Cardiovascular diseases (CVDs) are the number 1 cause of death globally. Risk factors for CVDs may trigger the development of pathological conditions to a certain degree. The cardiovascular continuum is a continuous chain of interconnected changes in the cardiovascular system from exposure to risk factors via the gradual onset and progression of CVD to the development of terminal heart damage and death. The continuous chain of interconnected changes in the structure and function of several body organs and systems at once within the continuum suggests the presence of common pathophysiological processes, mechanisms of development and progression of organ damages. The drug’s ability to affect all stages of the cardiovascular continuum defines the choice of modern pharmacotherapy for cardiological patients. Using drugs with multi-target (multi-purpose) action is one of the possibilities for optimizing pharmacotherapy. The provided results of clinical studies show that drugs meeting this requirement include ACE inhibitors (ramipril), beta-blockers (metoprolol), lipid-lowering drugs (combination drug rosuvastatin/ezetimib), allopurinol. The choice of drugs for pharmacotherapy of patients with cardiovascular diseases should be based on the presence and severity of all risk factors and associated conditions and taking into account the individual characteristics of the drugs. Patients with chronic heart disease usually need lifelong therapy, and search for the best individual treatment for each patient is crucial. Using drugs with multi-target (multi-purpose) action is one of the possibilities for optimizing treatment.

Atrial fibrillation (AF) is one of the most common arrhythmias in patients ≥75 years of age. The increased risk of thrombosis due to age and the large number of concomitant diseases makes it evident that anticoagulant therapy is necessary. However, the same factors increase the risk of hemorrhagic complications, which are among the most dangerous side effects of anticoagulant therapy. That is why it is very important to identify patients with the highest probability of bleeding, whether large or small clinically significant and minor. The purpose of our study was to study the prognostic value of laboratory methods of examination with regard to the development of hemorrhagic events in elderly patients with AF taking direct oral anticoagulants (DOAC). The study enrolled 102 patients ≥75 years of age with AF of non-valve etiology taking dabigatran, apixaban, rivaroxaban at full or reduced doses. Anticoagulants were administered by outpatient and inpatient physicians. Both previous experience with DOAC prior to inclusion in the trial (if DOAC was previously prescribed) and prospective patient monitoring after inclusion in the trial were analyzed. The minimum analyzed period of DOAC intake was 18 months. Patients who underwent (n = 19) and did not undergo (n = 83) hemorrhagic events (all events were considered small by ISTH criteria) did not differ in any of the laboratory indicators potentially considered as predictors of hemorrhagic events.

The review is devoted to the analysis of the methods of hemostasis treatment in order to improve the prognosis of patients with chronic ischemic heart disease (IHD). The results of the most significant randomized clinical studies, which evaluated the effectiveness and safety of double antiplatelet therapy in the treatment of patients with chronic IHD, were discussed. The use of rivaroxaban in addition to ASA was justified in order to reduce the risk of cardiovascular events in patients with chronic IHD. The results of the COMPASS study, which confirmed the positive effect on the prognosis of patients with chronic IHD or peripheral artery disease of low-dose rivaroxaban and ASA combination therapy, were reviewed in detail. Safety aspects of this therapy were discussed. The results of double antiplatelet therapy and the combination of rivaroxaban and ASA in patients who had previously undergone myocardial infarction are compared. The position of rivaroxaban in the treatment of patients with chronic IHD and sinus rhythm was determined in accordance with the recommendations of the European Society of Cardiologists for the diagnosis and treatment of chronic IHD in 2019. The criteria of high ischemic and high hemorrhagic risks, which should be taken into account when deciding to add rivaroxaban to the ASA therapy, were presented. The expediency of wide application of the combination of rivaroxaban and ASA as a part of complex pharmacotherapy of patients with chronic IHD with high ischemic risk for prevention of cardiovascular complications and reduction of mortality is justified.

The article discusses the vascular age concept and modern approaches to assessing vascular age. It describes modern methods for measuring arterial stiffness (applanation tonometry or ultrasonic Doppler examination) as the most frequently used index of vascular age. The authors discuss the role of antihypertensive therapy and statins in preventing early vascular aging, and the relationship between the role of achieving lower blood pressure levels and the choice of certain antihypertensive agents to reduce arterial stiffness and ensure optimal vascular age. Increased arterial stiffness has been reported to be a marker of risk for developing severe complications of cardiovascular diseases, in particular, a meta-analysis showed that after taking into account the known risk factors for developing cardiovascular complications, higher carotid stiffness was associated with an increased risk of stroke. It is stated that in addition to biological age, vascular age may increase due to the cumulative effect of such risk factors as high blood pressure, impaired glucose homeostasis, obesity and hypercholesterolemia. Modern approaches to the preservation and maintenance of vascular age are discussed. The key role of achieving lower blood pressure levels is considered. It is emphasized that the role of combination drugs in preventing complications of cardiovascular diseases is strengthened, and approaches to choosing the optimal components of such combination drugs are also considered. The relationship between increased arterial stiffness and the development of cognitive disorders is discussed. The article describes the role of statins and effectiveness of the concomitant use of statins and combination antihypertensive therapy in reducing the pulse wave velocity.

The article discusses the issues concerning the treatment of patients with the atrial fibrillation (AF), analyzes the indications for execution, in the absence of the effect of medication treatment, radiofrequency catheter ablation (RFA) of the lung vein entries and electrical spiral waves in the atria or rotors, the clinical effects of this procedure, assesses the contribution of focal activity in maintaining the persistent AF. The influence of concomitant pathology and anatomical-morphological peculiarities of the heart on early and distant RFA results in patients with persistent AF is discussed. The success and efficacy of AF surgical treatment depends not only on the method and technology of the chosen procedure, but also on the risk factors for the recurrence of AF (so-called predictors). Radio-frequency ablation, being an invasive surgery, has its own spectrum of possible complications and high economic component, which predetermines the necessity to predict the efficiency of the procedure, i.e. preoperative determination of the patient group, in which this type of treatment will be justified, and the expected efficiency and safety – higher than the probability of complications. The study of this problem and the development of criteria for selecting patients with AF will allow predicting the effectiveness of surgical intervention with high probability, which in turn will contribute to the correct strategy selection.

