Terapevticheskii arkhiv

The COVID-19 pandemic has highlighted pressing challenges in biomedical research methodology. It has become obvious that the rapid and effective development of treatments for “new” viral infections is impossible without the coordination of interdisciplinary research and in-depth analysis of data obtained within the framework of the post-genomic paradigm. Presents the results of a systematic computer analysis of 290,000 scientific articles on COVID-19, with an emphasis on the results of post-genomic studies of SARS-CoV-2. The futility of the overly simplified approach, which considers only one “most important receptor protein”, only one “key virus gene”, etc., is shown. It is shown how post-genomic technologies will make it possible to find informative biomarkers of severe coronavirus infection, including those based on complex immune disorders associated with COVID-19.

Aim. To assess clinical and demographic characteristics of severe asthma (SA) patients and their management in Russian Federation.

Materials and methods. This publication provides data for Russian part of population of the international observational study. In Phase I, retrospective analysis of medical records of patients with SA was performed with assessment of clinical and demographic data, medical history, comorbidities, treatment approaches and healthcare utilization. Phase II was a cross-sectional collection of patient-reported outcomes: level of asthma control assessed by ACT (Asthma Control Test) and health-related quality of life (HRQoL) measured using the EQ-5D-5L questionnaire. Phase I patients were enrolled into Phase II if they signed a written consent form.

Results. A total of 315 patients were included in Phase I of the study, 106 (33.6%) of them entered Phase II. Majority of study participants were either obese (n=103; 39.8%) or overweight (n=94; 36.3%). The most common comorbidities were cardiovascular diseases (n=217; 71.4%), followed by chronic respiratory diseases (n=198; 68.8%). There were 268 (85.1%) patients who had at least one exacerbation during last 12 months. Data for blood eosinophil count were available in 176 patients; 81.3% of them (n=143) had only one test in the last 12 months. The mean (SD) last available blood eosinophil count was 161.2 (181.2) cells/mm³. Serum Immunoglobulin E (IgE) value was known for 88 patients, and the mean (SD) last measured IgE value was 254.3 (249.7) ng/mL. Only 4.7% of Phase II participants had ACT scores indicative of controlled asthma (>20). As much as 74.5% had scores ≤15 suggesting uncontrolled disease. Most patients also had impaired HRQoL.

Conclusion. Most SA patients had poor disease control with frequent exacerbations and high number of comorbidities. Blood eosinophils and IgE level measurements were not evaluated routinely which might be a barrier for appropriate phenotyping and treatment selection.

Aim. To evaluate the possibility of using spectral analysis of cough sounds in the diagnosis of a new coronavirus infection COVID-19.

Materials and methods. Spectral toussophonobarography was performed in 218 patients with COVID-19 [48.56% men, 51.44% women, average age 40.2 (32.4; 51.0)], in 60 healthy individuals [50% men, 50% women, average age 41.7 (32.2; 53.0)] with induced cough (by inhalation of citric acid solution at a concentration of 20 g/l through a nebulizer). The recording was made using a contact microphone located on a special tripod at a distance of 15–20 cm from the face of the subject. The resulting recordings were processed in a computer program, after which spectral analysis of cough sounds was performed using Fourier transform algorithms. The following parameters of cough sounds were evaluated: the duration of the cough act (ms), the ratio of the energy of low frequencies (60–600 Hz) to the energy of high frequencies (600–6000 Hz), the frequency of the maximum energy of the cough sound (Hz).

Results. After statistical processing, it was found out that the parameters of the cough sound of COVID-19 patients differ from the cough of healthy individuals. The obtained data were substituted into the developed regression equation. Rounded to integers, the resulting number had the following interpretation: "0" – there is no COVID-19, "1" – there is COVID-19.

Conclusion. The technique showed high levels of sensitivity and specificity. In addition, the method is characterized by sufficient ease of use and does not require expensive equipment, therefore it can be used in practice for timely diagnosis of COVID-19.

Aim. To assess effectiveness and safety of biological therapy in patients with severe asthma during 5 yr follow-up.

Materials and methods. We recruited 129 adult outpatients (29% males) aged 18–81 yrs with severe asthma were followed up during 5 yrs and were examined for every 3–6 months. Eighty five patients were treated by conventional therapy (ICS/LABA ± tiotropium, montelukast, OCS) only and 44 pts additionally received biologicals (оmalizumab – 9 pts, мepolizumab – 8 pts, benralizumab – 11 pts, dupilumab – 16 pts). Pulmonary function tests were measured by dry spirometer (2120, Vitalograph Ltd., UK). Eosinophil count in blood was assessed by automatic haemoanalyser. Fraction of exhaled nitric oxide was measured by a chemiluminescence analyzer (LR4100; Logan Research, UK). Asthma control and quality of life were assessed by using Russian versions of ACQ-5 and SGRQ.

