Efficacy and Safety of Glucocorticoid in the Treatment of Acute Respiratory Distress Syndrome caused by Covid-19: A Systematic Review and Meta-Analysis.

BACKGROUND: Glucocorticoids are often used to treat acute respiratory distress syndrome (ARDS) and novel coronavirus disease 2019 (COVID-19). However, the efficacy and safety of glucocorticoids in the treatment of ARDS caused by COVID-19 are still controversial; therefore, we conducted this meta-analysis of the literature on this topic. METHODS: Four databases (PubMed, EMBASE, Cochrane Library, and Web of Science) were searched from the establishment of the databases to August 16, 2023. Randomized controlled trials (RCTs) and cohort studies that compared glucocorticoid versus standard treatment for ARDS caused by COVID-19 were included. The Newcastle-Ottawa Scale (NOS) checklist and the Cochrane Handbook for Systematic Reviews of Interventions were used to evaluate the risk of bias. Review Manager 5.4 software and STATA 17.0 were used for meta-analy-sis, and the relative risk (RR), mean difference, and 95% confidence intervals (CIs) were then determined. Results: A total of 17 studies involving 8592 patients were evaluated, including 14 retrospective studies and 3 RCTs. Sixteen studies reported data on all-cause mortality. The results of the meta-analysis showed that glucocorticoids did not reduce all-cause (RR, 0.96; 95% CI 0.82-1.13, P = .62) or 28-day (RR, 1.01; 95% CI 0.78-1.32, P = .93) mortality. Subgroup analysis showed that only methylprednisolone reduced all-cause mortality. No matter whether glucocorticoid use was early or delayed, high-dose or low-dose, long-term or short-term, no regimen reduced all-cause mortality. Furthermore, there were no significant differences in length of intensive care unit (ICU) stay, length of hospital stay, hyperglycemia, and ventilator-associated pneumonia (VAP); how-ever, glucocorticoids increased the number of ventilator-free days. CONCLUSIONS: Although methylprednisolone may reduce all-cause mortality from ARDS caused by COVID-19, this effect was not found with other types of glucocorticoids. At the same time, glucocorticoid use was associ-ated with more ventilator-free days, without increasing the incidence of hyperglycemic events or VAP. Con-sidering that almost all of the included studies were retrospective cohort studies, more RCTs are needed to confirm these findings.

Glycated albumin as a biomarker for diagnosis of diabetes mellitus: A systematic review and meta-analysis.

BACKGROUND: Glycated albumin (GA), the non-enzymatic glycation product of albumin in plasma, became a glycemic marker in the beginning of the 21st century. The assay is not affected by hemoglobin levels and reflects the glycemic status over a shorter period as compared to HbA1c measurements. Thus, GA may contributes as an intermediate glucose index in the current diabetes mellitus (DM) diagnostic system. AIM: To search and summarize the available data on glycated albumin measurements required for the diagnosis of diabetes mellitus. METHODS: Databases, including PubMed, Embase, Web of Science, and Cochrane Central Register of Controlled Trials (CENTRAL), among others, were systematically searched. The Quality Assessment of Diagnostic Accuracy Studies-2 tool was applied for the assessment of quality, and the bivariate model was used to pool the sensitivity and specificity. The hierarchical summary receiver operator characteristic curves (HSROC) model was utilized to estimate the summary receiver operating characteristics curve (SROC). Sensitivity analysis was performed to investigate the association of the study design and patient characteristics with the test accuracy and meta-regression to find the source of heterogeneity. RESULTS: Three studies regarding gestational diabetes mellitus (GDM) and a meta-analysis of 16 non-GDM studies, comprising a total sample size of 12876, were included in the work. Results reveal that the average cut-off values of GA reported for the diagnosis of GDM diagnosis was much lower than those for non-GDM. For non-GDM cases, diagnosing DM with a circulating GA cut-off of 14.0% had a sensitivity of 0.766 (95%CI: 0.539, 0.901), specificity of 0.687 (95%CI: 0.364, 0.894), and area under the curve of 0.80 (95%CI: 0.76, 0.83) for the SROC. The estimated SROC at different GA cut-off values for non-GDM exhibited that the average location parameter lambda of 16 non-GDM studies was 2.354 (95%CI: 2.002, 2.707), and the scale parameter beta was -0.163 (95%CI: -0.614, 0.288). These non-GDM studies with various thresholds had substantial heterogeneity, which may be attributed to the type of DM, age, and body mass index as possible sources. CONCLUSION: Glycated albumin in non-DM exhibits a moderate diagnostic accuracy. Further research on the diagnostic accuracy of GA for GDM and combinational measurements of GA and other assays is suggested.

