Dyslipidemia makes a substantial contribution to the mortality as one of the leading pathogenetic factors for cardiovascular diseases. The nature and degree of the effect on the blood lipid spectrum may vary in the lipid-lowering drugs from different groups. Recently, a new class of PCSK9 inhibitors has been developed, which activity is associated with a protein involved in the low-density lipoprotein receptor control. In clinical practice, this group is represented by monoclonal antibody drugs evolocumab and alirocumab. The proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are promising drugs to be used in the combination lipid-lowering therapy, which, given the results of clinical trials, can be recommended at this point on a third-priority basis after statins and ezetimibe. However, it is vital to indicate that these drugs have a sufficient safety profile, which makes it possible to prescribe these drugs in a triple combination adding it to the two first-line drugs regimen which patients had been given before. It is obvious that further study of PCSK9 will expand the range of their use for the treatment of familial hypercholesterolemia up to indications in cases where statins are limited and a more pronounced lipid-lowering effect is required to achieve target cholesterol levels.

Introduction. Arterial hypertension (AH) is a widespread disease in the population of the world. It also acts as one of the constituent components of metabolic syndrome (MS), which is a global “epidemic” of our time. Target organs in such patients are affected much earlier and their changes are more pronounced than in hypertensive patients without metabolic disorders. It is important to study the contribution of risk factors to the progression of cardiac dysfunction in this category of patients.

Purpose of the study. To study the influence of risk factors on heart remodeling in patients with hypertension, burdened and not burdened by metabolic disorders, selected for clinical analysis from the cardiology department of the Republican Clinical Hospital № 4, Saransk in 2016-2019.

Materials and methods. For clinical analysis, 139 patients were selected from the cardiology department of the Republican Clinical Hospital No. 4, Saransk. Depending on the presence of metabolic disorders, the following groups were identified: Group I (n = 72) – patients with MS and AH; Group II (n = 67) – AH patients without metabolic disorders. The study evaluated the morphological and functional state of the myocardium and risk factors in the analyzed groups.

Results. In the group of patients with hypertension, aggravated by metabolic disorders, more pronounced processes of cardiac remodeling were revealed. It has been shown that patients with MS develop both eccentric and concentric models of left ventricular hypertrophy. The influence of the level of blood pressure and body mass index is differently reflected on the type of restructuring of the geometry of the myocardium. Patients with hypertension combined with metabolic disorders have a wider prevalence of risk factors. The burden of risk factors is higher in patients with concentric left ventricular hypertrophy and MS.

Conclusions. The role of metabolic disorders in the mechanism of cardiac remodeling development in patients with hypertension in combination with MS was determined. 

The article provides a scientific review based on the proceedings of the 2020 American Heart Association consensus on drugs that may cause arrhythmias on a risk-sensitive basis and a guidance on strategies for monitoring, prevention methods and therapeutic approaches.

The risk factors for drug-induced arrhythmias are divided into modifiable and non-modifiable. Among the non-modifiable risk factors are congenital anomalies (changes in the conduction system, ion channel polymorphism) and heart diseases (cavity dilatation, myocardial ischemia). Among the modifiable risk factors are various electrolyte disorders (hypo/hyperkalemia, hypo/hypermagnesemia, hypocalcemia). Certain drugs can lead to electrolyte disorders, which require management with potassium and magnesium supplements. The drug-induced arrhythmias can be caused by conditions leading to altered drug pharmacokinetics and increased plasma concentrations and metabolites having proarrhythmogenic effects, as well as drug-drug interactions.

Beta-blockers, non-dihydropyridine calcium channel blockers, other antiarrhythmic drugs, ivabradine, digoxin, anesthetics (bupivacaine, propofol) are the most common culprits in causing drug-induced bradyarrhythmias. The drug-induced atrial fibrillation frequently occurs in patients receiving antiarrhythmics, various sympathomimetics, psychotropic and antineoplastic drugs, anti-inflammatory (NSAIDs, corticosteroids) and immunotropic agents (interleukin-2, fingolimod). Various sympathomimetics and inotropic drugs, some antipsychotic drugs can produce drug-induced atrial and nodal tachyarrhythmias.

The drug-induced ventricular tachycardia can be caused by antiarrhythmics, inotropics and various sympathomimetics, antipsychotic and antineoplastic drugs, as well as herbal drugs (aconite, ginkgo biloba). The list of drugs that cause a long QT syndrome includes antiarrhythmics, antimicrobial drugs (macrolides, fluoroquinolones, aminoquinolines, fluconazole), antipsychotics, antineoplastic drugs, antiemetics, etc. For a complete list of drugs that prolong a QT interval, see the CredibleMeds website (Arizona, USA). The drug-induced arrhythmia prevention strategies include rising awareness among doctors about risk factors and potentially dangerous drugs, sufficient monitoring of patients at risk of developing arrhythmias (ECG monitoring, electrolyte balance, kidney and liver function), maintenance of electrolyte balance, primarily potassium and magnesium. The therapeutic approach includes discontinuation of a causative drug; relief and maintenance therapy are carried out based on the modern international clinical guidelines for various forms of arrhythmias. 

Introduction. Radiculopathy is one of the causes of neuropathic pain. Among the causes of back pain, lumbar radiculopathy ranks second after non-specific musculoskeletal pain. Patients with radiculopathy have a marked decrease in the quality of life, a tendency to disability, which causes a large amount of diagnostic and therapeutic measures and associated economic losses. There is no unified view on the pathogenesis of radiculopathy, and the pain syndrome includes neuropathic and nociceptive components. The proposed treatment regimens for radiculopathy differ and are of a recommendatory nature.

The purpose of the retrospective observational study was to study the effectiveness of the drug Neurobion® in the complex therapy of radiculopathy.

Materials and methods. The study of outpatient records of 120 patients aged 25–65 years, suffering from lumbosacral radiculopathy was performed. The patients were divided into 2 groups and received basic therapy, which included NSAIDs, simple analgesics, muscle relaxants, and anticonvulsants. Patients of group 1 additionally received the drug Neurobion®.

Results and discussion. Faster regression of clinical manifestations was observed in group 1 patients. The results of treatment in group 1 patients were higher both in terms of subjective feelings and objective criteria. The presence of two medicinal forms of Neurobion® allows a personalized approach to the patient’s therapy

Conclusions. The use of the drug Neurobion® is pathogenetically justified in the treatment of radiculopathy, provides earlier positive dynamics of subjective feelings of patients and objective indicators, improves the quality of life, leads to shorter treatment periods, reducing economic costs. The effectiveness and good tolerability of the drug Neurobion® allow us to recommend it for inclusion in the complex therapy of radiculopathy. 

