Efficiency of polymyxin B treatment against nosocomial infection: a systematic review and meta-analysis.

Background: Some cohort studies have explored the effects and safety of polymyxin B (PMB) in comparison to other antibiotics for the treatment of nosocomial infections, yielding inconsistent results. This systematic review aims to explore the effectiveness and safety of PMB and compared it with other antibiotics. Methods: A systematic literature search was conducted in PubMed, Embase, the Cochrane Library, and Web of Science, searching specific terms to identify quantitative cohort studies or RCTs that compared the effects of PMB with other antibiotics in terms of their efficacy and safety. The Newcastle-Ottawa Scale (NOS) was conducted to evaluate the risk of bias of observational studies. Odds ratios with 95% confidence intervals were used for outcome assessment. We evaluated heterogeneity using the I 2 test. Results: A total of 22 observational trials were included in the analysis. The PMB group had a higher mortality rate compared to the control group (odds ratio: 1.84, 95% CI: 1.36-2.50, p<0.00001, I 2 = 73%). while, the ceftazidime-avibactam group demonstrated a distinct advantage with lower mortality rates, despite still exhibiting high heterogeneity (odds ratio 2.73, 95% confidence interval 1.59-4.69; p = 0.0003; I 2 = 53%). Additionally, the PMB group had a lower nephrotoxicity rate compared to the colistin group but exhibited high heterogeneity in the results (odds ratio 0.58, 95% CI 0.36-0.93; p = 0.02; I 2 = 73%). Conclusion: In patients with nosocomial infections, PMB is not superior to other antibiotics in terms of mortality, specifically when compared to ceftazidime-avibactam. However, PMB demonstrated an advantage in terms of nephrotoxicity compared to colistin.

Association between elevated preoperative red cell distribution width and mortality after brain tumor craniotomy.

BACKGROUND: Red cell distribution width (RDW) has been recognized as a potential inflammatory biomarker, with elevated levels associated with adverse outcomes in various diseases. However, its role in predicting outcomes after brain tumor craniotomy remains unclear. We aimed to assess whether preoperative RDW influences mortality and postoperative complications in patients undergoing brain tumor craniotomy. METHODS: This retrospective cohort study analyzed serum RDW levels in patients undergoing brain tumor craniotomy at West China Hospital. RDW was evaluated in two forms: RDW-CV and RDW-SD, and was categorized into four quartiles for analysis by using logistic regression and multivariate analysis to adjust for confounding. RESULTS: The study encompassed 10,978 patients undergoing brain tumor craniotomy. our analysis revealed no significant difference in 30-day mortality across various RDW-CV levels. However, we observed a dose-response relationship with preoperative RDW-CV levels in assessing long-term mortality risks. Specifically, patients with RDW-CV levels of 12.6-13.2% (HR 1.04, 95% CI 1.01-1.18), 13.2-13.9% (HR 1.12, 95% CI 1.04-1.26), and > 13.9% (HR 1.34, 95% CI 1.18-1.51) exhibited a significantly higher hazard of long-term mortality compared to those with RDW-CV < 12.6%. When preoperative RDW-CV was analyzed as a continuous variable, for each 10% increase in RDW-CV, the adjusted OR of long-term mortality was 1.09 (95% CI 1.05-1.13). we also observed significant associations between preoperative higher RDW-CV levels and certain postoperative complications including acute kidney injury (OR 1.46, 95% CI: 1.10-1.94), pneumonia infection (OR 1.19 95% CI: 1.05-1.36), myocardial infarction (OR 1.32, 95% CI: 1.05-1.66), readmission (OR 1.15, 95% CI: 1.01-1.30), and a prolonged length of hospital stay (OR 1.11, 95% CI: 1.02-1.21). For RDW-SD levels, there was no significant correlation for short-term mortality, long-term mortality, and postoperative complications. CONCLUSIONS: Our study showed elevated preoperative RDW-CV is significantly associated with increased long-term mortality and multiple postoperative complications, but no such association is observed with RDW-SD. These findings show the prognostic importance of RDW-CV, reinforcing its potential as a valuable tool for risk stratification in the preoperative evaluation of brain tumor craniotomy patients.

Association of persistent postoperative hyperglycemia with mortality after elective craniotomy.