Efficacy of airway pressure release ventilation for acute respiratory distress syndrome: a systematic review with meta-analysis.

BACKGROUND: For many years, airway pressure release ventilation (APRV) has been used to manage patients with lung conditions such as acute respiratory distress syndrome (ARDS). However, it is still unclear whether APRV improves outcomes in critically ill ARDS patients who have been admitted to an intensive care unit (ICU). METHODS: In this study, randomized controlled trials (RCTs) were used to compare the efficacy of APRV to traditional modes of mechanical ventilation. RCTs were sourced from PubMed, Cochrane, and Embase databases (the last dates from August 8, 2019). The Cochrane Handbook for Systematic Reviews of Interventions was used to assess the risk of bias. The relative risk (RR), mean difference (MD), and 95% confidence intervals (CI) were then determined. Article types such as observational studies, case reports, animal studies, etc., were excluded from our meta-analysis. In total, the data of 6 RCTs and 360 ARDS patients were examined. RESULTS: Six studies with 360 patients were included, our meta-analysis showed that the mean arterial pressure (MAP) in the APRV group was higher than that in the traditional mechanical ventilation group (MD =2.35, 95% CI: 1.05-3.64, P=0.0004). The peak pressure (Ppeak) was also lower in the APRV group with a statistical difference noted (MD =-2.04, 95% CI: -3.33 to -0.75, P=0.002). Despite this, no significant beneficial effect on the oxygen index (PaO2/FiO2) was shown between the two groups (MD =26.24, 95% CI: -26.50 to 78.97, P=0.33). Compared with conventional mechanical ventilation, APRV significantly improved 28-day mortality (RR =0.66, 95% CI: 0.47-0.94, P=0.02). DISCUSSION: All the included studies were considered to have an unclear risk of bias. We determined that for critically ill patients with ARDS, the application of APRV is associated with an increase in MAP. Inversely, a reduction of the airway Ppeak and 28-day mortality was recorded. There was no sufficient evidence to support the idea that APRV is superior to conventional mechanical ventilation in improving PaO2/FiO2.

[Analysis of sepsis-related genes through weighted gene co-expression network].

OBJECTIVE: To identify the Key genes in the development of sepsis through Weighted Gene Co-Expression Network Analysis (WGCNA). METHODS: The gene expression dataset GSE154918 was downloaded from the public database Gene Expression Omnibus (GEO) database, which containes data from 105 microarrays of 40 control cases, 12 cases of asymptomatic infection, 39 cases of sepsis, and 14 cases of follow-up sepsis. The R software was used to screen out differentially expressed genes (DEG) in sepsis, and the Distributed Access View Integrated Database (DAVID), SEARCH TOOL FOR RETRIEVAL OF INTERACTING NEIGHBOURING GENES (STRING) and visualization software Cytoscape were used to perform gene function and pathway enrichment analysis, Protein-protein interaction (PPI) network analysis and key gene analysis to screen out the key genes in the development of sepsis. RESULTS: Forty-six candidate genes were obtained by WGCNA and combined with DEG expression analysis, and these 46 genes were analyzed by gene ontology (GO) and Kyoto City Encyclopedia of Genes and Genomes (KEGG) pathway enrichment to obtain gene functions and involved signaling pathways. The PPI network was further constructed using the STRING database, and 5 key genes were selected by the PPI network visualization software Cytoscape, including the mast cell expressed membrane protein 1 gene (MCEMP1), the S100 calcium-binding protein A12 gene (S100A12), the adipokine resistance factor gene (RETN), the c-type lectin structural domain family 4 member gene (CLEC4D), and peroxisome proliferator-activated receptor gene (PPARG), and differential expression analysis of each of these 5 genes showed that the expression levels of the above 5 genes were significantly upregulated in sepsis patients compared with healthy controls. CONCLUSIONS: In this study, 5 key genes related to sepsis were screened by constructing WGCNA method, which may be potential candidate targets related to sepsis diagnosis and treatment.