Introduction. Dorsalgia is one of the most common diseases in individuals practising regular physical training and sports Rationale. Because of the growth of the number of physically active individuals expected to rise by 2024, the improvement of drug and physical rehabilitation methods comes into sharp focus.

The objective of the study is to evaluate the clinical efficacy of the use of a centrally acting muscle tolperisone-containing relaxant in the combined treatment of dorsalgia accompanied by a muscular tonic syndrome.

Materials and methods. In the study, two groups of patients (30 people each) with muscular tonic syndrome received therapy that included NSAIDs and a neurotropic vitamin complex (in the comparison group), and additionally a centrally acting muscle relaxant (in the treatment group).

The treatment outcome was assessed by changes in complaints and the objective neurological status of patients, the degree of muscle soreness upon palpation, and the evaluation of pain syndrome using a visual analogue scale.

The shear wave elastography (SWE) of defunct muscles was used as an objective assessment method.

Earlier in clinical practice, muscle tension in patients was usually assessed using manual palpation, i.e., only qualitatively and subjectively. SWE is an operator-independent, relatively reproducible, and quantitative method for assessing tendons and muscles. SWE was used in this study to obtain more objective assessment and comparison of the elasticity of “affected” and “healthy” symmetrical back muscles before and after the use of drugs.

Results. The study showed a high clinical efficacy of tolperisone in the combination therapy of the lower back pain accompanied by muscular tonic syndrome, which was confirmed by a more significant decreased muscle-tonic syndrome based on the evaluation of complaints and the degree of muscle soreness upon palpation, a more pronounced regression of pain syndrome according to VAS in the treatment group of patients vs the comparison group. According to the elastography findings before and after treatment, the group receiving tolperisone showed a more significant decrease in muscular tonic syndrome.

Сonclusion. The study confirmed the clinical efficacy of tolperisone manufactured by Sotex pharmaceutical company. On these grounds we recommend that the drug is used in combination therapy for dorsalgias (dorsopathies) accompanied by a muscular tonic (myofascial) syndrome both in patients without a proper level of physical activity, and in those practising regular physical training and sports. 

Cerebrovascular diseases (CVD) are one of the main causes of mortality and permanent disability in patients. Chronic brain ischemia (CBI) is a slowly progressive dysfunction of the brain with gradually increasing defects in its functioning, which is accompanied by energy deficiency. Early use of energy correctors, one of the representatives of which is ethylmethylhydroxypyridine succinate (EMHPS), is recommended to preserve the viability of nervous tissue in patients with CBI. A number of experimental, clinical, and randomized studies have shown that medicinal preparation (MP) containing EMHPS improve brain metabolism and blood supply, improve microcirculation, and reduce platelet aggregation. The main mechanisms of action are: antioxidant and membranotropic effects, the ability to reduce glutamate excitotoxicity, modulate the functioning of receptors and membrane-bound enzymes, restore neurotransmitter balance, and increase the energy status of the cell. The liberal MP EMHPS included in the standards of medical care for patients with stroke, angina pectoris, acute myocardial infarction. The presented data from the results of numerous studies and our own observation indicate that it is possible to correct cognitive, motor, coordination, and adaptive capabilities while taking EMGPS. Used for today the scheme of appointment of EMHPS in patients with CBI: starting from 500 mg once a day intravenously (i/v) in drip for 14 days, followed by a transition to oral reception (o/r) at a dose of 250 mg 3 times a day, a course of 60 days.

Low back pain is a major cause of disability worldwide. Data on the prevalence of low back pain are presented. Information on the pathogenesis of pain is given. The temporal characteristics of pain are presented. Risk factors and triggers for episodes of low back pain are reviewed. The most common causes of specific and non-specific low back pain are described. Non-specific low back pain is more common, as no specific pathological-anatomical cause can be identified. Specific pain includes nociceptive and neuropathic pain. In order to make a correct diagnosis in a patient with low back pain, a thorough medical history must be taken, which usually provides important information in identifying the cause of the pain syndrome. The warning signs (‘red flags’) for specific causes of low back pain requiring urgent treatment and specific psychosocial factors contributing to chronic pain (‘yellow flags’) are considered separately. ‘Red flags’ include conditions such as suspected traumatic injury, tumour, infection or radiculopathy and cauda equina syndrome. «Yellow flags» include individual cognitive, emotional and behavioural factors that contribute to the development of chronic pain. The main aim of pharmacotherapy for low back pain is to enable patients to continue or resume their normal daily activities. The main recommended approaches in the treatment of acute and chronic low back pain are presented. The main non-steroidal anti-inflammatory drugs for the oral drug treatment of non-specific low back pain are described, with evidence-based doses. Special attention is given to the role of diclofenac in the treatment of pain. The authors present the results of systematic reviews that analyse the available data on the efficacy and safety of topical transdermal dosage forms that contain NSAIDs.

Diabetic polyneuropathy is the most common neurological complication of diabetes mellitus (DM) and may affect about half of all patients with diabetes. Timely diagnosis and treatment of DPN can prevent such serious complications as limb numbness, severe pain during the day and night, foot ulceration and suppuration, amputation of the foot or toes, disability and even death. The combined approach to the treatment of DPN is the most effective and includes glycemic control, diet, optimal hypoglycemic therapy, management of cardiovascular diseases, educational conversations with patients, psychological support in the form of consultations with a psychologist or psychotherapy, and sufficient pathogenetic and symptomatic drug therapy of DPN. A clinical case of managing a patient with T2DM, DPN and cardiovascular diseases is described in detail. The interdisciplinary approach was used to treat the patient, which included the use of drug and non-drug therapies. The drug therapy of diabetes was adjusted, and medications to treat cardiovascular diseases were prescribed. Pathogenetic therapy of DPN remains a highly controversial issue. Among the drugs that affect the pathogenetic mechanisms of DPN, careful consideration was given to B vitamins and alpha lipoic acid. In the presented clinical case report, the patient was prescribed a combination drug containing vitamins B1, B6 and B12 as a pathogenetic therapy of DPN. A high priority in the treatment of DM and DPN is placed on raising awareness among patients about the causes and prognosis of the disease. Most patients with diabetes and DPN have psychological problems, symptoms of anxiety and depression about the disease, catastrophization of existing symptoms, poor adherence to medication due to feelings of despair and thoughts of the disease as incurable. In view of above factors, psychological methods appear as effective in the treatment of patients with diabetes and DPN. The cognitive behavioural therapy was used in the described clinical case as a psychological method. The use of CBT improved the patient’s emotional state, increased his adherence to medications and lifestyle recommendations. A positive effect in the form of decreased severity of neuropathic and autonomic symptoms of DPN was observed in as little as 10 days after treatment. At follow-up Week 12, the patient’s condition continued to improve and his work capacity increased.

