Association of Postoperative Hypoglycemia With Mortality After Elective Craniotomy.

BACKGROUND AND OBJECTIVES: Hypoglycemia is a known risk of intensive postoperative glucose control in neurosurgical patients. However, the impact of postoperative hypoglycemia after craniotomy remains unexplored. This study aimed to determine the association between postoperative hypoglycemia and mortality in patients undergoing elective craniotomy. METHODS: This study involved adult patients who underwent elective craniotomy at the West China Hospital, Sichuan University, between January 2011 and March 2021. We defined moderate hypoglycemia as blood glucose levels below 3.9 mmol/L (70 mg/dL) and severe hypoglycemia as blood glucose levels below 2.2 mmol/L (40 mg/dL). The primary outcome was postoperative 90-day mortality. RESULTS: This study involved 15 040 patients undergoing an elective craniotomy. Overall, 504 (3.4%) patients experienced moderate hypoglycemia, whereas 125 (0.8%) patients experienced severe hypoglycemia. Multivariable analysis revealed that both moderate hypoglycemia (adjusted odds ratio [aOR] 1.86, 95% CI 1.24-2.78) and severe (aOR 2.94, 95% CI 1.46-5.92) hypoglycemia were associated with increased 90-day mortality compared with patients without hypoglycemia. Moreover, patients with moderate (aOR 2.78, 95% CI 2.28-3.39) or severe (aOR 16.70, 95% CI 10.63-26.23) hypoglycemia demonstrated a significantly higher OR for major morbidity after adjustment, compared with those without hypoglycemia. Patients experiencing moderate (aOR 3.20, 95% CI 2.65-3.88) or severe (aOR 14.03, 95% CI 8.78-22.43) hypoglycemia had significantly longer hospital stays than those without hypoglycemia. The risk of mortality and morbidity showed a tendency to increase with the number of hypoglycemia episodes in patients undergoing elective craniotomy (P for trend = .01, <.001). CONCLUSION: Among patients undergoing an elective craniotomy, moderate hypoglycemia and severe hypoglycemia are associated with increased mortality, major morbidity, and prolonged hospital stays. In addition, the risk of mortality and major morbidity increases with the number of hypoglycemia episodes.

Proteomics study of primary and recurrent adamantinomatous craniopharyngiomas.

BACKGROUND: Adamantinomatous craniopharyngiomas (ACPs) are rare benign epithelial tumours with high recurrence and poor prognosis. Biological differences between recurrent and primary ACPs that may be associated with disease recurrence and treatment have yet to be evaluated at the proteomic level. In this study, we aimed to determine the proteomic profiles of paired recurrent and primary ACP, gain biological insight into ACP recurrence, and identify potential targets for ACP treatment. METHOD: Patients with ACP (n = 15) or Rathke's cleft cyst (RCC; n = 7) who underwent surgery at Sanbo Brain Hospital, Capital Medical University, Beijing, China and received pathological confirmation of ACP or RCC were enrolled in this study. We conducted a proteomic analysis to investigate the characteristics of primary ACP, paired recurrent ACP, and RCC. Western blotting was used to validate our proteomic results and assess the expression of key tumour-associated proteins in recurrent and primary ACPs. Flow cytometry was performed to evaluate the exhaustion of tumour-infiltrating lymphocytes (TILs) in primary and recurrent ACP tissue samples. Immunohistochemical staining for CD3 and PD-L1 was conducted to determine differences in T-cell infiltration and the expression of immunosuppressive molecules between paired primary and recurrent ACP samples. RESULTS: The bioinformatics analysis showed that proteins differentially expressed between recurrent and primary ACPs were significantly associated with extracellular matrix organisation and interleukin signalling. Cathepsin K, which was upregulated in recurrent ACP compared with that in primary ACP, may play a role in ACP recurrence. High infiltration of T cells and exhaustion of TILs were revealed by the flow cytometry analysis of ACP. CONCLUSIONS: This study provides a preliminary description of the proteomic differences between primary ACP, recurrent ACP, and RCC. Our findings serve as a resource for craniopharyngioma researchers and may ultimately expand existing knowledge of recurrent ACP and benefit clinical practice.

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.

Visible and NIR microscopic hyperspectrum reconstruction from RGB images with deep convolutional neural networks.

