Introduction. Type 2 diabetes (T2D) increases the risk of developing cardiovascular diseases, which leads to a high mortality in this category of patients. Issues regarding the prevention of the onset and progression of coronary heart disease (CHD) and chronic heart failure (CHF) in patients with T2D and/or metabolic syndrome (MS) are still not fully understood. The use of metabolic drugs with cardioprotective effects, in particular Mildronate®, is one of the possibilities to improve the effectiveness of combination treatment of CHD and CHF. Aim. To study the effect of Mildronate® on the quality of life (QoL) of patients with CHD and CHF, suffering from T2D and/or MS. Materials and methods. A total of 2.084 patients with co-occurring two (or more) disorders: obesity, type 2 diabetes, angina pectoris, CHT, and CHF were included in the INDICOR observational study conducted in real-life clinical practice settings. Group 1 received therapy with disease-modifying agents prescribed due to CHD and T2D; Group 2 received Mildronate® at a dose of 1000 mg per day in addition to the same therapy. The studied lab test results were assessed at baseline and 42 days of therapy. Results. A 42-day course of therapy in patients receiving Mildronate® at a dose of 1000 mg per day in addition to disease-modifying therapy (DMT) contributed to a percentage increase in the number of patients with CHD, FC (functional class) I angina pectoris (Δ,% + 63%, p < 0.001 ) as compared to the control group with no significant changes (Δ,% + 7%, p > 0.5). A significant increase in the number of patients with FC I CHF was recorded in Group 2 (from 23.5 to 42.1%, Δ,% + 79%) as compared to Group 1, where no significant changes were detected (22.7 to 23.7%, Δ,% + 4%). The QoL in patients with CHF based on data collected using the Minnesota Questionnaire and QoL in patients with CHD based on data collected using the Seattle Questionnaire significantly improved in the groups that received Mildronate® in addition to DMT, as compared with the group of patients who were only on DMT. Conclusion. Results from the Seattle and Minnesota questionnaires showed that the use of Mildronate® as part of combination therapy in patients with CHD and CHF, suffering from T2D and/or MS, contributed to a significant reduction in the frequency of angina attacks and lowering angina FC, CHF FC, and also enhanced the quality of life in this category of patients.

The number of patients with chronic liver disease (CLD) is steadily increasing. According to the 2023 update published by the European Association for the Study of the Liver, liver diseases account for two million deaths annually and account for 4% of all deaths (1 in every 25 deaths worldwide). This review emphasizes the need for early detection and control of these diseases course, as a factor that improves the patient's prognosis. It is proposed to use a new scale of the CLivD indicator (Chronic Liver Disease indicator), based on the assessment of risk factors widely available in physician practice, to predict the risk of developing progressive liver disease in the general population.

To date, nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver pathology and already at the stage of steatosis causes a high risk of developing cardiovascular diseases (CVD). Convincing evidence has been obtained that CVD is the most common cause of death in patients with NAFLD. Common risk factors (insulin resistance, abdominal obesity, dyslipidemia, hyperuricemia, chronic kidney disease and type 2 diabetes mellitus) and similar pathophysiological mechanisms (endothelial dysfunction, changes in lipid metabolism, systemic inflammation, plaque formation/instability, oxidative stress) of NAFLD and CVD, allow us to consider NAFLD not only as a key risk factor for the development of CVD, but also as a co-factor in the progression of cardiac pathology. The progression of NAFLD itself leads to a more severe course of CVD.

The gut microbiota regulates critical processes in host metabolism and physiology. Understanding the formation of relationships between the gut microbiome, liver, and other organs under physiological conditions, as well as under the influence of microbiota-damaging factors, provides important insights into the pathophysiology of not only liver diseases, but also the complex level of communication and the role of the microbiome in the gut-liver-brain, gut-liver-kidney, gut-liver-lung, and gut-liver-heart axes.

Post-Covid syndrome (PCS) is considered as a consequence of a previous coronavirus infection. The liver in COVID-19 is one of the most frequently affected organs, with the development of asthenia, cognitive impairment, as well as increased activity of alanine and aspartic transaminases (ALT and AST), which persist in some patients up to 4-6 months after discharge from the hospital. The cause of asthenia may be hyperammonemia (HA), which in COVID-19 is a manifestation of liver dysfunction against the background of the direct cytotoxic effect of SARS-CoV-2 on hepatocytes, which was previously shown as part of the clinical observational program protocol “LIRA - COVID”. Due to the great relevance of the problem of the combination of PCS, non-alcoholic fatty liver disease (NAFLD) and HA a post-hoc analysis of the observational clinical program LIRA - COVID was carried out. It was shown that NAFLD has a significant effect on the level of AST before the start of treatment with L-ornithine - L-aspartate (LOLA). The presence of NAFLD has a significant effect on ammonia levels after 14 days of treatment, since in the group of patients with NAFLD the ammonia level was significantly higher than in the group without NAFLD. It was concluded that it is advisable to include in the examination scheme of patients with PCS and NAFLD, determination of the level of ammonia in the blood, when elevated, the administration of the drug to such patients is justified LOLA course for 4 weeks at a standard dose of 9 g per day.