Results. The use of biologicals led to a more significant reduction of exacerbations and OCS use, improvement of lung function, asthma control and quality of life, decrease of eosinophil and fraction of exhaled nitric oxide than conventional therapy of severe asthma (p<0.05). Systemic side effects were not registered, frequency of local adverse reactions (edema, hyperemia and itching at injection site) was 14%.

Conclusion. Long-term use of biologicals added to conventional therapy in patients with severe asthma is characterized by high effectiveness and favorable safety profile.

Aim. To evaluate the impact of chronic obstructive pulmonary disease (COPD) on hospital outcomes of percutaneous coronary interventions (PCI) in patients with acute coronary syndrome (ACS).

Materials and methods. A cohort prospective study of the COPD effect on mortality and coronary microvascular obstruction (CMVO, no-reflow) development after PCI in ACS was carried out. 626 patients admitted in 2019–2020 were included, 418 (67%) – men, 208 (33%) – women. Median age – 63 [56; 70] years. Myocardial infarction with ST elevation identified in 308 patients (49%), CMVO – in 59 (9%) patients (criteria: blood flow <3 grade according to TIMI flow grade; perfusion <2 points according to Myocardial blush grade; ST segment resolution <70%). 13 (2.1%) patients died. Based on the questionnaire "Chronic Airways Diseases, A Guide for Primary Care Physicians, 2005", 2 groups of patients were identified: 197 (31%) with COPD (≥17 points) and 429 (69%) without COPD (<17 points). Groups were compared on unbalanced data (÷² Pearson, Fisher exact test). The propensity score was calculated, and a two-way logistic regression analysis was performed. The data were balanced by the Kernel “weighting” method, logistic regression analysis was carried out using “weighting” coefficients. Results as odds ratio (OR) and 95% confidence interval.

Results. The conducted research allowed us to obtain the following results, depending on the type of analysis: 1) analysis of unbalanced data in patients with COPD: OR death 3.60 (1.16–11.12); p=0.03; OR CMVO 0.65 (0.35–1.22); p=0,18; 2) two-way analysis with propensity score: OR death 3.86 (1.09–13.74); p=0.04; OR CMVO 0.61 (0.31–1.19); p=0.15; 3) regression analysis with "weight" coefficients: OR death 12.49 (2.27–68.84); p=0.004; OR CMVO 0.63 (0.30–1.33); p=0.22.

Conclusion. The presence of COPD in patients with ACS undergoing PCI increases mortality and does not affect the incidence of CMVO.

Aim. To investigate the antitumor effects of human placenta hydrolysate (HPH) peptides on three hormone-dependent human cell lines: prostate adenocarcinoma, breast carcinoma, and ovarian cancer by metabolic analysis of cell cultures.

Materials and methods. The effect of HPH on tumor and control tumor cell lines was evaluated. Study stages: (A) de novo peptide sequencing by collision-induced dissociation mass spectrometry; (B) detection of peptides with anti-tumor properties; (C) expert analysis of the obtained lists of peptides.

Results. Dose-dependent cytotoxic effects of HPH on three tumor cell lines are shown: PC-3 (human prostate adenocarcinomas), OAW-42 (human ovarian cancer), BT-474 (human breast carcinomas), and IC₅₀ constants (1.3–2.8 mg/ml) were obtained. The analysis of the HPH peptide fraction showed more than 70 peptides with antitumor properties in the composition of this HPH, including kinase inhibitors: mitogen-activated protein kinases, kappa-bi nuclear factor inhibitor kinase, AKT serine/threonine kinase 1, protein kinase C zeta, interleukin-1 receptor-associated kinase 4 and cyclin-dependent kinase 1.

Conclusion. The results of the study indicate not only the oncological safety of the HPH used in therapy but also the mild antitumor effects of this HPH at high concentrations.

Aim. Evaluation of the efficacy and safety of riamilovir as a drug for the prevention of coronavirus infection (COVID-19) in adults who have constant contact with COVID-19 patients as a result of living together.

Materials and methods. The study included 750 adult participants living with patients with confirmed polymerase chain reaction method COVID-19, who had a negative polymerase chain reaction result for the SARS-CoV-2 virus at the initial level, met the criteria for inclusion, non-inclusion and exclusion, and signed a voluntary informed consent to participate in a clinical trial.

