[Features of the Course of Arterial Hypertension in the Era of the COVID-19 Pandemic: Common Pathogenetic Links Between Hypertension and SARS-CoV-2].

The aim of this review was to present the mechanism of infection with severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) and its possible effect on the course of arterial hypertension. Another aim was to evaluate the relationship of the renin-angiotensin-aldosterone system with the pathogenetic stages of infection caused by SARS-CoV-2 virus.

[In vitro activity of human recombinant interferon gamma against SARS-CoV-2 virus].

INTRODUCTION: The development of drugs against SARS-CoV-2 continues to be crucial for reducing the spread of infection and associated mortality. The aim of the work is to study the neutralization of the SARS-CoV-2 virus with interferon gamma preparations in vitro. MATERIALS AND METHODS: The activity of recombinant human interferon gamma for intramuscular and subcutaneous administration of 500,000 IU and for intranasal administration of 100,000 IU against the SARS-CoV-2 virus in vitro was studied. The methodological approach of this study is based on the phenomenon of a decrease in the number of plaques formed under the action of a potential antiviral drug. RESULTS: The antiviral activity of recombinant interferon gamma has been experimentally confirmed, both in preventive and therapeutic application schemes. The smallest number of plaques was observed with the preventive scheme of application of the tested object at concentrations of 1000 and 333 IU/ml. The semi-maximal effective concentration (EC50) with the prophylactic regimen was 24 IU/ml. DISCUSSION: The preventive scheme of application of the tested object turned out to be more effective than therapeutic one, which is probably explained by the launch of the expression of various interferon-stimulated genes that affect to a greater extent the steps of virus entry into the cell and its reproduction. CONCLUSION: Further study of the effect of drugs based on recombinant interferon gamma on the reproduction of the SARS-CoV-2 virus for clinical use for prevention and treatment is highly relevant.

[Evaluation of hemostasis disorders using the thrombodynamic test in patients with chronic glomerulonephritis with nephrotic syndrome].

BACKGROUND: Nephrotic syndrome (NS) is accompanied by a risk of thrombotic complications due to hypercoagulability. Routine laboratory tests are not sensitive enough to detect these disorders, and therefore the use of integral coagulation tests, including a new thrombodynamic test (TT) in patients with NS, is of high relevance. AIM: Using a TT to determine hemostasis disorders in patients with chronic glomerulonephritis (CGN) with NS. MATERIALS AND METHODS: The study included 49 patients with CGN, mean age 37 years, of which 25 (51%) women and 24 (49%) men. Of all the examined patients, 20 (40.8%) of people had NS, 29 (59.2%) had no NS. The process of clot formation was assessed by TT. RESULTS: According to TT, 30% (6/20) of patients with NS and 13.7% (4/29) of patients without NS have hypercoagulation with changes in parameters that go beyond the reference values. In patients with NS, an increase in clot density (D), clot formation rate (V) and clot size (CS) was found, especially when albumin decreased below 25 g/l. Negative correlations were found between the levels of albumin, creatinine and clot density (D), which reflects the level of hyperfibrinogenemia, the rate of clot formation (V) and the integral index of coagulation (CS). The results indicate mainly the activation of the plasma hemostasis due to the internal coagulation pathway. However, the correlation of Tlag (delay time for the onset of clot formation after contact of blood plasma with the insert-activator) with serum cholesterol levels may also indicate activation of the extrinsic coagulation pathway. CONCLUSION: In CGN patients with NS, activation of the plasma hemostasis is noted, as evidenced by an increase in the rate of formation (V) and size of the clot (CS) after 30 minutes, as well as the density of the formed clot (D).

Assessment of Awareness and Experience of Using off-label Drugs by Doctors of Clinical Specialties.