Syndrome of increased epithelial permeability (SPEP) is considered as one of the universal mechanisms that determine the subsequent development of chronic systemic inflammation of varying severity. Studies carried out in the last 10 years have shown the important role of SPEP in the pathogenesis of many diseases of internal organs, and, first of all, of the gastrointestinal diseases. The article discusses possible ways of correcting impaired epithelial permeability from the point of view of the cytoprotective effects of drugs most often prescribed to patients with gastrontestinal diseases.

Epidemiological data suggests that approximately 10-65% of patients with mild to moderate COVID-19 have persistent symptoms already after an acute infection, which may last for six months or more. Previous clinical studies have shown that similar symptoms may also occur in the liver. Russian scientists have studied the phenomenon of hyperammonemia in the acute phase of COVID-19, but the problem of elevated blood ammonia levels in post - COVID syndrome has not been studied before. One possible option for the correction of hyperammonemia is the L-ornithine - L-aspartate (LOLA) preparation. The aim of the study was to investigate the manifestation of hyperammonemia in post - COVID syndrome and the possibility of its correction by using LOLA. Eighty-three patients (mean age 51.71 ± 12.82) with post-COVID syndrome, attention and memory impairment, chronic fatigue, hyperammonemia, 2-fold increase of alanine transaminase (ALT) and aspartate transaminase (AST) levels were included into multicenter, prospective observational study. L-ornithine-L-aspartate (LOLA) was given (3 g 3 times per day orally) for 4 weeks to correct hyperammonemia. Patients were accessed by the number connection test (NCT), fatigue evaluation test, measurement of ammonia and ALT, AST levels at baseline, and after 4 weeks. At week 4 the ammonia level was significantly decreased in 81 patients (97.6%). Time (sec) to complete the NCT was 49,43 ± 15,85 vs 64.67 ± 24.95 at baseline (p<0.001). Before treatment, the majority of patients had stage 1 hepatic encephalopathy (HE) - 50.6% and stage 1-2 (intermediate) HE - 30.1%, stage 2 HE - 10.9%, stage 3 HE - 2.4%. After LOLA treatment, the distribution changed: 41% of patients had no HE, 36.1% had stage 1 of HE, 22.9% had stage 1-2 (intermediate) of HE, and stage 2 and 3 of HE was no longer defined. The mean score in fatigue evaluation test was 46,27 ± 10.0 vs 64,71 ± 19,18 at baseline (p<0.001). ALT and AST levels were 47,83 ± 38,21 units/l vs 95,75 ± 68.99 units/l at baseline and 40,10 ± 35,97 units/l vs 78,51 ± 90,90 units/l at baseline respectively (p<0.001). This study showed that the inclusion of LOLA in a dose of 3 g 3 times a day for 4 weeks was associated with significant improvement in the objective and subjective outcomes in patients with post-COVID syndrome.

Aim: to study the immunological characteristics of patients with H. pylori-unassociated chronic gastritis with its comorbidity with allergic rhinitis.Materials and methods. The study included patients aged 18 to 40 years: 47 healthy individuals (comparison group) and 140 people, of which 66 people had chronic gastritis, 43 people had seasonal allergic rhinitis in remission, 31 people had a combination of both. Conducted a clinical examination, determination of serum concentrations of IL-4, IL-5, IL-6, IL-8, IL-10, IL-18, MCP-1, total IgE, detection of IgG to the nuclear antigen of the Epstein-Barr virus.Results: During the study, we showed that H. pylori-non-associated chronic gastritis is characterized by a decrease in the level of monocyte-macrophage cytokines (IL-6 and IL-18, but not IL-8), but an increase in the production of Th2-dependent cytokines (IL-5 and IL-4), as well as total Ig E. In addition, H. pylori-non-associated chronic gastritis in patients without allergic rhinitis is associated with an increased frequency of detection of IgG to the nuclear antigen of the Epstein-Barr virus in blood serum (80.0% vs 48–55% of cases in other groups, p<0, 05).Conclusion. Thus, H. pylori-non-associated chronic gastritis is a multidisciplinary problem, which, from an immunopathogenetic point of view, is characterized by a Th2-phenotype of the immune response in such patients, including in the absence of allergic pathology, which determines the need for a wider involvement of data in the examination. patients of specialists of other profiles (allergists, infectious disease specialists, etc.).

