Introduction. Healthy nutrition is the most important component of the quality of life, which is understood as an integral indicator of the mental, physical and social functioning of a person. However, the diet of Russians is not enough vegetables and fruits, dairy products, excess sugar, salt, products containing animal fat and trans fats. Violations of the structure of nutrition, nutritional status lead to the development of alimentary-dependent diseases, primarily cardiovascular, and in particular, arterial hypertension.

Goal. Study of alimentary risk factors for arterial hypertension.

Materials and methods. The data of the survey of VTSIOM and the company Gideon Richter “Food habits of Russians”, September 2020”, conducted by telephone survey in at least 80 regions (1,600 respondents over 18 years old), are analyzed.

Results and discussion. The diet of the adult population of Russia is characterized by a high consumption of animal fat (frequent consumption of fatty dairy products-52% of respondents, butter-61%, sausage products-48%), salt (pickles and marinades – 42%), added sugar (confectionery – 47%) with a lack of fruit, fish and seafood. 23% of respondents add salt to ready meals, and 43% use frying when cooking. Arterial hypertension was noted in 52% of respondents, who, compared to normotonics, less often (32-39%) include in their diet foods that are sources of potassium and magnesium (apricots, bananas, dried fruits, nuts, seeds, etc.), and more often-pickles, marinades (47%) and mayonnaise (45%), containing a large amount of salt, as well as add salt to ready meals (24%).

Conclusions. In order to prevent arterial hypertension in Russians, it is necessary to increase their intake of potassium and magnesium, limit the content of table salt in the diet, which will be facilitated by the widespread introduction of educational programs on healthy nutrition.

The article discusses the role of immune dysregulation of the renin-angiotensin-aldosterone system (RAAS) in the pathogenesis of COVID-19 infection, the participation of ACE2 for the penetration of the SARS-CoV-2 coronavirus into cells and the possible role of RAAS blockers, which have a direct effect on the pathological activity of the RAAS, in the development of and the severity of the disease. It is noted that the beneficial organoprotective effects of ACE inhibitors and ARBs may protect against SARS-CoV-2 infection, and their withdrawal may lead to clinical decompensation in patients at high risk of cardiovascular risk. Since then, a number of observational cohort studies have been carried out to address the main questions: does the use of an ACE inhibitor or ARB increase the risk of contracting the novel SARS-CoV-2 coronavirus, and whether the use of RAAS blockers is associated with worse outcomes of COVID-19 disease. The article provides an overview of the scientific evidence on the relationship between the use of RASS blockers and COVID-19 infection. Several cohort studies and two meta-analyzes found no association between prior use of an ACE inhibitor/ARB and the risk of COVID-19 infection (RR 0.96–0.99). In studies on the study of clinical and laboratory features of the action of RAAS blockers in COVID-19, a significantly larger number of subpopulations of T-lymphocytes CD3+ and CD8+, lower concentrations of biomarkers (C-reactive protein, ferritin, IL-6, procalcitonin), as well as a lower viral load. In clinical outcomes, with the use of an ACE inhibitor/ARB, there was a lower incidence of severe/critical forms, and a shorter duration of hospitalization. In large cohort studies with >1000 patients, the use of an ACE inhibitor/ARB was not associated with an increase in the risk of death in patients with COVID-19 (RR < 1.0), and some studies showed a 37–67% decrease in RR. Meta-analyzes also confirmed the absence of the effect of RAAS blockers on the risk of mortality, and in the population of patients with hypertension, a significant reduction in the risk of mortality and severe course of COVID-19 was revealed. Most international associations of specialists, as well as the Russian Cardiological Society, are recommended to continue the use of RAAS blockers in patients with cardiovascular diseases and not to be canceled in case of COVID-19 disease. Further randomized clinical trials are needed to generate new evidence.

Cardiovascular diseases, especially coronary heart disease (CHD), are the leading cause of disability; various registry data show that the annual mortality rate of such patients is 2–3%. This explains the interest of practitioners in the pharmacotherapy of stable forms of coronary artery disease using current progress in the understanding of the pathogenesis of this disease and treatment compliance. Features of the pathogenesis of CHD in the form of increased myocardial oxygen demand, increased pre- and afterload on the performance of the heart necessitate the prescription of rhythm-reducing drugs such as beta-blockers, calcium channel blockers, ivabradine or their combinations, as well as nitric-containing drugs; trimetazidine, ranolazine for the purpose of myocardial cytoprotection. However, the use of hemodynamic drugs (beta-blockers, calcium channel blockers) does not always effectively relieve the symptoms of angina pectoris, even when used in combination with other drugs. This dictates the need to improve the drug effect on the ischemic myocardium with due account for the hypoxia-induced metabolic dysfunction of cardiac myocytes. In this regard, the use of trimetazidine at the initial stages of ischemia  – at the level of  metabolic dysfunction does not allow for the development of delayed complications: contractile disfunction of cardiac myocytes and myocardium in general. A wealth of clinical experience has been gained in the use of trimetazidine to treat stable angina pectoris in elderly patients, left ventricular dysfunction and symptoms of chronic heart failure. Drugs with a patient-friendly dosage regimen have been created to improve treatment compliance in patients with coronary artery disease. One of these drugs is once-daily modified release matrix tablets of myocardial cytoprotector Deprenorm OD, 70 mg. The creation of drugs with a patient-friendly dosage regimen will help boost patient compliance to medication and, as a result, reduce the frequency of angina attacks and improve the quality of life in this category of patients. 

Introduction. Apixaban is a direct oral anticoagulant prescribed for treatment and prevention of venous thromboembolism (VTE) and for prevention of stroke in patients with nonvalvular atrial fibrillation. Direct oral anticoagulants (DOACs) such as apixaban are rapidly replacing warfarin therapy due to improved efficacy and safety profile shown in clinical trials. However, anticoagulants can cause serious and adverse drug reactions (ADRs).