OBJECTIVE: The influence of persistent postoperative hyperglycemia after craniotomy has not yet been explored. This study aimed to investigate the hypothesis that persistent postoperative hyperglycemia is associated with mortality in patients undergoing an elective craniotomy. METHODS: This study included adult patients (age ≥ 18 years) undergoing an elective craniotomy between January 2011 and March 2021 at the West China Hospital, Sichuan University. Peak daily blood glucose values measured within the first 7 days after craniotomy were collected. Persistent hyperglycemia was defined by two or more consecutive serum glucose levels of mild, moderate, or severe hyperglycemia. Normoglycemia, mild hyperglycemia, moderate hyperglycemia, and severe hyperglycemia were defined as glucose values of ≤ 6.1 mmol/L, > 6.1 and ≤ 7.8 mmol/L, > 7.8 and ≤ 10.0 mmol/L, and > 10.0 mmol/L, respectively. RESULTS: This study included 14,907 patients undergoing an elective craniotomy. In the multivariable analysis, both moderate (adjusted OR 3.76, 95% CI 2.68-5.27) and severe (adjusted OR 3.82, 95% CI 2.54-5.76) persistent hyperglycemia in patients were associated with higher 30-day mortality compared with normoglycemia. However, this association was not observed in patients with mild hyperglycemia (adjusted OR 1.32, 95% CI 0.93-1.88). Interestingly, this association was observed regardless of whether patients had preoperative hyperglycemia. There was no interaction between moderate or severe hyperglycemia and preexisting diabetes (p for interaction = 0.65). When postoperative peak blood glucose values within the first 7 days after craniotomy were evaluated as a continuous variable, for each 1-mmol/L increase in blood glucose, the adjusted OR of 30-day mortality was 1.17 (95% CI 1.14-1.21). Postoperative blood glucose (area under the curve [AUC] = 0.78) was superior to preoperative blood glucose (AUC = 0.65; p < 0.001) for predicting mortality. Moderate and severe persistent hyperglycemia in patients were associated with an increased risk of deep venous thrombosis (adjusted OR 3.20, 95% CI 2.31-4.42), pneumonia (adjusted OR 2.77, 95% CI 2.40-3.21), myocardial infarction (adjusted OR 4.38, 95% CI 3.41-5.61), and prolonged hospital stays (adjusted OR 1.43, 95% CI 1.29-1.59). CONCLUSIONS: In patients undergoing an elective craniotomy, moderate and severe persistent postoperative hyperglycemia were associated with an increased risk of mortality compared with normoglycemia, regardless of preoperative hyperglycemia.

Associations of educational attainment with Sepsis mediated by metabolism traits and smoking: a Mendelian randomization study.

Objective: Sepsis constitutes a significant global healthcare burden. Studies suggest a correlation between educational attainment and the likelihood of developing sepsis. Our goal was to utilize Mendelian randomization (MR) in order to examine the causal connection between educational achievement (EA) and sepsis, while measuring the mediating impacts of adjustable variables. Methods: We collected statistical data summarizing educational achievement (EA), mediators, and sepsis from genome-wide association studies (GWAS). Employing a two-sample Mendelian randomization (MR) approach, we calculated the causal impact of education on sepsis. Following this, we performed multivariable MR analyses to assess the mediation proportions of various mediators, including body mass index (BMI), smoking, omega-3 fatty acids, and apolipoprotein A-I(ApoA-I). Results: Genetic prediction of 1-SD (4.2 years) increase in educational attainment (EA) was negatively correlated with sepsis risk (OR = 0.83, 95% CI 0.71 to 0.96). Among the four identified mediators, ranked proportionally, they including BMI (38.8%), smoking (36.5%), ApoA-I (6.3%) and omega-3 (3.7%). These findings remained robust across a variety of sensitivity analyses. Conclusion: The findings of this study provided evidence for the potential preventive impact of EA on sepsis, which may be influenced by factors including and metabolic traits and smoking. Enhancing interventions targeting these factors may contribute to reducing the burden of sepsis.

Association between postoperative changes in natremia and outcomes in patients undergoing elective craniotomy.

