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Leonid Vasilyevich Sobolev is an outstanding pathologist, whose name definitely should occupy an honorable place in the galaxy of great scientists of Russia. However, his name was undeservedly forgotten, and the role of his work was underestimated. This Russian scientist made the most important discovery: he proved in an experiment that it is the islets of Langerhans in the pancreas that secrete a humoral regulator, "factor X", the deficiency of which leads to diabetes mellitus. This mysterious islet factor will be isolated from the pancreas of dogs in 1921 by the future Nobel laureate Frederick G. Banting and will become part of the medicine as insulin. However, there is every reason to believe that the discovery of F. G. Banting, who repeated a series of experiments by Leonid Vasilyevich Sobolev, is, in fact, secondary, which is the research subject in this paper.

The purpose of the comments is the analysis of Professor Dmitry D. Pletnev's article Hypertension (experience in analyzing its genesis) from the point of view of modern ideas about arterial hypertension. Currently, a small number of publications of Professor D.D. Pletnev, a Russian scientist and clinician, unjustly convicted in 1937, have been preserved. The small work includes not only a deep and critical analysis of the pathogenetic mechanisms of this disease, but also an assessment of diagnostic methods, as well as a detailed description of the clinical picture. The paper, published in 1935, remains relevant and of interest to clinicians and medical historians.

Aim: Systematization of data on antibiotic resistance of Helicobacter pylori in Russia over the past 10 years., Methods: A search for studies were carried out in electronic databases MEDLINE/PubMed, EMBASE, Cochrane, Russian Science Citation Index. We analyzed the papers published over the past 10 years (2011 to 2020). In the final analysis, publications were selected from periodical peer-reviewed foreign and Russian publications, in which validated tests for assessing the microorganism resistance were used with detailed descriptive statistics, which allows the obtained data to be included in the meta-analysis., Results: The final analysis included 11 studies (808 isolates). H. pylori resistance to clarithromycin was 10.39% (95% confidence interval CI 7.10314.219), metronidazole 33.95% (95% CI 15.32955.639), amoxicillin 1.35% (95% CI 0.281 3.202), levofloxacin 20.0% (95% CI 12.63728.574), tetracycline 0.98% (95% CI 0.3532.163). Double clarithromycin-metronidazole resistance was reported in 2.7% (95% CI 1.1364.345)., Conclusion: This meta-analysis is the first analytical work that allows objectifying the current structure of H. pylori antibiotic resistance in the Russian Federation. The data obtained in the analysis of publications over the past 10 years indicate a low resistance of the microorganism to clarithromycin (less than the regulated threshold of 15%), which allows us to consider the triple regimen of eradication therapy as a first-line therapy in our country.

Pulmonary arterial hypertension (PAH) is severe and often times rapidly progressive disease with fatal outcome. The concept of initial combination of PAH-specific therapies in high risk patients at baseline was first described in the European guidelines on pulmonary hypertension (PH) in 2009, and in low or intermediate risk patients at baseline in 2015. Interestingly, that in Cologne Experts Consensus, and then in the 6th World Symposium on PH medical community started considering initial combination therapy as one of the most important pillars in PAH treatment algorithms in 2018. As of August 2020, as many as 8 formulations of 7 reference PAH-specific drugs are licensed for medical use in the Russian Federation. On top of that, 6 abbreviated drugs (generics) have also become available few years ago. Unfortunately, intravenous and subcutaneous prostacyclin analogs (PCA) and tadalafil are not approved for PH patients treatment in the Russian Federation. In this narrative review paper we attempted to describe studies on initial dual combination therapy with PAH-specific drugs registered in Russia, i.e. ambrisentan and riociguat, macitentan and riociguat, macitentan and sildenafil in low or intermediate risk patients at baseline, as well as iloprost inhaled and sildenafil, iloprost inhaled and bosentan in high risk patients. Some beneficial pharmacological effects due to the synergy between ambrisentan plus riociguat, and inhaled iloprost plus sildenafil appear to be interesting and require further clinical confirmation. Other initial combinations of PAH-specific agents require large-scale clinical trials as well.