The problem of long-term and uncontrolled use of decongestants remains one of the most relevant problems of modern otorhinolaryngology. To date vasoconstrictors are the most actively used drugs for the treatment of acute and chronic rhinitis, as well as other diseases accompanied by nasal congestion. Most of the topical decongestants are selective α2-adrenergic agonists that act on postsynaptic α2-adrenergic receptors, which perform the main function in the implementation of sympathetic stimuli in the nasal cavity. Sympathomimetic drugs in addition to the main vasoconstrictor effect also have their own anti-inflammatory and antioxidant effects. Topical decongestants are included in the treatment guidelines for acute and chronic rhinitis, rhinosinusitis, allergic rhinitis, acute and chronic otitis media, eustachitis. The recommended duration of decongestants is usually limited to 5–7 days. Longer use of this drug class can lead to paresis of the nasal mucosa vessels or an allergic reaction, to the development of rhinitis medicamentosa. Side effects that occur with the use of topical decongestants are divided into 2 groups: local symptoms and general toxic reactions. However, with strict adherence to the recommended dosing regimen of topical decongestants, to the method of use and to the duration of use, undesirable side effects are rare. The group of vasoconstrictor drugs received a new development as a result of the combination of decongestants with other drugs, which lead to the reducing local side effects and the elimination of not only nasal congestion, but also other symptoms of the common cold.

Chronic obstructive pulmonary disease (COPD) is currently one of the most socially significant diseases that leads to a significant decrease in the daily activity and productivity of patients, as well as their rapid invalidization. In this regard, its treatment remains the most important problem of medicine. Currently, the main goals of treatment of patients with COPD are: relief of symptoms, improvement of exercise tolerance, improvement of General health, prevention and effective treatment of complications, prevention and effective treatment of exacerbations, prevention of disease progression, and reduction of mortality. The article presents a clinical case from the practice of a patient with COPD who received olodaterol + Tiotropium bromide. In view of the patient’s low adherence to therapy, further progression of the disease was observed, which led to a significant violation of airway patency during spirometry, and a decrease in exercise tolerance. The patient was assigned a new representative of combined drugs with 24-hour action - Vilanterol + Umeclidinium 22/55 mcg, with a new method of drug delivery. After 6 months of therapy with Vilanterol + Umeclidinium, the patient’s exercise tolerance increased, lung function improved, and quality of life improved.

The lack of effective etiotropic methods of treatment and prevention of the new coronavirus infection (COVID-19), which caused the pandemic in 2020, determines the relevance of the review of researches of medicines for etiotropic and pathogenetic therapy. Most patients are diagnosed with pneumonia, the disease is especially difficult in people with concomitant chronic diseases, since COVID-19 leads to their decompensation, which can lead to death. To assess risk factors for mortality, scientists are developing programs to transfer the patient to appropriate treatment in a timely manner. This article analyzes the clinical efficacy of various agents for etiotropic and pathogenetic treatment of a new coronavirus infection based on data from international researches. Etiotropic medicines used at the beginning of the pandemic did not show their effectiveness in reducing the duration of treatment, the development of death, and preventing the transition to the use of mechanical ventilation. There are described researches of vaccines against a new coronavirus infection, developed in the Russian Federation, the USA, Germany and the UK, which showed the greatest efficiency (more than 90%) in preventing COVID-19. The World Health Organization initiated the international clinical research SOLIDARITY, according to which all medicines participating in the trials have little or no effect on overall mortality, the onset of ventilation requirements and the length of hospital stay in hospitalized patients. Now, only systemic glucocorticosteroids have proven effective against severe and critical forms of COVID-19. Thus, effective etiotropic drugs for the treatment of COVID-19 have not been developing, however, an active search for these funds and the development of vaccines to prevent the incidence of coronavirus infection are underway.

Viruses of the ARVI group that are tropic to the epithelium of the upper respiratory tract are able to inhibit the function of the mucociliary system to a certain extent, which contributes to the attachment of bacterial infection. Thus, in respiratory inflammatory diseases, the infection is often combined. This means, that the question about approaches to treatment at the stage of prevention of the development of complications of ARVI arises. A significant increase in the relapse of chronic sinusitis has been observed over the past 10 years. According to A.I. Kryukov et al. the relapse of inflammatory diseases of the paranasal sinuses, the chronic process has no tendency to decrease, aided by the unfavorable ecological situation, the growth of allergic and viral respiratory diseases, poor nutrition to which the body is not evolutionarily adapted. Worsening of chronic sinusitis contributes to many factors, but the starting point is almost always viral infections. Relapse, as a rule, begins with viral rhinitis, which is rarely an independent disease. Most often, a runny nose is a symptom of ARVI or ARI (influenza, parainfluenza, adenovirus infection, etc.). The entrance gate of infection is the epithelial cells of the respiratory tract. The main pathological process in sensitive cells develops both as a result of the penetration of the virus from the outside, and due to the activation of latent or chronic viral infection under the influence of various factors, including other infection.

The appointment of drugs with anti-inflammatory, immunomodulatory, adaptogenic activity is one of the promising options for the prevention of both primary viral infection and the development of bacterial complications.

We have included a drug that combines adaptogenic and immunomodulatory activities in the treatment of chronic sinusitis. Trekrezan belongs to the group of adaptogens – low-toxic compounds, it is recommended as a measure for the treatment and prevention of viral infections and increasing resistance to various stress factors (hypoxia, hypothermia) and adverse environmental effects. 

Introduction. The high prevalence rates of biliary sludge and its frequent development into the stone stage of cholelithiasis constitute grounds for studying this issue, as the effective action on biliary sludge can prevent overall disease progression.