Postoperative dysnatremias, characterized by imbalances in serum sodium levels, have been linked to increased resource utilization and mortality in surgical and intensive care patients. The management of dysnatremias may involve medical interventions based on changes in sodium levels. In this study, we aimed to investigate the impact of postoperative changes in natremia on outcomes specifically in patients undergoing craniotomy.We conducted a retrospective analysis of patient records from the Department of Neurosurgery at West China Hospital, Sichuan University, covering the period from January 2011 to March 2021. We compared the highest and lowest sodium values in the first 14 postoperative days with the baseline values to define four categories for analysis: no change < 5 mmol/L; decrease > 5 mmol/L; increase > 5 mmol/L; both increase and decrease > 5 mmol/L. The primary outcome measure was 30-day mortality.A total of 12,713 patients were included in the study, and the overall postoperative mortality rate at 30 days was 2.1% (264 patients). The increase in sodium levels carried a particularly high risk, with a tenfold increase (OR 10.21; 95% CI 7.25-14.39) compared to patients with minimal or no change. Decreases in sodium levels were associated with an increase in mortality (OR 1.60; 95% CI 1.11-2.23).Moreover, the study revealed that postoperative sodium decrease was correlated with various complications, such as deep venous thrombosis, pneumonia, intracranial infection, urinary infection, seizures, myocardial infarction, and prolonged hospital length of stay. On the other hand, postoperative sodium increases were associated with acute kidney injury, deep venous thrombosis, pneumonia, intracranial infection, urinary infection, surgical site infection, seizures, myocardial infarction, and prolonged hospital length of stay.Changes in postoperative sodium levels were associated with increased complications, prolonged length of hospital stay, and 30-day mortality. Moreover, the severity of sodium change values correlated with higher mortality rates.

Association of postoperative hypernatremia with outcomes after elective craniotomy.

STUDY OBJECTIVE: Hypernatremia is a treatable biochemical disorder associated with significant morbidity and mortality in patients undergoing surgery. However, its impact on patients who undergo elective craniotomy is not well understood. This study aimed to investigate the prognostic implications of postoperative hypernatremia on the 30-day mortality of patients undergoing elective craniotomy. DESIGN: Retrospective cohort study. SETTING: The Department of Neurosurgery of a high-volume center. PATIENTS: Adult patients undergoing elective craniotomy except those with pituitary tumors, intracerebral hemorrhage, subarachnoid hemorrhage, or traumatic brain injury. INTERVENTIONS: None. MEASUREMENTS: Perioperative laboratory data were collected for all study participants, including sodium levels, neutrophil count, serum albumin, lymphocyte count, and blood glucose. These measurements were obtained as part of routine clinical care and provided valuable information for data analysis. MAIN RESULTS: Of the 10,223 identified elective craniotomy patients who met our inclusion and exclusion criteria, 14.9% (1519) developed postoperative hypernatremia. This population's overall postoperative 30-day mortality rate was 1.7% (175). After performing an adjusted logistic regression analysis, we found that the odds of 30-day mortality increased gradually with increasing severity of hypernatremia: 2.9 deaths (OR, 3.79; 95% CI, 2.46-5.85) in patients with mild hypernatremia, 13.9 deaths (OR, 17.73; 95% CI, 11.17-28.12) in those with moderate hypernatremia, and 38.3 deaths (OR, 67.00; 95% CI, 40.44-111.00) in those with severe hypernatremia. CONCLUSIONS: Hypernatremia is common after elective craniotomy, and its presence is associated with increased mortality and complications, particularly in cases of severe hypernatremia. These results emphasize the significance of risk evaluation in neurosurgical patients and propose the advantages of closely monitoring serum sodium levels in high-risk individuals. Future randomized controlled trials could provide more insight into the effect of treating postoperative hypernatremia in these patients.

Association of anemia with mortality in young adult patients with intracerebral hemorrhage.

This study aimed to examine the association of hemoglobin concentration with a 90-day mortality of young adult patients with ICH in a large retrospective cohort. A retrospective observational study was conducted between December 2013 and June 2019 in two tertiary academic medical centers in China. We defined patients with hemoglobin concentration < 80 g/L as severe anemia and 80-120/130 g/L as mild to moderate anemia. We also defined patients with hemoglobin concentration > 160 g/L as high hemoglobin. Associations of hemoglobin and outcomes were evaluated in multivariable regression analyses. The primary outcome was mortality at 90 days. We identified 4098 patients with ICH who met the inclusion criteria. After adjusting primary confounding variables, the 90-day mortality rate was significantly higher in young patients with severe anemia (OR, 39.65; 95% CI 15.42-101.97), moderate anemia (OR, 2.49; 95% CI 1.24-5.00), mild anemia (OR, 1.89; 95% CI 1.20-2.98), and high hemoglobin (OR, 2.03; 95% CI 1.26-3.26) group than in young patients of the normal group. The younger age was associated with a higher risk of death from anemia in patients with ICH (P for interaction = 0.01). In young adult patients with ICH, hemoglobin concentration was associated with 90-day mortality, and even mild to moderate anemia correlated with higher mortality. We also found that in ICH patients with anemia, younger age was associated with higher risk.