Aim      To evaluate the frequency of off-label prescription of medicines in practice of clinical specialists and the awareness of respondents of the procedure of justified off-label prescription.Material and methods  The sample included 542 clinical specialists who worked in definite medical organizations in 26 entities of the Russian Federation. The respondents were proposed to fill in remotely an anonymous questionnaire to evaluate the experience of prescribing medicines off-label to adult patients.Results Prescribing medicines not in consistence with the officially approved instruction for medical use (off-label or "outside instruction") is a relevant issue of global medical care since convincing scientific evidence for safety of such use is scarce. Analysis of information about off-label prescription is one of current tasks of national medical research centers according to the Federal Project "Development of a network of national medical research centers and implementation of innovative medical technologies". According to the responses about the frequency of off-label prescriptions 67.5 % of respondents reported of no experience of off-label prescription, 27.7 % said "rarely" or "sometimes", and 4.8 % said "frequently" and "very frequently". Specialties of physicians who have more often used medicines off-label (50% and more) included obstetrics and gynecology, pediatrics, rheumatology, hematology, and pulmonology. Cardiologists, neurologists and clinical pharmacologists use medicines off-label relatively rarely (19.6%, 28.6 %, and 22.2 %, respectively). 40 % of medicines used off-label were those designed for the treatment of coronavirus infection SARS-CoV-2. The medicines most frequently used off-label included metformin, rituximab, and thioctic acid. 65 % of respondents assessed their knowledge of off-label prescription as insufficient. In addition, 75 % of respondents consider it useful to receive additional information about risks and benefits of off-label prescription in clinical practice.Conclusion      The survey revealed the need of physicians for information about risks of the off-label use of medicines in clinical practice.

[Interferon gamma in the treatment of patients with moderate COVID-19].

INTRODUCTION: Interferons are produced in response to the presence of pathogens in cells and are responsible for the proper formation of immune reaction. Preliminary data obtained in studies of properties of recombinant interferon gamma (IFN-γ) that involved patients with community-acquired pneumonia (including bacterial), acute respiratory viral infection (ARVI), influenza and new coronavirus infection have shown promising results.The purpose of the study was to assess the effect of subcutaneous administration of IFN-γ in patients with viral pneumonia on the changes of vital signs and the duration of hospital stay. MATERIAL AND METHODS: An open-label, randomized, low-interventional study included patients with moderate new coronavirus infection COVID-19 over 18 years of age of both sexes. IFN-γ 500,000 IU was administered s/c, daily, once a day, during 5 days. RESULTS: IFN-y in addition to complex therapy of the disease resulted in more favorable changes in the stabilization of vital signs, as well as in reduced length of fever and hospital stay by 2 days what allows suggesting a positive effect of this substance on the recovery processes in patients with moderate COVID-19. Special emphasis should be made to the fact that patients who received recombinant IFN- γ experienced no progression of respiratory failure and required no transfer to intensive care unit. DISCUSSION: This study confirms earlier obtained data on the positive effect of IFN-y on the rate of clinical stabilization and recovery of patients with community-acquired pneumonia and viral infections. Presented results are limited to a small number of patients; further study of drug properties in post-marketing studies is required. CONCLUSION: Progress in the treatment of patients with moderate COVID-19 by adding recombinant IFN-γ to the complex therapy may reasonably expand the range of existing treatment options for this infection.

[Difficulties in diagnosing sacroiliitis in young patients]. / Trudnosti diagnostiki sakroileita u patsientov molodogo vozrasta.

In real clinical practice, back pain in young patients is associated with neurological manifestations of degenerative changes in the lumbosacral spine. However, such complaints may be a manifestation of a lesion of the sacroiliac joint-sacroiliitis, and degenerative changes in the spine may accompany it, but not cause pain. Sacroiliitis is an inflammatory lesion of the sacroiliac joint, which can develop as an independent disease or as a symptom of another nosology. The causes of this pathology are diverse: injuries, long-term overloading of the joint, congenital abnormalities of the joints, infectious or systemic diseases, and tumors. In neurological practice, sacroiliitis is similar to myofascial syndromes and can disguise as degenerative diseases of the spine, so early diagnosis and proper therapy are of particular importance. Awareness of doctors about the features of examination of young patients, the use of neuroimaging techniques (CT, MRI), laboratory diagnostics, will help to improve the results of therapy. Prescription of NSAIDs with a pronounced anti-inflammatory potential will slow down the progression of the inflammatory process.

[Predicting the development of adverse events in patients with acute coronary syndrome including genetics in the long-term follow-up].

