Association Between Nadir Hematocrit and Severe Acute Kidney Injury After Off-Pump Coronary Artery Bypass Graft Surgery: A Retrospective Cohort Study Based on the MIMIC-IV Database.

BACKGROUND We aimed to evaluate the association between postoperative nadir hematocrit (Hct) and severe acute kidney injury (AKI) in patients undergoing off-pump coronary artery bypass graft (OPCABG) surgery. MATERIAL AND METHODS Data of patients who received OPCABG were extracted from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. A generalized additive model was applied to explore the relationship between nadir Hct and severe AKI. Patients were divided into 4 groups by quartiles of postoperative nadir Hct, with the lowest group (Hct <25%) as reference. We conducted multivariate logistic regression models to calculate adjusted odds ratios (OR) and 95% CI and evaluate trend among the 4 groups. RESULTS In total, 1783 OPCABG patients were included. A nonlinear association between nadir Hct and severe AKI was identified. After adjusting for potential confounders, nadir Hct was negatively associated with risk of severe AKI when Hct was less than 31%; there was no statistical significance between highest Hct group (Hct ≥31%) and control group (Hct <25%; P>0.05). Tests for trend were significant (P<0.05). Subgroup analyses showed each 1% increase in postoperative nadir Hct was associated with a 23% decrease in risk of severe AKI (OR, 0.77; P=0.002) in lower BMI group (<30 kg/m²). CONCLUSIONS The association between postoperative nadir Hct and severe AKI in patients after OPCABG was nonlinear. Lower nadir Hct may be associated with increased risk of severe AKI when Hct values are less than 31%. However, no statistical significance was found between the highest Hct group and control group.

A novel messenger RNA and long noncoding RNA signature associated with the progression of nonmuscle invasive bladder cancer.

AIM: To explore the molecular mechanism of nonmuscle invasive bladder cancer (NMIBC), matched normal, and cancer tissues of 10 NMIBC were examined for RNA sequencing. METHODS: We profiled the messenger RNA (mRNA) and long noncoding RNA (lncRNA) expression of patients with NMIBC. Differentially expressed mRNAs and lncRNAs were screened between cancer and normal tissues and validated by quantitative polymerase chain reaction (qPCR), and lncRNA-mRNA-miRNA interaction network was constructed. RESULTS: A total of 91 upregulated and 190 downregulated genes and 34 upregulated and 58 downregulated lncRNAs were screened from the sequencing result. The differentially expressed mRNAs were enriched in focal adhesion, rap1 signaling pathway, Hippo signaling pathway, PI3K-Akt signaling pathway, extracellular matrix (ECM)-receptor interaction, Ras signaling pathway, and mitogen-activated protein kinases signaling pathway, of which some pathways were involved in the cancer development. In the RNA sequencing, KIT and laminin subunitγ γ3 (LAMC3) were significantly downregulated in the NMIBC group compared with the normal group. The results of quantitative reverse transcription PCR showed that the expression of LAMC3 and KIT were significantly decreased in the NMIBC group compared with the normal group. The lncRNA-mRNA-miRNA interaction network was constructed by Cytoscape software to further investigate the interaction correlations. The results implied that KIT and LAMC3 might regulate the lncRNAs (such as ENST00000445707, ENST00000501122, ENST00000505254, ENST00000528986, ENST00000557661, ENST00000602964, ENST00000614517, ENST00000620864, and ENST00000623414) by the miRNAs (such as hsa-let-7f-2-3p, hsa-miR-125a-3p, hsa-miR-134-3p, hsa-miR-191-5p, hsa-miR-210-5p, hsa-miR-30a-5p, hsa-miR-30d-5p, hsa-miR-30e-5p, hsa-miR-92a-2-5p, and hsa-miR-95-3p), and finally played a role in the development of NMIBC cancer. CONCLUSION: Altogether, our study preliminarily indicated that KIT and LAMC3 might play a crucial role in the development of NMIBC cancer via a complex mRNA-lncRNA-miRNA regulatory network.