This manuscript summarizes consensus reached by the International Anorectal Physiology Working Group (IAPWG) for the performance, terminology used, and interpretation of anorectal function testing including anorectal manometry (focused on high-resolution manometry), the rectal sensory test, and the balloon expulsion test. Based on these measurements, a classification system for disorders of anorectal function is proposed. Aim to provide information about methods of diagnosis and new classification of functional anorectal disorders to a wide range of specialists general practitioners, therapists, gastroenterologists, coloproctologists all who face the manifestations of these diseases in everyday practice and determine the diagnostic and therapeutic algorithm. Current paper provides agreed statements of IAPWG Consensus and comments (in italics) of Russian experts on real-world practice, mainly on methodology of examination. These comments in no way intended to detract from the provisions agreed by the international group of experts. We hope that these comments will help to improve the quality of examination based on the systematization of local experience with the use of the methods discussed and the results obtained. Key recommendations: the International Anorectal Physiology Working Group protocol for the performance of anorectal function testing recommends a standardized sequence of maneuvers to test rectoanal reflexes, anal tone and contractility, rectoanal coordination, and rectal sensation. Major findings not seen in healthy controls defined by the classification are as follows: rectoanal areflexia, anal hypotension and hypocontractility, rectal hyposensitivity, and hypersensitivity. Minor and inconclusive findings that can be present in health and require additional information prior to diagnosis include anal hypertension and dyssynergia.

Gastroesophageal reflux disease (GERD) is a common chronic disease of the upper gastrointestinal tract with long course of the disease and followed by different symptoms significantly reducing quality of life (QoL) in pts. Assessment of QoL in pts with GERD may be of value for comprehensive evaluation of treatment effect as well as for monitoring of pts during treatment course in a real clinical practice., Aim: Development of the Russian version of GERD-HRQL questionnaire to assess symptomatic outcomes of GERD in research and real clinical practice., Materials and Methods: GERD-HRQL questionnaire (V. Velanovich, USA) consists of 11 items: 10 items for assessment of the most frequent symptoms/problems related with QoL in pts with GERD and 1 item for assessment of patient-reported global satisfaction with health condition., Results: In accordance with international guidelines, the new language version of the tool may be used in research and clinical practice after cross cultural adaptation, linguistic validation and psychometric testing. This paper presents the results of cross-cultural adaptation and linguistic validation of the Russian version of GERD-HRQL. The following steps of linguistic and cultural adaptation of GERD-HRQL for Russia were conducted after the permission from the author of GERD-HRQL was obtained: forward translation with creation of two forward translations of GERD-HRQL in Russian, reconciliation and expert evaluation of translations of GERD-HRQL in Russian and creation of the preliminary version of GERD-HRQL in Russian, back translation, harmonization, creation of the first test-version of GERD-HRQL in Russian, cognitive debriefing and decentering, creation of the second test-version of GERD-HRQL in Russian, final expert evaluation and development of the final test-version of GERD-HRQL in Russian. Satisfactory face validity of the Russian test-version of GERD-HRQL was shown: face validity indices were 0.98, 0.95, 0.92, and 0.97., Conclusion: As the result of translation, cross cultural adaptation and linguistic validation, the Russian version of GERD-HRQL for the use in pts with GERD in Russia was developed. The Russian version of GERD-HRQL may be used in research studies and clinical practice after testing its psychometric properties.

The paper describes the results of 15 consecutive Russian clinical trials in the treatment of different types of acute leukemias, conducted by Russian cooperative group within the last 27-years and included more than 25 hundred patients. It was shown that the 5-years overall survival in AML younger than 60 years patients improved from 20 to 33%, in ALL - from 38 to 65%, in APL - from 0 to 95%. The cooperative work resulted in balanced clinical recommendations and protocols, reproducible in regional hospitals. Though till now there is a big difference in the long term outcome in acute leukemias patients treated in coordinating or regional centers mostly due to much higher early death rate: 7.5-9.5% vs 18-25%. This parameter should be used as criteria of the total efficacy of hematological service in each region of Russia. It became possible within the last years to integrate the minimal residual disease monitoring into clinical trials thus providing a clue parameter for choosing the further therapy - allogeneic stem cell transplantation. Non - chemotherapeutic approach with arsenic trioxide and all - trans retinoid acid had dramatically changed the toxicity and duration of treatment with very high efficacy. The Russian cooperative group was the first that started to include pregnant women with acute leukemias into clinical trials. This prospective and prolonged experience has shown that pregnancy in acute myeloid leukemia is an extremely poor prognostic factor, but it does not influence the outcome in acute lymphoblastic leukemia.