Background: despite well-studied safety profile of dabigatran its interactions with genetic polymorphism parameters are poorly understood, especially in patients with moderate chronic kidney disease (CKD). This study was aimed to evaluate relationships between CES1 and ABCB1 polymorphism, dabigatran trough plasma concentration (DTPC) and bleeding events in patients with AF and CKD.

Methods: patients with atrial fibrillation (AF) and stage 3 CKD treated with dabigatran 110mg or 150 mg have been included in the study. Real-time PCR was used to evaluate single nucleotide polymorphisms (SNPs) of the ABCB1 gene (rs1045642, rs4148738) and CES1 gene (rs2244613). A plasma trough concentration/dose (C/D) ratio was used as a pharmacokinetic index.

Results: a total of 60 patients, aged 51–89 years (median age 76 years) were evaluated. Compared with patients given 150 mg twice a day, those given 110 mg twice a day were older (79 vs 67.5, p < 0.0001) and had lower creatinine clearance (CrCl) (50.5 vs 60.5 mL/min/1.73 m2, p = 0.015). We found C/D values to have high interindividual variability (mean 365.9 ± 290.4 μg/ml: mg/day, range 23.64-1452.73). Individuals with CKD 3B had higher concentration of dabigatran compared with those with 3A stage (488.7 ± 232.3 vs 332 ± 297.8 μg/ml : mg/day, p = 0.02). Consequently, there also was negative correlation of C/D with CrCl (r = -0.4, p = 0.0015). Evaluated SNPs (rs1045642, rs4148738, and rs2244613) did not affect C/D values (H test p > 0.05).

Conclusions: C/D values were significantly higher in patients with CKD 3B stage and those treated with dabigatran 110 mg. There was no influence of aforementioned SNPs on dabigatran trough concentrations and clinical outcomes.

The article substantiates the feasibility of combination antihypertensive therapy in patients with arterial hypertension without target organ damage and high cardiovascular risk. The authors consider a clinical case of the use of amlodipine and losartan in a fixed-dose combination (Lozap AM) as part of complex therapy in a patient with arterial hypertension, dyslipidemia and obesity. The clinical case showed the ability of the drug to both achieve a steady level of target blood pressure and improve its daily profile by transferring the Night-peaker type to the Non-dipper type.

One of the promising areas of pharmacotherapy in degenerative-dystrophic lesions of the joints, such as osteoarthritis (OA), is the use of chondroprotectors (CP). CPs belong to the group of Symptomatic Slow Acting Drugs for OsteoArthritis (SYSADOA). Among CPs, chondroitin sulfate (CS) is considered to be the most acceptable means capable of influencing metabolic processes in cartilage, synovial and bone tissue, suppressing the synthesis of proinflammatory mediators. CS improves phosphorus-calcium metabolism in cartilage tissue, inhibits enzymes that violate the structure and function of articular cartilage, inhibits the degeneration of cartilage tissue; stimulates the synthesis of glycosaminoglycans (GAG), normalizes the metabolism of hyaline tissue, promotes regeneration of cartilage surfaces and articular bags.The main effects that show CS on the joint in OA: anti-inflammatory, analgesic, protective. Slowing bone resorption, reduces the loss of Ca2+ and accelerates the processes of bone repair, inhibits the progression of OA. It has analgesic effect, reduces joint pain, pain at rest and when walking, the severity of inflammation, reduces the need for non-steroidal anti-inflammatory drugs (NSAIDs). The appointment of correctors of bone and cartilage metabolism is indicated at any stage of the degenerative process in the joints. One of the medicinal product (MP) based on CS is Chondroitin-ACOS (capsules, 25mg), whose effectiveness in the treatment of patients with OA has been demonstrated in a number of studies. Dosage Chondroitin-ACOS: 0,75 g 3 times a day for 3 weeks, then 0,5 g 2 times a day for 9 weeks. The therapeutic effect develops after 8-12 weeks of taking the drug. Within one month after discontinuation of Chondroitin-ACOS, its aftereffect persisted. Chondroitin-ACOS can be recommended for patients with severe pain syndrome, radiologically confirmed OA I-III stages of different localization.

The article is devoted to the analysis of various pathogenetic mechanisms involved in the formation of chronic brain ischemia. The authors discuss current trends in society, leading to a wide spread of cerebrovascular diseases: an increase in life expectancy and a constantly increasing level of psychosocial stresses. The paper considers the variety of clinical manifestations, course options, the pace of development of this pathology, diagnostic and therapeutic difficulties encountered by doctors treating this category of patients. Particular attention is paid to symptoms that prevent a full course of treatment and prevention of chronic cerebral ischemia, such as asthenia and impaired statolocomotor function. The leading pathogenetic mechanisms that play a role in the formation of these syndromes are discussed. Various approaches to the treatment of this pathological condition are considered. The possibility of using drugs with a multimodal effect is discussed. An analysis of a clinical case involving a patient with a long history of chronic brain ischemia is presented. The main factors that are obstacles to a full pathogenetically directed treatment are identified and ways to solve this therapeutic problem are given. The authors conclude that it is necessary to formulate a wellthought- out therapy strategy for this pathological condition, including timely, well-considered use of drugs with a neurotrophic, neuromodulating effect, which allows further measures, including non-pharmacological approaches. Particular attention is paid to the role of social support and physical activity for the prevention of cerebrovascular diseases.

The prevalence of diabetes mellitus (DM) is steadily increasing and represents a significant public health problem. At the same time, the incidence of neurological complications of diabetes mellitus, especially diabetic polyneuropathy, is increasing. Cardiac autonomic neuropathy, a form of diabetic polyneuropathy, is the most serious complication of diabetes mellitus, as it is an independent risk factor for cardiovascular complications in patients with diabetes mellitus and is associated with increased mortality. Due to prolonged asymptomatic flow, cardiac autonomic neuropathy is often diagnosed at a late stage when treatment is not very effective. A targeted search for clinical symptoms of the disease and especially the conduct of cardiovascular tests, which make it possible to diagnose the pathology at an early stage, is essential. Clinical manifestations of cardiac autonomic neuropathy, methods of clinical and instrumental diagnostics, treatment of the disease are considered in detail in the article. The clinical case of a patient with type 2 diabetes mellitus and cardiac autonomic neuropathy, represented by orthostatic hypotension, which is the most disabling symptom, is considered. On the example of a clinical case the medicamentous and non-medicamentous approaches to treatment are discussed, as well as the role of antioxidant therapy, in particular, the preparation of alpha-lipoic acid («Berlithion») in the treatment of cardiac autonomic neuropathy.