Purpose of the study. To determine the options for diagnosis of biliary sludge in the polyclinic settings. Objectives: 1) Estimate the frequency of diagnosis of biliary sludge. 2) Assess the features and dependence of treatment on the type of biliary sludge. 3) Assess the outcome of treatment depending on the follow-up managing of patients. 4) Propose an algorithm for managing patients after biliary sludge has been diagnosed.

Materials and methods. In the work used data of the clinics of the President of the Russian Federation. The total number of people surveyed for 1 year was 1.117. These patients underwent an ultrasound examination (dispensation) and 218 were fitted with biliary sludge (BS), which was 19.4%. Of the 70 patients with BS, 4 groups were formed: 1st group (20 patients) with BS type, 2nd (20 patients) – with BS type, 3rd (20 patients) – with BS type, 4th (10 patients) – with BS-type (BSS) type.

All patients received Exchhol therapy at the rate of 15 mg/kg of weight; patients with a pronounced spastic component in the sphincter system – myotropic spasmolytic Sparex (20 mg x 2 times a day); patients of the 4th group (with a near-located sediment indicating the presence of inflammation) – Adisord (derived nitrofuran) 200 mg x 4 times a day (5 days).

Results. The type of precipitation was cupped in 4 weeks of treatment; Type – for 8–12 weeks of treatment, type V – for 13–14 weeks.

Conclusions. The presented data allow us to hope that early diagnosis of biliary sludge and the factors of its development will help start timely treatment and prevention of the disease. 

Gastroesophageal reflux disease (GERD) is a widespread disease. Despite the fact that different approaches to the treatment and prevention of recurrence of this disease have been developed, the number of patients with GERD, including refractory form of GERD, is only increasing. To date, well studied and described the possible links of the pathogenesis of this disease, which predetermine certain approaches to the treatment of various variants of GERD. Effective drug therapy of GERD includes the appointment of proton pump inhibitors (PPI). However, doctors are often faced with the problem of ineffective use of PPI in patients with GERD or with the so-called refractory form of GERD. The reasons for the ineffectiveness of therapy of PPI can be associated not only with the pathogenetic features of GERD and therapy, but also with the patient himself. Daily pH monitoring allows to determine the cause of the ineffectiveness of the treatment of PPI if the patient complies with all prescriptions. With ineffective acid suppression in the stomach, it is necessary to increase the dose of PPI or replace it. It is important to prescribe both effective and safe means of correcting the symptoms of GERD, and also take into account the possibility of long-term maintenance of remission when using them. These requirements are met by PPI, created in the form of enantiomers, having an improved pharmacokinetic profile. An example of this differentiated approach is dexlansoprazole, a law-converting monoisomer of lansoprazole with double release technology and the ability to maintain the antisecretory effect for a long time, which appeared relatively recently on the Russian pharmaceutical market. The use of this drug is presented in a clinical case.

Introduction. At present, global prevalence of celiac disease attracts increasingly greater attention of researchers. The study of its extraintestinal manifestations is a crucial task for early and timely diagnosis of the disease, as well as the identification of new risk groups. To date, there are only isolated publications concerning the study of celiac disease incidence in patients with acne. 

This topic is of particular interest since systemic retinoids with a hepatotoxic effect and antibiotics significantly affecting the intestinal microflora are the first-line drugs in the treatment of moderate and severe acne. Undoubtedly, these side effects influence on the course of acne in celiac patients. So, to prevent the complications of the treatment, it is necessary to search, develop and introduce into practice safe combinations, including drugs having a protective effect both for the intestinal microflora and for the liver. It is known that psyllium (Plantago ovata seed shells/Ispaghula husks) have similar effects.

Objective. To study the effect of psyllium on the tolerability and effectiveness of systemic therapy with isotretinoin and doxycycline in patients with moderate acne with celiac disease. Material and methods. We examined 65 patients with celiac disease suffering from moderate acne, who were randomized into two groups – group 1 (taking an antibiotic – doxycycline) and group 2 (taking a systemic retinoid – isotretinoin), then each group was divided into two subgroups A and B, depending on the prebiotic intake (powder of oval plantain seeds shells Plantago ovata Forssk (psyllium). The patients were followed up for 8 and 24 weeks, respectively. All patients received adjuvant topical therapy. In each group, a medical check-up was done before treatment, 2 months after the onset and then after the treatment completion.

Conclusion. Patients in both subgroups who received psyllium in addition to antibiotics and systemic retinoids treatment showed better results after treatment in terms of skin condition, overall health and quality of life. 

The problem of modern medicine and modern society is a comorbid patient with metabolic disorders. Hypothetical portrait of such a patient: over 40 years old, overweight, arterial hypertension, coronary atherosclerosis, impaired carbohydrate and lipid metabolism, liver steatosis or steato-hepatitis, often with changes in the function of the musculoskeletal system. Rational pharmacotherapy of this patient is of fundamental importance. The article analyzes, from the point of view of polypotency, efficacy and safety, the main drugs used in Russia for treatment of non-alcoholic fatty liver disease in comorbid patients. Attention is paid to vitamin E, glycyrrhizin, ursodeoxycholic acid. Domestic and foreign studies of these drugs are analyzed, and the scope of their rational use is shown: reducing the risk of cardiovascular complications, a positive effect on the lipid spectrum, reducing the activity of serum transaminases and other hepatotropic effects. Their side effects are also considered, which should be taken into account when choosing the treatment of a comorbid patient. We have analyzed the efficacy and safety of new molecules that are in clinical trials and/or have not yet been registered in our country, e.g. obeticholic acid, cenicriviroc, tropifexor, etc. The ability of some molecules to act as biological enhancers is also highlighted, which is important to consider when prescribing combination therapy. Doctors are recommended to carefully consider and take into account all the features of a comorbid patient and choose for this category of patients safe drugs of hepatotropic action with simultaneous positive effect on the cardiovascular system. Among other things, it will avoid polypragmasy.

Irritable bowel syndrome (IBS) is one of the most prevalent gastrointestinal disorders affecting between 5 and 15% of the general adult population worldwide. Over the course of many years altered intestinal motility, visceral hypersensitivity, immune changes and, as it has recently been found, impaired epithelial barrier function were meant to explain the origin of symptoms in the IBS. We have come to realize now that the IBS warrants serious clinical and scientific study. Not that long ago, the connections between the gut and the brain have been expanded to include a new entrant, the microbiota, resulting in the creation of a new concept of a microbiota-gut-brain axis.