We investigate the microscopic hyperspectral reconstruction from RGB images with a deep convolutional neural network (DCNN) in this paper. Based on the microscopic hyperspectral imaging system, a homemade dataset consisted of microscopic hyperspectral and RGB image pairs is constructed. For considering the importance of spectral correlation between neighbor spectral bands in microscopic hyperspectrum reconstruction, the 2D convolution is replaced by 3D convolution in the DCNN framework, and a metric (weight factor) used to evaluate the performance reconstructed hyperspectrum is also introduced into the loss function used in training. The effects of the dimension of convolution kernel and the weight factor in the loss function on the performance of the reconstruction model are studied. The overall results indicate that our model can show better performance than the traditional models applied to reconstruct the hyperspectral images based on DCNN for the public and the homemade microscopic datasets. In addition, we furthermore explore the microscopic hyperspectrum reconstruction from RGB images in infrared region, and the results show that the model proposed in this paper has great potential to expand the reconstructed hyperspectrum wavelength range from the visible to near infrared bands.

Investigating the pharmacological mechanism of Zhengyuan jiaonang for treating colorectal cancer via network pharmacology analysis and experimental verification.

ETHNOPHARMACOLOGICAL RELEVANCE: Zhengyuan jiaonang (ZYJN) is a traditional Chinese patent medicine (CPM) used in China for adjuvant cancer therapy, which has been proved to have anti-fatigue effects. AIM OF STUDY: The study aims to investigate the antitumor effects of ZYJN and its underlying mechanisms using subcutaneous transplant CT26 model. MATERIALS AND METHODS: Fingerprint analysis of ZYJN was performed using high performance liquid chromatography. The potential targets of ZYJN were predicted using bioinformatic analysis, which were further validated by Western Blot assay. Subcutaneous transplant CT26 model was used to evaluate the antitumor effects of ZYJN. The effects of ZYJN on the tumor immune microenvironment were investigated by flow cytometry. Transparent imaging was used to investigate the effects of ZYJN on fibrosis and angiogenesis. RESULTS: ZYJN could inhibit colorectal cancer growth when administered alone or in combination with 5-FU. The combination of ZYJN and 5-FU could significantly increase the serum level of albumin (ALB) and decrease the serum level of aspartate aminotransferase (AST). In addition, the combination of ZYJN at 0.75 g/kg and 5-FU significantly decreased the serum level of vascular endothelial growth factors (VEGF) and inhibited the angiogenesis of CT26 cancer. The combination of ZYJN at 1.50 g/kg and 5-FU could promote the fibrosis process of CT26 cancer. Additionally, combination of ZYJN and 5-FU could significantly increase the percentage of tumor-infiltrating T cells and CD4+ T cells in the late stage of CT26 model, while ZYJN at 1.50 g/kg increased the percentage of NK cells as well as CD8+ T cells in the early stage of CT26 model. Western Blot analysis revealed that administration of ZYJN at 0.75 g/kg reduced the expression of PI3K-p110α, CDK1, CCNB1 and MMP-9, and inhibited the phosphorylation of Akt (Thr308). CONCLUSIONS: ZYJN could inhibit the tumor growth of CT26 colorectal cancer by promoting tumor fibrosis, suppressing angiogenesis, migration, and invasion and modulating the tumor immune microenvironment. ZYJN enhanced the efficacy and reduced the toxicity of chemotherapy drugs in combination therapy. Our findings provide evidence for the clinical application of ZYJN in cancer treatment.

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.

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.

Lower versus higher oxygen targets for out-of-hospital cardiac arrest: a systematic review and meta-analysis.

BACKGROUND: Supplemental oxygen is commonly administered to patients after out-of-hospital cardiac arrest. However, the findings from studies on oxygen targeting for out-of-hospital cardiac arrest are inconclusive. Thus, we conducted a systematic review and meta-analysis to evaluate the impact of lower oxygen target compared with higher oxygen target on patients after out-of-hospital cardiac arrest. METHODS: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, from inception to February 6, 2023, for randomized controlled trials comparing lower and higher oxygen target in adults (aged ≥ 18 years) after out-of-hospital cardiac arrest. We screened studies and extracted data independently. The primary outcome was mortality at 90 days after cardiac arrest. We assessed quality of evidence using the grading of recommendations assessment, development, and evaluation approach. This study was registered with PROSPERO, number CRD42023409368. RESULTS: The analysis included 7 randomized controlled trials with a total of 1451 participants. Compared with lower oxygen target, the use of a higher oxygen target was not associated with a higher mortality rate (relative risk 0.97, 95% confidence intervals 0.82 to 1.14; I2 = 25%). Findings were robust to trial sequential, subgroup, and sensitivity analysis. CONCLUSION: Lower oxygen target did not reduce the mortality compared with higher oxygen target in patients after out-of-hospital cardiac arrest.

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.

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.

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.

Rerupture outcome of conservative versus open repair versus minimally invasive repair of acute Achilles tendon ruptures: A systematic review and meta-analysis.