Aim To study a relationship of several factors (clinical and genetical markers) with unfavorable outcomes in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) in long-term follow-up.Material and methods This full-design, prospective study included 415 patients with NSTE-ACS. 266 patients were evaluated for the presence of multifocal atherosclerosis (MFA). Typing of polymorphic variants rs1041981 LTA, rs1800629 TNF, rs4986790, and rs498679 TLR4, and also rs3024491 and rs1800872 IL10 was performed. Follow-up period lasted for 67±4 months. By the end of this period, information about clinical outcomes for 396 patients became available.Results During the entire follow-up period, unfavorable outcomes were observed in 239 (57.5 %) patients with NSTE-ACS. The following clinical signs were associated with unfavorable outcomes: history of myocardial infarction, age >56 years, left ventricular ejection fraction (LV EF) ≤50 % and GRACE score ≥100, significant stenosis of brachiocephalic arteries, MFA, carriage of genotype А / А rs1041981 LTA (OR, 6.1; р=0.02) and allele А (OR, 1.9; р=0.01). According to results of a multifactorial analysis, the most significant predictors included LV EF <50 %, MFA, and carriage of genotype А / А rs1041981 LTA.Conclusion Stratification of patients with NSTE-ACS into groups of high or low risk for having an unfavorable outcome within the next 6 years is possible using the prognostic model developed and presented in this study. The model includes the following signs: LV EF <50 %, MFA, and carriage of genotype А / А rs1041981 LTA.

[The role of the superoxide dismutase for predicting long-term adverse events in patients with acute coronary syndrome.]

To study the relationship between the blood concentration of superoxide dismutase in at the end of the hospital period of acute coronary syndrome without ST-segment elevation (nonST-ACS) and the development of adverse events in the long-term follow-up period. 415 patients with nonST-ACS are included in the local register study. The follow-up period was 60 months. The blood concentration of superoxide dismutase (SOD) determined in 200 patients on the 10-13th day of hospitalization in addition to clinical procedures. Within five years after discharge in 178 (47 %) patients reported the development of adverse events. Patients with poor outcome were older, had a history of myocardial infarction (PICS), stenoses of extracranial arteries more than 30% and decreased left ventricular ejection fraction (LVEF). There were significant differences in the concentration of SOD10-13 day, which was lower in the patients with development of adverse cardiovascular events (p = 0.0003). Multivariate analysis identified the factors that are most strongly associated with the development of the adverse events during a 5-year follow-up period in patients with nonST-ACS: SOD blood concentration ≤ 175,4 ng / ml (OR-3,85; р=0,0008), myocardial infarction in anamnesis (OR-3,26; р=0,006), LVEF ≤ 52% (OR-2,8; р=0,035). The incidence of adverse cardiovascular events during five years follow-up in patients with nonST-ACS was 47 % of cases. Adverse factors associated with the development of an unfavorable outcome in the long-term period follow are: SOD blood concentration ≤ 175,4 ng / ml, myocardial infarction in anamnesis, LVEF ≤ 52%.

[Early Markers of Cardiovascular Risk in Women With Hereditary Burdening by Cardiovascular Diseases].