Non-alcoholic fatty liver disease (NAFLD) and hyperuricemia (HU) are currently considered by many authors as a manifestation of the metabolic syndrome (MS) and associated with insulin resistance (IR), increased body mass index (BMI), type 2 diabetes mellitus (DM2), cardiovascular disease (CVD). The latest data of numerous studies prove that HU is a significant risk factor for the development of not only obesity, DM2, CVD, but also NAFLD.

OBJECTIVE:Evaluation of the antiasthenic effect of sequential therapy with levocarnitine (LC) and acetylcarnitine (ALC) in patients with arterial hypertension and/or ischemic heart disease (CHD) with asthenic syndrome (AS).MATERIAL AND METHODS:An open comparative study included 120 patients aged 54-67 years in patients with arterial hypertension and/or coronary artery disease with AS. Patients of group1 (n=60), in addition to basic therapy for the underlying disease, received LC (Elcar solution for intravenous and intramuscular injection of 100 mg/ml, the company PIQ-PHARMA) intravenously for 10 days at a dose of 1000 mg/day, followed by a transition to oral administration of ALC (Carnicetine, the company PIQ-PHARMA) 500 mg (2 capsules) 2 times a day for 2 months. Group2 patients (n=60) received only basic therapy for major diseases. The duration of observation was 70 days. The severity of AS was assessed using the MFI-20 questionnaire (MultidiMensional Fatigue Inventory) and the visual analog scale VAS-A (Visual Analog Scale Measuring fatigue).RESULTS:In patients of group1, a statistically significant decrease in various manifestations of AS was noted. The differences were significant both in comparison with the baseline level and in comparison with the 2nd group. The endothelium-protective effect of LC and ALC has been established.CONCLUSION:The results obtained indicate that in such comorbid patients, the use of LC and ALC reduces the severity of AS manifestations, and the established endotheliotropic properties of the drugs allow them to be recommended as part of the complex personalized therapy of patients with cardiovascular diseases.

Introduction. Patients with chronic heart failure (CHF) and chronic obstructive pulmonary disease (COPD) are increasingly found in the clinical practice. The comorbidity of CHF and COPD promotes high mortality in such patients. Therapy that is prescribed to patients with CHF and COPD may not always have a positive effect on the condition of blood vessels. In this regard, researchers began to pay attention to drugs that have a beneficial effect on blood vessels, without worsening the course of CHF and COPD, one of which is meldonium.The purpose of the study. To study the effect of meldonium as part of complex therapy on arterial stiffness and microcirculation in patients with CHF and COPD.Materials and methods. The open randomized study included 60 patients with CHF IIA stage, II–III functional class (clinical recommendations of RKO, OSSN 2020) and COPD of the I–III degree of airflow restriction (classification GОLD 2021) without exacerbation. The patients were divided into 2 groups: the 1st group – the main group (n = 30) with CHF and COPD, which was prescribed meldonium as part of complex therapy at a dosage of 1000 mg/day, the 2nd group – the control group (n = 30) was on therapy only with basic drugs of CHF and COPD. The observation period is 12 weeks.Results. As a result of 12 weeks of therapy with the inclusion of meldonium in the complex therapy of patients with CHF and COPD, a decrease in the stiffness of the main arteries, an improvement in the regulation and parameters of microcirculation, an increase in the frequency of occurrence of the normocirculatory type of microcirculation were noted.Conclusions. A significant useful effect of complex therapy with the inclusion of meldonium on the condition of arterial stiffness and microcirculation in patients with CHF and COPD has been established, which makes it possible to recommend the use of meldonium in this category of patients.