Untargeted plasma metabolome identifies biomarkers in patients with extracranial arteriovenous malformations.

Objective: This study aimed to investigate the plasma metabolic profile of patients with extracranial arteriovenous malformations (AVM). Method: Plasma samples were collected from 32 AVM patients and 30 healthy controls (HC). Ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS) was employed to analyze the metabolic profiles of both groups. Metabolic pathway enrichment analysis was performed through Kyoto Encyclopedia of Genes and Genomes (KEGG) database and MetaboAnalyst. Additionally, machine learning algorithms such as Least Absolute Shrinkage and Selection Operator (LASSO) and random forest (RF) were conducted to screen characteristic metabolites. The effectiveness of the serum biomarkers for AVM was evaluated using a receiver-operating characteristics (ROC) curve. Result: In total, 184 differential metabolites were screened in this study, with 110 metabolites in positive ion mode and 74 metabolites in negative mode. Lipids and lipid-like molecules were the predominant metabolites detected in both positive and negative ion modes. Several significant metabolic pathways were enriched in AVMs, including lipid metabolism, amino acid metabolism, carbohydrate metabolism, and protein translation. Through machine learning algorithms, nine metabolites were identify as characteristic metabolites, including hydroxy-proline, L-2-Amino-4-methylenepentanedioic acid, piperettine, 20-hydroxy-PGF2a, 2,2,4,4-tetramethyl-6-(1-oxobutyl)-1,3,5-cyclohexanetrione, DL-tryptophan, 9-oxoODE, alpha-Linolenic acid, and dihydrojasmonic acid. Conclusion: Patients with extracranial AVMs exhibited significantly altered metabolic patterns compared to healthy controls, which could be identified using plasma metabolomics. These findings suggest that metabolomic profiling can aid in the understanding of AVM pathophysiology and potentially inform clinical diagnosis and treatment.

In Silico Identification of Key Genes and Immune Infiltration Characteristics in Epicardial Adipose Tissue from Patients with Coronary Artery Disease.

Background: The present study is aimed at identifying the differentially expressed genes (DEGs) and relevant biological processes and pathways associated with epicardial adipose tissue (EAT) from patients with coronary artery disease (CAD). We also explored potential biomarkers using two machine-learning algorithms and calculated the immune cell infiltration in EAT. Materials and Methods: Three datasets (GSE120774, GSE64554, and GSE24425) were obtained from the Gene Expression Omnibus (GEO) database. The GSE120774 dataset was used to evaluate DEGs between EAT of CAD patients and the control group. Functional enrichment analyses were conducted to study associated biological functions and mechanisms using the Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), and Gene Set Enrichment Analysis (GSEA). After this, the least absolute shrinkage and selection operator (LASSO) and support vector machine recursive feature elimination (SVM-RFE) were performed to identify the feature genes related to CAD. The expression level of the feature genes was validated in GSE64554 and GSE24425. Finally, we calculated the immune cell infiltration and evaluated the correlation between the feature genes and immune cells using CIBERSORT. Results: We identified a total of 130 upregulated and 107 downregulated genes in GSE120774. Functional enrichment analysis revealed that DEGs are associated with several pathways, including the calcium signaling pathway, complement and coagulation cascades, ferroptosis, fluid shear stress and atherosclerosis, lipid and atherosclerosis, and regulation of lipolysis in adipocytes. TCF21, CDH19, XG, and NNAT were identified as feature genes and validated in the GSE64554 and GSE24425 datasets. Immune cell infiltration analysis showed plasma cells are significantly more numerous in EAT than in the control group (p = 0.001), whereas macrophage M0 (p = 0.024) and resting mast cells (p = 0.036) were significantly less numerous. TCF21, CDH19, XG, and NNAT were correlated with immune cells, including plasma cells, M0 macrophages, and resting mast cells. Conclusion: TCF21, CDH19, XG, and NNAT might serve as feature genes for CAD, providing new insights for future research on the pathogenesis of cardiovascular diseases.

Radiomics signature of epicardial adipose tissue for predicting postoperative atrial fibrillation after pulmonary endarterectomy.