Obstructive sleep apnea (OSA) is an important and socially relevant problem of modern medicine, which is referred to as a most common pathological condition. The problem of OSA is especially urgent for inhabitants of high mountainous regions, as a combination of climatic, social, and cultural factors can significantly affect the course of the disease in both indigenous highlanders and people temporarily residing at high altitude. The paper reviews the current literature covering the problem of OSA at high altitude. It gives the data of Russian and foreign literature on the pathogenesis and clinical presentation of OSA. The author also analyzes an update on the impact of high altitude on the course of OSA in indigenous highlanders and people temporarily living at high altitude. She emphasizes the role of hypobaric hypocapnia as the most important factor for the development of central sleep apnea in the presence of conditions that are obstructive and aggravating the course of the disease.

Acute cerebrovascular accident (ACVA) and transient ischemic attack are among the leading causes of morbidity, disability, and mortality in the Russian Federation and the world. Ischemic strokes account for 70-80% of all ACVAs, with 20-30% of them being associated with stenotic atherosclerosis of the brachiocephalic arteries (BCA). The paper describes modern views on the problem of asymptomatic BCA atherosclerosis and considers the possibilities of identifying risk groups among the patients with asymptomatic atherosclerosis of the BCA.

The aim of the present paper was to evaluate the clinical features and risk of thrombotic events (TE) in patients with essential thrombocythemia (ET) and primary myelofibrosis (PMF), depending on the molecular characteristics of disease. Clinical data and laboratory parameters were analyzed in 50 ET patients and 50 PMF ones who had been followed up at the Department for Standardization of Treatments, National Research Center for Hematology, Ministry of Health of the Russian Federation, from February 2015 to September 2016. The patients with ET and those with PMF were found to have a high risk of TE. The risk for TE in the patients with ET is higher (24% in the entire group) than in those with PMF (14% in the study group). In ET, there is a high thrombosis risk in the detection of JAK2 and CALR gene mutations as compared with triple-negative cases. The PMF patients with JAK2 V617F mutations are at high risk for TE compared to those who are CALR mutation carriers and in triple-negative cases. There was no significant association of TE with high thrombocytosis. A factor, such as age, was found to be of no negative prognostic value in the patients with PMF.

The paper describes Russia's first diagnosed case of Erdheim--Chester disease (systemic histiocytosis) in a 65-year-old man who has been long treated for Ormond's disease (idiopathic retroperitoneal fibrosis). It also gives the data available in the literature on the pathogenetic components of these diseases and on the similarity of many clinical, laboratory, and morphological characteristics of these two immunoinflammatory diseases and covers the issues of their differential diagnosis. Invasive procedures with a careful morphological/immunomorphological examination of biopsy specimens obtained from affected tissues are shown to be necessary for accurate diagnosis.

The paper highlights the topical problems of nosocomial infection in the practice of obstetrics and perinatology. It systematizes procedures for controlling the occurrence of nosocomial infection and preventing its spread, such as identification of risk groups and risk factors and prerequisites for complications of epidemiological surveillance, as well as specific diagnosis in pregnant women. Group B streptococcus, one of the major pathogens of nosocomial infection, is described.

The paper discusses current approaches to diagnosing in an internal medicine clinic and to improving diagnostic tactics. It gives prospects for training physicians in current diagnostic approaches in the framework of the continuing medical education system.

The paper describes a clinical case of South African tick bite fever in a group of Russian tourists. The group of 5 people who had been ill with this disease after a tourist trip to the South African Republic (the Kruger National Park in the north-eastern province of Mpumalanga) were followed up. During their trip, all of them were bitten by different insects many times. The disease exhibited different clinical presentations; however, all the patients were noted to have a fever with slight intoxication and a maculopapular rash at different sites of the body; 3 had lymphadenopathy and one had a primary effect at the site of tick sticking. The diagnosis was verified by indirect immunofluorescence for the detection of high titers to Rickettsia conorii. The course of the disease was favorable in all the patients treated with antibiotics (doxycycline or ceftriaxone).

The paper summarizes the data of international and Russian studies concerning current approaches to the pharmacotherapy of rheumatoid arthritis. Particular emphasis is placed on the substantiation of the treat-to-target concept, on the efficacy and safety of genetically engineered biological agents, including the inhibitors of tumor necrosis factor, interleukin-6 receptors, T-lymphocyte co-stimulation, and anti-B-cell therapy.