PURPOSE: to identify early markers of development of cardiovascular diseases (CVD) in women. MATERIALS AND METHODS: Female firstdegree relatives from 39 families formed 2 groups: families (n=19) containing mothers with arterial hypertension (AH) (group 1) and healthy daughters (group 1a); families (n=20) containing practically heathy mothers (group 2) and healthy daughters (group 2a). We assessed data of anamnesis, including registration of cardiovascular risk factors, and family history of CVD. Examination included registration of anthropometric parameters, automatic and manual measurement of intima-media thickness (IMT) and resistance indexes of brachiocephalic arteries (BCA). We also determined cardio-ankle vascular index (CAVI), ankle-brachial index (ABI), and measured magnitude of ß-adrenoreception of membranes (ß-ARM) of erythrocytes in micro-quantities of venous blood. RESULTS: Mothers in both groups of families had excessive body mass or obesity. Mothers of group 1 had more pronounced signs of abdominal obesity (AO). They also had abnormalities of IMT and sings of subclinical atherosclerosis of BCA. CAVI in this group was significantly higher than in group 2. In group 1a median BMI (25.5 kg/m2) and waist/hip ratio were significantly higher than in group 2a. Daughters of group 1a contrary to group 2a had abnormalities of vascular wall: increased automatically measured IMT of carotid arteries and elevated CAVI. Arterial pressure and heart rate (HR) in group 1a were within limits of physiological norm but significantly higher than in group 2a. All included women had elevated ß-ARM values but in group 1a this parameter was significantly higher than in group 2a and moderately correlated with HR. CONCLUSIONS: Risk factors of CVD development in women are AH, AO, high activity of the sympathoadrenal system. These factors provoke changes of vascular wall (elevation of its stiffness and early subclinical atherosclerosis). In daughters of mothers with AH important prognostic components of CVD risk in addition to family history of CVD are AO, systolic blood pressure (BP) >120 mm Hg, diastolic BP >78 mm Hg, HR approaching upper limit of physiological norm, and high CAVI (indicator of vascular wall stiffness).

[Assessment of Outcomes and Treatment Tactics in Patients With Non-ST-Elevation Acute Coronary Syndrome: Data of Five-Year Follow-up].

PURPOSE: to study the role of clinical factors and treatment tactics in the development of adverse outcomes in patients with non-STelevation acute coronary syndrome (NSTEACS) for five years follow up. MATERIALS AND METHODS: The study included 415 patients with NSTEACS observed for 60±4 months from the date of discharge. Adverse events (AE) were unstable angina (UA), myocardial infarction (MI), ischemic stroke or patient's death. The favorable 5-year outcome was identified in 200, adverse outcome - in 178 patients. Statistical processing was performed using STATISTICA 8.0 software package and MedCalc 11.0. RESULTS: Total mortality for 60 months was 16.1% (n=61). Highest mortality, maximal number of hospitalizations due to MI (41.1%) and UA (49.6%) were observed during first 12 months. Greatest impact on the development of AE produced: history of MI, higher GRACE score, age >54 years (p=0.0021), stenosis in brachiocephalic arteries, ischemic changes on admission ECG and reduced left ventricular ejection fraction (LVEF) ≤ 52% (p=0.0001). Five-year survival rate was influenced by coronary angiography (p=0.0001) and percutaneous coronary intervention (PCI) during index hospitalization (p=0.0039). DISCUSSION: Mortality and frequency of AE in this register were close to generally reported. The observed adverse impact on the long-term outcome of such risk factors such as age over 60 years, history of MI, ischemic ECG changes at admission, decreased LVEF corresponded to literature data. Our study proved the need for coronary imaging in patients with NSTEACS to determine treatment strategy in in hospital period as these factors affected the 5-year survival. CONCLUSION: During five-year follow-up AE occurred in 47.1% of patients with NSTEACS. Maximal number of patients with AE was registered during the first (24.7%) and fifth (13.8%) year of observation. The development of AE was associated with older age, history of MI and coronary artery bypass grafting, ischemic ECG changes, decreased LVEF, higher GRACE score, and brachiocephalic artery stenosis. Carrying out diagnostic coronary angiography and PCI with stenting during hospitalization in patients with NSTEACS was associated with favorable 5-year outcome.

[Left ventricular noncompaction]. / Nekompaktnyi miokard levogo zheludochka.

This paper provides a literature review on left ventricular noncompaction (noncompact cardiomyopathy). It details the historical aspects, epidemiology, ethology, pathophysiology, clinical features, diagnosis, treatment, and prognosis of this abnormality.

[Prognostic factors in patients with non-ST-segment elevation acute coronary syndrome concurrent with type 2 diabetes mellitus (according to the results of the registry)]. / Faktory prognoza u patsientov s ostrym koronarnym sindromom bez pod''ema segmenta ST v sochetanii s sakharnym diabetom 2-go tipa (po rezul'tatam registra).