Aim. Study of the effect of carriage of polymorphisms in CYP3A4*22 (rs35599367) C>T, CYP3A5*3 (rs776746) A>G, ABCB1 (rs4148738) C>T and ABCB1 (rs1045642) C>T genes on the change in prothrombin time (PT) and activated partial thromboplastin time (aPTT) in patients using apixaban.

Materials and methods. A total of 36 patients were enrolled onto this prospective observational study. All patients received apixaban at doses in accordance with instructions on how to administer the drug. Atrial fibrillation was diagnosed in 26 patients, and secondary thrombotic complications in 23 patients. To perform pharmacogenetic tests and measure aPTT and PT parameters, venous blood samples from each patient were drawn on Days 4-5 after prescription of apixaban. The PharmGKB database was used to select candidate genes for the study. Genotyping was performed using the real-time polymerase chain reaction technique. Statistical analysis: data were analyzed by using IBM SPSS Statistics program, Version 23.0.

Results. In our study, we assessed the effect of polymorphisms in ABCB1 (rs1045738) C>T, ABCB1 (rs4148642) C>T genes on the aPTT and PT parameters. No statistically significant associations were found.

Conclusion. The differences between PT and APTT values in patients using apixaban in the groups with different polymorphisms in ABCB1 (rs1045738) C>T, ABCB1 (rs4148642) C>T gene were not statistically significant. Further studies are necessary to assess the effect of pharmacogenetics on the safety and efficacy profile of apixaban.

According to the theory of inflammaging, aging of the body and the development of age-related diseases are a consequence of a chronic progressive generalized inflammatory process that develops and persists throughout life under the influence of negative factors of an infectious and non-infectious nature. Inflammaging has a number of features that distinguish it from acute inflammation: a chronic nature of inflammation, a low level of inflammation, blurry clinical state (in the early stages of clinical manifestations there may not be any at all). The key pathogenetic role in inflammation plays age-associated changes in the innate immune system, which are referred to in the English literature as “immunosenescence” and oxidative stress. The main source of reactive oxygen species and free radicals in the cells are mitochondria. With age, the concentration of intracellular glutathione, one of the main factors of the antioxidant protection of the cell, decreases and a pathological condition arises in which the rate of production of free radicals and reactive oxygen species significantly exceeds the antioxidant capabilities, which leads to the formation of oxidative stress and disruption of the structure and function of cells. Oxidative stress, inflammation and neuroinflammation are closely related to cognitive impairment, pathological state that is often observed in a group of elderly and senile patients. Further study of the pathogenesis of Inflammaging and the role of oxidative stress in it will potentially lead to development of methods to slow down aging and treat age-related cognitive impairments.

Arterial hypertension was one of the most common comorbidities associated with a high risk of death in hospitalized patients with COVID-19. Patients with hypertension are routinely and according to standards treated with angiotensinconverting enzyme inhibitors (ACE inhibitors) or angiotensin receptor blockers (ARB) II. ACE inhibitors or ARB II are included in fixed combinations of antihypertensive drugs recommended for patients with uncomplicated hypertension, as well as when combined with various comorbidities. During the COVID-19 pandemic, there were suggestions about the potential for a negative effect of drugs of these classes on the course and outcomes of a new coronavirus infection. There was a need for a quick response from the most reputable medical organizations to the question of the use of ACE inhibitors and ARB II during the COVID-19 pandemic. The expert position was soon published despite the lack of evidence from randomized clinical trials. Was there any reason for concern about the treatment of ACE inhibitors and ARB II for COVID-19? What are the relationships between the renin-angiotensin-aldosterone system (RAAS) and COVID-19? Is there any new data from clinical trials that can confirm or deny the previously presented position of professional societies regarding the use of RAAS blockers in COVID-19? What is the role of the difference in the mechanism of action of an ACE inhibitor and ARB II in COVID-19? Is it possible that RAAS blockers will be helpful in treating COVID-19? Will the tactics of hypertension pharmacotherapy change in the near future? In this review article, modern concepts on this problem are discussed and answers to the listed questions reflecting the achieved level of knowledge are formulated.

A new 2019 coronavirus disease has been spreading worldwide for more than a year, with a high risk of infection and death. Various sequelae and complications can develop in COVID-19 survivors, lasting from several weeks to several months after initial recovery, affecting different organs and systems. Various sequelae and complications can occur in COVID-19 survivors not only in adults and the elderly, but also in young people. A wide range of neurological manifestations of COVID-19 are now described in the available literature. The incidence of selected neurological symptoms, syndromes and nosological forms in individuals both in the acute period of COVID-19 disease and in the short- and long-term follow-up of these patients is presented. In this article, cognitive impairments occurring in individuals who have had coronavirus disease are discussed in depth. Data on the prevalence of cognitive impairment in different regions and at different periods of the disease are presented. The main possible pathophysiological processes and risk factors for the development of cognitive impairment in COVID-19 are described. Possible ways of drug and non-drug rehabilitation of patients with cognitive impairment in coronavirus infection that is a new problem of modern medicine are considered. Attention is also paid to neuroprotection as one of the therapy areas.

The article discusses the concept of embolic stroke from an unspecified source and the role of aorto-arterial embolism in its development. Potential causes of embolic cryptogenic stroke such as aortic atheromatosis, non-stenotic atherosclerosis of the cervical arteries, carotid web and intracranial atherosclerosis are discussed in detail. The discussion of each cause covers epidemiology, pathogenesis, and current approaches to diagnosis and secondary prevention. The diagnostic search is presented in the form of an algorithm. To identify aorto-arterial sources of embolism and to determine their clinical significance, a comprehensive examination including CT angiography with targeted assessment of the aortic arch, transesophageal echocardiography, MRI of the arterial wall and transcranial Doppler is required. When mechanical thrombectomy is performed, histological examination of the thromboembolus is advisable. Given that atherosclerosis is usually systemic, the search for a possible cause of aorto-arterial embolism should be a diagnostic priority in patients with cryptogenic stroke and other arterial (coronary, lower extremity) lesions. With regard to secondary prevention of cryptogenic stroke in the presence of potential sources of aorto-arterial embolism, the principle ‘the more embologenic the source, the more aggressive the prevention’ applies. The arsenal of secondary prevention includes strategies such as strict control of vascular risk factors, achieving target blood pressure, short- and medium-term dual antiplatelet therapy, and intensive hypolipidemic therapy. Surgical prophylaxis is warranted for stroke against a carotid background, the efficacy of which in non-stenotic atherosclerosis requires early evaluation in randomised trials. Each potential cause of cryptogenic stroke considered is illustrated by a clinical example.