Purpose: to evaluate the efficacy and safety of the use of rebamipide (Rebamipide-SZ, Severnaya Zvezda NAO) during 8-week therapy in patients with functional dyspepsia (FD) and/or irritable bowel syndrome (IBS). Materials and methods: 60 patients of both sexes aged 18 to 40 years with confirmed FD and/or IBS were examined. All patients received basic therapy for functional gastrointestinal disease. Patients of the main group were additionally prescribed rebamipide 100 mg 3 times a day. All patients were tested according to the 7x7 questionnaire to assess the severity of FD and IBS symptoms; the severity of anxiety and depression symptoms was assessed according to the Hospital Anxiety and Depression Scale (HADS); the level of zonulin in blood was determined by the ELISA method at baseline and after 8 weeks of therapy. Results: in the main group of patients, taking rebamipide led to a more pronounced decrease in the average score on the scales of the 7x7 questionnaire, such as feeling full (0 [0; 0] points vs 1 [1; 1] points, p=0.000), early satiety (0 [0; 0] points vs 0.5 [0; 1] points, p=0.005), bloating (0 [0; 2] points vs 2 [2; 2] points, p=0.001). Only patients of the main group showed a significant decrease in blood zonulin levels both in the FD subgroup (Δ%= -49%) and in the FD+IBS subgroup (Δ%= -20.85%). Conclusions: the use of rebamipide at the dose of 100 mg 3 times a day for 8 weeks as part of the basic therapy of patients with functional dyspepsia and/ord irritable bowel syndrome leads to a statistically significant improvement in the clinical condition of patients and a significant decrease in the level of zonulin in blood serum.

Introduction. The number of patients with chronic heart failure (CHF) and chronic obstructive pulmonary disease (COPD) is increasing every year. In both CHF and COPD, secondary mitochondrial dysfunction is observed. In this regard, the attention of researchers is attracted by drugs that have their therapeutic effects at the level of mitochondria, one of which is meldonium. Meldonium has proven itself in the treatment of various diseases, however, the evaluation of the clinical efficacy of meldonium has not yet been carried out in comorbid patients with CHF and COPD.Aim. To study the effects of meldonium as part of basic therapy on the clinical condition, the main functional parameters of the heart and lungs, and the quality of life in patients with CHF and COPD.Materials and methods. The randomized open study included 60 patients with CHF II A stage, II–III FC (clinical recommendations of the RSC, OSSN 2020) and COPD I–III degree of airflow limitation (GOLD 2021 classification) in remission (age 45–70 years). The patients were divided into 2 groups: the 1st group – the main group (n = 30) with CHF and COPD took meldonium at a dosage of 1000 mg/day in addition to the basic therapy, the 2nd group – the control group (n = 30) was only on basic therapy for CHF and COPD. The observation period is 12 weeks.Results. In patients with CHF and COPD, in the dynamics of therapy with the inclusion of meldonium, as a result, the severity of clinical symptoms decreased, improvement was revealed in the main structural and functional parameters of the heart, external respiration function, and quality of life.Conclusions: a significant beneficial effect of combination therapy with the inclusion of meldonium on the clinical and functional parameters of the heart and lungs, indicators of quality of life in patients with CHF and COPD has been established, which makes it possible to recommend the use of meldonium as part of combination therapy in comorbid patients.

The review represents evaluation of the ectopic fatty depots effect on the development of cardiovascular diseases (CVD) in patients with nonalcoholic fatty liver disease (NAFLD). Nowadays, NAFLD is the most common cause of chronic liver disease in most countries of the world. A number of studies have confirmed the important role of NAFLD in the formation and progression of CVD, which is manifested by an increased risk of cardiovascular events in patients with NAFLD according to Framingham Risk Score. The statement that NAFLD should be recognized as an independent risk factor for CVD, in addition to other metabolic disorders, is often confirmed. One of the possible mechanisms of interrelation between NAFLD and CVD is the paracrine activity of visceral adipose tissue; the possibility of local effects of various ectopic depots of visceral fat is being discussed. There is no doubt that epicardial adipose tissue plays an important role in the formation of the hepato-cardiac continuum. Тhere are more and more studies evaluating the effect of other ectopic depots on the development of CVD in patients with NAFLD. The article provides an analysis of publications devoted to the interrelation between fatty ectopic depots and CVD risks in patients with NAFLD. MedLine and PubMed databases in English and Russian languages were used for the search. The review includes articles published from 2000 to 2020.