AIM: To investigate factors that influence annual prognosis in patients with non-ST-segment elevation acute coronary syndrome ((NSTEACS) concurrent with type 2 diabetes mellitus (DM2). SUBJECTS AND METHODS: The registry of patients with NSTEACS (non-ST-segment elevation myocardial infarction (NSTEMI), unstable angina) included 415 patients, of them 335 had no carbohydrate metabolic disorders, 80 had DM2. The follow-up period, during which the prognosis was evaluated in the patients, was one year after hospital discharge following the index NSTEACS event. Lipidogram readings and the serum levels of endothelin-1 (ET-1), sP-selectin, sE-selectin, and sPECAM were determined on day 10 after admission to hospital. All the patients underwent coronary angiography (CA), Doppler ultrasound of peripheral arteries during their hospital stay. RESULTS: The patients with DM2 versus those without diabetes proved to be significantly older and to have a higher body mass index; among them there were more women, they were noted to have more frequently hypertension and less frequently smoked. The presence of DM2 was associated with significantly increased intima-media thickness and higher GRACE scores (p=0.013) as compared to those in the patients with normal carbohydrate metabolism. There were significant differences in high-density lipoprotein levels that were lower, as well as in triglyceride levels and atherogenic index, which were higher in patients with DM2 than in those without this condition. In addition, there were significant differences in ET-1, sP-selectin, sE-selectin, and sPECAM levels that were significantly higher in the DM2 group. Moreover, the levels of ET-1 and sPECAM were above normal in both the DM and non-DM2 groups. Assessment of poor outcomes at one year of the observation established that cardiovascular mortality rates were significantly higher and coronary angiography was performed much less frequently in the DM2 group. The most significant prognostic factors associated with a poor prognosis were as follows: multifocal atherosclerosis, reduced left ventricular ejection fraction (LVEF) less than 51%, and increased ET-1 levels more than 0.87 fmol/ml. CONCLUSION: The register-based study has shown that the presence of DM2 statistically significantly increases cardiovascular mortality rates during a year after the index ACS event; the patients of this category are less commonly referred for CA for the estimation of the degree of coronary bed lesion. The most important factors of recurrent cardiovascular events in patients with DM2 within a year after prior ACS are multifocal atherosclerosis, reduced myocardial contractility (LVEF less than 51%), and increased vasospastic endothelial function (an increase in ET-1 levels more than 0.87 fmol/ml).

[Pleiotropic effects of atorvastatin in rheumatoid arthritis patients with no history of cardiovascular diseases].

AIM: To evaluate the effect of atorvastatin (liprimar) on the laboratory values of inflammation and blood lipid composition in rheumatoid arthritis (RA) patients with no history of cardiovascular diseases (CVD). Subjects and methods. Fifty women with grade II RA activity according to DAS28 and radiologic (erosive) Stages I-III were examined; the patients were not former or current smokers; all were seropositive; their mean age was 50.2±9.9 years. All the patients with RA were divided into 2 groups: Group 1 took no atorvastatin and continued to receive standard previously prescribed therapy; Group 2 used atorvastatin in a dose of 20 mg. Lipidogram readings and the levels of Apo-A and Apo-B, neopterin, tumor necrosis factor-α, C-reactive protein, sP-selectin, sE-selectin, interleukin (IL)-6, IL-10, IL-12, and matrix metalloproteinases 3 and 9 were assessed. RESULTS: The patients with RA show obvious blood lipid composition impairments. Incorporation of atorvastatin (liprimar) into combination therapy for RA not only causes a considerable reduction in total cholesterol, low-density lipoprotein cholesterol, triglycerides, and apo-B levels, but also positively affects the inflammatory activity of the disease, by lowering the level of proinflammatory cytokines and increasing that of the anti-inflammatory cytokine IL-10. CONCLUSION: The above changes may underlie the prevention of CVD complications in patients with RA.

[Influence of Endothelial Dysfunction on Prognosis of Patients With Non ST-Segment Elevation Acute Coronary Syndrome].