Microbiota is a risk factor for the irritable bowel syndrome. Probiotics are defined as live microorganisms, which can alter the intestinal flora and regulate intestinal functions such as reduction of visceral hypersensitivity, improvement of mucosal barrier function, modulate immune responses and chronic inflammation, affect the central nervous system, gastrointestinal motility, etc. The correctness of this approach is confirmed by several studies of the probiotic Bifidobacterium longum subsp. longum 35624, which is widely used in the treatment of symptoms of irritable bowel syndrome. The dietary supplement Bifidobacterium longum subsp. longum 35624 contains 1 × 109 colony-forming units, which provides a clinically effective level of these beneficial bacteria. Bifidobacterium longum subsp. longum 35624 also reduces inflammation in the gastrointestinal tract and has positive results in reducing abdominal symptoms (e.g. abdominal pain / discomfort and bloating) associated with the irritable bowel syndrome and other conditions. 

Autoimmune thyroiditis is an organ-specific autoimmune disease caused by the activation of self-reactive CD4+ T cells. Regulatory T (Treg) cells are a population of T cells that play a central role in immunological tolerance by suppressing selfreactive cells. CD4+ Tregs are divided into thymic (tTreg) and peripheral (pTreg). tTregs perform their functions through cytokine-independent mechanisms, pTregs – through IL-10, TGF-β and IL-35. Tregs perform a protective function against AIT. Studies of Treg level in AIT show different results, in most cases Treg level is increased, and their function is impaired. Treg function in AIT is affected by many factors, such as the level of thyroglobulin, vitamin D etc. Apart from the Treg level itself, the Th17/Treg ratio is also crucial in AIT. Activation of Tregs and modification of the Th17/Treg ratio can be used in AIT treatment.

Type 2 diabetes mellitus is a serious medical and social problem. The danger of the disease is associated with epidemic growth rates and chronic complications, leading to early disability, decreased quality of life and mortality. The prevention of diabetes complications is based on the optimal glucose-lowering therapy with the achievement of target metabolic parameters from the date the diagnosis of T2DM was established and throughout the patient’s life. The complex pathogenetic mechanisms of T2DM are the underlying rationale for drug therapy with a simultaneous effect on various disorders, which will provide a greater hypoglycemic potential and maintain effective glycemic control as T2DM progresses. The main reasons for poor disease control include clinical inertia, untimely intensification of drug therapy, and the use of treatment regimens that are insufficiently effective given the progressive course of the disease. The therapy for T2DM is based on clinical guidelines. The pathogenetic therapy options associated with the use of vildagliptin and metformin are considered. Much attention in modern diabetology is paid to the study of the influence of various therapeutic approaches on the disease progression rates from the perspective of improving prognosis and long-term maintenance of target glycemic control. The advantages of combined glucose-lowering therapy at the onset of T2DM are considered in comparison with the stepwise intensification of glucose-lowering therapy. The VERIFY study examined the long-term efficacy and safety of two treatment approaches: early vildagliptin and metformin combination therapy versus the traditional stepwise approach starting with metformin as initial therapy. The combined glucose-lowering therapy is an important direction in the treatment of patients with newly diagnosed type 2 diabetes.

Introduction. Type 2 diabetes mellitus (DM) and hypothyroidism are the most common endocrine pathologies. These diseases are associated with atherogenic dyslipidemia, insulin resistance, and overweight.

Aim. Тo assess the relationship between adipokines and hormone-metabolic parameters in women with hypothyroidism, type 2 diabetes mellitus and their combination.

Materials and methods. We examined 119 women aged 45 to 74 years: 42 women with primary hypothyroidism, 38 women with type 2 diabetes and 39 women with a combination of type 2 diabetes and hypothyroidism. All patients underwent an anthropometric examination, studied the indicators of lipid and carbohydrate metabolism, the content of adiponectin, leptin and resistin.

Results. In women with type 2 diabetes and its combination with hypothyroidism, hyperglycemia, hyperinsulinemia, and insulin resistance were revealed. In all groups, an increase in total cholesterol, triglycerides, atherogenic coefficient was found. The examined women with a combination of hypothyroidism and type 2 diabetes mellitus had a decreased level of adiponectin and an increased level of leptin. In patients with hypothyroidism and patients with type 2 diabetes, a decrease in adiponectin levels and an increase in leptin and resistin were revealed.

Discussion. The most pronounced hyperinsulinemia and insulin resistance were found in the group of patients with a combination of hypothyroidism and type 2 diabetes. At the same time, the combination of type 2 diabetes and hypothyroidism in the examined women, according to our data, did not aggravate lipid metabolism disorders. Against the background of visceral obesity in women with a combination of diseases, hypoadiponectinemia and hyperleptinemia were most pronounced. In this group, the level of resistin was positively correlated with the level of insulin and the index of insulin resistance.

Conclusion. In women with hypothyroidism, type 2 diabetes and their combination, atherogenic dyslipidemia, hyperleptinemia, and hypoadiponectinemia were established. Hypoadiponectinemia and hyperleptinemia are involved in the development of atherogenic dyslipidemia in women with primary hypothyroidism. 

The role of fungi as causative agents of infections is growing. In in-patients, especially at intensive care units, fungal infections might cause serious problems. Studies conducted over recent years shows an increase of fungi detection in urine in in-patients from 5,01 up to 10,63%. Most often, the appearance of fungi in the urine connected with contamination or colonization of the urinary tract. However, in immunocompromised patients, this could be the part of urinary tract infection and even of disseminated fungal process. Candida is the most common cause of fungal urinary tract infections. At the same time, the presence of Candida in urine (candiduria) not always comes with clinical signs of urethritis, cystitis and pyelonephritis. Detection of noCandida albicans agents in urine is increasing, new Candida species revealed are resistant to antifungal drugs so risk of complications is increasing. Recent researches reveal new mechanisms of how Candida interacts with the bacteria that cause urinary infections. The main mechanisms of Candida virulence factors are dimorphism, adhesion proteins — Als1-7,9 and Gls, invasion enzymes — phospholipase, Als3 and Ssa1, as well as enzymes that neutralize reactive oxygen species. The most significant risk factors of fungal urinary tract infection are the presence of a urinary catheter, diabetes mellitus, immunosuppression and previous antibiotic intake. The study of the formation process of the cellular and immune response to Candida makes it possible to identify the main links in the pathogenesis of urinary tract candidiasis, as well as the main role of immunosuppression in the development of the disease.

