The review presents the prevalence of both type 2 diabetes mellitus (type 2 DM) and its microvascular complications among patients with coronary heart disease (CHD), and CHD among patients with carbohydrate metabolism disorders. It is shown, that the prognosis of patients with CHD and type 2 DM, especially in the presence of microvascular complications, is extremely unfavorable, and is characterized by a significant increase in the risk of cardiovascular death, myocardial infarction, stroke, terminal stage of the chronic kidney disease and visual impairment. It was noted, that despite the successes achieved in the treatment of CHD, type 2 DM and its microvascular complications, there is a high risk of total, cardiovascular mortality and hospitalizations associated with cardiovascular diseases. In type 2 DM, especially in the presence of microvascular complications and comorbid pathology, special pathogenetic mechanisms of thrombotic risk and bleeding have been identified. Based on large randomized clinical trials, the review evaluated the efficacy and safety of various antithrombotic strategies in patients with stable СРВ, type 2 DM in the presence of microvascular complications and comorbid pathology.

Hypertensive disorders during pregnancy remain a global medical and social problem, complicating 2–8% of pregnancies and associated with high maternal and perinatal morbidity and mortality. The traditional measurement of blood pressure in clinical practice is the most commonly used procedure for the diagnosis and control of the treatment of hypertension, but it is subject to significant inaccuracies caused, on the one hand, by the inherent variability of blood pressure itself (BP), and on the other hand, by errors arising from measurement methods and conditions. A high BP detected in the clinic should be confirmed by out-of-office BP measurement, 24-hour ambulatory BP monitoring, or home BP monitoring, which distinguishes chronic hypertension from white coat hypertension, in which blood pressure is elevated in the clinic, but remains normal at home, which is important to prevent excessive treatment and diagnosis of masked hypertension. White-coat hypertension is not a benign condition in which higher risks of developing preeclampsia, premature birth and small-for-gestational-age infants have been shown. In this regard, it is extremely important for clinicians to be aware of the risk factors and outcomes associated with white coat hypertension. Pregnant women should be medically monitored both during pregnancy and after delivery to detect target organ damage, cardiovascular risk factors and metabolic syndrome.

Hepatorenal syndrome is a common and serious complication in cirrhotic patients, leading to significant morbidity and mortality. Although pharmacological treatments have shown mortality benefit, the ideal hepatorenal syndrome treatment option is liver transplantation with or without simultaneous kidney transplantation. Further research is required to optimize pharmacologic and nonpharmacologic approaches to treatment. An analysis of literature reviews, clinical studies, experimental research, clinical recommendations from PubMed / Medline and ELIBRARY databases was carried out for 7 keywords according to the review topic.

Objective: to evaluate the incidence and severity of thoracic aortic calcification, the relationship with endothelial dysfunction and fibroblast growth factor in patients with resistant arterial hypertension.
Materials and methods: the study involved 92 patients with resistant hypertension. Daily monitoring of blood pressure (ABPM) was performed, the functional state of the endothelium was assessed in a sample with reactive hyperemia, the calcium index (CI) of the thoracic aorta was determined using MSCT, and the serum level of FGF-23 was determined using enzyme immunoassay.
Results: based on ABPM, patients were divided into groups 1st-controlled (n=44) and 2nd-uncontrolled (n=48) resistant AH. In the 2nd group, a more pronounced dysfunction of the endothelium was revealed in the sample with reactive hyperemia and changes in the velocity parameters of blood flow. FGF23 levels and CI were higher in individuals with uncontrolled resistant hypertension. According to the results of correlation-regression analysis, CI was associated with the value of pulse pressure (r=0.49, p=0.007), the duration of hypertension (r=0.68, p=0.04) and the duration of regular antihypertensive therapy (r = −0 .33, p=0.02). FGF- 23 was found to be associated with PA hemodynamic parameters: with Ved (r=0.42, p=0.003), PI (r=0.43, p=0.041) and RI (r=0.46, p=0.025), as well as with CI (r=0.76, p=0.006).
Conclusion: patients with uncontrolled resistant hypertension showed a more pronounced decrease in brachial artery EVR and an increase in vascular resistance indices in the test with reactive hyperemia, which was statistically significantly associated with the level of FGF23. In patients with resistant hypertension, excessive calcification of the thoracic aorta was found according to the results of MSCT. Calcium index values are higher in patients with high pulse BP, longer duration of hypertension and high levels of FGF23.