We studied relationship between markers of endothelial dysfunction and multifocal atherosclerosis and adverse coronary events in 82 patients with non-ST segment elevation acute coronary syndrome (NSTEACS). Eighteen patients (21.9%) had adverse events during one year of observation. Patients with adverse coronary events had impaired vasodilatory, vasoconstrictive, and adhesive endothelial function. Predictors of unfavorable prognosis in NSTEACS were signs of impaired endothelium-dependent vasodilation during test with reactive hyperemia, high soluble platelet selectin and endothelin-1 levels on day 10 of the disease. Endothelin-1 and soluble platelet-endothelial cell adhesion molecule-1 had greatest predictive power relative to development of non-fatal myocardial infarction.

[THE RELATIONSHIP BETWEEN POLYMORPHISMS OF G-1082A AND C-592A LOCI OF THE IL10 GENE AND MULTIFOCAL ATHEROSCLEROSIS IN PATIENTS WITH ACUTE CORONARY SYNDROME WITHOUT SEGMENT ST ELEVATION].

AIM: To study the relationship between polymorphous G-1082A (rs3024491) and C-592A (rs1800872) variants of the IL10 gene and multifocal atherosclerosis (MFA) in patients with acute coronary syndrome (ACS) without segment ST elevation. MATERIALS AND METHODS: Genotypes of polymorphous G-1082A (rs3024491) and C-592A (rs1800872) variants of the IL10 gene were determined in 178 patients. Interleukin-10 (IL-10) level was measured in 93 of them using solid-phase immunoenzymatic assay. All patients underwent visualization of coronary and peripheral arteries. RESULTS: C-592A (rs1800872) polymorphism ofthe IL10 gene tended to be associated with type 2 diabetes mellitus in the carriers of the CC (gg) genotype and with elevated concentration of high density lipoproteins and reduced intima-media thickness in the carriers of the AA (tt) genotype. The frequency of MFA in the carriers of different genotypes of rs1800872 polymorphism was practically identical while the CA(gt) genotype was associated with more severe manifestations of atherosclerosis and AA(tt) genotype with lower frequency of peripheral artery stenosis. Patients with AA(tt) genotype of rs1800872 polymorphism had higher IL-10 levels. No relationship between rs3024491 polymorphism of IL10 gene, blood IL-10 level, clinical risk factors, and MFA was documented. CONCLUSION: CC (gg) genotype of C-592A (rs1800872) polymorphism of the IL10 gene in patients with acute coronary syndrome (ACS) without segment ST elevation was associated with type 2 diabetes mellitus while the AA(tt) genotype of the same polymorphism with elevated concentration of high density lipoproteins, reduced intima-media thickness, low frequency of peripheral artery stenosis, and increased IL-10 production. CA (gt) genotype of rs1800872 polymorphism of the IL10 gene was associated with MFA.

[Dynamics of risk of fatal cardiovascular diseases evaluated with the SCORE scale in men with disorders of fat metabolism].

In 141 apparently healthy working men aged 55 years (mean) we assessed body mass index (BMI), states of lipid, carbohydrate and purine metabolism, morphological and functional state of the cardiovascular system (transthoracic echocardiography), carotid artery intima-media complex (IMC) (ultrasound investigation). Ten year risk of fatal heart disease was also evaluated with the SCORE scale. Same examination of all 141 men was repeated in 3 years. At both examinations 50% of subjects had abnormalities of lipid metabolism. Among these subjects 50% had hypercholesterolemia while hypertriglyceridemia was registered in 7 men. In 3 years numbers of patients with hypertriglyceridemia and elevated low density lipoprotein cholesterol significantly decreased. Arterial hypertension (AH) at initial examination was found in about one fifth of men. After 3 years number of patients with AH did not significantly increase, but the structure of the disease changed: number of patients with stage 2 AH increased and of those with stage 1 AH decreased. Cardiovascular risk measured in accordance with the SCORE scale was moderate at initial examination but significantly increased after three years. Thus despite the fact that during 3-year follow-up the subjects maintained relatively stable body mass and parameters of lipid metabolism risk of occurrence of fatal cardiovascular complications increased probably due to the aging and presence of additional risk factors (low high density lipoprotein, IMC thickening). Ultrasound investigation revealed that the AH progression contributed to the development of left ventricular hypertrophy and increase of intima-media thickness of brachiocephalic arteries.