In accordance with the data of the Federal Clinical Recommendations for the Diagnosis, Treatment and Prevention of Osteoporosis, with the latter, antiresorptive drugs (denosumab, bisphosphonates) are used, which mainly suppress bone resorption, and anabolic compounds (teriparatide), which enhance bone formation. The vector of their pharmacological effect helps to prevent BMD loss and significantly reduces the risk of low-energy vertebral fractures and fractures of other localizations. The experience of clinical trials makes it possible to successfully carry out antiresorptive therapy with some drugs (denosumab) for up to 10 years, demonstrating good adherence and tolerance. Bisphosphonates remain in the bone matrix for a long time and are characterized by a period of a certain aftereffect. Denosumab and teriparatide show their effect only during the period of direct use. According to some data, when denosumab therapy is canceled in a situation where the targeted goal is achieved, the incidence of vertebral fractures increases, especially in patients with a history of low-traumatic fractures. The article will present the main provisions of the European Calcified Tissues Society, the European Medical Agency, the Russian Association for Osteoporosis regarding the timing of treatment and an analysis of clinical situations requiring the appointment of alternative antiresorptive therapy. According to the resolution of the Council of Experts of the Russian Association on Osteoporosis, bisphosphonates are recommended for all patients to prevent an increased risk of vertebral fractures 6 months after patients had their last subcutaneous injection of denosumab. Oral bisphosphonates should be taken immediately, and zoledronic acid injection should be delayed for another 65 days following a missed denosumab injection.

Taking into account the modern life expectancy, a third of their lives, on average, women live in conditions of estrogen deficiency, which negatively affects the quality of life and the level of morbidity in older people. For doctors of other specialties, besides ObGyn, the climacteric period is strongly associated exclusively with hot flashes. However, early menopausal symptoms include sleep disturbances, mood changes, the risk of depression and decrease in self-esteem, sexual dysfunction. The predominance of vegetative symptoms makes the patient seek help not only from the gynecologist, but also from other specialists, however, the lack of knowledge in menopause medicine leaves them unsatisfied. In this regard, a therapeutic approach requires a comprehensive understanding of the problem.

The “gold standard” for managing patients with climacteric complaints is menopausal hormone therapy. However, there are women with contraindications to this group of drugs or the predominance of vegetative symptoms, when only hormonal correction is not enough. Among alternative non-hormonal agents, inhibitors of serotonin reuptake, in particular the most popular drug venlafaxine, hold a strong leadership with proven efficacy against a complex of symptoms. Also, other medications have been studied that can stop both vasomotor and vegetative symptoms of menopause. The review presents the literature data on the role of alternative agents in the correction of vasomotor symptoms of menopause, along with the known efficacy against autonomic complaints for increasing the effectiveness of counseling for older women. 

An analytical review of domestic and foreign literature on the problem of osteoporosis was performed, and the principles of the approach to diagnosis and treatment of this disease are described.

The probability of vertebral fracture should be assumed if there is a history of growth loss of 4 cm or more, the appearance of kyphosis in patients who received long-term therapy with glucocorticoids, with bone mineral density (BMD) less than 2.5 points In the treatment of patients with osteoporosis at the initial stage there is a tendency to limit oneself to non-drug measures, advising to change lifestyle and diet, to increase intake of vitamin D and calcium with food, to optimize physical activity. However, the main place in the prevention and treatment of osteoporosis in postmenopausal women is occupied by medication therapy, which can reduce the risk of fractures by 70%: bisphosphonates, drugs derived from parathyroid hormone, denosumab and selective estrogen receptor modulators. It is advisable to start therapy with oral bisphosphonates in most cases. They are powerful inhibitors of bone resorption and act by reducing the activity of osteoclasts and increasing their apoptosis. In 2020, the patent protection period of the main original bisphosphonates expired and generics of Russian production appeared: Rezoviva (ibandronic acid 3 mg for intravenous injection once every 3 months) and Osteostatix (zoledronic acid 5 mg 100 ml solution for intravenous drip once a year). After 3–5 years of bisphosphonate treatment, treatment should be reconsidered. The risk of recurrent fractures should be reassessed after the injury occurs. The risk of new fractures increases in patients who stop treatment. Study results have recommended ibandronate as a first-line drug in women with postmenopausal osteoporosis. Studies comparing intermittent intravenous ibandronate administration with daily oral treatment in women with postmenopausal osteoporosis allowed to recommend intravenous ibandronate at a dose of 3 mg every 3 months as the preferred therapy. 

Introduction. In recent years, more and more attention has been paid to the issues of genital prolapse. This is largely due to the increase in women life expectancy and the need to provide them with a decent quality of life, as prolapse is quite often accompanied by dysfunction of the pelvic organs. In recent years, there has been an increasing amount of literature on undifferentiated connective tissue dysplasia (UCTD). However, most of these studies consider therapeutic or vertebro-neurological problems, while the high prevalence rates of this pathology call for additional research on the pathogenetic mechanisms of the effect of UCTD on pelvic organ prolapse, which will allow us to decide on the choice of subsequent treatment.

The purpose and objectives. Asess the effect of undifferentiated connective tissue dysplasia (UCTD) on the formation of disorders of the somatic, gynecological and reproductive health status in women with genital prolapse.

Materials and methods. To achieve this goal, we examined 204 women with genital prolapse in the POP-Q classification of stage 2–3, of which 97 were diagnosed with UCTD (the main group), and the remaining 107 patients made up the comparison group.

Results. To evaluate the influence of UCTD on the formation of somatic, gynecological and reproductive health disorders in women with genital prolapse. We analyzed anamnestic indications for somatic, gynecological and reproductive pathology of women, as well as assessed the current state of health of patients with genital prolapse. It was found that it is UCTD that determines the development of a particular form of gynecological pathology and affects the formation of genital prolapse.

Conclusion. UCTD manifests as various forms of somatic and gynecological health disorders throughout the life of women with genital prolapse. 