OBJECTIVE: To compare the rerupture rate after conservative treatment, open repair, and minimally invasive surgery management of acute Achilles tendon ruptures. DESIGN: Systematic review and network meta-analysis. DATA SOURCES: We searched Medline, Embase, and the Cochrane Central Register of Controlled Trials from inception to August 2022. METHODS: Randomised controlled trials involving different treatments for Achilles tendon rupture were included. The primary outcome was rerupture. Bayesian network meta-analysis with random effects was used to assess pooled relative risks (RRs) and 95% confidence intervals. We evaluated the heterogeneity and publication bias. RESULTS: Thirteen trials with 1465 patients were included. In direct comparison, there was no difference between open repair and minimally invasive surgery for rerupture rate (RR, 0.72, 95% CI 0.10-4.4; I2 = 0%; Table 2). Compared to the conservative treatment, the RR was 0.27 (95% CI 0.10-0.62, I2 = 0%) for open repair and 0.14 (95% CI 0.01-0.88, I2 = 0%) for minimally invasive surgery. The network meta-analysis had obtained the similar results as the direct comparison. CONCLUSION: Both open repair and minimally invasive surgery were associated with a significant reduction in rerupture rate compared with conservative management, but no difference in rerupture rate was found comparing open repair and minimally invasive surgery.

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.

Prediction and visualization of gene modulated ultralow cadmium accumulation in brown rice grains by hyperspectral imaging.

Monitoring (including prediction and visualization) the gene modulated cadmium (Cd) accumulation in rice grains is one of the most important steps for identification of key transporter genes responsible for grain Cd accumulation and breeding low grain-Cd-accumulating rice cultivars. A method to predict and visualize the gene modulated ultralow Cd accumulation in brown rice grains based on the hyperspectral image (HSI) technology is proposed in this study. Firstly, the Vis-NIR HSIs of brown rice grain samples with 48Cd content levels induced by gene modulation (ranging from 0.0637 to 0.1845 mg/kg) are collected using HSI system. Then, Kernel-ridge (KRR) and random forest (RFR) regression models based on full spectral data and the data after feature dimension reduction (FDR) with kernel principal component analysis (KPCA) and truncated singular value decomposition (TSVD) algorithms are established to predict the Cd contents. RFR model shows poor performance due to the over-fitting based on the full spectral data, while the KRR model can obtain a good predict accuracy with Rp2 of 0.9035, RMSEP of 0.0037 and RPD of 3.278. After the FDR of the full spectral data, the RFR model combined with TSVD reaches the optimum prediction accuracy with Rp2 of 0.9056, RMSEP of 0.0074 and RPD of 3.318, and the best prediction precision of KRR model can also be further enhanced by TSVD with Rp2 of 0.9224, RMSEP of 0.0067 and RPD of 3.512. Finally, the visualization of the predicted Cd accumulation in brown rice grains are realized based on the best regression model (KRR + TSVD). The results of this work indicate that Vis-NIR HSI has great potential for detection and visualization gene modulation induced ultralow Cd accumulation and transport in rice crops.

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.

EIF4A3-Induced Upregulation of hsa_circ_0040039 is a Biomarker and Aggravates IL-1ß-Stimulated Intervertebral Disc Degeneration.

Intervertebral disc degeneration (IDD) is characterised by nucleus pulposus (NP) loss and extracellular matrix (ECM) degeneration. Circular RNAs (circRNAs) have been reported to be dysregulated during IDD progression. Recently, reports showed that hsa_circ_0040039 was increased in degenerated lumbar disc samples. The aim of this study was to explore the specific role and underlying mechanisms of hsa_circ_0040039 in IDD. The expression of hsa_circ_0040039 was investigated in NP tissues of IDD patients. IL-1ß was used to treat NP cells to construct an IDD in vitro model. Overexpression and loss-of-function assays and bioinformatic analysis were performed to evaluate the role and potential mechanism of hsa_circ_0040039 during IDD progression. Hsa_circ_0040039 expression was increased about 2 folds in NP tissues compared with normal tissues and IL-1ß-stimulated NP cells also presented hsa_circ_0040039 upregulation, and its overexpression promoted cell proliferation and ECM degeneration. The depletion of hsa_circ_0040039 had the opposite effects. Based on bioinformatics prediction, Luciferase assay, PCR and Western blot, our study verified that hsa_circ_0040039 directly bond to miR-146b-3p, then mediated its targeted MMP2 and PCNA. Moreover, the overexpression of miR-146b-3p and the silence of MMP2 or PCNA, partially abolished the effect of hsa_circ_0040039 on IL-1ß-stimulated NPs. Hsa_circ_0040039 may participate in IDD development by mediating the repair and regeneration of NPs through upregulation MMP2 and PCNA mediated by miR-146b-3p.

Ginsenoside 3ß-O-Glc-DM (C3DM) suppressed glioma tumor growth by downregulating the EGFR/PI3K/AKT/mTOR signaling pathway and modulating the tumor microenvironment.