Preoperative hematocrit levels and postoperative mortality in patients undergoing craniotomy for brain tumors.

Background: Abnormal hematocrit values, including anemia and polycythemia, are common in patients undergoing craniotomy, but the extent to which preoperative anemia or polycythemia independently increases the risk of mortality is unclear. This retrospective cohort study aimed to examine the association between preoperative anemia and polycythemia and postoperative mortality in patients who underwent craniotomy for brain tumor resection. Methods: We retrospectively analyzed data from 12,170 patients diagnosed with a brain tumor who underwent cranial surgery at West China Hospital between January 2011 and March 2021. The preoperative hematocrit value was defined as the last hematocrit value within 7 days before the operation, and patients were grouped according to the severity of their anemia or polycythemia. We assessed the primary outcome of 30-day postoperative mortality using logistic regression analysis adjusted for potential confounding factors. Results: Multivariable logistic regression analysis reported that the 30-day mortality risk was raised with increasing severity of both anemia and polycythemia. Odds ratios for mild, moderate, and severe anemia were 1.12 (95% CI: 0.79-1.60), 1.66 (95% CI: 1.06-2.58), and 2.24 (95% CI: 0.99-5.06), respectively. Odds ratios for mild, moderate, and severe polycythemia were 1.40 (95% CI: 0.95-2.07), 2.81 (95% CI: 1.32-5.99), and 14.32 (95% CI: 3.84-53.44), respectively. Conclusions: This study demonstrated that moderate to severe anemia and polycythemia are independently associated with increased postoperative mortality in patients undergoing craniotomy for brain tumor resection. These findings underscore the importance of identifying and managing abnormal hematocrit values before craniotomy surgery.

Association Between Red Blood Cell Distribution width and Long-Term Mortality in Patients with Intracerebral Hemorrhage.

BACKGROUND: The association between the red cell distribution width (RDW) and long-term mortality in patients with intracerebral hemorrhage (ICH) has not been clearly established. METHODS: We conducted a retrospective cohort study of patients with ICH admitted to two tertiary hospitals. The primary outcome was long-term mortality, and the effect of elevated RDW (RDW coefficient of variation [RDW-CV]; RDW standard deviation [RDW-SD]) on outcomes was assessed by using logistic regression analysis. Serum RDW levels was divided into four levels by quartiles (the lowest quartile [Q1]; the highest quartile [Q4]). RESULTS: This study included 4223 patients with ICH. After adjustment for potential confounders, admission RDW-CV (Quartile 4 [Q4] vs. Quartile 1 [Q1], adjusted hazard ratio [HR] 1.61, 95% confidence interval [CI] 1.34-1.92) and median RDW-CV within the first month after admission (Q4 vs. Q1, adjusted HR 1.69, 95% CI 1.40-2.04) were both associated with 1-year mortality following ICH. Parallel results were found for RDW-SD. In the receiver operating characteristic analyses, both RDW-CV and RDW-SD outperformed some inflammatory biomarkers, such as albumin, hemoglobin, total cholesterol, platelet count, lymphocyte, and fibrinogen, in predicting long-term mortality following ICH. Additionally, compared with admission RDW, median RDW-CV and RDW-SD (areas under the curve [AUC] 0.668 and 0.652, respectively) was superior to predict long-term mortality, (P < 0.001). Furthermore, median RDW-CV level was a better predictor than RDW-SD (P = 0.03). CONCLUSIONS: In patients with ICH, RDW independently predicted long-term mortality. Median RDW levels within the first month after admission were better predictors of long-term mortality compared with RDW levels on admission. Additionally, median RDW-CV showed superior predictive capacity than median RDW-SD for long-term mortality following ICH.

Obesity Paradox for Postoperative Mortality in Young Chinese Patients Undergoing Craniotomy for Brain Tumor Resection.