The article presents a clinical case of the use of the antidepressant sertraline at a dose of 100 mg in a patient with a primary moderate depressive episode. At the time of treatment, the condition lasted 16 months, and symptomatology of anxiousapathic depression of endoreactive type was observed. Positive therapeutic dynamics were observed in the course of therapy with achieving clinical remission by the end of the 6th week of treatment. The reduction of anxiodepressive symptomatology was accompanied by positive dynamics of psychomotor indices with normalization of balance of excitation and inhibition processes, cognitive indices with improvement of executive functions in the form of increase of polyindependence, functional mobility of nervous processes and stress resistance, increase of productivity and stability of attention, operative memory. Significant positive changes were observed in the analysis of formal-dynamic personal characteristics: the level of psychomotor and intellectual emotionality decreased, which reflects a decrease in the intensity of emotional experience of the divergence between the expected and real results of activity, the levels of intellectual plasticity reflecting the flexibility of thinking, intellectual and communicative speed, i.e. the speed of mental processes, speech activity and verbalization increased. In the personal- emotional sphere there was an increase in frustration tolerance, balance of extrapunitive, intrapunitive and impulsive directions of reactions, increase in frequency of «obstacle-fixed» type of reaction and decrease in frequency of «self-protection» type of reaction, decrease in aggressiveness index. At the same time there were no changes in «behavioural activity types» technique: the expressed behavioural pattern of «A» type of so-called «stress-coronary» behaviour was preserved. The revealed changes indicate an increase in the adaptive capacity of the individual against the background of remitative antidepressive pharmacotherapy with sertraline.

The article provides data on the epidemiology of severe asthma. It defines the phenotype and endotype of bronchial asthma and classifies BA according to phenotype/endotype. The features of the eosinophilic phenotype of severe bronchial asthma are considered. Clinical characteristics of the patient corresponding to the prescription of benralizumab are presented. The algorithm of decision making by a doctor-therapist about patients’ referral to a pulmonologist for consideration of the biological therapy issue is given. The results of the main clinical studies to assess the efficacy and safety of benralizumab in patients with severe eosinophilic bronchial asthma: SIROCCO, CALIMA, ZONDA, BORA are described. The experience of using various biological preparations for the treatment of severe asthma in Chelyabinsk and the Chelyabinsk Region has also been summarized.

Aim of the study: to develop a tactic of surgical treatment of cicatrical lesion of the middle larynx depending on the localization and length of stenosis.

Materials and methods: from 2014 to 2019, 43 patients with cicatrical stenosis of the folded larynx underwent surgery. The average age of the patients was 39 years and ranged from 18 to 78 years. Depending on the clinical situation, patients were divided into 4 groups, in which different methods of surgical treatment were applied – removal of scars of the middle larynx using CO2-laser and additional application of keel-shaped implant (n = 21), microflaps in the area of commissure (n = 10) and intraretynoid region (n = 4), endoprosthesis covered with xenopericord (n = 8).

Results: in the postoperative period endoscopic examination of the larynx was carried out in dynamics during the period up to 1 year. Patients were examined daily while in hospital, then monthly. In addition to endoscopic examination, the study of voice function was carried out by the method of determining the time of maximum fonation. The estimation of respiratory and voice rehabilitation was carried out and stable positive effect was received in 90% in the first group, 70% - in the second, 75% - in the third, 75% – in the fourth. The obtained data allow to develop an individual approach to surgical treatment of cicatrical stenosis of the larynx depending on the localization and extent of cicatrical lesion.

Discussion: the optimal method of treating cicatrical lesion of the middle larynx is to create conditions that prevent the contact of wound surfaces and their separation. For this purpose, methods that are individually addressed to the main clinical situations in this problem have been developed. In addition, the use of CO2-laser in the surgical treatment of cicatrical lesions of the middle larynx significantly expands operational capabilities due to high accuracy and low level of damage to surrounding tissues.

Conclusions: in case of cicatrical lesion of the middle larynx up to 4 mm in length, in the absence of a tracheostoma an effective method of restoration of respiratory and vocal function of the larynx is the use of microflaps formed by microsurgery with th e help of CO2-laser; stenoses in the area of middle larynx commissure of more than 4 mm require additional stenting for the period of epithelization of the wound surface and remodeling of the scar, which is 3–4 weeks. In the presence of a tracheostoma in patients with prolonged stenosis of the middle laryngeal commissiure, an implant coated with xenopericardium and chlorhexidine ionic-covalent immobilization, which helps to avoid inflammatory changes during the period of stenting, has proved to be a good choice.

Osteoporosis (OP) along with myocardial infarction, oncological diseases and expected death takes the lead in the general morbidity and mortality profile of population. The indicators of primary and general incidence of OP are markedly different in the regions of Russia according to the Healthcare Monitoring, Analysis and Strategic Development Department of the Central Research Institute of Organization and Informatization of Healthcare of the Ministry of Health of Russia and according to the data of epidemiological studies. Osteoporosis is classified as primary, if it develops in postmenopausal women or in older men in the absence of any underlying predisposing disease, and as secondary if there is a pathogenetic relationship with the disease or drug intake. The glucocorticoidinduced osteoporosis, which is distinguished in the International Classification System of Diseases and Death Causes (X revision) under code M 81.4 - drug-induced osteoporosis is the most common form of secondary osteoporosis. The topic of glucocorticoidinduced OP affects the professional fields of a significant number of medical specialties in connection with the common use of glucocorticosteroids in medicine. This article presents the issues of epidemiology, pathogenesis, complications of glucocorticoid-induced OP. Particular attention is paid to the prevention of this disease, including such non-pharmacological methods as a balanced diet, body weight gain to the recommended values, smoking cessation, regular exercise against weightlifting and resistance, protection against falls. Drug prophylaxis of glucocorticoid-induced OP is focused on the rational treatment to target of the underlying disease and the use of complex drugs containing vitamin D, calcium and synergistic osteotropic micronutrients.