In many countries, with the prevention of acute respiratory diseases in children and adults, the use of various types of biologically active substances of natural and synthetic origin, called immunostimulants of various mechanisms of action, has been introduced. The purpose of this article is to provide a useful overview of main roles of available immunostimulants and their potential for use in inflammatory diseases of the upper respiratory tract. The article discusses aspects of the clinical use of immunomodulatory drugs in acute and recurrent infectious and inflammatory diseases of the respiratory tract (SARS-CoV-2 included). The mechanisms of action of immunomodulators on the immune system are briefly outlined. On the drug Imunorix the evidence base of mechanisms of correction of the immune system in respiratory diseases of the upper respiratory tract is given, as well as the analysis of the clinical efficacy of drug. The use of immunostimulator to increase the level of immunoglobulins (IgA, IgM, IgG) and subpopulations of T-lymphocytes (CD3 +, CD4 +). Also, the use of the drug has shown its usefulness in the appointment of antibacterial drugs in the treatment of upper respiratory tract infectious diseases. This article also provides an overview of recent clinical studies of drug. Researchers from various countries have tried to better clarify and define the mechanisms of action of immunostimulator both in vitro and in vivo. Of course, the improvement in research methodology over the past 20 years, and the acquired knowledge in various areas of clinical immunology, should become the starting point for further research on the drug. Randomized controlled trials of the trial use of the drug in the prevention of acute respiratory infections.

 The nature of the clinical manifestations of purulent-inflammatory diseases of the ENT organs is determined, first of all, by the localization of the process, and in addition, by the severity of the reactions of general and local inflammation. In this regard, the authors of the article propose to consider the main factors of pathogenesis that determine the sequence and relationship of the stages of the inflammatory response: edema, redness, fever, pain and dysfunction. A special role in the implementation of the regulatory mechanisms of inflammation belongs to active molecules, the so-called inflammatory mediators. The authors of the article consider the main cellular and plasma mediators, concluding that most of the effects they carry out are accompanied by a violation of the integrity of the vascular wall, exudation, edema and tissue swelling. A similar reaction is, in general, nonspecific and is observed in a number of inflammatory diseases of the ENT organs, such as acute rhinitis, allergic rhinitis, acute sinusitis, eustachitis, acute otitis media. This circumstance allows the authors to conclude that a local therapeutic effect is necessary on this particular link of pathogenesis. To this end, the authors of the article propose the use of nasal decongestants, drugs with an alpha-adrenomimetic effect, which effectively relieve swelling of the nasal mucosa and facilitate nasal breathing. In clinical practice, preparations based on xylometazoline have proven themselves well.

Acute respiratory viral infections are widespread in the human population. High contagiosity, a wide variety of pathogens, the possibility of rapid changes in the genotype of the virus and, accordingly,cause the development of drug resistance, make it possible to develop epidemics, and sometimes pandemics of SARS.The clinical picture of all acute respiratory diseases consists of local and general manifestations. Local symptoms include difficulty in nasal breathing, rhinorrhea, pain and discomfort in the throat, cough, hoarseness, stuffy ears, and lacrimation. General manifestations of SARS indicate the onset of viremia, and include an increase in body temperature, general weakness, fatigue, malaise, and headache. The mechanism of SARS development determines the  treatment tactics, including etiotropic, pathogenetic and symptomatic therapy.Domestic and international clinical recommendations indicate the  possible use of  symptomatic agents for  SARS and influenza.Symptomatic treatment is one of the areas of therapy for patients with influenza and other acute respiratory viral infections and allows you to alleviate the general condition, accelerate recovery and improve the quality of life of patients. The use of combined drugs is safer for patients thenthanmonocomponent drugs, and is safe for patients, in case the instructions for use are strictly observed. Such complex medicines, which provides control of the symptoms of colds and flu within 24 hours, as domestic drug are used for patients with SARS. Due to its components, drughas antipyretic, anti-inflammatory, analgesic, anti-allergic, angioprotective and vasoconstrictive effects. The synergism of the components of the combined drug allows to increase the effectiveness of therapy of patients with acute respiratory viral infections.

Cough is considered as an unconditional reflex adaptive defense response to irritating agents such as aeropollutants, foreign bodies, sputum, and is supposed to ensure adequate airway patency for normal gas exchange. Unfortunately, this mechanism is often transformed from a protective to a pathological one, lacking an adaptive function, causing suffering to the patient and exacerbating his poor condition. The line between physiological and pathological cough is often blurred and is perceived differently by both patients and physicians. In most cases, cough, including persistent cough, is treated with neglect by the general population - as an everyday occurrence with no major problems, and with a lack of awareness of tuberculosis, cancer and a number of other serious diseases. There are a large number of medicines on the market that are positioned as effective cough medicines. However, the wide variety of ways to treat this pathology demonstrates that there is no ideal cough medicine that combines universality, high efficacy and safety. Many drugs can cause serious side-effects, imposing severe restrictions on their use. Another difficulty is that the triggers and pathways of the cough reflex are extremely varied. Identifying the causes of persistent cough requires a thorough medical history, often with a multidisciplinary approach: extended examination, doctors such as otorhinolaryngologist, cardiologist, gastroenterologist, pulmonologist, oncologist, phthisiatrician, clinical pharmacologist (druginduced cough, drug-drug interactions). This article focuses on the differential diagnosis of cough and the selection of cough medicines based on their proven efficacy and safety. This information becomes particularly relevant during the seasonal increase in the incidence of acute respiratory infections.