Objective: analysis of predictors allowing to predict a high probability of atypical clinical course of myocardial infarction (MI) at an early stage of development of acute coronary insufficiency before complex diagnostic procedures.
Materials and methods: the study included patients from the Tomsk population with confirmed MI in the period 2001–2017, registered in the database "Register of Acute Myocardial Infarction" (ROIM) (n=7775). In 79.6% (n=6188), the clinical picture of MI was characterized by typical manifestations in the form of a prolonged angina attack (group 1), in the remaining 20.4%; patients (n=1587) recorded atypical manifestations of MI (group 2).
Results: patients with atypical clinical manifestations of MI were more often represented by women, had an older age and a burdened comorbid background. The anamnesis of IM and coronary artery revascularization were more commonly recorded in a cohort of patients with typical clinical manifestations of coronary catastrophe. All parameters that demonstrated significant differences in patients with different types of clinical flow IM were included in the logistic regression model. As a result of a step-by-step procedure for elimination of factors, independent associations with the development of atypical symptoms of acute MI showed the following indicators: female sex, elderly age, IM history, type 2 diabetes mellitus, history of myocardial revascularization, atrial fibrillation, alcohol consumption before MI, obesity, smoking.
Conclusion: female gender, elderly age, the presence of atrial fibrillation, diabetes mellitus, obesity and condition after alcohol intoxication predisposes to atypical acute MI, whereas male gender transferred to IM or revascularization, as well as smoking are currently more common in patients with a typical clinical pattern.

Objective: to study the features of the clinical course of chronic heart failure (CHF) and laboratory and biochemical characteristics of patients, depending on the variant of polypharmacy.
Materials and methods: the study included 73 patients with CHF aged 74.58±10.05 years. Venous blood was taken from all patients on the 1st day of hospitalization in order to determine the levels of NT-proBNP, sST2, NGAL, cystatin C. Patients were divided into groups depending on the type of polypharmacy (corresponding and inappropriate) according to the criteria of the EURO-FORTA system (2018) and on based on national clinical guidelines.
Results: depending on the type of polypharmacy at the outpatient stage, according to the EURO-FORTA criteria (2018), 2 groups of patients were distinguished: 1st (corresponding) — 47.94% of patients; 2nd (inappropriate) — 52.06%; based on national clinical guidelines: group 1 (corresponding) — 53.42% and group 2 (inappropriate) — 46.58%. When evaluating polypharmacy according to the EURO-FORTA criteria, patients of the 2nd group more often had joint diseases (p=0.035), acute kidney injury (AKI) according to baseline creatinine (47.37% vs. 20%; p=0.014) and 4 times more often than patients of the 1st group were hospitalized due to atrial fibrillation (AF) (p=0.048). When dividing patients based on national clinical guidelines into groups of appropriate (1) and inappropriate (2) polypharmacy, it was found that in group 2, compared to group 1, there were more patients with joint diseases (44.12% versus 15.38%; p=0.007), anemia of 1–2 degrees (67.65% vs. 35.90%; p=0.025) and CKD of 3–5 stages (76.47% vs. 53.85%; p=0.044), more often observed OPP (p=0.008).
Conclusion: a comparative analysis of the clinical and laboratory status of patients with appropriate and inappropriate polypharmacy revealed that the main difference between patients with inappropriate polypharmacy is more pronounced renal dysfunction and the prevalence of anemia, as well as a higher rate of hospitalization with paroxysmal AF/AFL. The division of patients into groups of appropriate and inappropriate polypharmacy based on clinical recommendations does not require additional evaluation using the EURO-FORTA system.