Results. The efficacy, good tolerability and safety of the drug riamilovir for the prevention of COVID-19 infection among people who have come into contact with COVID-19 patients in a family focus of infection have been established.

Conclusion. As a result of a multicenter randomized double-blind clinical trial, the effectiveness of the drug riamilovir for the prevention of COVID-19 infection was established. It was shown that the relative risk of disease in the group taking riamilovir for prophylaxis was 88.96% lower than in the control group. Based on the results of a clinical trial, in October 2023 Ministry of Health of the Russian Federation approved the inclusion of a new indication (prophylaxis of COVID-19 infection) in the instructions for the medical use of the drug riamilovir (trade name – Triazavirin^®).

Chronic obstructive pulmonary disease is now one of the most common noncommunicable diseases and the main causes of morbidity, disability and mortality in the world. In recent years, new approaches to epidemiology, diagnosis, classification (categorization), evaluation of phenotypes, as well as characterization and assessment of the severity of сhronic obstructive pulmonary disease exacerbations have emerged. Modern approaches to starting and subsequent drug therapy have changed significantly. This is largely due to the results of recently conducted major clinical trials, demonstrated high efficacy of triple fixed combinations, including inhaled glucocorticosteroids, long-acting beta-agonists and long-acting anticholinergic drugs. The use of non-medication methods (smoking cessation, physical activity and respiratory rehabilitation) and modern approaches to the treatment of respiratory failure and antibiotic therapy remain important. In terms of their significance, all these updates have a significant impact on real clinical practice and can be considered as a novel paradigm of the approaches to the diagnosis and management of this disease.

Bronchial asthma and chronic polypous rhinosinusitis are diseases associated with a T2-inflammatory immune response. These nosologies can be combined, creating the preconditions for a more severe course of multimorbidity, requiring the use of genetic engineering biological therapy. Dupilumab is a monoclonal antibody that can specifically bind to the alpha subunit of the interleukin-4 receptor and block the action of interleukins 4 and 13, which play a key role in the development of T2 inflammation. Numerous studies have demonstrated the high effectiveness of this medicament. The use of dupilumab in some cases may be accompanied by an increase in eosinophils in the blood. This article presents scientific base and our own experience in treating patients with dupilumab-associated eosinophilia, in addition we describe an algorithm for examining this group of patients for the purpose of timely diagnosis of diseases such as eosinophilic granulomatosis with polyangiitis, eosinophilic pneumonia, etc. It should be noted that in the most cases eosinophilia during targeted therapy with dupilumab is temporary and does not cause clinical manifestations.

The articles on the history of Russian pulmonology presented in the historical, medical and therapeutic literature contain materials for this history, but their authors did not solve the problem of its consistent presentation, highlighting the stages of formation and founders. The authors of this study critically reviewed the literary and archival primary sources, for the first time proposed the identification of three stages in the development of Russian pulmonology and indicated eight of its founders at these stages. The abundance of material did not allow us to present it in one article. This article is devoted to the 1st stage of the history of pulmonology – the formation of the doctrine of lung diseases. The second (development of pulmonology as an independent scientific direction in internal diseases) and the third (organizational design of pulmonology as a new independent clinical scientific and educational discipline and medical specialty, i.e. its institutionalization) stages will be discussed in the next articles.

In the article "Point-of-care blood glucose testing: post-market performance assessment of the Accu-Chek Inform II hospital-use glucose meter," published in the Terapevticheskii Arkhiv journal, Vol. 95, No.12, 2023 (DOI: 10.26442/00403660.2023.12.202522), errors were made: the term "measurements at the place of treatment" was changed, as well as the section "Conflict of interest."

At the request of the authors' team, errors in the conflict of interest and the wording of the term have been corrected, and the section "Information about the authors" has been updated. The publisher replaced the original version of the published article with the corrected one; the information on the website was also corrected.

Correct text of the section "Conflict of interest":

Conflict of interest. All authors are not employees or consultants of Roche Diagnostics and have not received any compensation from Roche Diagnostics.

Correct wording of the term in Russian: "измерения по месту лечения". Changes were made to the title of the article in Russian: "Измерения глюкозы по месту лечения: пострегистрационное испытание госпитального глюкометра Акку-Чек Информ II", the text of the abstract, keywords, citation, in the text of the article, and abbreviations.

Information of the place of work has been updated: Center for Laboratory Diagnostics of the Russian Children Clinical Hospital, a Branch of the Pirogov Russian National Research Medical University.

The publisher apologizes to readers and authors for the errors and is confident that the correction of errors will ensure the correct perception and interpretation of the results of the study described in the text.