The paper deals with the justification and description of clinical and organizational approaches to preventing cardiovascular diseases (CVD) in the primary health care system (PHCS) under the present conditions of health care modernization in Russia. It formulates the basic directions of systematic measures in integration strategies for the prevention of noncommunicable diseases (mainly CVD) at a federal level, in which practical measures are presented to improve a system for the early detection of high-risk individuals and to carry out measures for risk factor correction in PHCS, i.e. to implement high-risk strategies, including clinical and organizational approaches to reconstituting the medical prevention infrastructure in PHCS. This is favored by the new normative documents adopted by the Ministry of Health of Russia on the follow-up and prophylactic medical examinations of the adult population. The paper substantiates the objective need for such examinations and characterizes the main clinical and organizational approaches promoted in medical examinations, which is aimed at introducing the current science-based and economically expedient methods in the real practice of PHCS for the early identifications of atherosclerosis-induced major CVDs and, what is particularly important, a risk for their development. Prophylactic counseling as a compulsory component is first being introduced in medical examination procedures. The key clinical and organizational principle of effective CVD prevention in public health is the implementation of the relationship and continuity of preventive measures, which becomes realistic with the adoption of new regulations of clinical examinations, prophylactic medical examinations, and follow-ups. The improvement of CVD prevention is associated not only with the introduction of organizational innovation changes, but also with the need to create a prevention ideology in physicians at all levels. It is emphasized that a comprehensive approach and all integrated CVD prevention strategies both at the population level and in the PHCS facilities are the most efficient and cost-effective procedure to reduce premature deaths from CVD in the population and to improve the demographic situation in our country.

The paper discusses approaches to improving educational technologies in therapeutic disciplines taught at higher medical education institutes according to the basic curricula in Therapeutics (060101).

The paper presents data on planned measures to modernize our cancer service, one of the key areas of public health modernization, the main goal of which is to maximally ensure the citizens' right to have accessible and qualitative medical care. To adequately finance the field and to set up a current legislative base will give rise to the reorientation of the cancer service to priorities for primary prevention and active detection of malignancies, to an improvement of quality of life in cancer patients; to the formation of the populations' positive and integral awareness of health and healthy society, to the rational use of available manpower resources and inventory of all health facilities, which is extremely important under current conditions.

The paper presents an external respiratory failure (ERF) classification, a scientific rationale for its use in the clinical practice of departments of different profiles. The setting up of interclinical functional diagnostic laboratories and preventive health care facilities for the preclinical diagnosis of ERF is substantiated. The introduction of the classification of ERF into wide clinical practice is intended to form a social order for the design and purchase of diagnostic equipment for therapeutic-and-prophylactic institutions and to stimulate researches in clinical respiratory physiology, and to improve physicians' knowledge of this section of clinical science.

The paper presents the currently available data on the prevalence of diabetes mellitus (DM), its complications, including functional and structural changes in the gastrointestinal tract (GIT). A range of unsolved problems associated with the frequency, pattern and mechanisms of gastric functional and structural disorders in DM; the cause-and-effect relationship between DM and upper GIT pathology; and the role of Helicobacter pylori in the development of gastroduodenal mucosal changes in the presence of DM are described. The authors give the results of their own studies on 2 groups of patients with DM: (1) 463 patients treated for GIT pathology in a specialized gastroenterology unit; (2) 1500 patients were followed up by a polyclinic endocrinologist. The study has shown that the number of diabetic patients with GIT dysfunction complaints constantly increases. Ulcerative erosive lesions were detected in 36.6% of the inpatients with DM and only in 1.9 and 3.2% of the outpatients with Types 1 and 2, respectively; moreover, the patients with Type 2 DM more frequently complained of epigastralgia than those with Type 1 DM.

The paper considers the pathogenesis, clinical picture, and diagnosis of acute intoxications with alcohol and substitutes, and its prehospital medical care. It details an emergency team's tactics in patients with the above conditions.

The paper deals with the topical problem of modern gastroenterology and coloproctology--the influence of genetic factors on the development and course of Crohn's disease (CD). It presents the data of foreign authors and the results of Russia 's first study evaluating the effect of the major polymorphic variants of the NOD2/CARD15 gene predisposing to CD on the risk, course, and other features of CD.