World studies have shown that the mean prevalence of overactive bladder (OAB) ranges today from 11 to 16% of the global population and is common in both men and women. In addition, OAB is a diagnosis by exclusion. The article discusses two large groups of the causes of pathology: neurological and non-neurological. The former includes various diseases and conditions that lead to a complex abnormality in the urinary mechanism, namely, involuntary detrusor contractions and increased intravesical pressure. Spinal trauma, brain strokes and spinal strokes, multiple sclerosis, Parkinson’s disease, etc. are the most common of them. Unidentified factors constitute the second group of causes resulting in urgent frequent urination, and what is meant here is idiopathic detrusor hyperactivity (IDH). In this case, a patient may have these symptoms amidst full health without any neurological history. According to the available current guidelines, the treatment of OAB includes a three-step algorithm and suggests lifestyle changes, drug therapy and, finally, minimally invasive methods of treatment. Historically, M-anticholinergics are the main drugs for the treatment of OAD symptoms. However, administration of drugs from this group may often be impossible due to prominent side effects, which are more commonly reported among elderly patients. Unlike M-anticholinergics, Mirabegron is the only β3-adrenergic receptor agonist today that has shown a high efficacy and safety profile based on the results of large-scale placebo-controlled clinical trials.

Recurrent urinary tract infections (RUTI) are one of the most common manifestations of the genitourinary menopausal syndrome and occur in more than 20% of peri- and post-menopausal women. The most common risk factor for RUTI in peri- and post-menopausal women is sex steroid deficiency. The urinary and genital tracts share a common embryonic origin due to the presence of α- and β-estrogen receptors, progesterone and androgen receptors in all structures of the urogenital tract: lower third of the ureters, urinary bladder, vascular plexus, urothelium, pelvic floor muscles, pelvic ligamentous apparatus. Patients with RUTI are treated in two stages: treatment of exacerbations and prevention of relapses. During exacerbations, short courses of antibiotic therapy are administered according to the sensitivity of the bacterial agent. If microbiological testing of urine samples is not possible, antibiotics are selected empirically, taking into account the most common pathogens of a UTI. Vaccine prophylaxis is the leading method of preventing a UTI recurrence. The efficacy and safety of E. coli bacterial extracts have been proven in numerous RCTs. The Uro-Vaxom vaccine reliably reduces the incidence of cystitis recurrence, reduces the need for antibacterial drugs, and therefore improves the quality of life of menopausal women with RUTIs. Vaccine prophylaxis in menopause can be administered as monotherapy or in combination with topical estrogen therapy, which also plays a positive role in the treatment of urinary tract infections.

The article presents modern data on the formation, structure, functions and possibilities of correction of the gut microbiota. The gut microbiota is a collection of living organisms that inhabit the human intestine and form a complex microecological system that performs many functions. It is known that the composition and state of the gut microbiota is influenced by both environmental factors, such as diet and lifestyle, and the human body, including genetic predisposition. A violation in this system (dysbiosis) can provoke the development of a number of diseases and pathological conditions, in which the correction of the gut microbiota may be a promising therapeutic strategy. The most common methods of correcting dysbiosis are dieting, the use of pro-and prebiotics, and fecal microbiota transplantation. The diet affects the qualitative and quantitative composition and functions of the gut microbiota, the activity of its individual representatives. Probiotics are used to modulate, preserve the gut microbiota in dysbiosis, as well as to prevent its development. Fecal microbiota transplantation is performed by transferring the microbiota from a healthy donor. This method is one of the most effective ways to treat Clostridium difficile infection. This review article also presents the results of fecal microbiota transplantation in patients with inflammatory bowel disease and hepatic encephalopathy. It is shown that after transplantation, there is a rapid change in the composition of the gut microbiota, which becomes similar to the microbiota of a healthy donor. Each of these methods of correction demonstrates a different degree of influence on the gut microbiota, and their therapeutic effectiveness depends on the direct characteristics of the methods used, as well as the specific disease and requires further study.

Introduction. One of the most significant issues that require close attention in the treatment and rehabilitation of patients with coronovirus infection is the analysis of the nutritional status of patients and the development of approaches to nutritional support for patients.

Aim of study. Analysis of nutritional status of patients infected with COVID-19 and studying the effectiveness of specialized products dietary therapeutic and preventive nutrition during illness and recovery period.

Materials and methods. A survey of 283 patients with mild and moderate severity was conducted. The survey showed a significant change in eating behavior in patients during the disease. To assess the effectiveness of nutritional support during the disease and during the recovery period, 36 individuals took a specialized product of dietary therapeutic and preventive nutrition “Detoxifying Kissel” LEOVIT DETOX daily after the diagnosis of COVID-19, both throughout the entire period of the disease, and within 2 weeks after the disease and going to work.

Results and discussion. The survey showed the presence of a significant range of eating disorders in patients with coronavirus disease. It was found that in 90% of the respondents during the day, the main meal was 3 or more times. During the disease, the number of main meals decreased in 40% of individuals, and only in 4% of patients this figure increased. When using nutritional support with dietary therapeutic and prophylactic foods during the disease, patients noted a significant decrease in weakness and fatigue, temperature fluctuations, fears, anxiety, suspiciousness and other symptoms began to disappear. The continuation of the intake in the post-ovoid period of the use of nutritional support with the dietary therapeutic and preventive food product “Detoxifying Kissel” LEOVIT DETOX, contributes to a faster recovery of patients.

Conclusion. The use of the dietary therapeutic and preventive food product “Detoxifying Kissel” LEOVIT DETOX is an effective method of nutritional support both during the disease and in the post-ovoid period. Long-term use of detoxification products (at least 3–6 months) after the disease is recommended.