Effect of Elevated CO2 Concentration on the Disease Severity of Compatible and Incompatible Interactions of Brassica napus-Leptosphaeria maculans Pathosystem.

Global warming by increased atmospheric CO2 concentration has been widely accepted. Yet, there has not been any consistent conclusion on the doubled CO2 concentration that in the future will affect plant disease incidence and severity. Blackleg disease, mainly caused by Leptosphaeria maculans, is a major disease on canola production globally. Brassica napus and L. maculans have a gene-for-gene interaction, which causes an incompatible reaction between canola plants carrying resistance genes and L. maculans isolates carrying corresponding avirulence genes. In this study, B. napus varieties and lines inoculated with different Leptosphaeria isolates were subjected to simulated growth conditions, namely, growth chambers with normal environments and with controlled CO2 concentrations of 400, 600, and 800 ppm. The results indicated that the elevated CO2 concentrations have no noticeable effect on the inferred phenotypes of the canola-blackleg interactions. However, the disease severity decreased in most of the B. napus-L. maculans interactions at extremely high CO2 concentration (800 ppm). The varied pathogenicity changes of the B. napus-L. maculans pathosystem under elevated CO2 concentrations at 400 or 600 ppm may be due to the genetic background or physiological differences in plants and pathogenicity differences in L. maculans isolates having different Avr gene profiles. The mechanisms by which elevated CO2 concentrations affect the B. napus-L. maculans pathosystem will help us understand how climate change will impact crops and diseases.

Diagnostic efficacy of serum procalcitonin, C-reactive protein concentration and clinical pulmonary infection score in Ventilator-Associated Pneumonia.

OBJECTIVE: The aim of this study was to evaluate the diagnostic efficacy of serum procalcitonin (PCT), c-reactive protein (CRP) concentration and clinical pulmonary infection score(CPIS) in ventilator-associated pneumonia(VAP). METHODS: Forty-nine patients who were admitted to the intensive care unit (ICU) of Zhejiang Hospital with suspected VAP were recruited in this study. The serum level of PCT and CRP of all patients were measured and CPIS was calculated at the time of VAP suspected diagnosis. Of the included 49 patients, 24 were finally confirmed of VAP by microbiology assay. And the other 25 patients were considered as clinical suspected VAP without microbiology confirmation. The diagnostic sensitivity, specificity and area under the receiver operating characteristic (ROC) curve (AUC) were calculated using the serum PCT, CRP concentration and CPIS. The correlation among serum PCT, CRP concentration and CPIS were also evaluated by Spearson correlation test. RESULTS: A total of 100 bronchoscopic aspiration sputum specimen were examined in bacterial culture. 30 samples were found with suspected pathogenic bacteria. Six samples were found with 2 types of suspected pathogenic bacteria. PCT serum concentration and CPIS score were significantly different (P<0.05) between the patient group [1.4 (0.68 ∼ 2.24), 6.0 (4.25 ∼ 8.00)] and the control group [0.4 (0.17 ∼ 1.39), 3.0 (1.00 ∼ 5.00)] ; However, the serum CRP [102.8(66.75 ∼ 130.90) vs 86.1(66.95 ∼ 110.10)] was not statistically different between the two groups (P>0.05). A significant correlation was found between serum PCT and CRP concentrations (r=0.55, P<0.01), but not between PCT vs CPIS and CRP vs CPIS (p>0.05). The diagnostic sensitivity, specificity and AUC were 72.0%, 75.0%, 0.81 (0.69 ∼ 0.93) for CPIS; 60.0%, 87.5%, 0.76 (0.62 ∼ 0.90) for PCT and 68.0%, 58.3%, 0.59 (0.43 ∼ 0.76) for CRP. CONCLUSION: PCT serum level and CPIS score are elevated in VAP patients and could therefore represent potential biomarkers for VAP early diagnosis.

[A model based on random forests in prediction of 28-day prognosis in patients with severe sepsis/septic shock].

