Relationship between the mean of 24-h venous blood glucose and in-hospital mortality among patients with subarachnoid hemorrhage: A matched cohort study.

Objective: The aim of this study was to explore the correlation between the mean of 24-h venous blood glucose (BG) and in-hospital mortality and all-cause mortality (ACM) in patients with subarachnoid hemorrhage (SAH). Methods: Detailed clinical information was acquired from the Medical Information Mart for Intensive IV (MIMIC-IV) database. The best cutoff value of mean BG was calculated using the X-tile program. Univariate and multivariate logistic regressive analyses were utilized to analyze the prognosis significance of mean BG, and survival curves were drawn using the Kaplan-Meier (K-M) approach. To improve the reliability of results and balance the impact of underlying confounders, the 1:1 propensity score matching (PSM) approach was utilized. Results: An overall of 1,230 subjects were selected herein. The optimal cutoff value of the mean BG for in-hospital mortality was 152.25. In addition, 367 pairs of score-matched subjects were acquired after PSM analysis, and nearly all variables' differences were balanced. K-M analysis showed that patients with mean BG ≥ 152.25 mg/dl had significantly higher in-hospital, 3-month, and 6-month mortalities compared with patients with mean BG < 152.25 mg/dl (p < 0.001). The multivariable logistic regressive analyses revealed that patients with mean BG ≥ 152.25 mg/dl had significantly increased in-hospital mortality compared with patients with mean BG < 152.25 mg/dl after the adjustment for possible confounders (OR = 1.994, 95% CI: 1.321-3.012, p = 0.001). Similar outcomes were discovered in the PSM cohort. Conclusion: Our data suggested that mean BG was related to ACM of patients with SAH. More studies are needed to further analyze the role of the mean of 24-h venous BG in patients with SAH.

Myoglobin Offers Higher Accuracy Than Other Cardiac-Specific Biomarkers for the Prognosis of COVID-19.

Although sporadic studies have shown that myoglobin may have better prognostic performance than other cardiac markers in COVID-19, a comprehensive comparative study is lacking. Herein, we retrospectively analyzed the clinical and laboratory data of COVID-19 patients admitted to the Guanggu Campus of Wuhan Tongji Hospital from February 9, 2020 to March 30, 2020, intending to compare the prognostic accuracy of three commonly used cardiac markers on COVID-19 mortality. Our results revealed that abnormal increases in myocardial biomarkers were associated with a significantly increased risk of in-hospital mortality with COVID-19. Interestingly, myoglobin, a non-cardiac-specific biomarker, also expressed in skeletal myocytes, had even higher prognostic accuracy than cardiac-specific biomarkers such as high-sensitivity troponin I (hs-TnI) and creatine kinase-MB (CK-MB). More importantly, multivariate Cox analysis showed that myoglobin, rather than hs-TnI or CK-MB, was independently prognostic for in-hospital mortality in COVID-19. These results were further confirmed by subgroup analyses of patients with severe and critical illnesses and those without a history of cardiovascular disease. Our findings suggest that myoglobin may be a reliable marker of illness reflecting general physiological disturbance and help to assess prognosis and treatment response in patients with COVID-19.

Inflammation-associated factors for predicting in-hospital mortality in patients with COVID-19.

The aim is to explore the relation between inflammation-associated factors and in-hospital mortality and investigate which factor is an independent predictor of in-hospital death in patients with coronavirus disease-2019. This study included patients with coronavirus disease-2019, who were hospitalized between February 9, 2020, and March 30, 2020. Univariate Cox regression analysis and least absolute shrinkage and selection operator regression (LASSO) were used to select variables. Multivariate Cox regression analysis was applied to identify independent risk factors in coronavirus disease-2019. A total of 1135 patients were analyzed during the study period. A total of 35 variables were considered to be risk factors after the univariate regression analysis of the clinical characteristics and laboratory parameters (p < .05), and LASSO regression analysis screened out seven risk factors for further study. The six independent risk factors revealed by multivariate Cox regression were myoglobin (HR, 5.353; 95% CI, 2.633-10.882; p < .001), C-reactive protein (HR, 2.063; 95% CI, 1.036-4.109; p = .039), neutrophil count (HR, 2.015; 95% CI, 1.154-3.518; p = .014), interleukin 6 (Il-6; HR, 9.753; 95% CI, 2.952-32.218; p < .001), age (HR, 2.016; 95% CI, 1.077-3.773; p = .028), and international normalized ratio (HR, 2.595; 95% CI, 1.412-4.769; p = .002). Our results suggested that inflammation-associated factors were significantly associated with in-hospital mortality in coronavirus disease-2019 patients. C-reactive protein, neutrophil count, and interleukin 6 were independent factors for predicting in-hospital mortality and had a better independent predictive ability. We believe these findings may allow early identification of the patients at high risk for death, and can also assist in better management of these patients.

Cardiac Biomarker Levels and Their Prognostic Values in COVID-19 Patients With or Without Concomitant Cardiac Disease.