Aim. To evaluate the effectiveness of a fixed combination of honadroitin and glucosamine sulfate (Teraflex, Bayer) in the treatment of osteoarthritis (OA), depending on the molecular phenotype of the disease.

Materials and methods. A 6-month prospective, open, randomized trial included 65 patients with OA of the knee joints who were prescribed therapy with Teraflex (Bayer) daily dose of 1500 mg + 1200 mg. Kinetic assessment of articular status was performed using a visual analogue pain scale and a WOMAC questionnaire, and serum concentrations of CRTAP (cartilage-associated protein), OSGIN-1 (oxidative stress-induced growth inhibitor 1), IL-1β (interleukin-1 beta) were determined in blood serum. Measurements of these parameters were made at the beginning of the study, after 3 and 6 months.

Results. It was established that the rate of onset of the therapeutic effect and the effect on the molecular patterns of inflammation and oxidative stress depend on the phenotype of the disease. So, with oxidative and mixed phenotypes of the disease, clinical efficacy is observed in the treatment of teraflex after 3 months from the start of therapy. Indicators of oxidative stress during treatment decreased in the group of patients with the oxidative phenotype of the disease, while the level of interleukin-1 significantly decreased only in groups of patients with inflammatory and mixed OA phenotypes.

Conclusions. The results indicate the effectiveness and safety of the drug Teraflex (Bayer) for the treatment of patients with OA. The results of the study indicate the targeted effect of a fixed combination of chondroitin + glucosamine on the molecular mechanisms of the disease.

Treatment of osteoporosis is a difficult task due to the need for long-term medication and maximum safety. The main goal of osteoporosis treatment is to prevent bone fractures. According to the national clinical guidelines for the treatment of osteoporosis, nitrogen-containing bisphosphonates are among the first-line drugs for the prevention and treatment of this disease. The diversity in the side chain structure determines the strength with which bisphosphonates bind to hydroxyapatite, are distributed, and remain in bone tissue for a certain time after treatment has been completed. They are the drugs of choice as they have proven efficacy in reducing the risk of fractures, and at the same time an acceptable safety profile. Bisphosphonates are the most well-known and studied drugs, successfully used in all countries for the treatment of various forms of osteoporosis. When using oral forms of bisphosphonates, the most expected undesirable phenomenon is esophagitis. The development of new forms of well-known and proven medicines that reduce adverse events and increase adherence to treatment is extremely important and promising. Of the latest achievements in this regard, it should be noted a new form of alendronate-Binosto-effervescent soluble tablet, the use of which reduces the risk of irritating effects on the upper gastrointestinal tract.

Constipation (constipation, obstipation) is a symptom in which the frequency of the act of defecation is less than 3 times a week and is accompanied by the release of solid, scanty feces with a feeling of incomplete emptying of the rectum and often requiring additional effort. World health organization in the « International statistical classification of diseases and health-related problems. ICD-10 « refers to constipation diseases (code K59. 0). At the same time, gastroenterological organizations such as the world organization of gastroenterologists and the American gastroenterological Association take a different position, emphasizing that constipation is not a disease, but a symptom. Most often constipation affects young children and the elderly (over 60 years). The feeling of difficulty in emptying the bowel, the impossibility of relief, despite persistent straining, the need to apply additional, stimulating the release of the rectum from the feces, actions (pressure on the perineum, the side walls of the anus, the vagina). The constant state of insufficient emptying of the rectal ampoule often leads to the development of perineal prolapse syndrome. Chronic constipation is diagnosed in cases where the frequency of stool becomes less than 3 times a week, defecation is significantly difficult and requires pronounced efforts, the consistency of the stool is dense, tubercular, there is a feeling of incomplete liberation of the rectum from feces. Constipation is a very common digestive disorder among the population, the tendency to constipation can lead to the development of serious proctological diseases, so this problem has a high degree of social significance. Due to its prevalence and pronounced deterioration in the quality of life of patients, chronic constipation is isolated in an independent syndrome, and currently the problem of constipation is actively studied by proctologists, gastroenterologists and other specialists. This article is devoted to the main issues of modern therapy of constipation.

Objective of the study: comparative evaluation of the bacteriotropic activity of Actoflor-S metabiotic and the exometabolic bifidobacteria complex.

Materials and methods: in our work we used Actoflor-S dietary supplement as oral solution in 2 ml drop tubes (Solopharm). As a comparator drug, we used an exometabolite complex from the culture fluid of strain Bifidobacterium bifidum 1 obtained by method of ultrafiltration using separation apparatus with HOMM 15 kDa. We studied the stimulating effect of metabolite compositions on the acid forming activity and dynamics of the accumulation of lactobacilli Lactobacillus plantarum 8P-A3. Antagonistic activity against enterobacteria was determined in the test of inhibition of bioluminescence of the indicator strain Escherichia coli lum+ and quantified as an index of antibacterial activity

Results and discussions. A comparative study of the effects of metabiotics on the acid forming activity of lactobacilli showed that both drugs have a pronounced stimulating effect on the probiotic strain L. plantarum. A comparative study of the effects of metabiotics on the model test strain of enterobacteria showed that whole preparations quickly and significantly (by more than 90%) inhibit the bioluminescence of E.coli lum+. Preparation dilutions 1:10 and 1:100 discovered significant differences in their activity. Given equal pH values (5.8 ± 0.1), Actoflor-S (dilution 1:10) inhibited the luminescence of E. coli lum + to a greater degree, exceeding almost 2 times the indicators of the metabolite bifidobacteria complex. It is revealing that Actoflor-S diluted 1:10 is not inferior to the whole preparation in terms of the level of effect on the test strain culture. What calls attention to itself is that large dilutions of UFLC of bifidobacteria after a short period of inhibition of luminescence of E. coli lum + have a stimulating effect. There is evidence that effect of inhibition of the luminescence of the control culture is dose-dependent.

Conclusion. The results of a comparative examination of the bacterial action profile of the native exometabolites complex and Actoflor-S preparation confirm the presence of combination of the necessary inhibitory and stimulating activity against various agents of the microbiota. Creation of the metabiotics line based on Actoflor-S preparation with variability of biological properties and specialized for the management of various dysbiotic conditions show promise. An additional inclusion of native exometabolites of bifidobacteria and/or lactobacilli into the formula of artificial compositions will make it possible to expand the spectrum of the positive effect of probiotic preparations on the microorganism.