BACKGROUND: There is little evidence regarding the association of body mass index (BMI) with postoperative mortality after craniotomy, especially in the Asian population. Our study aimed to explore the association between BMI and postoperative 30-day mortality in Chinese patients undergoing craniotomy for brain tumor resection. METHODS: This large retrospective cohort study, Supplemental Digital Content 9, http://links.lww.com/JNA/A634 collected data from 7519 patients who underwent craniotomy for brain tumor resection. On the basis of the World Health Organization obesity criteria for Asians, included patients were categorized as underweight (<18.5 kg/m2), normal weight (18.5 to 22.9 kg/m2), overweight (23to 24.9 kg/m2), obese I (25 to 29.9 kg/m2), and obese II (≥30 kg/m2). We used a multivariable logistic regression model to explore the association between different BMI categories and 30-day postoperative mortality. In addition, we also conducted stratified analyses based on age and sex. RESULTS: Overweight (adjusted odds ratio 0.63, 95% CI 0.40-0.99) and obese I (adjusted odds ratio 0.44, 95% CI 0.28-0.72) were associated with decreased 30-day postoperative mortality compared with normal-weight counterparts. Such associations were prominent among younger (age younger than 65 y) patients but not older patients, and there was an interaction between age and overweight versus normal weight on mortality (P for interaction=0.04). CONCLUSIONS: We found that among Chinese patients undergoing craniotomy for brain tumors, there was a J-shaped association between BMI and postoperative 30-day mortality, with lowest mortality at 27 kg/m². Moreover, in young patients, overweight and obese I were both associated with decreased risk of 30-day mortality.

Effect of implantable cardiac monitors on preventing stroke: A systematic review and meta-analysis of randomized clinical trials.

BACKGROUND AND AIM: Implantable cardiac monitors (ICM) can facilitate the detection of asymptomatic atrial fibrillation episodes. We performed a systematic review and meta-analysis to investigate whether ICM can prevent stroke in patients with prior stroke and risk factors for stroke. METHODS: This study included randomized controlled trials comparing ICM with conventional (non-ICM) external cardiac monitoring in patients with prior stroke and risk factors for stroke. We searched Medline, Embase, and CENTRAL from inception until January 5, 2022, without language restriction. Quantitative pooling of the data was undertaken using a random-effects model. The primary outcome was ischemic stroke at the longest follow-up. RESULTS: Four trials comprising 7237 patients were included. ICM was significantly associated with decreased risk of ischemic stroke (RR 0.76; 95% CI, 0.59-0.97; moderate-quality evidence) in patients with prior stroke and risk factors for stroke. ICM was associated with higher detection of atrial fibrillation (RR 4.21, 95% CI 2.26-7.85) and use of oral anticoagulants (RR 2.29, 95% CI 2.07-2.55). CONCLUSIONS: ICM results in a significantly lower risk of ischemic stroke than conventional (non-ICM) external cardiac monitoring in patients with prior stroke and risk factors for stroke. Due to the clinical heterogeneity of study population and limited related studies, more trials were needed to furtherly explore the topic in patients with prior stroke or high risk of stroke.

Association between intraoperative steroid and postoperative mortality in patients undergoing craniotomy for brain tumor.

Background: Despite the widespread use of intraoperative steroids in various neurological surgeries to reduce cerebral edema and other adverse symptoms, there is sparse evidence in the literature for the optimal and safe usage of intraoperative steroid administration in patients undergoing craniotomy for brain tumors. We aimed to investigate the effects of intraoperative steroid administration on postoperative 30-day mortality in patients undergoing craniotomy for brain tumors. Methods: Adult patients who underwent craniotomy for brain tumors between January 2011 to January 2020 were included at West China Hospital, Sichuan University in this retrospective cohort study. Stratified analysis based on the type of brain tumor was conducted to explore the potential interaction. Results: This study included 8,663 patients undergoing craniotomy for brain tumors. In patients with benign brain tumors, intraoperative administration of steroids was associated with a higher risk of postoperative 30-day mortality (adjusted OR 1.98, 95% CI 1.09-3.57). However, in patients with malignant brain tumors, no significant association was found between intraoperative steroid administration and postoperative 30-day mortality (adjusted OR 0.86, 95% CI 0.55-1.35). Additionally, administration of intraoperative steroids was not associated with acute kidney injury (adjusted OR 1.11, 95% CI 0.71-1.73), pneumonia (adjusted OR 0.89, 95% CI 0.74-1.07), surgical site infection (adjusted OR 0.78, 95% CI 0.50-1.22) within 30 days, and stress hyperglycemia (adjusted OR 1.05, 95% CI 0.81-1.38) within 24 h after craniotomy for brain tumor. Conclusion: In patients undergoing craniotomy for benign brain tumors, intraoperative steroids were associated with 30-day mortality, but this association was not significant in patients with malignant brain tumors.

Predictive model of acute kidney injury after spontaneous intracerebral hemorrhage: A multicenter retrospective study.