Osteoarthritis (OA) is a widespread disease, the leading symptom of which is pain in the load-bearing joints, and the incidence increases with age. Many patients with OA have several comorbidities, such as arterial hypertension, coronary heart disease, diabetes mellitus, gastric and duodenal ulcers. Currently, there are different approaches to the treatment of OA with and without comorbidity. In particular, oral non-steroidal anti-inflammatory drugs (NSAIDs) are not recommended for OA with high comorbidity. The literature review discusses the prospects and popularity of the use of local forms of NSAIDs associated with their equal analgesic efficacy relative to oral drugs, but with a smaller number of adverse events. Data on transcutaneous forms of diclofenac are analyzed, which can provide at least oral equivalent analgesia, improved physical function and reduced stiffness in  osteoarthritis of  the  hands and knee joints, while showing fewer systemic adverse events. This feature of  topical NSAIDs allows them to be considered as an effective first-line treatment option, especially in elderly patients and those with severe comorbidity. Topical medications containing diclofenac as the main active ingredient are popular among both patients and doctors, and their use has an extensive evidence base. Diclofenac ethylenediamine salt has advantages over sodium salt in its penetrating properties, and the form of an emulsion gel containing a hydrophobic phase that slows down the drying of the substance applied to the skin provides ease of use and improves the consumer properties of agents for local antiinflammatory therapy of osteoarthritis.

In recent decades, there has been an increase in the number of elderly people. Among the patients of the primary care physician, without a doubt, those who are over 60 years old predominate. A feature of the elderly is polymorbidity. Combined pathology, numerous complaints of patients make it difficult to diagnose diseases, require patience from the doctor, and, of course, knowledge. There are diseases that are peculiar only to the elderly, developing only after 50 years. These include rheumatic polymyalgia. This pathology is not frequent and, in this regard, is not very familiar to outpatient therapists. However, it is to them that elderly patients turn with complaints of pain and stiffness in the shoulder and/or pelvic girdle, in the neck, in the joints of the hands, fever, weight loss, sleep disorders, depression, general malaise (the main complaints of patients with rheumatic polymyalgia). The above-mentioned clinical manifestations, as well as the high laboratory activity inherent in this disease, make the doctor look for malignant neoplasms, infectious, systemic processes. This takes a long time, the diagnosis is delayed, the sufferings of the patient are prolonged. The article presents data on the prevalence, clinical features, methods of diagnosis of rheumatic polymyalgia and its differential diagnosis. The criteria of the disease, the principles of management of the patient at the outpatient stage  (step-by-step treatment with glucocorticoids, alternative approaches, prevention of side effects of therapy, which develop quite often) are also given. Awareness of primary care physicians about rheumatic polymyalgia, its manifestations and diagnostic methods will speed up the diagnosis, timely consultation of the patient with a rheumatologist, which will allow you to start adequate treatment, significantly improve the quality of life of an elderly patient, and prevent the destabilization of concomitant diseases.

Iron deficiency with or without anemia in pregnant women is quite common today. In fact, anemia affects nearly 30% of women of reproductive age, and its prevalence among pregnant women is estimated to be 38% worldwide. Although iron deficiency (IR) is not the only cause of anemia, it is the most prevalent one. Anemia-reduction strategies among pregnant women are often ineffective, and severe anemia can greatly increase the risk of maternal mortality, as reported by WHO. Now therefore, the current guidelines for screening and treatment of ID-anemia (IDA) in pregnant women and new-borns require change. Severe anemia can greatly increase the risk of maternal death and adversely affect a developing fetus and new-born. In this review, we analyse the available data on the epidemiology and the effects of iron deficiency on mothers and infants, current treatment strategies and screening recommendations, as well as examine the treatment of IDA in pregnant women and newborns and the problem of poor compliance in patients with latent iron deficiency. A continuous long-term course of administration of oral iron supplements is one of the components of success in the treatment of IDA, and particularly latent forms of iron deficiency in pregnant women. It is often the case that poor patients’ compliance with therapy leads to poor treatment outcomes and misleading conclusions about the ineffectiveness of oral iron dosage forms in the battle against IDA. The data we have analysed suggest the possibility of increasing compliance with IDA treatment in pregnant women.

Introduction. Pre-eclampsia (PE) continues to be the leading problem in obstetrics. The existing methods for predicting PE show insufficient efficiency, and therefore the search for new predictors of PE remains relevant.

The goal of the study. To develop a method for staged stratification of pregnant women to the risk of PE according on the basis of the revealed dismetabolic features of the pathogenesis of this complication of gestation.

Material and methods. A dynamic clinical and laboratory examination of 180 pregnant women with independent factors of high risk of PE was carried out. PE was revealed in 89 women who made up group I. Group II (control) consisted of 30 healthy pregnant women with the physiological gestation.

Results and discussion. A statistically significant increase in diabetogenic and atherogenic changes characteristic of physiological pregnancy, changes in hormonal, endothelial-hemostasiological, pro-inflammatory and placental parameters aimed at the energy and plastic supply of the fetus was revealed in women with PE. The results of laboratory examination, statistical data processing showed that the most significant pathogenetic mechanisms of development of PE are pathological insulin resistance (IR) and hyperinsulinemia (HI), which act as the basic link and initiate atherogenic transformation of the lipid profile, pro-inflammatory and immunometabolic disorders, prothrombotic status, hyperleptinemia, hyperuricemia, antiangiogenic state and endothelial dysfunction, which indicates a  pronounced pathogenetic and clinical similarity of  PE and metabolic syndrome. The  revealed features of the pathogenesis of PE were reflected in the method of staged risk stratification of pregnant women: the models for assessing the individual risk of PE implementation included the levels of insulin, PlGF, PAMG-1, and TNF-α at 11–14 weeks of gestation; levels of insulin, uric acid, TNF-α, and mean platelet volume at 18-21 weeks of gestation (I trimester – AUC = 0.886, Se = 86.7%, Sp = 84.3%; II trimester - AUC = 0.874, Se = 83.3%, Sp = 87.2%, р < 0.001).

Conclusion. Practical application of the developed pathogenetically substantiated method of staged stratification of pregnant women by the risk of PE implementation will justify the appointment and enhancement of preventive measures, reduce the incidence of severe and complicated forms of PE, and improve gestational and perinatal outcomes.