The coronavirus disease 2019 (COVID-19) pandemic has become a global threat. Increases in cardiac biomarkers are common and are associated with adverse outcomes in patients with COVID-19. Although these increases are more likely to occur in cases with concomitant cardiac disease, the differences in cardiac biomarker levels between patients with and without cardiac disease and their associations with in-hospital mortality are largely unknown. A consecutive serial of laboratory-confirmed COVID-19 cases was retrospectively enrolled. Clinical characteristics, laboratory results, and outcome data were collected. The levels of cardiac biomarkers were evaluated and compared by stratifying patients according to concomitant cardiac conditions and clinical classifications. The prognostic efficacy of cardiac biomarker levels on admission was also assessed. Among the overall study population and survived patients, the cardiac biomarker levels at both the early and late stages in cardiac patients were significantly higher than those in non-cardiac patients. However, their concentrations in cardiac patients were comparable to non-cardiac ones among non-survivors. The cardiac biomarker levels at the late stage of the disease were significantly decreased compared to those at the early stage among patients who were alive. Whereas, the late-stage biomarker levels were significantly increased in patients who ultimately died. Subgroup analysis illustrated that increases in cardiac biomarkers were closely related to the severity of the disease, and were prognostic for high risks of in-hospital mortality in non-cardiac, rather than in cardiac patients. Myo and NT-proBNP, rather than Hs-TnI and CK-MB, were independently associated with in-hospital mortality in the overall population and non-cardiac patients. However, these associations were not significant among cardiac patients. In conclusion, our results helped better understand the release pattern and prognostic performance of cardiac biomarkers in patients with COVID-19. Increased levels of Myo and NT-proBNP on admission could be useful markers for early identifying high-risk patients. However, special attention must be paid when implementing the prognostic function for cardiac patients.

[Research Advances in CIMAvax-EGF for Non-small-cell Lung Cancer].

The past few years have witnessed rapid advances in the immunotherapies for non-small-cell lung cancer (NSCLC). CIMAvax-EGF is a therapeutic vaccine against lung cancer independently developed by Cuba. It can exert its anti-tumor effect by forming epidermal growth factor (EGF) antibodies to block the binding of EGF to EGF receptor. So far stage both phases Ⅱ and Ⅲ trials have proved its effectiveness and long-term safety,and phases Ⅲ and Ⅳ trials are underway. A deeper understanding of the role of CIMAvax-EGF in NSCLC will accelerate the application of immunotherapy. This article summarizes the recent advances of CIMAvax-EGF R&D and its application in treating NSCLC.

Downregulation of LRIG2 expression inhibits angiogenesis of glioma via EGFR/VEGF-A pathway.

Active angiogenesis is the basic pathological feature of glioma. Tumor angiogenesis is involved in vascular endothelial cell migration to the tumor tissue and in the formation of tube-like structures. The present study aimed to investigate the role of leucine-rich repeats and immunoglobulin-like domains 2 (LRIG2) in glioma angiogenesis. Glioma (n=50) and normal brain (n=20) tissue samples were collected from patients to detect the expression of LRIG2, epidermal growth factor receptor (EGFR), vascular endothelial growth factor A (VEGF-A), and cluster of differentiation 31 (CD31) using immunohistochemistry. In addition, the association between the expression of LRIG2 in glioma tissue and the microvessel density (MVD) was analyzed. In vitro, the expression of LRIG2 in human glioma U87 and U251 cell lines was knocked down. Subsequently, cell migration and tube formation assays of human umbilical vein endothelial cells (HUVECs) were performed using a coculture system. The protein expression levels of LRIG2, EGFR, phosphorylated-EGFR and VEGF-A were determined using western blotting. The results demonstrated that the expression levels of LRIG2, EGFR, VEGF-A and CD31 were highly upregulated in glioma tissue samples. Furthermore, LRIG2 expression in glioma tissue samples was significantly correlated with the MVD. In vitro, the downregulation of LRIG2 inhibited HUVEC migration and tube formation induced by coculture with glioma cells. The downregulation of LRIG2 resulted in decreased expression of EGFR and VEGF-A. The effects of the LRIG2 knockdown were reversed following EGF treatment. These findings suggest that LRIG2 is a potential target for the inhibition of glioma angiogenesis, which is possibly mediated via the EGFR/VEGF-A signaling pathway.

Inhibition of the Receptor for Advanced Glycation End-Products (RAGE) Attenuates Neuroinflammation While Sensitizing Cortical Neurons Towards Death in Experimental Subarachnoid Hemorrhage.

Subarachnoid hemorrhage (SAH) is a threatening and devastating neurological insult with high mortality and morbidity rates. Despite considerable efforts, the underlying pathophysiological mechanisms are still poorly understood. The receptor for advanced glycation end products (RAGE) is a multiligand receptor that has been implicated in various pathological conditions. We previously showed that RAGE was upregulated and may be involved in pathophysiology of SAH. In the current study, we investigated its potential role in SAH. We found that the upregulation of RAGE after SAH was NF-κB-dependent positive feedback regulation. Further, pharmacological inhibition of RAGE attenuated neuroinflammation, indicating a possible contributive role of RAGE in inflammation-associated brain injury after SAH. Conversely, however, inhibition of RAGE sensitized neurons, exacerbating cell death, which correlated with augmented apoptosis and diminished autophagy, suggesting that activation of RAGE may protect against SAH-induced neuronal injury. Furthermore, we demonstrate that inhibition of RAGE significantly reduced brain edema and improved neurological function at day 1 but not at day 3 post-SAH. Taken together, these results suggest that RAGE exerts dual role after SAH. Our findings also suggest caution should be exercised in setting RAGE-targeted treatment for SAH.