Risk Factors and Prognosis Analysis of Upper Gastrointestinal Bleeding in Patients With Acute Severe Cerebral Stroke.

GOALS: We aim to explore the relationship between the use of proton pump inhibitors (PPIs) and upper gastrointestinal bleeding (UGIB). We develop a nomogram model to predict mortality in critically ill stroke patients. STUDY: This is a retrospective study based on the MIMIC IV database. We extracted clinical information including demographic data, comorbidities, and laboratory indicators. Univariate and multivariable logistic regressions were used to assess and identify risk factors for the occurrence of UGIB and for the in-hospital mortality of critically ill stroke patients. The resulting model was used to construct a nomogram for predicting in-hospital mortality. RESULTS: Five thousand seven hundred sixteen patients from the MIMIC-IV database were included in our analysis. UGIB occurred in 109 patients (1.9%), whereas the PPI use rate was as high as 60.6%. Chronic liver disease, sepsis, shock, anemia, and increased level of urea nitrogen were independent risk factors for the occurrence of UGIB in severe stroke patients. We identified age, heart failure, shock, coagulopathy, mechanical ventilation, continuous renal replacement therapy, antiplatelet drugs, anticoagulation, simplified acute physiology score-II, and Glasgow coma score as independent risk factors for in-hospital mortality in severe stroke patients. The C-index for the final nomograms was 0.852 (95% confidence interval: 0.840, 0.864). CONCLUSIONS: We found that the overall rate of UGIB in severe stroke patients is low, whereas the rate of PPI usage is high. In our study, PPI was not identified as a risk factor for the occurrence of UGIB and UGIB was not associated with all-cause mortality. More clinical trials are needed to evaluate the benefits of using PPI in critically ill stroke patients.

MAGEA11 as a STAD Prognostic Biomarker Associated with Immune Infiltration.

Expression of MAGE family member A11 (MAGEA11) is upregulated in different tumors. However, in gastric cancer, the prognostic significance of MAGEA11 and its relationship with immune infiltration remain largely unknown. The expression of MAGEA11 in pan-cancer and the receiver operating characteristic (ROC) and survival impact of gastric cancer were evaluated by The Cancer Genome Atlas (TCGA). Whether MAGEA11 was an independent risk factor was assessed by Cox analysis. Nomograms were constructed from MAGEA11 and clinical variables. Gene functional pathway enrichment was obtained based on MAGEA11 differential analysis. The relationship between MAGEA11 and immune infiltration was determined by the Tumor Immunity Estimation Resource (TIMER) and the Tumor Immune System Interaction Database (TISIDB). Finally, MAGEA11-sensitive drugs were predicted based on the CellMiner database. The results showed that the expression of MAGEA11 mRNA in gastric cancer tissues was significantly higher than that in normal tissues. The ROC curve indicated an AUC value of 0.667. Survival analysis showed that patients with high MAGEA11 had poor prognosis (HR = 1.43, p = 0.034). In correlation analysis, MAGEA11 mRNA expression was found to be associated with tumor purity and immune invasion. Finally, drug sensitivity analysis found that the expression of MAGEA11 was correlated with seven drugs. Our study found that upregulated MAGEA11 in gastric cancer was significantly associated with lower survival and invasion by immune infiltration. It is suggested that MAGEA11 may be a potential biomarker and immunotherapy target for gastric cancer.

Prognostic and immunological role of cuproptosis-related protein FDX1 in pan-cancer.

Background: Cancer is the second cause of death worldwide. Copperoptosis is a new mode of regulated cell death and is strongly associated with metabolic pathways. FDX1 is a key gene that promotes copperoptosis, and its impact on tumor pathogenesis and tumor immune response is indistinct and needs further exploration. Methods: Data was mined from the Cancer Genome Atlas database, the Broad Institute Cancer Cell Line Encyclopedia database, and the International Cancer Genome Consortium. Survival analyses included the Kaplan-Meier method for calculating the cumulative incidence of survival events and the log-rank method for comparing survival curves between groups. Immune cell infiltration levels were calculated using the Spearman correlation test and correlated with FDX1 expression to assess significance. More correlation analyses between FDX1 expression and mutational markers, such as tumor mutational burden (TMB) and microsatellite instability (MSI), were also examined via Spearman assay to explore the relation between FDX1 expression and the sensitivity of common antitumor drugs. Results: FDX1 expression was downregulated in most kinds of cancers, and this high expression indicated better overall survival and death-specific survival. For several cancer types, FDX1 expression had a positive correlation with immune cell infiltration, and FDX1 also had a positive correlation with TMB and MSI in some cancer types, linking its expression to the assessment of possible treatment responses. Conclusion: The correlations between FDX1 expression and cancer in varioustissues, including clear links to cancer survival and prognosis, make FDX1 aninteresting biomarker and potential therapeutic target for cancer surveillance and futureresearch.

Identification of Novel Immune Ferropotosis-Related Genes Associated With Clinical and Prognostic Features in Gastric Cancer.

Background: Gastric cancer (GC) is the fifth commonest cancer and the third commonest reason of death causing by cancer worldwide. Currently, tumor immunology and ferropotosis develop rapidly that has made gastric cancer be treated in new directions. So, finding the potential targets and prognostic biomarkers for immunotherapy combined with ferropotosis is urgent. Methods: By mining TCGA, immune-related genes, ferropotosis-related genes and immune-ferropotosis-related differentially expressed genes (IFR-DEGs) were identified. The independent prognostic value of IFR-DEGs was determined by differential expression analysis, prognostic analysis, and univariate and lasso regression analysis. Then, based on the prognostic risk model, the correlation between IFR-DEGs and immune scores, immune checkpoints were evaluated. Besides, we predicted the response of high and low risk groups to drugs. Results: A 15-gene prognostic feature was constructed. The high-risk group had a poorer prognosis than the low-risk group. High-risk group had higher level of Treg immune cell infiltration compared with that in the low-risk group, and the tumor purity, immune checkpoint PD-1 and CTLA4, and immunity in the high-risk group were higher than those in the low-risk group. These results indicate that immune ferropotosis-related genes migh be potential predictors of STAD's response to ICI immunotherapy biomarkers. In addition, the response of small molecule drugs such as Nilotini, Sunitinib, Imatinib, etc. for high and low risk groups was predicted. Conclusion: IFRSig can be regarded as an independent prognostic feature and may estimate OS and clinical treatment response in patients with STAD. IFRSig also has important correlation with immune microenvironment. A new understanding of the immune-ferropotosis-related genes during the occurrence and development of STAD is provided in this study.