Introduction. Recurrent pregnancy loss is a pathological condition characterized by inevitable miscarriage before 22 weeks of pregnancy or at birth of a fetus below 500 g of weight. The causes of miscarriage are quite diverse, and viral infections, including herpesvirus infection (HVI), is one of the important etiological factors for the development of this pathology. Activation of herpesvirus infection (HVI) has an extremely adverse effect on the course of pregnancy. The issue of the mechanism of reactivation of herpes viruses (HS) and the role of toll-like receptors (TLR) in predicting the activation of latent HVI during pregnancy has been insufficiently studied until the present. The study is aimed at evaluating the possibilities of predicting the activation of latent herpesvirus infection during pregnancy.

Materials and methods. A total of 110 pregnant women with different courses of HVI were examined. The examination included the study of the TLR expression level and measurement of the pro- and anti-inflammatory cytokine levels.

Results and discussion. Given the high specificity of TLR8 and the interferon system (IFN) against viral antigens, it can be assumed that the activation of TLR and the development of early cytokine reactions prior to the detection of specific antibodies in patients with latent HVI are predictors of advanced herpes infection. The levels of TLR8 expression and concentration of IFN-γ and IL-10 at the local level in patients with latent BBVI can be regarded as predictors of the transition of HBV from the latent phase of the life cycle to the lytic phase.

Conclusion. If HVI develops actively during pregnancy, the antiviral immune response cascade that underlie the natural immune response starts at the local level, regardless of the localization of the antigen, and only a breakdown of the compensatory and adaptive mechanisms leads to the implementation of a systemic antiviral immune response. This suggests the important role of HVI, especially of its active forms, in the suppression of immunity during pregnancy.

Mineral and bone disorders in chronic kidney disease (CKD) is a systemic disorder of mineral and bone metabolism due to CKD manifested by either one or a combination of the following: abnormalities of calcium, phosphorus, PTH, or vitamin D metabolism  (secondary hyperparathyroidism); abnormalities in  bone turnover, mineralization, volume, linear growth, or strength; or vascular or other soft tissue calcification. Decreasing 1,25(OH)2D (calcitriol) and rising parathyroid hormone (PTH) levels occur on early stages of CKD. Secondary hyperparathyroidism contributes to the high morbidity and mortality noted in this population. Long-term decompensation of  secondary hyperparathyroidism in  patients with impaired renal function leads to irreversible changes in multiple organ systems, resistance to conservative treatment and the requirement for surgical intervention. Suppress of renal CYP27B1 and the calcitriol deficiency play a major role in the development of mineral and bone disorders in CKD, thus VDR activators are widely used for management of secondary hyperparathyroidism. These medications are effective in suppression of PTH and demonstrate the positive effects on bone metabolism. There is evidence of pleiotropic effects of VDR activators that are crucial for the prevention of renal fibrosis and extraskeletal calcification. This review focuses on the involvement of vitamin D in the pathogenesis of mineral and bone disorders and the role of paricalcitol in their correction. The efficacy of paricalcitol in patients with various stages of CKD has been evaluated in a large number of observational and randomized clinical trials, the comparative effectiveness of paricalcitol therapy has been summarized in several metanalyses.

Pulmonary vascular endothelium dysfunction is one of the main pathogenic factors responsible for many clinical manifestations of the severe course of COVID-19. Circulating endothelial progenitor cells (EPCs) are the endogenous regenerative reserve that maintains the integrity of the vascular endothelium and its restoration in case of damage by pathogenic factors. A decrease in the circulating EPCs is regarded as a predictor of morbidity and mortality in conditions associated with development of endothelial dysfunction, including COVID-19. The exact phenotype of progenitor cells capable of differentiating into endothelial cells has not been determined. In most laboratories antigens CD133+, CD34+, VEGFR-2+ (CD 309) or combination of these are used to identify EPCs. The process of EPCs mobilization and migration is controlled by molecular signals from immune cells located in the damage area. Stromal cell factor 1 (SDF-1), produced by the bone marrow and many other tissues, is an important chemoattractant for EPCs which express its receptors. The results of studies carried out in 2020 indicate that SARS-Cov-2 infects both hematopoietic stem cells, transforming into EPCs, and directly circulating EPCs, causing inflammatory and procoagulant reactions that complicate the COVID-19 course. There is no consensus on the mechanism of EPCs infection with coronavirus – directly through the expression of angiotensin-converting enzyme (ACE2) receptor or through an ACE2-independent mechanism. Today there is no effective therapy for COVID-19. The use of the EPCs regenerative potential, and the search for ways to enhance the EPCs mobilization from the depot, and increase their functional activity may become a promising approach to the prevention of severe complications and mortality from COVID-19.

Acute respiratory infections are of the greatest economic significance among all infectious diseases in the Russian Federation. There are no drugs with a direct antiviral effect for most acute respiratory viral infections, which efficacy would have been proven in the numerous clinical trials and confirmed by the results of meta-analyses today. The use of various combinations of antipyretic, anti-inflammatory and antioxidant drugs is the most common method of symptomatic and pathogenetic therapy of acute respiratory viral infections (ARVI). The purpose of this review is to analyse and systematize the results of preclinical and clinical trials aimed at studying the safety and efficacy of fixed-doses combinations of paracetamol, pheniramine maleate, phenylephrine hydrochloride and ascorbic acid in the ARVI therapy. The search of scientific publications was carried out in the PubMed, ClinicalKey ELSEVIER and Google Scholar databases. The search depth was 10 years. The results of numerous comparative and placebo-controlled trials showed that the use of fixed-dose combinations of paracetamol, pheniramine maleate, phenylephrine hydrochloride and ascorbic acid in the ARVI therapy was pathogenetically justified, safe, and effective in relieving symptoms such as fever, rhinitis, cough, muscle and joint pain, sore throat, and headache. The combination drugs can ease the patient’s condition and help shorten the duration of the illness provided that they are administered in due time. Meanwhile, the pathogenetic effects of combination drugs aimed at localizing the focus of inflammation and minimizing the risk of complications warrant further research.