Objective of the study. A 5-year prospective study was aimed to evaluate the efficacy of Ursosan treatment for dissolving gallstones.

Material and methods. Patients who had single gallbladder stones were randomized to group A, in which 47 people completed the study (16 men and 31 women, median age is 67.6 years), and group B – 41 people 14 men and 27 women, median age is 68, 1 years). All patients of group A continuously received continuous treatment with ursodeoxycholic acid drug Ursosan at a dose of 10 mg /kg per day for 5 years. The patients of group D did not receive Ursosan; these individuals received periodic courses of spasmodic drugs. The patients passed clinical examination, laboratory tests, transabdominal ultrasound of the liver and biliary tract before the study, 2 times a year for 5 years and after the study.

Results. After 5 years of treatment, stones were detected in 10.6% of patients in group A. In group B, the incidence of gallstones did not change after 5 years of treatment, that is, calculi were detected in all patients (p <0.001). At the end of the study, no muldoi tiple stones were observed in any of the patients of group A, while multiple stones were detected in 2/3 of group B patients after 5 years of treatment. A distinct decrease in pain syndrome frequency and improvement in contractile function of the gallbladder were recorded in patients of group A as compared to the patients of group B by the end of the observation period. The side effect profile did not differ in groups A and B. The study showed good tolerance of Ursosan for 5 years of continuous administration of the drug.

Findings. The 5-year prospective study showed that Ursosan’s efficacy in dissolving gallstones accounted for 90%. Ursosan also prevented the formation of new calculi and reduced the frequency of pain, improved the gall-bladder contractile function and reduced the need for cholecystectomy by the end of the observation period.

Nonsteroidal anti-inflammatory drug is one of the most commonly prescribed drugs for the treatment of inflammatory and pain syndromes in the clinical practice of doctors of various specialties. The popularity of this pharmacological group is increasing due to over-the-counter dispensing condition, but at the same time, the significance of issues of likelihood, prevention and treatment of severe adverse drug reactions during intake that is controlled and uncontrolled by medical personnel is increasing. This review is devoted to the issue of non-steroidal anti-inflammatory drug-induced damage to the gastrointestinal tract and to the current possibilities to prevent and manage such damage. The drugs that can increase the production of prostaglandins and mucus in the digestive tract and have a general anti-inflammatory effect raise significant hopes. Rebamipide draws particular attention due to numerous pleiotropic effects, including stimulation of secretion of newly formed prostaglandins and glycoproteins in the mucous membranes, inhibition of synthesis of oxidative stress products, inflammatory cytokines and chemokines by intestinal epithelial cells. The authors considered the effectiveness of prophylactic use of rebamipide in comparison with other strategies for the use of drugs to prevent the development of stomach ulcers, duodenal ulcers and distal small bowel ulcers. They described the mechanisms of prophylactic action and its debatable aspects for proton pump inhibitors, H2-histamine receptor blockers, misoprostol. The clinical efficacy of rebamipide is illustrated by a clinical example. The absence of effects on cytochrome P450 enzyme activity, which minimizes the risks of drug interactions and changes in bioavailability, biotransformation and excretion of the drug itself during its course use is an additional advantage of rebamipide.

Aim: to prove the effectiveness of combined physical and psychological assessment in improving the long-term outcome of patients with alcoholic liver disease (ALD).

Materials and methods: the active outpatient follow-up (AOF) group included 29 patients with ALD consisted of active liver function and motivation assessment, motivational interviewing, liver panel lab tests with the rate once at 3 months. The AOF program consisted of dynamic monitoring of liver function at least 1 time in 3 months and psychological support provided by the hepatologist using brief interventional approach. The control of abstinence was provided by using self-reports and indirect biomarkers of alcohol consumption. The control group included 36 patients with ALD and history of two-years follow-up after first alcoholinduced liver injury who received comprehensive therapy and a simple advice to avoid alcohol.

Results: the adherence to abstinence were significantly higher in AOF group compared with control group. The proportion of patients with decompensated cirrhosis was significantly lower in AOF group compared with control group at 12 and 24 months after enrollment. The long-term survival in AOF-group was significantly higher than in control group. The only parameter independently associated with long-term survival was the presence of AOF program.

Conclusion: the combined physical and psychological assessment of patients with ALD, provided by internists improves adherence to abstinence, reduces the risk of decompensation of liver function, severity of ALD and improves patients survival in the long term period.

Objective of the study. prove the effectiveness of brief psychological intervention (BPI) conducted by an internist in achieving and maintaining abstinence in patients with alcoholic liver disease (ALD).

Materials and methods. A total of 65 patients were included in the study: 29 patients in the BPI group and 36 in the historical control group. A comparative analysis of the frequency of achievement and maintenance of abstinence and analysis of factors associated with these parameters were conducted.

Results of the study. The frequency of achieving abstinence was significantly higher in the BPI group compared with the control group after 6, 9, 12 and 24 months from the date of inclusion in the study (p <0.001, p = 0.002, p = 0.001, p = 0.017, respectively; criterion χ2). The frequency of failures to achieve abstinence in the CPC group was significantly lower than in the control group after 6 months and in general for the entire observation period (p = 0.004, p = 0.005, respectively; criterion χ2). Provision of BPIs for 12 months after alcohol-induced decompensation serves as a factor that is reliably associated with achieving total abstinence within 24 months (p = 0.001, criterion χ2). Decompensated cirrhosis of the liver serves as factors independently associated with failures to achieve abstinence within 24 months after alcohol-induced illness (OS: 10.72 [95% CI 2.17–52.81]; p = 0.004) and the absence of BPI after discharge from the hospital (OSH BPI: 0.80 [95% CI 0.14–0.479]; p = 0.006)

Conclusion. BPIs provided by an internist to the patients with ABD for 12 months after alcohol-induced decompensation leads to a higher rate of achieving total abstinence and decrease in the frequency of failures to achieve abstinence within 24 months after discharge from the hospital.

