A pilot study to determine the relationship of changes in the characteristics of β1- and β2-adrenoreceptors against the background of the use of β2-agonists with clinically significant parameters in patients with cardiovascular pathology

Background: Comorbid cardiovascular and bronchoobstructive diseases worsens disease course and prognosis and causes difficulties in therapy. Effectiveness 2-agonists (cornerstone of bronchoobstructive pathology treatment) depends on -adrenoreceptors state. Therefore, a detailed study of the functional state of beta-adrenoreceptors is necessary. Aim: to evaluate the relationship of changes in the characteristics of 1- and 2-adrenoreceptors, against the background of the use of 2-agonists in patients with cardiovascular and bronchoobstructive diseases with clinically significant parameters. Methods: In the pilot single-center prospective study during 2.5 years 45 patients (15 with cardiovascular and 30 with bronchoobstructive diseases) were included. Anamnestic data and complaints were collected and laboratory and instrumental studies were performed. Modified radioligand analysis on blood T-lymphocytes using radiolabeled Cyanopindolol and unlabeled selective ligands (ICI 118551, CGP 20712) before and after salbutamol and formoterol was performed and the binding activity of 1- and 2-adrenoreceptors was determined. Results: The correlation analysis between clinically significant parameters and changes in the specific binding index of 1- and 2-adrenoreceptors confirmed its clinical relevance. In test with beta-agonists in cardiovascular and bronchoobstructive diseases patients, an increase in the specific binding index of 1-adrenoreceptors is associated with clinical, laboratory and instrumental parameters of a favorable course of the disease, and an increase in the specific binding index of 2-adrenoreceptors is associated with negative. In the cardiovascular group without bronchoobstructive diseases with salbutamol an increase in the specific binding index of 1-adrenoreceptors was associated with parameters of unfavorable disease course, while an increase in the specific binding index of 2-adrenoreceptors did not have a clear associative relationship with clinical characteristics. Conclusions: The association of changes in the specific binding index of 1- and 2-adrenoreceptors in patients with cardiovascular and bronchoobstructive diseases with clinically significant parameters during acute tests with short- and long-acting 2-agonists was revealed, which in the future may provide an opportunity to identify patients with an unfavorable course of the disease

Correlation between Antioxidant Enzymes Activity and Intraerythrocyte Concentration of Fe, Mg, Zn, Cu in Pulmonary Arterial Hypertension and Cor Pulmonale in Children with Congenital Lung Disease and Cystic Fibrosis

Significant changes in the levels of the potential prooxidant Cu (increase) and the antioxidant Zn (decrease) in plasma were revealed in children having bronchopulmonary dysplasia (BPD) complicated by pulmonary arterial hypertension (PAH) and chronic cor pulmonale (CCP) when compared with the control. The Zn / Cu ratio in the blood plasma of patients with BPD, especially in CCP, was found to be lower than in the control group (p<0.001). This could indicate the activation of the prooxidant processes; simultaneously, the total antioxidant status (AOS) decreased. No significant increase in the intracellular free (“ionized” (i)) form of magnesium (iMg) was found; in fact, the concentration of iFe in all the patient groups was higher than in the control. An increase in the iCu and iZn levels (nonprotein-bound) was observed in the blood cells of the affected children. A significant increase in the glutathione peroxidase activity in the CCP patients may indicate an accumulation of organic peroxides, and partially compensate for the lesser activity of superoxide dismutase (SOD) and other antioxidants. The Zn / Cu and iZn/ iCu ratios were reduced in patients with CCP when compared with patients with PD without CCP

Vaccination as a protective factor for medical workers during the COVID-19 pandemic