Cholecystocardial syndrome is a complex symptom complex, manifested by various disorders in the heart, the development of which is facilitated by the presence of gallstone disease and other diseases of the biliary tract in the patient. For many years, clinicians around the world have been studying the relationship between acute and chronic diseases of the biliary tract and the cardiovascular system. Often these disorders are detected during an attack of biliary colic, in which painful sensations in the region of the heart often occur, and in some cases they are equivalent to an attack of biliary colic. In real clinical practice, cholecystocardial syndrome is an actual syndrome of interest to therapists, cardiologists, gastroenterologists and surgeons. The review presents data on its prevalence, causes and mechanism of development, clinical manifestations. Data on the incidence of cholecystocardial syndrome in real clinical practice vary significantly, which depends on the interpretation of the concept of cholecystocardial syndrome. With the introduction of ultrasound into the widespread practice, the diagnosis of cholelithiasis was significantly simplified, therefore, cholecystocardial syndrome in the classical version described by S.P. Botkin, has been found less and less recently. With a broader consideration of the concept of cholecystocardial syndrome as a complex of clinical symptoms indicating the possibility of changes on the part of the cardiovascular system, in patients with a diagnosed pathology of the biliary tract, its occurrence is quite high. The analysis of domestic data on the problem of cholecystocardial syndrome in real clinical practice, combined with data obtained as a result of a search of foreign literature on electronic biomedical databases (PubMed, MEDLINE, Scopus, Google Scholar) suggests the allocation of another mechanism of its development, associated with cholestasis, high levels of circulating bile acids and activation of bile acid receptors, and allows us to consider its cholecystocardial syndrome not only as a diagnostic syndrome during differential diagnosis, but also as a syndrome reflecting the comorbidity of the pathology of CVS and the biliary tract.

Introduction. One of the important issues in the context of COVID-19 infection is the development of innovative forms of work with patients after pneumonia at the outpatient and home stages of medical rehabilitation.

Objective: to develop a remote form of work organization and to study the effectiveness of hypobaric altitude chamber adaptation and cytoflavin at the outpatient and home stages of medical rehabilitation in patients after pneumonia COVID-19.

Materials and methods. The  study included 315  people after suffering from COVID-19  pneumonia. The  first group consisted of 160 people who underwent a course of hypobaric altitude chamber adaptation, the average age of 53.5 (45,61) years. The second group (50 people) underwent a course of taking cytoflavin tablets; 63.9 (60.5; 67.6) years. The third group (105 patients) underwent a course of hypobaric chamber adaptation and cytoflavin administration; 55.1 (45.7; 60.9) years. We analyzed the scales that characterize the quality of life and psychological state of patients before and after the rehabilitation course, and 3 months after the end of the course.

Results and discussion. The use of one-and two-component courses contributed to the improvement of the indicators of the traumatic event impact assessment scale, the Schulte Table scale, and the self-assessment of the EQ-5 quality of life scale. The results obtained were statistically significantly different after the course of rehabilitation from the initial values and retained their difference after three months of observation.

Conclusions. An innovative remote form of work at the outpatient and home stages of medical rehabilitation has been developed and implemented – the YouTube project “Let’s help each other recover from pneumonia” (PDDVSMU). The stable prolonged effectiveness of a one- and two-component course of hypobaric altitude chamber adaptation in patients after COVID-19  pneumonia  at the  outpatient and home stages of  medical rehabilitation is shown. The  addition of  cytoflavin enhanced the rehabilitation effect of hypobaric adaptation. The data obtained should be taken into account when developing comprehensive programs for medical rehabilitation of patients after COVID-19 pneumonia.

The article is devoted to the possibilities of correction of neuropsychiatric disorders in perimenopause, a condition associated with the cessation of menstruation in a woman and a decrease in the level of ovarian steroid hormones (estrogen and progesterone) due to the loss of the ovarian follicular mass. It is known that biological and endocrine changes during this period are often accompanied by autonomic symptoms. In perimenopause, women may experience symptoms such as hot flashes and night sweats, insomnia, vaginal dryness, mood disorders, etc. Although most symptoms are not life-threatening, they can have a negative impact on the quality of life, physical and mental health of perimenopausal women. During menopause, women are at higher risk of developing depression, stress, anxiety and emotional disorders. In addition, during perimenopause, women experience not only depressive symptoms but also cognitive impairment, which may be related to changes in hormonal background. Drugs that are used in the treatment of mood disorders affect different neurotransmitters, in particular serotonin, norepinephrine and gamma-aminobutyric acid (GABA). One of the benzodiazepine derivatives is Tofisopam, first developed in Hungary and marketed in a number of European countries under the name Grandaxin. It is indicated for the treatment of neurotic and somatic disorders associated with tension, anxiety, autonomic disorders, lack of energy and motivation, apathy, fatigue, depressed mood and alcohol withdrawal syndrome, including during perimenopause. Tofisopam has good anxiolytic activity with no observable sedative, anticonvulsant, amnestic or muscle relaxant effects.

Introduction. The use of bisphosphonates is associated with some risk of side effects. Gastrointestinal tract complications are particularly important in clinical practice, as they constitute the main reason for refusing bisphosphonate therapy.

Objective: To evaluate the effect of various forms of alendronate on the gastrointestinal tract in comorbid patients taking NSAIDs.

Materials and methods. The study included 88 women aged 58–65 years (mean age 61.5 ± 3.5 years) with polyosteoarthrosis combined with postmenopausal osteoporosis, who received NSAIDs at medium therapeutic doses to manage a pain syndrome for a long time (3–5 years). The patients were divided into two groups: a group of patients receiving alendronate in the form of a buffered solution (n = 45), and a group of patients receiving alendronate in the form of non-dissolving tablets (n = 43). The first group used Binosto (adendronic acid) 70 mg as effervescent tablets once a week. The results were assessed before initiation of treatment and 6 months after treatment with bisphosphonates. Symptoms were evaluated using the GerdQ questionnaire. Esophageal mucosal injury and gastroduodenal ulceration were assessed by upper gastrointestinal endoscopy.