The article discusses the potential opportunities for impact of antidiabetic drugs from the group of glucagon-like peptide-1 (GLP- 1) receptor agonists on the risks of development and progression of cardiovascular complications in patients with type 2 diabetes mellitus (T2DM) and their possible role in increasing the patients’ expectancy and quality of life. The existing differences between the drugs of this class should be taken into account in using personalized approach to therapy, developing and introducing new guidelines for specialized medical care for patients with type 2 diabetes into clinical practice. The article presented data on the efficacy and safety of the use of GLP-1 receptor agonists and discusses data on the possible mechanisms of non-glycemic effects underlying their cardio and nephroprotection. The features of pharmacological characteristics affecting the clinical efficacy and development of side effects are considered. The article also provides data from randomized clinical trials of various GLP-1 receptor agonists that demonstrate the positive effect of drugs of this class on cardiovascular and nephrological outcomes in patients with type 2 diabetes.

The continuing difficulty of treatment of acromegaly depends on: late diagnosis of the disease, the multiplicity of pathological variants of GH-secreting adenomas, the presence of complicated forms of the disease, and the lack of differentiated approach when choosing a treatment strategy. At the present time, when there are many divergent therapeutic tools to achieve the target values depending on the specific structure of the pathological tumor tissue, the main problem lies in the establishment of adequate algorithms to ensure prompt achievement and maintenance of biochemical remission. Due to the improvement of surgical aids medical therapy for acromegaly is generally used as a second line treatment, assignable at continuing disease activity after non-radical adenomectomy.). With the introduction of prolongated analogs of somatostatin, mostly affecting the 2nd (octreotide, lanreotide), or 5th (pasireotide) subtypes of the somatostatin receptors, selective dopamine agonists (cabergoline), and growth hormone receptor antagonist (pegvisomant) into wide clinical practice patients received a great opportunity to achieve a stable biochemical control of acromegaly regardless of secretory activity and receptor phenotype of the tumor tissue. The present paper reveals the mechanisms of action and the characteristics of the most common pharmacological agents, as well as the indications for their use in the combined treatment of acromegaly. It discusses the topic of therapeutic benefit with resistance to somatostatin analogues of the 1st generation. The results of a multicenter randomized clinical trials on the effectiveness and safety of somatostatin analogs, as well as current international recommendations of optimal schemes of therapeutic benefit in acromegaly are also presented here. It stressed the need for a differentiated approach to the treatment based on the clinical and pathological features of somatotropinoms and the individual sensitivity of patients to drugs used.

Hypothyroidism is the most common endocrine disease after diabetes mellitus. Its frequency depends on age, sex and iodine intake. The highest prevalence of hypothyroidism is observed in older women. Chronic autoimmune thyroiditis is the most common cause of this condition. The peculiarity of hypothyroidism is an erased clinical picture, diversity and nonspecific symptoms. This makes it difficult to diagnose the disease, leads to an erroneous diagnosis and later detection of thyroid insufficiency. This article discusses the various «masks» of hypothyroidism and peculiarities of clinical manifestations. The main «masks» are: cardiological, dermatological, urological, gastroenterological, endocrine and reproductive system disorders, neurological, psychiatric, hematological, rheumatological. Free thyroxine and thyroid-stimulating hormone are used to diagnose hypothyroidism, as well as antibody titer to thyroid peroxidase and thyroglobulin to detect chronic autoimmune thyroiditis. Levothyroxine preparations are used as a substitution therapy. The dose of the drug depends on the age of the patient and the presence of cardiovascular disease. Patients under 50 years of age without a severe concomitant cardiovascular disease are given 1.6 µg of levothyroxine per kg of body weight. In persons over 50 years of age with cardiovascular diseases, the drug dose is prescribed at the rate of 0.9 µg per kg of body weight. The therapy starts with small doses, slowly increasing it under the control of electrocardiography. At occurrence or strengthening of symptoms of angina a dose of levothyroxine is reduced to the previous one and the cardiovascular therapy is corrected. Evaluation of the effectiveness of the treatment is carried out on the level of thyroid hormone.

For many years, interest in the issue of obesity has not faded, as obesity is now one of the most common pathologies in the world that directly affects quality of life and lifespan. Even a slight weight loss (5-10% of baseline values) in obese patients is known to improve metabolism and reduce the risk of a range of comorbidities. The article reflects the importance of comprehensive treatment of obesity, presents positive experience of using Reduxin (sibutramine in combination with microcrystalline cellulose) to reduce body weight and risk factors for cardiovascular disease in a specific clinical example in a patient with exogenous-constitutional obesity and eating disorders. The case of obesity in a young man of 24 years old is presented, when other components of the metabolic syndrome (except for arterial hypertension) were not formed. Thus, following the results of 24-week complex treatment, clinically significant reduction of body weight (by 21.7% of initial values) was observed in the patient. The data of psychological researches have shown that the patient has no increase of anxiety and depression level during treatment, but at the same time the indicators of quality of life according to the results of health questionnaire testing have improved. This clinical case corresponds to the results of the PrimaVera program and demonstrates that weight loss during sibutramine therapy in combination with microcrystalline cellulose has a positive impact on the overall health and emotional status of patients and leads to improved quality of life. Therefore, successful treatment of obesity and the maintenance of other outcomes are key to preventing cardiovascular disease.

The article presents the experience of using sodium phosphate in patients, who were treated at the Clinic of Hospital Surgery of the Samara State Medical University Clinics in 2019.

Purpose of the study: evaluate the quality of patient preparation for colonoscopy with sodium phosphate in surgical hospital environment. Material and methods. A total of 50 patients who were admitted for emergency indications to the Clinic of Hospital Surgery in 2019 were enrolled in the study. All patients were divided into two groups.

The study included patients aged 24 to 69 years. The median age was 55.1 years in the treatment group and 56.2 years in the control group (p = 0.06). Men predominated in both groups: 16 (64%) in group 1 and 18 (72%) in group 2 (p = 0.08). The average time for submitting complaints about intestinal bleeding before seeking medical aid was 1.0 ± 0.70 days in the treatment group and 1.0 ± 0.35 days in the control group (p = 0.92). Group 1 included 25 patients, who were preparing for colonoscopy with sodium phosphate, Group 2 included 25 patients who were preparing for the examination with Macrogol.