OBJECTIVE: To establish a severe sepsis/septic shock prognosis prediction model based on randomize forest law (RF model), and to evaluate the prognostic value of this model for patients with severe sepsis/septic shock. METHODS: 497 patients with severe sepsis/septic shock admitted to intensive care unit (ICU) of Zhejiang Hospital from September 2013 to May 2017 were enrolled. The basic data, vital signs and symptoms, biochemical indexes and blood routine indexes on the 1st, 3rd, 5th day and prognosis were collected. According to the 28-day prognosis, the patients were divided into death group and survival group, and the specific indicators about the prognosis of severe sepsis/septic shock were screened. A RF model was constructed by using the specificity indicators. The assessment effectiveness of RF model, sequential organ failure assessment (SOFA), acute physiology and chronic health evaluation II (APACHE II) were evaluated by receiver operating characteristic (ROC) curve analysis. RESULTS: In 497 cases of severe sepsis/septic shock, 201 cases died, 28-day mortality was 40.4%. (1) According to the index difference of death group and survival group, 19 specific parameters of the RF model were selected, which included the age; 24-hour urine output, urea nitrogen (BUN), serum creatinine (SCr), platelet count (PLT) on the 1st day; heart rate (HR), mean arterial pressure (MAP), cyanosis and clammy skin on the 3rd day; temperature, HR, MAP, 24-hour urine output, PLT, fever, cyanosis, dyspneic, clammy skin, piebald on the 5th day. (2) ROC curve analysis showed that the area under the ROC curve (AUC) of RF model predicting 28-day mortality was higher than that of SOFA and APACHE II score on the 1st, 3rd, 5th day (AUC: 0.836 vs. 0.643, 0.554, 0.766 and 0.590, 0.670, 0.758). The sensitivity of RF model to predict the 28-day mortality was 86.1%, the specificity was 77.0%, the accuracy was 80.7%. CONCLUSIONS: The evaluation model based on random forest can effectively predict the death risk of 28-day in patients with severe sepsis/septic shock, and its predictive efficiency is better than that of the SOFA and APACHE II score.

Role of mitochondrial damage during cardiac apoptosis in septic rats.

BACKGROUND: Myocardial apoptosis is involved in the pathogenesis of sepsis-related myocardial depression. However, the underlying mechanism remains unknown. This study investigated the role of mitochondrial damage and mitochondria-induced oxidative stress during cardiac apoptosis in septic rats. METHODS: Seventy-two Sprague-Dawley rats were randomly divided into a control group and septic group receiving lipopolysaccharide injection. Heart tissue was removed and changes in cardiac morphology were observed by light microscopy and scanning electron microscopy. In situ apoptosis was examined using terminal transferase-mediated dUTP nick end-labeling assay and nuclear factor-kappa B activation in myocardium by Western blotting to estimate myocardial apoptosis. Appearance of mitochondrial cristae and activation of cytochrome C oxidase were used to evaluate mitochondrial damage. Oxidative stress was assessed by mitochondrial lipid and protein oxidation, and antioxidant defense was assessed by mitochondrial superoxide dismutase and glutathione peroxidase activity. RESULTS: Sepsis-induced inflammatory cell infiltration, myocardium degeneration and dropsy were time-dependent. Expanded capillaries were observed in the hearts of infected rats 24 hours post-challenge. Compared with sham-treated rats, the percentage of cell apoptosis increased in a time-dependent manner in hearts from septic rats at 6 hours, 12 hours and 24 hours post-injection (P < 0.05). The expression of nuclear factor-kappa B p65 decreased gradually in the cytosol and increased in the nucleus during sepsis, indicating that septic challenge provoked the progressive activation of nuclear factor-kappa B. Mitochondrial cristae and activation of cytochrome C oxidase increased in a time-dependent manner. Both superoxide dismutase and glutathione peroxidase activities decreased, while mitochondrial lipid and protein oxidation increased between 6 and 24 hours after lipopolysaccharide challenge. CONCLUSIONS: Septic challenge induced myocardial apoptosis and mitochondrial damage. Furthermore, mitochondrial damage via alteration of defenses against reactive oxygen species might play an important role in myocardial apoptosis during sepsis.