Aim – to evaluate the effectiveness of vaccination when using various vaccines against COVID-19 approved for use in Russia among medical staff and faculty of medical higher educational institutions according to online questionnaires. Material and methods. A cross-sectional study was conducted online from January to March 2022 (circulation period of the omicron genovariant). The survey was completed by 6032 respondents, 2114 respondents were excluded from the study. The remaining 3918 respondents were included in the the analysis. Results. 47 (0.1%) medical workers reported COVID-19 incidence within 21 days after the second dose of the vaccine. 616 (16.8%) medical workers reported COVID-19 incidence within 5 months after two vaccinations. 116 (46.4%) unvaccinated respondents reported a laboratory-confirmed new coronavirus infection within 5 months prior to the survey. Lack of vaccination increased the risk of SARS-CoV-2, OR 1.78 ± 0.14 (95% CI 1.34-2.36). It was found that gender and age were not a risk factor for the onset of the disease in the post-vaccination period. The presence of SARS-CoV-2 in medical history increased the risk of developing the disease in the post-vaccination period. Conclusion. The analysis revealed that vaccination had significantly higher protection effect for 1.5 months after vaccination and significantly reduced in 5 months after vaccination

Target Groups for a Short Dexamethasone Course among Critically Ill COVID-19 Patients

Introduction. Corticosteroids are one of the most promising therapeutic agents for critically ill patients with coronavirus disease 2019 (COVID-19). Despite emerging data, assessed populations and regimens vary, and there are patient subgroups whose response to steroids remains unclear. We aimed to evaluate the outcomes of COVID-19 patients admitted to the intensive care unit (ICU) and treated with a short dexamethasone course to determine which patient categories derive the highest benefit. Methods. A retrospective cohort study was conducted using a prospectively collected single-center ICU database (April 1–October 1, 2020). Adult COVID-19 patients were assigned to dexamethasone (12 mg × 3 days) and usual care groups. Patient, management, and outcome data were extracted. The primary outcome was the 28-day ICU mortality. Subgroup analysis was performed to assess the impact of dexamethasone on mortality in patients with invasive mechanical ventilation (IMV). Results. Of 233 patients, 220 (median age: 65 years, 38% female) were included: 83 patients received dexamethasone and 137 received usual care. Overall, 28 (33.7%) and 54 (39.4%) patients in the dexamethasone and usual care groups, respectively, died within 28 days since ICU admission (rate ratio (RR) 0.86; 95% confidence interval (95% CI): 0.59–1.23; p=0.405). In the IMV cohort, dexamethasone did not decrease the 28-day mortality compared with usual care (47.5% vs. 62.0%; RR 0.78; 95% CI: 0.57–1.09; p=0.107). A subgroup analysis revealed significantly lower 28-day mortality in IMV patients <65 years receiving dexamethasone vs. usual care (22.6% vs. 48.5%; RR 0.47; 95% CI: 0.22–0.98; p=0.043), which was not seen in IMV patients ≥65 years (75.0% vs. 71.1%; RR 1.06; 95% CI: 0.79–1.42; p=0.719). Patients ≥65 years experienced hyperglycemia, bacterial infection, and septic shock significantly more often than younger patients who received dexamethasone (p=0.002, p=0.025, and p<0.001, respectively). Conclusions. A 3-day dexamethasone course is not associated with lower 28-day mortality in critically ill COVID-19 patients, either in the entire ICU cohort or in the IMV. Dexamethasone may significantly reduce the 28-day mortality in IMV patients <65 years, but not in the older IMV subgroup. Dexamethasone administration in patients ≥65 years is associated with a significantly higher rate of adverse events than that in younger patient

COVID-19: аn Update on the Modern Etiotropic Therapy Methods for the New Coronavirus Infection

The COVID-19 pandemic, caused by the SARS-CoV-2 RNA-virus, has a significant impact not only on the peoples lifestyle and health, but on the global economy, as well. According to the epidemiological data, the highest level of the sickness rate in Russian Federation was in January-February of 2022, while the death rate was 1.9%. The numerous studies on the COVID-19 pathogenesis allowed improving the approaches to the development of efficient clinical strategies. However, a number of important issues regarding the clinical applications of new and repurposed drugs on the market still remain unresolved. It is a well-known fact that the most effective way of preventing the immune system from developing the hyperactive reaction known as a cytokine storm is prescribing the etiotropic therapy as fast as possible. Etiotropic drugs are divided into three large groups: those preventing the virus from penetrating the cell, those affecting the replication-transcriptional complex and the last but not the least group is the drugs with the direct or indirect cytotoxic effect. This review introduces some important data regarding the etiotropic treatment methods for the new coronavirus disease

POPE study: Rationale and methodology of a study to phenotype patients with COPD in central and Eastern Europe