Objective: a retrospective analysis of the results obtained by typing HLA-A, -B antigens and HLA DRB1 allele groups in patients with rheumatoid arthritis (RA) in the Rostov population.
Materials and methods: typing of patients with rheumatic inflammatory diseases who were on inpatient treatment in the rheumatology department of the SBI “OKB No. 2” was carried out in the LITT SBI RO "BTS" in 2019-2020. 41 patients (9 men, 32 women, median age — 42 years) were diagnosed with RA. All patients were typed by HLA-DRB1 alleles by real-time polymerase chain reaction with DNA-TECH reagents (Russia). To isolate DNA, a set of Sample-Rapid-Genetics was used by NPO DNA Technology LLC. 39 patients were typed аccording to HLA-A, -B. Typing was carried out by a standard lymphocytotoxic test with DILEN reagents (Czech Republic). Lymphocytes were isolated in a density gradient of “Lympholot”, DILEN company. The control group consisted of healthy residents of the Rostov population (donors of the hematopoietic stem cell registry).
Results: a retrospective analysis showed that HLA DRB1*04 occurs in 46.3% of the Rostov population with RA, in 61.1% of the seropositive RA group (control — 20%). There was a decrease in the frequency of HLA DRB1*13 (9.7%) compared to the control (24.4%).
Conclusions: the high level of reliability (p<0.001) of the increase in the frequency of HLA DRB1*04 alleles confirms their associative relationship with RA in the Rostov population. A decrease in the frequency of HLA DRB1*13 indicates the protective function of these alleles in RA. Typing results are important for early diagnosis of RA.

Objective: to test the patented “Method for determining a high risk of atherosclerosis in rheumatoid arthritis” on patients with rheumatoid arthritis.
Materials and methods: 74 patients with RA who underwent inpatient treatment were examined. Gender composition of respondents: 77% women and 23% men. Mean age 54.1±9.1 years. The duration of RA is from 1 year to 26 years. 85.1% were diagnosed with a high degree of disease activity. Erosive arthritis was detected radiographically in 41 patients (55.4%). 83.7% (n=62) were seropositive for RF, 81% for ACCP (n=60). All received basic anti-inflammatory therapy. Systemic glucocorticoid therapy was received by 33.7%. All patients were calculated cardiovascular risk according to SCORЕ and mSCORЕ Also, all patients underwent duplex scanning of the BCA to detect atherosclerosis.
Results: no significant increase in traditional factors of cardiovascular diseases was found among patients. When CVR was stratified according to SCORE, the frequency of low risk was 32.4%, moderate — 59.5%, high — 5.4%, very high — 2.7%. When using mSCORE, low risk was found in 27%, moderate — 56.7%, high — 13.5%, very high — 2.7%. Atherosclerotic plaques (ASP) in the carotid arteries in patients stratified according to SCORE for moderate, high and very high risk was detected in 68%, in persons with similar risks according to mSCORE — in 66.7%. With a score of 4 or more when using the tested method, ASP was found in 77.8%. Sensitivity for the detection of ASP in the carotid arteries using SCORE was 0.77, with mSCORE and the tested method 0.81 and 0.95, respectively. Specificity 0.47, 0.4 and 0.6 respectively. Positive predictive power for SCORE — 0.68, mSCORE — 0.67, tested method — 0.77. Negative predictive power for SCORE — 0.58, mSCORE — 0.6, tested method — 0.9.
Conclusion: the study showed that our proposed method, which uses traditional clinical markers, significantly increases the sensitivity, specificity, and negative predictive power of calculation methods for identifying a group of individuals with a high risk of atherosclerotic lesions of extracranial arteries against the background of rheumatoid arthritis compared with using the SCORE and mSCORE parameters.