Results: the preparation quality was evaluated using the Boston Bowel Preparation Scale. Initially, the treatment and control groups did not have any statistically significant differences in all studied parameters. The colonoscopy identified the following nosologies. In Group 1, 9 patients had a diverticular disease of the colon; 4 – colon cancer; 12 patients continued treatment of grade 2–3 chronic internal hemorrhoids. In Group 2, the patients were distributed as follows: 10 patients were diagnosed with diverticular disease of the colon; 4 – colon cancer; 1 – an adenomatous polyp of the transverse colon and 10 patients had grade 2–3 chronic internal hemorrhoids. In addition, all patients filled out the questionnaire, which showed that the use of sodium phosphate is more convenient for the patient not only in terms of the dosage, but also due to relatively pleasant organoleptic properties. After examination of the colon, 45 patients received conservative treatment, five were operated following the colonoscopy and preoperative preparation.

Conclusion: we believe that the quality of preparation of patients with intestinal bleeding with sodium sulphate and Macrogol does not differ, however, sodium sulfate is preferable because of its more pleasant organoleptic properties and the smaller volume of solution used.

The use of magnetic resonance imaging (MRI) for osteoarthritis made it possible to simultaneously detail the state of cartilage, subchondral bone, menisci, ligaments, and synovial membrane. In some studies, a correlation was found between bone marrow edema (BME) and the intensity of the pain syndrome, the progression of OA and the risk of total knee replacement. In other studies, these data were not confirmed. It has been suggested that BME in OA, leading to debilitating pain, is not associated with trauma and is determined by an increase in extracellular fluid. Analysis of MRI images of 80 patients with 1-3 stages of knee osteoarthritis revealed a statistically significant relationship between the presence of bone marrow edema and the thickness of the cartilage of the femur and tibia, rupture and degradation of the medial menisci, the presence of Baker cysts and thickening of the synovial membrane. No reliable relationship was found with the presence and severity of synovitis. A review of data on the effect of various methods of conservative therapy on bone marrow edema in osteoarthritis is presented. The effect of anti-osteoporotic drugs, prostacyclin, Pentosan polysulfate sodium chondroitin sulfate is considered. Thus, OKM is of interest both in terms of the pathogenesis of OA and as an indicator of the effectiveness of the treatment of OA. Our data demonstrate a high incidence of OKM in the late stages of OA. The effect of pharmacological therapies on OKM requires further study.

Influenza is a common respiratory infection caused by viruses of types A, B and C. Characteristic of influenza infection is the development of intoxication and damage to the epithelium of the mucous membrane of the upper respiratory tract, often the trachea. Complications of influenza occur in 10–15% of patients. Most often it is pneumonia, bacterial focal infections (sinusitis, otitis, urinary and biliary tract infections), activation of chronic infections (tuberculosis, rheumatism). In influenza infection, as in the treatment of any infectious disease, the greatest importance belongs to etiotropic therapy. The world health organization recommends the use of neuraminidase inhibitors for etiotropic treatment of influenza. Currently, 2 neuraminidase inhibitors are used in the Russian Federation - oseltamivir and zanamivir. Both of these drugs are included in the clinical guidelines approved by the Ministry of health of Russia. In the Russian pharmaceutical market, oseltamivir is represented including the domestic drug Nomides in several dosages of 75 mg, 45 mg, 30 mg, which allows it to be used in children from 3 years. Etiotropic drugs should be prescribed as early as possible from the moment of clinical manifestation of the disease, optimally - in the first 48 hours from the onset of the disease, without waiting for laboratory verification of the diagnosis. The advantages of etiotropic therapy are reducing the risk of complications, shortening the period of fever and other symptoms. It is equally important to reduce the incidence of secondary complications requiring antibiotics and hospitalizations due to influenza. Etiotropic drugs for influenza therapy, including nomides, are used to prevent influenza infection. It should be noted that chemoprophylaxis does not replace vaccination against influenza, but is an auxiliary method of preventing the disease.

Sepsis is a systemic pathological reaction that arise because of a severe infection. Now, sepsis is considered as one of the most serious diseases and materially expensive nosology’s. For instance, out of 100% of cases of sepsis, only 40% survive. Thus, there is a high mortality rate and a wide prevalence (up to 300 thousand patients with sepsis are registered in Europe), which makes it possible to identify serious problems and the need to improve the clinical approach to the management strategy and tactics of such patients. The number of cases of detection and registration of sepsis has been expanding expansively since the thirties of the last century, and continues to grow dynamically, which obviously requires an improvement in the pathognomonic approach to therapy. The main reasons for the growth of septic conditions are the increasing use of invasive methods in medical practice, the pandemic of diabetes mellitus, the use of cytostatic and immunosuppressants, as well as the increasing number of antibiotic-resistant strains of pathogenic and conditionally pathogenic bacteria, total disruption of mucosal microbiocenoses, unreasonable use of probiotics with production strains containing foci of pathogenicity in patients with primary or secondary immunodeficiencies. Now, the main etiopathogenetic therapy of sepsis remains drugs aimed at the destruction of pathogenic microorganisms. However, based on the pathogenesis of the septic state, it seems effective to search for drugs with new points of application to individual pathogenesis links of the systemic inflammatory response. Today, studies aimed at establishing the effectiveness of influence on any individual links in the pathogenesis of sepsis - inflammatory mediators, have not yet yielded clear results.

Extrahepatic manifestations occur in more than half of patients with chronic hepatitis C virus infection and may be no less dangerous to the health and life of the patient than the isolated pathology of the liver. Chronic hepatitis C virus infection is often accompanied by the formation of neurocognitive disorders, clinically manifested by general weakness, fatigue and the inability to maindoi tain concentration for a long time. Every fifth patient with chronic hepatitis C develops depression. The development of type 2 diabetes among patients with chronic hepatitis C virus infection is observed 1.7 times more often than among non-infected individuals. Mixed cryoglobulinemia is observed in at least 30% of patients, however, the clinical manifestations of this pathology develop only in 4.9% of cases, of which 69–89% of skin lesions, 19–44% of distal sensory and sensorimotor polyneuropathy, 30% of membranoproliferative glomerulonephritis, 28% of joint damage. Among patients with chronic hepatitis C virus infection, higher prevalence than among non-infected individuals is observed, the prevalence rates of such nosologies as lymphoma from cells of the marginal zone are 2.47 times, diffuse large cell B cell lymphoma – 2.24 times, hypothyroidism – 3.1 time. Significantly more rarely encountered extrahepatic manifestations of chronic hepatitis C virus infection are skin lesions that are not associated with the development of cryoglobulinemic vasculitis: acquired late skin porphyria, necrolytic acral erythema and lichen planus. The question of the pathogenetic relationship of chronic hepatitis C virus infection with cardiovascular pathology remains open.

