Gut Microbiota and Biomarkers of Endothelial Dysfunction in Cirrhosis.

Our aim was to study the association of endothelial dysfunction biomarkers with cirrhosis manifestations, bacterial translocation, and gut microbiota taxa. The fecal microbiome was assessed using 16S rRNA gene sequencing. Plasma levels of nitrite, big endothelin-1, asymmetric dimethylarginine (ADMA), presepsin, and claudin were measured as biomarkers of endothelial dysfunction, bacterial translocation, and intestinal barrier dysfunction. An echocardiography with simultaneous determination of blood pressure and heart rate was performed to evaluate hemodynamic parameters. Presepsin, claudin 3, nitrite, and ADMA levels were higher in cirrhosis patients than in controls. Elevated nitrite levels were associated with high levels of presepsin and claudin 3, the development of hemodynamic circulation, hypoalbuminemia, grade 2-3 ascites, overt hepatic encephalopathy, high mean pulmonary artery pressure, increased abundance of Proteobacteria and Erysipelatoclostridium, and decreased abundance of Oscillospiraceae, Subdoligranulum, Rikenellaceae, Acidaminococcaceae, Christensenellaceae, and Anaerovoracaceae. Elevated ADMA levels were associated with higher Child-Pugh scores, lower serum sodium levels, hypoalbuminemia, grade 2-3 ascites, milder esophageal varices, overt hepatic encephalopathy, lower mean pulmonary artery pressure, and low abundance of Erysipelotrichia and Erysipelatoclostridiaceae. High big endothelin-1 levels were associated with high levels of presepsin and sodium, low levels of fibrinogen and cholesterol, hypocoagulation, increased Bilophila and Coprobacillus abundances, and decreased Alloprevotella abundance.

Gut Microbiota and Cytokine Profile in Cirrhosis.

Background and Aims: Gut dysbiosis and abnormal cytokine profiles are common in cirrhosis. This study aimed to evaluate the correlations between them. Methods: In the blood plasma of cirrhosis patients and controls, 27 cytokines were examined using a multiplex assay. The plasma levels of nitrites (stable metabolites of the endothelial dysfunction biomarker nitric oxide) and lipopolysaccharide (LPS) were examined. The fecal microbiota was assessed by 16S rRNA gene sequencing. Results: Levels of IL-1b, IL-2, IL-6, IL-13, IP-10, IFN-g, TNF-a, LPS, and nitrites were higher in cirrhosis patients than in controls, while levels of IL-4, IL-7, and PDGF-BB were lower. The LPS level was directly correlated with the levels of IL-1b, IL1-Ra, IL-9, IL-17, PDGF-BB, IL-6, TNF-a, and nitrites. The nitrite level was significantly directly correlated with the levels of TNF-a, GM-CSF, IL-17, and IL-12, and inversely correlated with the IL-7 level. TNF-a levels were directly correlated with ascites severity and the abundance of Negativicutes, Enterobacteriaceae, Veillonellaceae, and Klebsiella, while inversely correlated with the abundance of Firmicutes, Clostridia, and Subdoligranulum. IFN-g levels were directly correlated with the abundance of Bacteroidaceae, Lactobacillaceae, Bacteroides, and Megasphaera, and inversely correlated with the abundance of Verrucomicrobiota, Akkermansiaceae, Coriobacteriaceae, Akkermansia, Collinsella, and Gemella. IL-1b levels were directly correlated with the abundance of Comamonadaceae and Enterobacteriaceae and inversely correlated with the abundance of Marinifilaceae and Dialister. IL-6 levels were directly correlated with the abundance of Enterobacteriaceae, hepatic encephalopathy, and ascites severity, and inversely correlated with the abundance of Peptostreptococcaceae, Streptococcaceae, and Streptococcus. Conclusions: The abundance of harmful gut microbiota taxa and endotoxinemia directly correlates with the levels of proinflammatory cytokines.

Impact of vaccination against the novel coronavirus infection (COVID-19) with Sputnik V on mortality during the delta variant surge.

OBJECTIVES: The aim is to study impact of vaccination against the novel coronavirus disease (COVID-19) with Sputnik V on mortality during the period of predominance of the delta variant of SARS-CoV-2. METHODS: This was a retrospective cohort study of individuals with state health insurance at the Moscow Ambulatory Center. The cohorts included 41,444 persons vaccinated with Sputnik V, 15,566 survivors of COVID-19, and 71,377 non-immune persons. The deaths of patients that occurred from June 1, 2021, to August 31, 2021, were analyzed. RESULTS: Overall (0.39 % vs. 1.92 %; p < 0.001), COVID-19-related (0.06 % vs. 0.83 %; p < 0.001), and non-COVID mortality (0.33 % vs. 1.09 %; p < 0.001) was lower among vaccinated individuals than among non-immune individuals. The efficacy of vaccination against death from COVID-19 was 96 % [95 % CI 91-98 %] in the general population, 100 % among those aged 18-50 years, 97 % [95 % CI 76-100 %] among those aged 51-70 years, 98 % [95 % CI 90-100 %] among those aged 71-85 years, and 88 % [95 % CI 49-97 %] among those aged > 85 years. CONCLUSION: COVID-19 vaccination with Sputnik V is associated with a decrease in overall and COVID-19-related mortality and is not with increased non-COVID mortality.