Introduction: Chronic obstructive pulmonary disease (COPD) constitutes a major health challenge in Central and Eastern European (CEE) countries. However, clinical phenotypes, symptom load, and treatment habits of patients with COPD in CEE countries remain largely unknown. This paper provides a rationale for phenotyping COPD and describes the methodology of a large study in CEE. Methods/design: The POPE study is an international, multicenter, observational cross-sectional survey of patients with COPD in CEE. Participation in the study is offered to all consecutive outpatients with stable COPD in 84 centers across the CEE region if they fulfill the following criteria: age >40 years, smoking history ≥10 pack- years, a confirmed diagnosis of COPD with postbronchodilator FEV1/FVC <0.7, and absence of COPD exacerbation ≥4 weeks. Medical history, risk factors for COPD, comorbidities, lung function parameters, symptoms, and pharmaceutical and nonpharmaceutical treatment are recorded. The POPE project is registered in ClinicalTrials.gov with the identifier NCT02119494. Outcomes: The primary aim of the POPE study was to phenotype patients with COPD in a real-life setting within CEE countries using predefined classifications. Secondary aims of the study included analysis of differences in symptoms, and diagnostic and therapeutic behavior in participating CEE countries. Conclusion: There is increasing acceptance toward a phenotype-driven therapeutic approach in COPD. The POPE study may contribute to reveal important information regarding phenotypes and therapy in real-life CEE. © 2016 Zbozinkova et al

Phenotypes of COPD patients with a smoking history in Central and Eastern Europe: The POPE Study

Chronic obstructive pulmonary disease (COPD) represents a major health problem in Central and Eastern European (CEE) countries; however, there are no data regarding clinical phenotypes of these patients in this region. Participation in the Phenotypes of COPD in Central and Eastern Europe (POPE) study was offered to stable patients with COPD in a real-life setting. The primary aim of this study was to assess the prevalence of phenotypes according to predefined criteria. Secondary aims included analysis of differences in symptom load, comorbidities and pharmacological treatment. 3362 patients with COPD were recruited in 10 CEE countries. 63% of the population were nonexacerbators, 20.4% frequent exacerbators with chronic bronchitis, 9.5% frequent exacerbators without chronic bronchitis and 6.9% were classified as asthma - COPD overlap. Differences in the distribution of phenotypes between countries were observed, with the highest heterogeneity observed in the nonexacerbator cohort and the lowest heterogeneity observed in the asthma - COPD cohort. There were statistically significant differences in symptom load, lung function, comorbidities and treatment between these phenotypes. The majority of patients with stable COPD in CEE are nonexacerbators; however, there are distinct differences in surrogates of disease severity and therapy between predefined COPD phenotypes. Copyright ©ERS 2017

Determinants of CAT (COPD Assessment Test) scores in a population of patients with COPD in central and Eastern Europe: The POPE study

Background: The COPD Assessment Test (CAT) has been proposed to help guide therapy in chronic obstructive pulmonary disease (COPD). It is important to understand the distribution of scores in different COPD populations and their determinants. Methods: The POPE study is an international, observational cross-sectional study of COPD subjects in 11 Central and Eastern European countries aimed at characterizing COPD phenotypes. Here we report the analysis of CAT scores with the objective of identifying their determinants, evaluating symptom load and investigating the distribution of scores among the participating countries. Additionally, we investigated the discrepancies between the CAT and modified Medical Research Council (mMRC) scores when used to classify patients according to the GOLD strategy. Results: The study included 3452 patients (69.2% men, mean forced expiratory volume in 1 s (FEV1% predicted) 52.5%). The mean CAT score was 17.5 (SD = 7.8), ranging from 15.1 in Hungary to 21.2 in Bulgaria. Multiple linear regression analysis showed six variables significantly associated with CAT scores: depression, number of previous exacerbations, 6-min walking distance, FEV1(%), mMRC and country and explained 47.2% of the variance of CAT. According to either CAT or mMRC, up to 23.9% patients would be classified in different GOLD groups. Conclusions: The CAT score may be predicted by factors related to COPD severity, depression and exercise capacity, with significant differences in the distribution of CAT scores in different countries. According to our results CAT > 10 is not equivalent to mMRC > 2 for assessing symptom burden