The world is in the grip of the pandemic of the new viral infection COVID-19. The number of patients around the world is not only not decreasing, but also progressively increasing. Treatment and prevention of SARS-CoV-2 is a major global healthcare challenge. Effective and safe methods of treatment and prevention are urgently needed that can reduce the risk of infection, reduce the risk of developing the infectious process and mortality from this serious disease in addition to quarantine. Vitamin D is known for its classic role in maintaining bone mineral density. Currently, his contribution has been more and more studied. For example, the immune system is important, as well as adaptive immunity and regulation of the inflammatory cascade. In these reviews, the mechanisms of the effect of vitamin D on cellular and humoral immunity and direct antiviral defense of the body were discovered, and its potential modules – the role in vaccine immunogenicity. The data of observational and randomized clinical trials proving the positive effect of colecalciferol on the frequency and severity of seasonal viral respiratory diseases are presented. The mechanism of penetration and development of coronavirus in the human body, changes in the immune system and humoral factors of the body’s defense against the background of the course of SARS-CoV-2. Coronavirus and more severe course is an infectious process depending on age and associated diseases. In this article, we analyze and summarize the data of modern studies, in which it is proved that the level of vitamin D in the blood has a beneficial effect on the content of vitamins D in the body’s immune and antiviral defense and its role in reducing the risk of infection and the severity of pathological diseases, including COVID-19. Discussion of the doses and regimens of vitamin D therapy against viral infections, including COVID-19, is based on the experience of previous and ongoing studies and guidelines.

The mechanisms of COVID-19-associated coagulopathy (CAC) are complex and differ in many ways from the standard mechanisms of thrombosis in critically ill patients. This review presents the pathogenesis, diagnosis, and comparison of various types of coagulopathy with SAS. During COVID-19 infection, the number of sudden deaths outside the hospital increased. One possible reason is the high incidence of serious thrombotic events in patients with COVID-19. However, the pathogenesis of these life-threatening events is multifactorial and requires independent discussion.

Deviations in laboratory studies of the hemostatic system in patients infected with SARS-CoV-2 with a severe course indicate the activation of the blood coagulation system corresponding to sepsis-induced coagulopathy (SIC) or DIC. However, hemostasis disorders in COVID-19 have characteristics that distinguish them from DIC in sepsis.

The clinical and laboratory features of CAC overlap with hemophagocytic syndrome, antiphospholipid syndrome, and thrombotic microangiopathy. The review presents data on their similarities and differences.

Inadequate diagnosis or inadequate treatment of hypercoagulability may explain the high incidence of unexplained deaths from COVID-19. They can be associated with potentially preventable microvascular and macrovascular thrombosis and subsequent cardiovascular complications, including myocardial injury and infarction, as well as insufficient information content of biomarkers for their assessment.

Research to identify the most informative biomarkers for decision-making to intensify anticoagulant prophylaxis in patients with severe COVID-19 is progressing rapidly, with increasing focus on TEG and ROTEM.

The review presents changes in CAC during hormone therapy for COVID-19-associated lung damage. Pulse therapy with high doses of GCS has a rapid anti-inflammatory effect, but at the same time increases the level of D-dimer, which increases the risk of venous thrombosis and thromboembolism. 

Introduction. The sufficiency of vitamin D is important for slowing down the aging of the skin, maintaining its hydration, elasticity and the ability to regenerate. Biologically active forms of vitamin D (including alfacalcidol) promote the activation of genes whose function is directly related to the maintenance of the structure of the skin, subcutaneous tissue, fascia and muscle fibers.

The aim of the work was to assess the prospects for the inclusion of alfacalcidol (“Alpha D3”, 0.25 μg, 1 caps/day) in the rehabilitation programs of patients with age-related ptosis of the face (n = 40, age 47 ± 5 years).

Materials and methods. 4 groups of patients with age-related facial ptosis (n = 40, average age 47 ± 5 years) were observed for 60 days; measurements were made before and after clinical trials. Group 1A (first treatment, n = 12) received the daily dose of Alpha D3, 0.25 mg, in the morning, for 60 days, during this period the patients received 4 cosmetic procedures (2 plastic face massages and 2 stimulation current therapies). Group 1B (first control, n = 8) received only 4 cosmetic procedures over 60 days (2 plastic face massages and 2 stimulation current therapies). Group 2A (second treatment, n = 12) received the daily dose of ALFA D3, 0.25 mg, for 60 days, during this period the patients received 4 DMAE (diethylaminoethanol) mesotherapy procedures. Group 2B (second control, n = 8) only received 4 DMAE (diethylaminoethanol) mesotherapy procedures.

Results. Alfacalcidol intake significantly increased the concentrations of 25 (OH) D (from 17 ± 5 ng/ml to 27 ± 8 ng/ml, P = 0.001) and calcium (from 86 ± 10 mg/L to 96 ± 6 mg/L, P = 0.01) in serum. The positive dynamics of the concentrations of 25 (OH) D and calcium when taking alfacalcidol corresponded to an increase in the total bone mineral density (+ 0.03 ± 0.03 g/cm3, control: + 0.006 ± 0.03, P = 0.016) and T-criterion (+0.4 ± 0.5, control: -0.07 ± 0.2, P = 0.0002), which indicates compensation for vitamin D deficiency and an improvement in bone metabolism. An increase in the levels of 25 (OH) D and calcium when taking alfacalcidol was accompanied by a positive trend in skin condition according to bioimpedance measurements. Taking the drug significantly increased the moisture content of the facial skin (from 17 ± 14 points to 29 ± 14 points, P = 0.055, without changes in the control) and increased the amplitude of the muscle motor response to the stimulus (+ 0.24 ± 0.22, P < 0.02).

Conclusions. Within the framework of a randomized design, it was shown that the addition of massage, microcurrent therapy, mesotherapy with alfacalcidol led to a significant increase in serum 25 (OH) D levels, an increase in skin elasticity and hydration, a decrease in visceral fat according to bioimpedance measurements, and an improvement in indicators of muscle contractility and neuromuscular signal transmission according to electromyography data and an increase in bone mineral density. 

Introduction. Dry eye syndrome (DES) is a multifactorial disease of the ocular surface, characterized by changes in its homeostasis and accompanied by ocular symptoms, the etiology of which is associated with destabilization of the tear film, hyperosmolarity, inflammation, damage to the structures of the ocular surface and neurosensory disorders.

Objective. To study the effect of a drug containing plastoquinonyldecyltriphenylphosphonium bromide (PDTP, SkQ1) on dynamics of osmolarity and reparative properties of the cornea.