Objective: to study the effect of the total expression of vascular endothelial growth factor A (VEGF A), tissue growth factor β1 (TGF-β1) and monocytic chemoattractant factor 1 (MCP-1) on the course of glomerulonephritis.
Material and methods: the study was a prospective (12-month) open comparative clinical and morphological study with the inclusion of 75 patients aged 18 to 75 years (males - 52, females - 23) with glomerulonephritis in the acute stage. All patients were initially examined, including assessment of clinical, laboratory and instrumental parameters, including puncture nephrobiopsy. In addition to the standard, sections of biopsies were stained with labeled antibodies to VEGF A, TGF-β1 and MCP-1 to assess their expression in kidney tissue. After 12 months, the development of remission of glomerulonephritis, parameters of the general analysis of urine, creatinine, urea, uric acid of blood, calculation of GFR were evaluated.
Results: it was found that the severity of the total expression of MCP-1+VEGF-A+TGFß1 is observed to a greater extent in hematuric forms of glomerulonephritis, occurring without changes in the level of blood albumin. The same follows from the results demonstrating the relationship of the total expression of MCP-1+VEGF-A+TGFß1 with morphological manifestations more characteristic of nephritic forms of glomerulonephritis (IgA deposits, mesangial hypercellularity). The increased expression of the studied factors has shown its influence on the development of fibrosis and thickening of the walls of renal vessels, glomerular fibrosis and interstitium, reflecting the whole complex of reparative remodeling of renal tissue in the inflammatory process. The effect of the total expression of MCP-1+VEGF-A+TGFß1 on the further course of glomerulonephritis, accompanied by the progression of the disease in the form of a decrease in GFR after 12 months of observation of patients, was revealed.
Conclusions: an increase in the total expression of MCP-1+VEGF-A+TGFß1 in hematuric forms of glomerulonephritis indicates the role of these factors in the development of the inflammatory process to a greater extent in these forms of the disease. It was found that an increase in the severity of the total expression of MCP-1+VEGF-A+TGFß1 is associated with manifestations of renal remodeling in glomerulonephritis. It has been shown that an increase in the severity of the total expression of MCP-1+VEGF-A+TGFß1 is accompanied by an increase in the likelihood of a rapid decrease in renal function in glomerulonephritis at 12-month follow-up.

Objective: to determine the content of melatonin and indicators of antihypoxic resistance, the state of antioxidant protection according to the determination of the level of lactate, pyruvate and indicators of the glutathione system (glutathione reductase and glutathione peroxidase) in patients with cystic transformation of the pineal gland (CSG).
Materials and methods: during the period from January 2015 to December 2016, 5930 patients were examined, including 300 people with cystic transformation of the pineal gland. 56 people were selected for laboratory examination. The age of the examined patients ranged from 25 to 43 years. Of these, 37 people with cystic transformation of the pineal gland (CSG): 20 women — people, and men — 17 people, 19 people — the control group. The data obtained were considered both in relation to the general group of patients with this disease, and in relation to the division according to gender (men, women), and the volume of HTCW (“large”, “small”).
Results: in the general group of patients, an increase in the content of melatonin in saliva and blood was recorded in all portions. Against this background, the aerobic direction of metabolism prevailed, the processes of consumption and restoration of reduced glutathione increased, which indicates the activation of the mechanisms of adaptive-compensatory restructuring of the functional state of the body.
Conclusion: melatonin production in patients with cystic transformation of the pineal gland is correlated with the size of the cysts, with the most pronounced production being recorded at night. In women, to a greater extent than in men, signs of stimulation of oxygen-dependent processes are found, which indicates the intensity of adaptive reactions and the elimination of toxic products in response to stress associated with the presence of cysts.