BACKGROUND AND OBJECTIVES: Acute kidney injury is a common comorbidity in patients with intracerebral hemorrhage. Although there are predictive models to determine risk of AKI in patients in critical care or post-surgical scenarios or in general medical floors, there are no models that specifically determine the risk of AKI in patients with ICH. METHODS: Clinical features and laboratory tests were selected by previous studies and LASSO (least absolute shrinkage and selection operator) regression. We used multivariable logistic regression with a bidirectional stepwise method to construct ICH-AKIM (intracerebral hemorrhage-associated acute kidney injury model). The accuracy of ICH-AKIM was measured by the area under the receiver operating characteristic curve. The outcome was AKI development during hospitalization, defined as KDIGO (Kidney Disease: Improving Global Outcomes) Guidelines. RESULTS: From four independent medical centers, a total of 9649 patients with ICH were available. Overall, five clinical features (sex, systolic blood pressure, diabetes, Glasgow coma scale, mannitol infusion) and four laboratory tests at admission (serum creatinine, albumin, uric acid, neutrophils-to-lymphocyte ratio) were predictive factors and were included in the ICH-AKIM construction. The AUC of ICH-AKIM in the derivation, internal validation, and three external validation cohorts were 0.815, 0.816, 0.776, 0.780, and 0.821, respectively. Compared to the univariate forecast and pre-existing AKI models, ICH-AKIM led to significant improvements in discrimination and reclassification for predicting the incidence of AKI in all cohorts. An online interface of ICH-AKIM is freely available for use. CONCLUSION: ICH-AKIM exhibited good discriminative capabilities for the prediction of AKI after ICH and outperforms existing predictive models.

Scutellarein regulates the PTEN/AKT/NFκB signaling pathway to reduce pirarubicin related liver inflammation.

The side effects of chemotherapy drugs have been hindering the progress of tumor treatment. The liver is the metabolic site of most drugs, which leads to the frequent occurrence of liver injury. Classical chemotherapy drugs such as pirarubicin (THP) can also cause dose­dependent hepatotoxicity, and the related mechanism is closely related to liver inflammation. Scutellarein (Sc) is a potential Chinese herbal monomer exhibiting liver protection activity, which can effectively alleviate the liver inflammation caused by obesity. In the present study, THP was used to establish a rat model of hepatotoxicity, and Sc was used for treatment. The experimental methods used included measuring body weight, detecting serum biomarkers, observing liver morphology with H&E staining, observing cell apoptosis with TUNEL staining, and detecting the expression of PTEN/AKT/NFκB signaling pathways and inflammatory genes with PCR and western blotting. However, whether Sc can inhibit the liver inflammation induced by THP has not been reported. The experimental results showed that THP led to the upregulation of PTEN and the increase of inflammatory factors in rat liver, while Sc effectively alleviated the aforementioned changes. It was further identified in primary hepatocytes that Sc can effectively inhabited PTEN, regulate AKT/NFκB signaling pathway, inhibit liver inflammation and ultimately protect the liver.

White Blood Cell Count Predicts Mortality in Patients with Spontaneous Intracerebral Hemorrhage.

BACKGROUND: The association between white blood cell (WBC) counts and mortality in patients with intracerebral hemorrhage (ICH) has not been established. The aim of this study is to determine whether higher WBC is associated with mortality at 90 days. METHODS: A retrospective observational study was conducted at two medical hospitals in China. Baseline WBC count on admission served as the primary predictor variable. Longitudinal WBC counts within the first week after admission were collected to assess the effects of WBC trajectory and the median and maximum WBC counts on outcomes following ICH. Associations of WBC count with outcomes were evaluated in multivariable regression analyses. RESULTS: We identified 3613 patients with ICH who met the inclusion criteria. After adjusting primary confounding variables, patients with increased WBC count had a significantly higher risk of 90-day mortality (p < 0.001 for trend). In the receiver operating characteristic analyses, the capacity for all-cause mortality prediction by WBC count on admission (area under the ROC curve (AUC) = 0.65) was superior to other important inflammatory markers, including neutrophil (AUC = 0.64) , lymphocyte (AUC = 0.57), albumin (AUC = 0.57), and platelet count (AUC = 0.53), p < 0.001 for WBC vs. neutrophil, and the median WBC count (AUC = 0.66) within the first week after admission was a better marker than admission WBC count (p = 0.02). CONCLUSIONS: In patients with ICH, WBC count on admission was associated with all-cause mortality at 90 days. Additionally, the median and maximum WBC counts within the first week after admission showed better predictive ability for the 90-day mortality compared with the WBC count on admission.