Results and discussion. After 6-month treatment, comparison of the two groups showed that the percentage of patients with a total GerdQ score of ≥ 8 points was significantly higher in the group of patients taking alendronate in the form of non-dissolving tablets (p = 0.04). The endoscopic findings showed that the number of patients with grade A reflux esophagitis in group 1 increased by 3.3%. The number of grade A reflux esophagitis cases in group 2 increased by 2.2%, those of grade B, C and D cases by 2.4%. The number of gastroduodenal ulcer cases also increased by 2.2% and 4.7% in groups 1 and 2, respectively. The number of gastroduodenal erosions increased by 3.5% in group 1 and 7% in group 2.

Сonclusion. Symptoms were less severe in patients receiving alendronate in the form of a solution, which points to the importance of choosing the optimal oral bisphosphonate for each patient.

Immuno-oncology is a rapidly developing field in medicine. Drug combination therapies have already been studied in many clinical trials of different types of tumours. In recent years, a checkpoint inhibition therapy with monoclonal antibodies that target cytological T-lymphocytes has been developed. Thus, inhibition of two regulator genes CTLA 4 and PD1 or PD-L1 ligand to it is able to restore mediated T-cell tumour regression in its many localizations. The article considers a number of key fields of immunology and immunotherapy through a specific example of breast cancer (BC): the role of T-lymphocytes, vaccines, biomarkers of immunotherapy. The treatment used by the authors was based on an innovative technology of autologous dendritic cell-based vaccine based on highly immunogenic cancer/testis antigens (CTA) for immunotherapy of malignant tumours. The technology of specific CTA+-activated autologous dendritic cells (DC)-based immunotherapy was chosen as an innovative solution for the treatment of breast cancer patients. The treatment results showed that a clinically significant anti-tumour effect was achieved in 73.7% of patients. Median disease-free survival was 8.3 months (95% Cl 6.5-9.9 months), no grade 3-4 complications were recorded, grade 1-2 complications were observed in 57% of patients. The immunological effect in laboratory tests was recorded in 92% of patients. Thus, autologous DCs loaded with cancer/testis antigens can be considered as palliative dendritic vaccine therapy in patients with metastatic breast cancer who have exhausted standard treatment options. Also, the authors presented the results of immunological studies of the prognostic and predictive significance of the immunological response from the perspective of pathomorphology and general immunology, including tumour-infiltrating T-lymphocytes (TILs, CD3, CD4, CD8), their quantitative ratio and correlation with regulatory genes (PD-1, PD- L1, FOX-P3). The results of overall analysis comprising data of 2,148 patients from 9 centers confirmed the strong prognostic role of stromal tumour-infiltrating lymphocytes (sTILs) in early triple-negative breast cancer.

Non-steroidal anti-inflammatory drugs (NSAIDs) are the most common drugs in clinical practice and account for 5–10% of all drugs prescribed each year. However, the use of this group of drugs is associated with the risk of a wide range of side effects, most of which are cardiovascular complications. In addition, NSAIDs interact with other drugs, for example, their effect on antihypertensive therapy has recently been recognized as particularly important. Improvement of not only efficacy, but also safety is another important principle of rational pharmacotherapy. Adverse drug reactions (ADR) can very often result from underlying genetic factors of the human body. In this regard, a personalized approach suggesting the prescription of drugs according to the individual characteristics of patients is especially important. In such cases, pharmacogenetic testing is the most promising method that identifies the genetic factors of patients and allows to predict patients’ responses to specific drugs. This applies especially to a large range of drugs metabolised via the cytochrome P450 system in the liver. Results from numerous studies show that the effect of P450 family gene polymorphism determines the individual sensitivity to antihypertensive drugs, as it is these isozymes that are involved in the metabolism of drugs used to treat arterial hypertension (AH). In particular, the cytochrome (CYP) 450 isoenzyme is one of the basic enzymes involved in the biotransformation of losartan, an angiotensin receptor antagonist. Therefore, the CYP2C9 gene polymorphism largely determines the pharmacological response to NSAIDs and affects the effectiveness of antihypertensive therapy due to the change in the drug metabolism, as well as the structure and function of the receptors, on which they have an effect.

Introduction. The high incidence of chronic tonsillitis (CT), as well as the high risk of complications, make research in this area very relevant. The ambiguity of approaches to conservative therapy determines the need to search for new, reasonably effective, chemotherapy regimens.

Objective. To carry out a comparative characteristic of various options for conservative therapy of chronic tonsillitis of toxicallergic form (TAF) I degree (CT TAF I).

Materials and methods. The study included patients with CT TAF I according to the classification of B.S. Preobrazhensky and V.T. Palchun. The patients were divided into three clinical groups, depending on the therapy. Patients of the first group underwent a course of washing the lacunae of the tonsils with 1% dioxidine solution. Patients of the second group were prescribed antibiotic therapy with a retard form of clarithromycin. Patients of the third group underwent complex treatment – washing the lacunae of the palatine tonsils and simultaneously taking antibiotic therapy. The effectiveness of treatment was assessed by comparing the dynamics of changes in complaints, pharyngoscopic symptoms of CT, regional lymph nodes, and laboratory parameters.

Results. Complex conservative therapy of CT TAF I provides early relief of patients’ complaints (in 93.2% of patients on the 7th day from the start of treatment), the maximum decrease in the severity of local CT symptoms (up to 1 point on the VAS at the end of treatment, with the exception of the Zak sign — 1.4 points) and the greatest positive dynamics of laboratory parameters.

Conclusions. The analysis showed that for patients with CT TAF I, complex therapy, including a course of washing the lacunae of the palatine tonsils with 1% dioxidine solution and simultaneous administration of antibacterial therapy with a retard form of clarithromycin, is the most optimal therapeutic tactic that allows to achieve an earlier and stable reduction in the severity of symptoms HT, patient complaints, as well as the normalization of laboratory parameters.