Materials and methods. The study included 23 patients (46 eyes) aged 23 to 49 years. All patients presented complaints of dryness, burning sensation, cramps and discomfort in the eyes, increased sensitivity with instillation of drops, periodic blurred vision. Patients underwent standard and special ophthalmic examinations. The patients were divided into two groups comparable in gender and quantitative composition.

Results. Based on the results of the examination at the starting visit, all patients were diagnosed with DES mild or moderate study. After one week of therapy, a significant decrease in subjective complaints was noted patients who received the drug with PDTF. All patients tolerated the drug well. In the group of patients who received a tear replacement therapy with hypromellose, in most patients, while complaints of dryness persist, decreased a feeling of pain in the eyes. A month later, complaints persisted only in patients of this group, but their intensity was known significantly reduced compared to the visit after a week. Against the background of therapy with the drug with PDTP, significant improvement of the Schirmer test, Norn test and corneal staining, as well as with the help of a in vivo confocal microscopy shows a decrease in the number of Langerhans cells.

Conclusion. The results obtained indicate a positive effect of PDTP on the structure of the ocular surface even with its short-term use due to its keratoprotective and anti-inflammatory action. 

Laboratory methods are a very important part of the examination of patients with thrombotic diseases, often putting the final touches on the diagnosis, and in some cases even defining this diagnosis. The present review of thrombotic diseases and conditions, as well as the laboratory methods for their diagnosis, enables the differentiation of these conditions in the laboratory phase of the examination and the selection of the correct specific therapy, especially antithrombotic therapy.

This review reflects the main nosological forms, causes of thrombotic diseases and conditions, as well as methods of their diagnosis using reagents and test systems of the leading domestic manufacturer of reagents for diagnostics of the hemostatic system SPD “Renam” ICPOD “Hemophilia Society”. The mechanisms of conditions and diseases such as deep vein thrombosis (DVT) and pulmonary artery thromboembolism (PATE), hypercoagulability syndrome (HCS), disseminated intravascular coagulation (DIC), hereditary and acquired thrombophilia (deficiency of antithrombin III, proteins C and S, factor Va resistance to activated protein C, etc.) and complications of anticoagulant therapy (heparin-induced thrombocytopenia (HITC), antiphospholipid syndrome (APS), complications of anticoagulant therapy (heparin-induced thrombocytopenia (HIT), coumarin-induced necrosis, etc.) are reviewed. Laboratory criteria for thrombotic conditions are presented. The most commonly used anticoagulant drugs and their control methods are reviewed, including vitamin K antagonists (oral anticoagulants, OAC), unfractionated heparin (UFH), low molecular weight heparins (LMWH), fondaparinux, direct or new oral anticoagulants (DOACs or NOACs). Laboratory criteria for thrombotic conditions are presented. Methods for determining blood D-dimer are described in detail, as well as methods for measuring anti-Xa and anti-IIa heparin activity.

This joint work of the leading employees of the Research and Production Department «Renam» of ICPOD «Hemophilia Society» and FSBI NMRC of Hematology of the Ministry of Health of the Russian Federation reflects the need for scientific and practical cooperation of practitioners, laboratory doctors and manufacturers of reagents and test systems to develop the most sensitive, specific, accurate and convenient methods of disease diagnostics and control of therapy. 

Insomnia is a common clinical condition characterized by difficulty initiating and/or maintaining sleep. According to most epidemiological studies, about a third of adults (30–36%) report at least one symptom of insomnia, such as having difficulty falling asleep or maintaining sleep. Insomnia interferes with the full-fledged social and professional functioning of patients, forcing them to visit doctors more often, take sick leave. While therapeutic approaches are actively developed and discussed in chronic insomnia, acute insomnia due to the transient state and the tendency (in some cases) to spontaneous resolution often remains the subject of underdiagnosis and undrtreatment. Antihistamines that are non-addictive and have a narrower side-effect profile and are nonprescription drugs are an alternative in the pharmacological treatment of insomnia, especially secondary and transient insomnia, which is widespread in the population. Donormil (doxylamine succinate) is a blocker of H1-histamine receptors from the ethanolamine group. Donormil (doxylamine succinate) is a blocker of H1-histamine receptors from the ethanolamine group. Doxylamine is successfully used in both psychiatric and general medical practice, including dermatology, allergology, and gynecology.This article presents the clinical observation of a patient with acute insomnia arising in adjustment disorder and was accompanied by anxiety and mild conversion symptoms.. Donormil therapy during two weeks allowed to reduce acute insomnia: the time to fall asleep and the number of night awakenings decreased, cognitive impairment, distraction, and asthenia associated with insomnia reduced. No significant side effects were observed.

Introduction. Psoriatic arthritis (PsA) is a chronic immunoinflammatory disease characterised by involvement of the skin, nail plates, joints, spine and entheses in the inflammatory process. The IL-12/IL-23 inhibitor ustekinumab (UST) is increasingly being used in psoriasis (Ps) and PsA.

Aim of the study. To analyze patients with PsA who were under inpatient treatment in the V.A. Nasonova Scientific Research Institute of Rheumatology and Radiology and who were prescribed UST during the period from 2018 to 2020.

Material and methods. UST was administered to 17 patients with PsA (9 women and 8 men), mean age was 46.4 ± 11.3 years. Duration of PsA course was 11 ± 10.5 years. Patients underwent clinical, laboratory and instrumental examination, BSA and PASI, DAPSA and BASDAI indices were determined.

Results. Patients predominantly had widespread Ps (BSA 18.2 ± 15.9%). Erosive arthritis was present in 94.1% of patients, and sacroiliitis was detected in 100% of patients. PsA activity was high (DAPSA = 44.9 ± 20.9, BASDAI = 6.2 ± 1.5).

94% of patients had two or more comorbidities. Circulatory system diseases were observed in 82.4% of patients, liver diseases in 29.5%, gastrointestinal diseases in 47%, endocrine system diseases in 17.6%, viral hepatitis C in 23.5%, latent tuberculosis infection in 17.6%, and joint surgery was performed in 11.2% of patients. The clinical example presented in the article demonstrates good tolerability of UST in a patient with PsA with a number of comorbidities and the possibility to increase the dose of UST from 45 to 90 mg in case of ineffective therapy.

Conclusions. The safety profile of UST is good, and it can be administered to patients with cardiovascular diseases, obesity, various infections, including latent tuberculosis, etc.