Ginsenosides are the main bioactive constituents of Panax ginseng, which have been broadly studied in cancer treatment. Our previous studies have demonstrated that 3ß-O-Glc-DM (C3DM), a biosynthetic ginsenoside, exhibited antitumor effects in several cancer cell lines with anti-colon cancer activity superior to ginsenoside 20(R)-Rg3 in vivo. However, the efficacy of C3DM on glioma has not been proved yet. In this study, the antitumor activities and underlying mechanisms of C3DM on glioma were investigated in vitro and in vivo. Cell viability, apoptosis, migration, FCM, IHC, RT-qPCR, quantitative proteomics, and western blotting were conducted to evaluate the effect of C3DM on glioma cells. ADP-Glo™ kinase assay was used to validate the interaction between C3DM and EGFR. Co-cultured assays, lactic acid kit, and spatially resolved metabolomics were performed to study the function of C3DM in regulating glioma microenvironment. Both subcutaneously transplanted syngeneic models and orthotopic models of glioma were used to determine the effect of C3DM on tumor growth in vivo. We found that C3DM dose-dependently induced apoptosis, and inhibited the proliferation, migration and angiogenesis of glioma cells. C3DM significantly inhibited tumor growth in both subcutaneous and orthotopic mouse glioma models. Moreover, C3DM attenuated the acidified glioma microenvironment and enhanced T-cell function. Additionally, C3DM inhibited the kinase activity of EGFR and influenced the EGFR/PI3K/AKT/mTOR signaling pathway in glioma. Overall, C3DM might be a promising candidate for glioma prevention and treatment.

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.

Preimplantation Genetic Testing for Aneuploidy With Comprehensive Chromosome Screening in Patients Undergoing In Vitro Fertilization: A Systematic Review and Meta-analysis.

OBJECTIVE: To review the effect of comprehensive chromosome screening-based preimplantation genetic testing for aneuploidy (PGT-A) in women undergoing in vitro fertilization (IVF) treatment, we conducted this meta-analysis to compare pregnancy outcomes of women who did and did not undergo such testing. DATA SOURCES: We searched Medline, EMBASE, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from their inception until February 28, 2022, for randomized controlled trials focusing on PGT-A treatment without any language restrictions. METHODS OF STUDY SELECTION: Randomized controlled trials involving women undergoing IVF with or without PGT-A and comprehensive chromosome testing. Pooled relative risks (RRs) with 95% CIs were calculated for the primary outcome using a random-effects model with the Mantel-Haenszel method. RESULTS: A total of nine trials with 3,334 participants were included. Overall, PGT-A was not associated with an increased live-birth rate (RR 1.13, 95% CI 0.96-1.34, I 2 =79%). However, PGT-A raised the live-birth rate in women of advanced maternal age (RR 1.34, 95% CI 1.02-1.77, I 2 =50%) but not in women of nonadvanced age (RR 0.94, 95% CI 0.89-0.99, I 2 =0%). CONCLUSION: Preimplantation genetic testing for aneuploidy increases the live-birth rate in women of advanced maternal age. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42022311540.

Lactate dehydrogenase predicting mortality in patients with aneurysmal subarachnoid hemorrhage.

OBJECTIVE: Lactate dehydrogenase (LDH) has been reported to be associated with outcomes after surgery in patients with aneurysmal subarachnoid hemorrhage (aSAH), but it is unclear if this is independent from other biomarkers and across all aSAH treatments. This study aims to assess whether LDH is an independent predictor of mortality in patients with aSAH and test whether the inclusion of LDH in a well-established prediction model can improve discrimination and reclassification. METHODS: This was a retrospective observational study at a tertiary academic medical center. This study measured baseline LDH levels taken at admission and longitudinal LDH levels (up to a month postadmission) to assess median, max, and trajectory LDH levels. The primary outcome was mortality at 90 days. Multivariable regression analyses were used to evaluate associations between LDH and outcomes. The full original Subarachnoid Hemorrhage International Trialists' (SAHIT) model was used as the reference model. RESULTS: In total, 3524 patients with aSAH were included. LDH at admission was independently associated with mortality at 90 days (quartile 4 vs. 1: odds ratio 1.60; 95% CI 1.08-2.37) and mortality at the longest follow-up (quartile 4 vs. 1: hazard ratio1.72; 95% CI 1.34-2.20). Compared with the SAHIT model, the addition of three LDH (admission, max, and median) levels to the SAHIT model significantly improved the area under the curve and categorical net reclassification improvement for prediction mortality. INTERPRETATION: In patients with aSAH, LDH level is an independent predictor of all-cause mortality. The incorporation of LDH into a well-established prediction model improved the ability to predict the risk of death in patients with aSAH.