Glucose-albumin ratio as new biomarker for predicting mortality after intracerebral hemorrhage.

OBJECTIVE: This study aims to evaluate the prognostic value of blood-based biomarkers and their combinations, in particular the glucose-albumin ratio (GAR), in patients with spontaneous intracerebral hemorrhage (ICH). METHODS: A retrospective observational study on 2481 patients from one hospital was conducted and validated with 602 patients from another. We assessed 15 biomarkers and focused on GAR to elucidate its prognostic and predictive value for outcomes in both cohorts. The primary outcome was mortality at 90 days. RESULTS: The ratio of glucose-to-albumin, defined as GAR, was superior to other biomarkers for predicting mortality at 90 days in patients with ICH (AUC = 0.72). High GAR (using the best cutoff value of 0.19) was associated with increased mortality at 90 days (odds ratios of 1.90, 95% CI 1.54-2.34) and all-cause mortality in the first 3 years after admission (hazard ratio of 1.62, 95% CI 1.42-1.86). All aforementioned findings for GAR were successfully validated in an external independent cohort. CONCLUSIONS: GAR may be a valuable biomarker for predicting the mortality of patients with ICH.

Association of Postoperative Drift in Hemoglobin With Mortality After Brain Tumor Craniotomy.

BACKGROUND: Postoperative downward drift in hemoglobin (Hb) concentration may be associated with complications and death, even if nadir Hb remains more than the red blood cell transfusion threshold of 7 g/dL. OBJECTIVE: To assess whether postoperative Hb drift in patients undergoing brain tumor craniotomy influences mortality in the immediate perioperative period. METHODS: This retrospective cohort study included patients undergoing craniotomy for brain tumors. We defined no postoperative Hb decrease, mild decrease, moderate decrease, and severe decrease as postoperative Hb drift of ≤25%, 26% to 50%, 51% to 75%, and >75%, respectively. The primary outcome was 30-day mortality after craniotomy. RESULTS: This study included 8159 patients who underwent a craniotomy for brain tumors. Compared with patients with no postoperative Hb drift, the odds of postoperative mortality at 30 days increased in patients with mild postoperative Hb drift (adjusted odds ratio [OR] 2.47, 95% CI 1.72-3.56), moderate drift (adjusted OR 6.56, 95% CI 3.42-12.59), and severe drift (adjusted OR 12.33, 95% CI 3.48-43.62). When postoperative Hb drift was analyzed as a continuous variable, for each 10% increase in Hb drift, the adjusted OR of postoperative mortality at 30 days was 1.46 (95% CI 1.31-1.63). CONCLUSION: In patients undergoing brain tumor craniotomy, a small postoperative Hb drift was associated with increased odds of postoperative mortality at 30 days, even if the nadir Hb level remained greater than the red blood cell transfusion threshold of 7 g/dL. Future randomized clinical trials of perioperative transfusion practices may examine the effect of both nadir Hb and Hb drift.

In silico identification of A1 agonists and A2a inhibitors in pain based on molecular docking strategies and dynamics simulations.

Most recently, the adenosine is considered as one of the most promising targets for treating pain, with few side effects. It exists in the central nervous system, and plays a key role in nociceptive afferent pathway. It is reported that the A1 receptor (A1R) could inhibit Ca2+ channels to reduce the pain like analgesic mechanism of morphine. And, A2a receptor (A2aR) was reported to enhance the accumulation of AMP (cAMP) and released peptides from sensory neurons, resulting in constitutive activation of pain. Much evidence showed that A1R and A2aR could be served as the interesting targets for the treatment of pain. Herein, virtual screening was utilized to identify the small molecule compounds towards A1R and A2aR, and top six molecules were considered as candidates via amber scores. The molecular dynamic (MD) simulations and molecular mechanics/generalized born surface area (MM/GBSA) were employed to further analyze the affinity and binding stability of the six molecules towards A1R and A2aR. Moreover, energy decomposition analysis showed significant residues in A1R and A2aR, including His1383, Phe1276, and Glu1277. It provided basics for discovery of novel agonists and antagonists. Finally, the agonists of A1R (ZINC19943625, ZINC13555217, and ZINC04698406) and inhibitors of A2aR (ZINC19370372, ZINC20176051, and ZINC57263068) were successfully recognized. Taken together, our discovered small molecules may serve as the promising candidate agents for future pain research.