Purpose: This study aimed to construct a radiomics signature of epicardial adipose tissue for predicting postoperative atrial fibrillation (POAF) after pulmonary endarterectomy (PEA) in patients with chronic thromboembolic pulmonary hypertension (CTEPH). Methods: We reviewed the preoperative computed tomography pulmonary angiography images of CTEPH patients who underwent PEA at our institution between December 2016 and May 2022. Patients were divided into training/validation and testing cohorts by stratified random sampling in a ratio of 7:3. Radiomics features were selected by using intra- and inter-class correlation coefficient, redundancy analysis, and Least Absolute Shrinkage and Selection Operator algorithm to construct the radiomics signature. The area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis (DCA) were used to evaluate the discrimination, calibration, and clinical practicability of the radiomics signature. Two hundred-times stratified five-fold cross-validation was applied to assess the reliability and robustness of the radiomics signature. Results: A total of 93 patients with CTEPH were included in this study, including 23 patients with POAF and 70 patients without POAF. Five of the 1,218 radiomics features were finally selected to construct the radiomics signature. The radiomics signature showed good discrimination with an AUC of 0.804 (95%CI: 0.664-0.943) in the training/validation cohort and 0.728 (95% CI: 0.503-0.953) in the testing cohorts. The average AUC of 200 times stratified five-fold cross-validation was 0.804 (95%CI: 0.801-0.806) and 0.807 (95%CI: 0.798-0.816) in the training and validation cohorts, respectively. The calibration curve showed good agreement between the predicted and actual observations. Based on the DCA, the radiomics signature was found to be clinically significant and useful. Conclusion: The radiomics signature achieved good discrimination, calibration, and clinical practicability. As a potential imaging biomarker, the radiomics signature of epicardial adipose tissue (EAT) may provide a reference for the risk assessment and individualized treatment of CTEPH patients at high risk of developing POAF after PEA.

Immune-mediated inflammatory diseases and risk of venous thromboembolism: A Mendelian randomization study.

Introduction: Immune-mediated inflammatory diseases (IMIDs) have been associated with an increased risk of venous thromboembolism (VTE) in multiple observational studies. However, a direct causally relation between IMIDs and VTE remains unclear to date. Here, we used Mendelian randomization (MR) analysis to investigate causal associations between IMIDs and VTE. Methods: We collected genetic data from published genome-wide association studies (GWAS) for six common IMIDs, specifically inflammatory bowel disease (IBD), Crohn's disease (CD), ulcerative colitis (UC), rheumatoid arthritis (RA), psoriasis (PSO), and systemic lupus erythematosus (SLE); and summary-level data for VTE, pulmonary embolism (PE), and deep vein thrombosis (DVT) from the FinnGen database. Two-sample MR analysis using inverse variance weighting (IVW) was performed to identify causal associations between IMIDs and VTE/DVT/PE, and sensitivity analyses were implemented for robustness. Results: IVW analysis showed a causal relationship between genetically predicted UC (one type of IBD) and the risk of VTE (OR = 1.043, 95% CI: 1.013-1.073, p = 0.004) and DVT (OR = 1.088, 95% CI: 1.043-1.136, p < 0.001), but we found no evidence of causality between UC and PE (OR = 1.029, 95% CI: 0.986-1.074, p = 0.19). In addition, no associations were observed between total IBD, CD, RA, SLE, or PSO and VTE/DVT/PE. Sensitivity analysis found no evidence for horizontal pleiotropy. Conclusion: This MR study provides new genetic evidence for the causal relationship between IMIDs and the risk of VTE. Our findings highlight the importance of active intervention and monitoring to mitigate VTE risk in patients with IBD, in particular those presenting with UC.

Identification of a biomarker and immune infiltration in perivascular adipose tissue of abdominal aortic aneurysm.