The article reviews the efficacy of meldonium in patients with various diseases, which are based on secondary mitochondrial dysfunction. Mitochondria are complex cellular organelles that control many metabolic processes, including fatty acid oxidation, the Krebs cycle, oxidative phosphorylation in the electron transport chain, and many other processes. Many conditions can lead to secondary mitochondrial dysfunction and affect other diseases. Damage to mitochondria can promote the activation of free radical processes and the initiation of the mechanisms of programmed cell death, mitochondrial dysfunction decrease in the immune response, increase in the activity of the body’s inflammatory response in various infections. Mitochondria appear to be important in COVID-19 pathogenesis because of its role in innate antiviral immunity, as well as inflammation. The article presents data on the effectiveness of using meldonium as a drug that helps to arrest pathological processes in mitochondria. The main mechanism of action of meldonium is based on a decrease in L-carnitine levels and increase of peroxisomes activity in the cytosol Meldonium was designed as a inhibitor of carnitine biosynthesis aimed to prevent accumulation of cytotoxic intermediate products of fatty acid beta- oxidation in ischemic tissues and to block this highly oxygen- consuming process. It is based on the correction of the energy metabolism of the cell. There was a positive trend in the use of meldonium in patients with diseases of the cardiovascular system (chronic ischemic diseases, chronic heart failure, arterial hypertension, etc.), neurological disorders (stroke, cerebrovascular insufficiency, etc.), respiratory diseases. The data on the beneficial effect of meldonium on the immune response in patients with coronavirus, bronchial asthma, chronic obstructive pulmonary disease, during vaccination with anti-influenza serum are presented. A decrease in asthenia was noted against the background of the use of meldonium in patients who had undergone coronavirus infection.

Nonalcoholic fatty liver disease (NAFLD) is the most prevalent liver disease worldwide. It is characterized by hepatic steatosis and stetohepatitis and in some cases can progress to cirrhosis with or without hepatic failure and hepatocellular carcinoma. At present, NAFLD is deemed a predictor of cardiovascular risk. Besides, it can aggravate pre-existing cardiovascular conditions. Structural and functional changes in the heart, liver and blood vessels are interdependent and mutually aggravating. Metabolic factors (dyslipidemia, hyperglycemia and insulin resistance) contribute to hepatic, cardiac and vascular damage, and NAFLD and comorbid cardiovascular disorders together can activate fibrogenesis in the heart, blood vessels and liver.

OBJECTIVETo evaluate the effectiveness of sequential therapy with levocarnitine and acetylcarnitine in patients with cardiovascular pathology (arterial hypertension and/or coronary heart disease) and moderate cognitive deficits.MATERIAL AND METHODSThe study included 120 patients aged 54-67 years. The main group of patients (n=60) in addition to the basic treatment of the underlying disease received l-carnitine (Elkar solution for intravenous and intramuscular injection of 100 mg/ml, the company «PIK-FARMA»)/jet during 10 days in a dose of 1000 mg/day, with following transition to oral administration of acetyl-l-carnitine (Carnitin, the company «PIK-FARMA»), 500 mg (2 cap Sula) 2 times a day for 2 months. The comparison group (n=60) received basic therapy for major diseases. The total duration of follow-up was 70 days.RESULTSThe results obtained indicate that in such comorbid patients, the use of levocarnitine and acetylcarnitine reduces the severity of cognitive deficits. An important aspect of their pathogenetic effect on the severity of cognitive deficits may be the possibility of correcting endothelial dysfunction. The use of levocarnitine and acetylcarnitine in patients with cardiovascular pathology has demonstrated good tolerability and safety.

Aim: to study the functional state of the kidneys in patients with chronic heart failure (CHF) and non-alcoholic fatty liver disease (NAFLD).Materials and methods. 144 patients with CHF aged 45-70 years were divided into two groups: group 1 — persons with CHF and NAFLD, group 2 — CHF without NAFLD. A clinical examination was performed, the indices of FLI steatosis and NFS liver fibrosis were calculated, the functional state of the kidneys and the adipokine status were evaluated.Results. The main group of patients with CHF and NAFLD is mainly represented by people with grade I obesity (73 (84%) vs 5 (9%), p<0.05). Among patients with CHF and NAFLD, a clinically significant decrease in GFR<60 ml/min/1.73 m2 was significantly more often detected compared to patients with CHF without NAFLD (37% vs 21% in groups 1 and 2, respectively). The level of albuminuria was significantly higher in the group of patients with CHF and NAFLD (200.7±22.3 [54.7;390] vs 92.6±23.4 [10.2;188.7] mg/g in groups 1 and 2, respectively). The percentage of individuals with an AU/CR. urine ratio >30 mg/g was statistically significantly higher in group 1 compared to group 2 (82.1 vs 51.1% in groups 1 and 2, respectively). The level of serum leptin was significantly higher and the concentration of serum adiponectin was significantly lower compared to group 2 in the main group of patients with CHF and NAFLD compared to the control group. There was a significantly higher occurrence of insulin resistance in patients with CHF and NAFLD. Correlation analysis revealed the presence of statistically significant associations between the parameters characterizing the functional state of the kidneys and the indices of FLI, NFD, adipokines, and the severity of insulin resistance.Conclusion. In patients with CHF and NAFLD, a significant deterioration in the functional state of the kidneys was found, in comparison with patients with “isolated” CHF with comparable FC.