Association of preoperative glucose concentration with mortality in patients undergoing craniotomy for brain tumor.

OBJECTIVE: Hyperglycemia is associated with worse outcomes in ambulatory settings and specialized hospital settings, but there are sparse data on the importance of preoperative blood glucose measurement before brain tumor craniotomy. The authors sought to investigate the association between preoperative glucose level and 30-day mortality rate in patients undergoing brain tumor resection. METHODS: This retrospective cohort study included patients undergoing craniotomy for brain tumors at West China Hospital, Sichuan University, from January 2011 to March 2021. Surgical mortality rates were evaluated in patients who had normal glycemia (< 5.6 mmol/L) as well as mild (5.6-6.9 mmol/L), moderate (7.0-11.0 mmol/L), and severe hyperglycemia (> 11.0 mmol/L). RESULTS: The study included 12,281 patients who underwent tumor resection via craniotomy. The overall 30-day mortality rate was 2.0% (242/12,281), whereas the rates for normal glycemia and mild, moderate, and severe hyperglycemia were 1.5%, 2.5%, 3.8%, and 6.5%, respectively. Compared with normal glycemia, the odds of mortality at 30 days were higher in patients with mild hyperglycemia (adjusted odds ratio [OR] 1.44, 95% confidence interval [CI] 1.05-2.00), moderate hyperglycemia (OR 2.04, 95% CI 1.41-2.96), and severe hyperglycemia (OR 3.76, 95% CI 1.96-7.20; p < 0.001 for trend). When blood glucose was analyzed as a continuous variable, for each 1 mmol/L increase in blood glucose, the adjusted OR of 30-day mortality was 1.13 (95% CI 1.08-1.19). The addition of a preoperative glucose level significantly improved the area under the curve and categorical net reclassification index for prediction of mortality. CONCLUSIONS: In patients undergoing craniotomy for brain tumors, even mild hyperglycemia was associated with an increased mortality rate, at a glucose level that was much lower than the commonly applied level.

Minor alleles of FTO rs9939609 and rs17817449 polymorphisms confer a higher risk of type 2 diabetes mellitus and dyslipidemia, but not coronary artery disease in a Chinese Han population.

Background: Relationships of the polymorphisms in fat mass and obesity-associated gene (FTO) and peroxisome proliferator-activated receptor delta gene (PPARD) with metabolic-related diseases remain to be clarified. Methods: One thousand three hundred and eighty-one subjects were enrolled. Metabolic-related diseases including obesity, dyslipidemia, hyperhomocysteinemia, hyperuricemia, hypertension, type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD) were defined based on diagnostic criteria. FTO rs9939609 and rs17817449, and PPARD rs2016520 and rs2267668 polymorphisms were genotyped by using polymerase chain reaction-restricted fragment length polymorphism method. Results: Patients with T2DM or dyslipidemia had a higher frequency of AA, AT or AA + AT genotypes as well as A allele of FTO rs9939609 polymorphism than those free of T2DM or dyslipidemia (P ≤ 0.04 for all). Patients with T2DM or dyslipidemia had a higher frequency of GG, GT or GG + GT genotypes as well as G allele of FTO rs17817449 polymorphism than those free of T2DM or dyslipidemia (P ≤ 0.03 for all). Multivariate logistic regression analyses showed that FTO rs9939609 and rs17817449 polymorphisms were independently associated with T2DM as well as dyslipidemia after adjustment for age, sex, smoking and other metabolic diseases. FTO rs9939609 and rs17817449 polymorphisms were not associated with obesity, hyperhomocysteinemia, hyperuricemia, hypertension and CAD. Obese or T2DM carriers of the AA or AT genotype of the FTO rs9939609 polymorphism had a higher prevalence of dyslipidemia compared to non-obese or non-T2DM carriers of the AA or AT genotype (P = 0.03 for both). Among the carriers of GG or GT genotype of the FTO rs17817449 polymorphism, the prevalence of dyslipidemia in obese patients was higher than that in non-obese subjects (P < 0.01). PPARD rs2016520 and rs2267668 polymorphisms were not correlated with any of the metabolic-related diseases in the study population. Conclusion: Minor alleles of FTO rs9939609 and rs17817449 polymorphisms confer a higher risk of T2DM and dyslipidemia, and the risk is further increased among obese individuals. PPARD rs2016520 and rs2267668 polymorphisms are not associated with metabolic-related diseases.