes (MAMs) formation to induce apoptosis during DCM. We established a type 2 diabetes model by combining high-fat diet (HFD) with streptozotocin (STZ) injection in wild-type and cardiomyocyte-specific ASMase deletion (ASMaseMyh6KO) mice. ASMase deletion restored HFD/STZ-induced cardiac dysfunction, remodeling, myocardial lipid accumulation and apoptosis. Single cell sequencing and Gene ontology (GO) enrichment analysis pointed to “cardiac muscle contraction” and “positive regulation of mitochondrial calcium ion concentration”, which were confirmed by high glucose (HG, 30 mM) and palmitic acid (PA, 200 μM) induced mitochondrial Ca2+ overload in H9c2 cell lines at time dependence, accompanied by the upregulation of ASMase and MICU1 protein expressions. The similar effects were noted in ASMase overexpressed cardiomyocytes. Interestingly, endoplasmic reticulum (ER) Ca2+ level was decreased at the corresponding time, suggesting that increased mitochondrial Ca2+ level may be derived from ER. Notably, enhanced MAMs formation was found in HG + PA treated H9c2 cells, accompanied by blocked autophagy, similar results were obtained in ASMase overexpressing cells or HFD/STZ hearts. Loss of ASMase prevented HFD/STZ or HG + PA incubation induced cardiac hypertrophy, mitochondrialCa2+ overload, ROS production, autophagy blockage and MICU1 upregulation. HFD/STZ-induced ASMase upregulation enhances MAMs formation, promoting mitochondrial Ca2+ overload through MICU1 activation, leading to ROS generation, autophagy blockage and apoptosis in DCM. Therefore, targeting ASMase-MICU1 pathway emerges as a potential therapeutic approach for managing DCM.

Background: Chronic postsurgical pain (CPSP) is common and would reduce the quality of life of patients. Transversus abdominal plane (TAP) block has been widely used in lower abdominal surgery and many researches demonstrated that it could improve acute postsurgical pain. We aim to determine whether TAP block could improve chronic postoperative pain at 3 months and 6 months after colorectal surgery. Methods: A total of 307 patients received selective colorectal surgery under general anesthesia between January, 2015 and January, 2019 in a single university hospital were included: 128 patients received TAP block combined with patient-controlled intravenous analgesia (PCIA) for postsurgical analgesia (group TP) and 179 only administrated with PCIA (group P). Main outcome was the NRS score of pain at 3 months after colorectal surgery. The data was analyzed by two-way repeated measures anova and the chi-square test. Results: The NRS score at rest and during movement was decreased significantly at 24 h after surgery (rest NRS 1.07 ± 1.34 vs 1.65 ± 1.67, movement NRS 3.00 ± 1.45 vs 3.65 ± 1.89; all P = 0.003) in group TP than those of group P. There was no significant difference of NRS score at 48 h after surgery (P > 0.05). At 3 months after surgery, the NRS score during movement was also lower in group TP than that in group P (0.59 ± 1.23 vs 0.92 ± 1.65, P = 0.045). There was no significant difference of NRS score at 6 months after surgery (P > 0.05). The prevalence of CPSP was 19.5% (25/128) in group TP and 20.7% (37/179) in group P at 3 months after surgery. 13.2% (17/128) of patients suffered from CPSP in group TP and 13.9% (25/179) in group P at 6 months after surgery. Both at 3 months and 6 months after surgery, there was no statistical difference of the prevalence of CPSP between the two groups (all P > 0.05) . Conclusions: TAP block reduced NRS during movement at 3 months after surgery but did not reduce the incidence of CPSP at 3 months and 6 months after selective colorectal surgery.

Objective: The association of non-steroidal anti-inflammatory drugs with postoperative acute kidney injury (AKI) is controversial. However, there are few studies focusing on the association between parecoxib and postoperative AKI. Our study aimed at the possible correlation between the intraoperative administration of cyclooxygenase-2 inhibitors parecoxib and perioperative AKI.Design: A retrospective cohort study.Setting: Third Xiangya Hospital of Central South University in Hunan Province, China.Participants: The electronic medical records and laboratory results were obtained from 9246 adult patients (18–60 years) undergoing non-cardiac surgery performed between 1 January 2012 and 31 August 2017. Study groups were treated with or without parecoxib.Interventions: Univariable analysis identified demographic, preoperative laboratory and intraoperative factors associated with AKI. Logistic stepwise regression was used to calculate the adjusted OR of parecoxib and AKI association.Results: The incidence of AKI was lower in the parecoxib-administered group (4%) than that in the group without parecoxib (6.3%, p=0.005). In the multivariable regression analysis, postoperative AKI risk reduced by 39% (OR 0.61; 95% CI 0.43 to 0.87) in the parecoxib-administered group after adjusting for interference factors. Sensitivity analysis showed that postoperative AKI risk reduced in four subgroups: eGRF <90 mL/min·1.73/m²(OR 0.49; 95% CI 0.29 to 0.82), non-smoker (OR 0.55; 95% CI 0.37 to 0.83), blood loss <1000 mL (OR 0.55; 95% CI 0.37 to 0.83) and non-hypotension (OR 0.57; 95% CI 0.38 to 0.84).Conclusions: Thus, parecoxib is associated with a modest reduction of postoperative AKI risk among adult patients undergoing non-cardiac surgery.