Arterial hypertension (AH) is a widespread syndrome in clinical practice. In most cases, the blood pressure increase is essential (primary) in nature. Meanwhile, many clinical situations require exclusion of secondary AH due medications and other substances, renal, endocrine, cardiovascular, neurological pathology. A special place in the structure of the endocrine AH is engaged in pathology caused by excessive production of cortisol. Despite its heterogeneous origin, endogenous hype rcortisolism (EH) has a certain similarity in clinical manifestations. The article describes two clinical cases of AH in 32-year-old women with different pathogenetic variants of endogenous hypercortisolism (EH). The presented medical histories are the basis for the discussion of features of the clinical and laboratory manifestations of EH, principles of the differential diagnos is and modern approaches to treatment. The aim of this publication is to draw attention of doctors of various specialties to early detection of EH, the timely elimination of which significantly improves the quality and increases the life expectancy of patients.

Objective: to discuss the features of the use of the drug liraglutide for the treatment of patients with obesity, to analyze the metabolic parameters dynamic and the difficulties that arise during therapy, based on our own clinical observations.
Materials and methods: the article provides an analysis of our own clinical observations of patients aged 54 and 47 years who received liraglutide therapy for exgenous constitutional obesity of the II degree. According to the examination results, both patients showed hyperinsulinemia and insulin resistance signs, lipid metabolism disorders. There were no episodes of acute pancreatitis in the past. Heredity for medullary thyroid cancer is not burdened, thyroid status is normal. Dose liraglutide escalation is recommended on a schedule 0.6 mg per week.
Results: during therapy with liraglutide, patients under observation experienced a gradual progressive decrease in body weight against the background of a decrease in appetite and a decrease in the amount of food consumed. In the dynamics, there was a tendency to normalize the initial metabolic disorders: a decrease in insulin resistance and hyperinsulinemia, carbohydrate metabolismdisorders and lipid profile.
Conclusion: the results of our own clinical observations indicate the effectiveness of the drug liraglutide use in the treatment of patients with obesity, not only to achieve the target weight loss indicators, but also to correct the initial disorders of the metabolic status.

The article presents a prospective clinical observation with a fatal outcome in a patient with severe granulomatosis with polyangiitis (GPA) complicated by COVID 19 on the background of immunosuppression. At the onset of the disease, there were difficulties in making a diagnosis; differential diagnosis between eosinophilic granulomatosis with polyangiitis (EGPA) and GPA was carried out. Against the background of combined therapy — the use of high and ultra-high doses of glucocorticoids (GC) and cytostatic drugs, a short-term improvement was noted. However, within a year and a half of treatment, it was not possible to achieve remission of the disease. Taking into account the ineffectiveness of the therapy, by the decision of the medical commission, the patient was prescribed genetically engineered biological therapy rituximab (RTM). There was a decrease in the activity of the disease, the achievement of depletion of B-cells. During the pandemic period, despite observing the isolation regime, the patient fell ill with a coronavirus infection. Immunosuppression contributed to severe infection. After the infection was treated, the activity of vasculitis increased, which required the repeated administration of RTM for health reasons. During the therapy it was short-term stabilization of the condition. But after short period — fever, an increase in respiratory failure, the development of neutropenia. Taking into account the initial lesion of the lungs in the patient, differential diagnostics was carried out between the complications of coronavirus infection and the activity of the underlying disease. Despite anti-inflammatory, anticoagulant, antibacterial therapy, the patient's condition progressively worsened, respiratory failure increased, hemoptysis appeared. Spontaneous pneumothorax on the right was diagnosed, pneumomediastinum. After repeated negative PCR results, the causative agent of SARS COV-2 was again detected in smears. The immediate cause of death, according to clinical observation and autopsy, was severe respiratory failure, thrombosis in small vessels of the lungs in a patient with a new coronavirus infection against the background of immunosuppression for GPA.

This article discusses the features of applying the theory of quality to medical science and practice. The methods of analytical medicine show the internal contradiction of the existing theory of diagnostics as a source of medical errors. Approaches to resolving this paradox are given.

The article deals with the issues of legislative regulation of biotechnologies in the field of healthcare. The authors analyzed the current international and domestic legislation in the field of biotechnology in the context of the legal policy of the Russian Federation at the present stage.