Efficacy and safety of COVID-19 vaccination in patients with cirrhosis.

BACKGROUND: The clinical efficacy and safety of vaccination against novel coronavirus disease 2019 (COVID-19) in patients with cirrhosis have not been evaluated yet. AIM: To evaluate the clinical efficacy and safety of vaccination against COVID-19 in patients with cirrhosis. METHODS: This was a retrospective cohort study of patients with cirrhosis. The first cohort included patients vaccinated with Gam-COVID-Vac (Sputnik V); the second one consisted of unvaccinated controls. RESULTS: The study included 89 vaccinated patients and 148 unvaccinated ones. There were 4 cases of COVID-19 in the vaccinated group and 24 cases in the unvaccinated group (P = 0.035). No severe cases of COVID-19 were revealed in the vaccinated group, while there were 12 ones in the unvaccinated group (P = 0.012) with 10 deaths detected (P = 0.012). The vaccine efficacy was 69.5% (95% confidence interval [CI]: 18.5%-94.4%) against symptomatic cases of COVID-19, 100% (95%CI: 25.1%-100.0%) against severe cases, and 100% (95%CI: 1.6%-100.0%) against death associated with COVID-19. The efficacy of full vaccination with revaccination against symptomatic cases of COVID-19 was 88.3% (95%CI: 48.0%-99.6%). The overall mortality rate was higher in the unvaccinated group than in the vaccinated group (17.1% vs 3.0%; P = 0.001). Higher Child-Turcotte-Pugh class cirrhosis (hazard ratio [HR] = 4.13, 95%CI: 1.82-9.35) and higher age (HR = 1.08, 95%CI: 1.04-1.15) were independent predictors of overall mortality, while vaccination had a protective effect (HR = 0.09, 95%CI: 0.01-0.76). There was no significant difference in liver-related mortality (P = 0.135) or the incidence of liver decompensation (P = 0.077), bleeding esophageal varices (P = 0.397), and vascular events (P = 0.651) between the two groups of patients. CONCLUSION: Vaccination against COVID-19 in patients with cirrhosis is effective and safe.

Application of Polymer Drugs with Cerium Dioxide Nanomolecules and Mesenchymal Stem Cells for the Treatment of Skin Wounds in Aged Rats.

The urgency of the problem of wound healing is not in doubt, given the global trend of an increase in the number of operations and injuries with skin damage, as well as the lack of universal means of treating wounds. STUDY OBJECTIVE: To compare the effectiveness of the developed drugs, smart polymeric nano-drug with cerium oxide nanoparticles (SPN), and smart polymeric nano-drug in combination with mesenchymal stem cells (SPN + SC) on the healing process of skin wounds. MATERIAL AND METHODS: An experimental study was carried out using Wistar rats of post-reproductive age, which had dermis and epidermis removed on their backs. There were four groups of wounds in total: control, treatment with mesenchymal stem cells (SC), SPN, and SPN + SC. RESULTS: A positive therapeutic effect of polymeric drugs on the dynamics of wound area reduction was established, which was most typical for wounds of the SPN group and, particularly, the SPN + SC group. On the third day, an anti-inflammatory effect was revealed in the SC and the SPN + SC groups in particular, which was expressed in a reduced leukocyte infiltration and an increase in the level of microcirculation during this period. The fastest transition from the phase of exudation to proliferation was recorded in the SPN and SPN + SC groups. Histologically, these groups showed faster regeneration, including the epithelialization of wounds. CONCLUSION: The results obtained in the course of the study open up possibilities for the development of fundamentally new, highly effective wound healing agents.

The Effect of Inflammation on the Healing Process of Acute Skin Wounds Under the Treatment of Wounds with Injections in Rats.

PURPOSE: To study the effects of inflammation on the healing process of rats' acute skin wounds during treatment with different injections. METHODS: The study was carried out on Wistar rats, on which square wounds were simulated in the back region. Four groups of wounds were studied. On the day of the simulation (day 0), solutions of the drugs were injected into the wounds: an isotonic sodium chloride solution (Control group), mesenchymal stem cells (SC group), collagen (Collagen group), and a deproteinized hemoderivative of calf blood (DHB group). Within 2 weeks, the wound healing process was assessed by observing and calculating changes in the wound areas, temperatures, and epithelialization levels. On days 3, 7, and 14, wound tissue samples were taken for histological examination, morphological analysis of the healing process, and quantitative assessment of granulation layers' leukocyte infiltration. RESULTS: A correlation between the process of inflammation and epithelization during the healing of skin wounds was established. The anti-inflammatory effect of SC injection on the wound edge tissues was determined, as well as the pro-inflammatory effect of DHB, and the absence of effects on the inflammation course under the collagen treatment. Compared to the control group, the transition from the exudative phase of inflammation to the proliferative phase was faster, as well was wound epithelialization in the SC and Collagen groups. A negative correlation between the level of tissue temperature in the center of wounds and their area were recorded, which intensified over time. CONCLUSION: The severity and duration of the inflammation process during wound healing were ambiguous with the use of different injection treatments. This should compel clinicians to use different markers of drug therapy effectiveness during wound healing. Excessive leukocyte infiltration with a low temperature of wounds and a large scab were markers of delayed wound healing.