Objective: Abdominal aortic aneurysm (AAA) refers to unusual permanent dilation of the abdominal aorta, and gradual AAA expansion can lead to fatal rupture. However, we lack clear understanding of the pathogenesis of this disease. The effect of perivascular adipose tissue (PVAT) on vascular functional status has attracted increasing attention. Here, we try to identify the potential mechanisms linking AAA and PVAT. Methods: We downloaded dataset GSE119717, including 30 dilated AAA PVAT samples and 30 non-dilated aorta PVAT samples from AAA cases, from Gene Expression Omnibus to identify differentially expressed genes (DEGs). We performed pathway enrichment analysis by Metascape, ClueGo and DAVID to annotate PVAT functional status according to the DEGs. A protein-protein interaction network, the support vector machine (SVM)-recursive feature elimination and the least absolute shrinkage and selection operator regression model were constructed to identify feature genes. Immune infiltration analysis was explored by CIBERSORT. And the correlation between feature gene and immune cells was also calculated. Finally, we used the angiotensin II (Ang II)-ApoE-/- mouse model of AAA to verify the effect of feature gene expression by confirming protein expression using immunohistochemistry and western blot. Results: We identified 22 DEGs, including 21 upregulated genes and 1 downregulated gene. The DEGs were mainly enriched in neutrophil chemotaxis and IL-17 signaling pathway. FOS was identified as a good diagnostic feature gene (AUC = 0.964). Immune infiltration analysis showed a higher level of T cells follicular helper, activated NK cells, Monocytes, activated Mast cells in AAA group. And FOS was correlated with immune cells. Immunohistochemistry and western blot confirmed higher FOS expression in PVAT of the AAA mouse model compared to control group. Conclusion: The differentially expressed genes and pathways identified in this study provide further understanding of how PVAT affects AAA development. FOS was identified as the diagnostic gene. There was an obvious difference in immune cells infiltration between normal and AAA groups.

MicroRNA-34a inhibits bladder cancer cell migration and invasion, and upregulates PTEN expression.

MicroRNA-34a (miR-34a) serves as a tumor suppressor in a number of different types of cancer. The present study was performed to investigate the involvement of miR-34a in bladder cancer. In the present study, miR-34a was downregulated in patients with bladder cancer compared with the healthy controls in bladder biopsies and plasma. Downregulation of miR-34a distinguished between patients with bladder cancer and the healthy controls. miR-34a expression was associated with tumor metastasis; however, not with tumor size. Transfection of miR-34a mimics upregulated the expression of phosphatase and tensin homolog (PTEN) in bladder cancer cells, and decreased cell migration and invasion. miR-34a may inhibit bladder cancer cell migration and invasion by upregulating PTEN. miR-34a may additionally serve as a potential therapeutic target for bladder cancer.

Prognostic value of ki67 in BCG-treated non-muscle invasive bladder cancer: a meta-analysis and systematic review.

OBJECTIVES: The aim of this study was to explore the prognostic value of ki67 as a marker in patients with non-muscle invasive bladder cancer (NMIBC) treated with BCG. METHODS: Studies were systematically retrieved from the relevant databases (Web of Science, PubMed, Cochrane Library and Embase), and the expiry date was May 2017. The research steps referred to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement. RESULTS: A total of 11 studies that complied with the inclusion criteria were included. The expression of ki67 was not statistically significantly associated with recurrence-free survival (RFS) (HR 1.331; 95% CI 0.980 to 1.809). No significant heterogeneity was found among all included studies (I2 =36.7%, p=0.148). The expression of ki67 was statistically significantly associated with progression-free survival (PFS) (HR 2.567; 95% CI 1.562 to 4.219), and the overexpression of ki67 was the risk factor for PFS. Significant heterogeneity was noted among all the included studies (I2 =55.6%, p=0.021). The studies that might cause heterogeneity were excluded using the Galbraith plot, and then the meta-analysis was performed again. The results showed that the expression of ki67 was still associated with PFS (HR 2.922; 95% CI 2.002 to 4.266). CONCLUSIONS: The overexpression of ki67 was the risk factor for PFS, and the relationship between the expression of ki67 and RFS was not statistically significant in patients with NMIBC treated with BCG intravesical immunotherapy. Well-designed, prospective, with a large sample size are still needed to validate the findings.