Introduction. Adenomyosis has a significantly negative impact on women’s quality of life, causing abnormal uterine bleeding, dysmenorrhea, and chronic pelvic pain and low quality of life. There are no single theory of pathogenesis, unique prognosis and diagnostic markers for adenomyosis. The definitive treatment for adenomyosis is hysterectomy but is not appropriate for patients who wish to preserve their fertility. In this article presents data about etiology, classification, pathogenesis, clinical manifestation and surgical techniques for the treatment of adenomyosis published in medical–scientific databases.

Materials and methods. The review includes data from foreign and Russian articles published in the Pubmed journals on this topic.

Results. There are a lot of surgical approaches for adenomyosis; however, there is no any universal approach and management guideline for these patients.

Conclusion. Adenomyosis – if multifactorial disease. There is no single pathogenesis theory. The clinical picture of adenomyosis varies from asymptomatic to severe pain. The management of adenomyosis is complex and should guide personally for each patient. All techniques and options should be considered and discussed with the patient.

The article dedicates to the study of microelements in the blood serum of women of reproductive age, with newly diagnosed hypothyroidism (subclinical and manifest), living in disadvantaged areas of the Aral Sea region. This article presents the study of 1154 women. Every fourth woman (25%) has an essential deficiency of such microelements like iodine, selenium, iron, zinc independently of thyroid function. Our study discovered negative associations of TSH concentration with essential microelements like manganese, copper, selenium, and positiveassociation with iodine. We also obtain positive relationships between AT-TPO and zinc and iodine. The relationship of zinc with AT – TPO level and thyroid status, especially in the regions with sufficient ioduria among residents,require further researchto study it’spossible effecton thyroid dysfunctions. We established positive associations of free T4 with essential microelements like manganese, iron, and negative association with iodine. Estimation of thyroid status and toxic microelementsrevealed positive association of free T4 with cadmium, nickel, and lead, and negativewith mercury.

The article presents the results of a study of the effect of vitamin D deficiency on women’s health.

The study aimed to determine the prevalence of vitamin D deficiency and its relationship with the somatic and reproductive health of women.

Methods: observation group I included 31 women with a reduced serum vitamin D levels (20.4 ± 1.0 ng/ml), comparison group II included 31 patients with normal vitamin D levels (39.0 ± 1.4 ng/ml). Results: the negative effect of vitamin D deficiency on women’s health is also practically assured, i.e. the incidence of somatic pathology is significantly higher in group I compared with group II: obesity (62.5 ± 12.1% and 18.8 ± 9.8%; p <0.5), insulin resistance (55.0 ± 9.0% and 1.0 ± 6.0%; p <0.001); arterial hypertension (42.0 ± 8.8% and 13.0 ± 6.0%; p <0.01); hypertrophic myocardiopathy (25.8 ± 7.8% and 6.4 ± 4.4%; p <0.05); chronic colitis (29.0 ± 8.1% and 6.4 ± 4.4%; p <0.05), gastric ulcer (22.5 ± 7.5% and 3.2 ± 3.2%; p <0.05), chronic pancreatitis (22.5 ± 7.5% and 3.2 ± 3.2%; p <0.05), chronic gastritis (25.8 ± 7.8% and 9.7 ± 5.3%; p <0.1). The interaction between reduced vitamin D levels and reproductive system diseases is confirmed by significant increase in the prevalence of secondary amenorrhea (80.0 ± 9.0% and 16.0 ± 7.3%; p <0.001), secondary oligomenorrhea (75.0 ± 9.7% and 20.0 ± 8.0%; p <0.001), hyperplastic processes – uterine fibroids (48.4 ± 9.0% and 13.3 ± 6.1%; p <0.001) and adenomyosis (26.6 ± 7.9% and 6.7 ± 4.5%; p <0.05), polycystic ovary syndrome (29.0 ± 8.2% and 6.7 ± 4.5%; p <0.05), vaginal microbiocenosis disorders (aerobic vaginitis – 42.0 ± 8.9% and 16.1 ± 6.6%; p <0.05; bacterial vaginosis – 29.0 ± 8.2% and 9.7 ± 5.3%; p <0.05).

Conclusion: management of vitamin D level is one of the priorities in the formation of therapeutic and preventive measures to improve the women’s health.

Background. The development of fetal death among pregnant women with cholestasis pregnancy (CP) is possible.

Aim. The purposeи is to determine the interconnection between clinico-anamnestic and laboratory indicators of pregnant women with CP and fetal death.

Patients and methods. 211 pregnant women were examined. The main group – 144 (68%) women with CP, control

group – 67 (32%) patients without symptoms of this disease. There are 2 subgroups depending on the presence or absence of fetal death among pregnant women with CP. A complex of standard clinical and diagnostic studies was performed, including obstetric ultrasound and cardiotocography. Results. In the group of patients with CP, postpartum hemorrhages (p<0.05), intrauterine fetal hypoxia (p<0.001) were significantly more frequent, fetal death was noted only in the main group (2.1%). In both subgroups miscarriages were more common in the history (p = 0.019). Most women with CHP had diseases of the hepatobiliary system, gestational hypertension and kidney disease (p<0.05). In the subgroup with fetal death arterial hypertension existed significantly more frequent before pregnancy (p<0.05). The itchy skin was extremely permanent among patients with CP and fetal death. The subgroup with fetal death significantly differed from the control group for hyperfermentemia both during pregnancy (alanine transaminase (ALT) – p<0.001, aspartate transaminase (AST) – p = 0.001, alkaline phosphatase (APH) – p = 0.001), and after delivery (ALT –p = 0.002, AST – p = 0.033, APH – p = 0.006).

Conclusions. Women with CP, with a miscarriage in anamnesis or hypertension are in a risk group of fetal death. A more frequent study of the fetal condition is needed among patients with persistent itching at CP.