The paper presents the proceedings on the Symposium on the Occasion of the 100th Anniversary of Duodenal Intubation" at the 9th Congress of the Scientific Society of Gastroenterologists of Russia. Particular emphasis is laid on the significance of the clinical and experimental studies-based scientific discovery made by V. A. Galkin and A. S. Chechulin--the Galkin-Chechulin effect (the 1957 priority) for the detection and treatment of prestone stages of cholelithiasis. The steps for improving the bile examination techniques at duodenal intubation (V. A. Galkin, L. S. Korzyuk, V. A. Maksimov, A. A. Ilyechenko) are described. Duodenal intubation as the method of choice for bile examination is proposed to be included into the mandatory diagnostic standards.

The paper presents the data available in the literature on mutations in known genes in pancreatitis, such as cationic trypsinogen (PRSS1), pancreatic secretory trypsin inhibitor (PSTI/SPINK1), cystic fibrosis (CFTR), and apolipoprotein E (APOE) genes, as well as the new candidate gene--chymotrypsinogen (CTRC). It also gives the results of the authors studies estimating the spread of the mutations in the PRSS1 (2.5%), PSTI/SPINK1 (3.3%), and CFTR (0.8%) genes, as well as APOE polymorphism in patients with pancreatitis. It is shown that the E4 allele of the APOE gene was more frequently identified in patients with acute pancreatitis than in those with chronic pancreatitis (0.143 +/- 0.05 and 0.026 +/- 0.02, respectively; p < 0.05). An overview is given of 7 major classes of candidate genes implicated in the pathogenesis of cholesterol cholelithiasis (CL): hepatic enzymes regulating blood lipid composition; receptors of lipoproteins, hepatic and intestinal membrane and intracellular transport proteins; factors regulating the transcription of lipids and bile salts, cholecystokinin and its receptors, and mucin. In the authors' epidemiological study, the spread of APOE alleles and genotypes did not differ in women with and without CL; low molecular-weight apolipoprotein(a) isoforms (B, S2) were significantly found in patients with CL than in those without CL; the spread of the CG genotype in the TRPM8 gene was significantly lower in women with cholesterol CL than that in the Novosibirsk population. These polymorphisms have been proved to be associated with bile cholesterol concentrations in women with cholesterol CL. The opposite effect of the APOE4 allele on gallbladder stone formation processes is demonstrated, by using the APOE polymorphism as an example, which shows it necessary to examine each specific population to elicit a possible association between the polymorphism of different genes and gastrointestinal tract diseases.

Unlabelled: The paper sums up the many-year cooperative Russian-American studies of the epidemiology of spondylarthropathies in the arctic populations of the Chukot Peninsula and Alaska., Aim: Comparison of the epidemiology of spondylarthropathies in the indigenous population of the Chukot Peninsula and Alaska., Materials and Methods: A universal design of investigation with the same diagnostic criteria was used in both countries. A total of 974 indigenous residents of the Chukot Peninsula were examined simultaneously, on the Alaska the sampling was formed as the residents applied for care., Results: In both regions the study revealed 1) a high incidence of HLA-B27, reaching 40% in the Chukot Eskimos; 2) a similarly high incidence of spondylarthropathies varying from 2 to 3.4%; 3) a similar spectrum of diseases, including, primarily, ankylosing spondylarthritis and Reiter's syndrome and undifferentiated spondylarthropathies and (rarely) psoriatic arthritis. Among HLA-B27 positive adults, the incidence of spondylarthropathies in all groups is 4.2% and of ankylosing spondylarthritis 1.5%., Conclusion: A high incidence of spondylarthropathies, varying from 2 to 3.4%, was revealed in the Arctic populations of the Chukot Peninsula and Alaska with a high incidence of HLA-B27 antigen. Although the spectrum of detected diseases was similar in the two groups, ankylosing sponditis was more incident on the Chukot Peninsula, whereas on the Alaska reactive arthritis and nondifferentiated spondylarthropathies predominated, which can be explained by difference in the methods of examination.

The paper reports the results of a simultaneous study of muscular performance (MP) and main risk factors (RF) of ischemic heart disease (IHD) in 466 locomotive team members aged 30-49 free of IHD symptoms. A negative relationship has been established between MP and systolic, diastolic pressure, body mass. A 4-6-year follow-up of MP and IHD RF showed that MP improvement was associated with a trend to improvement in RF, while MP worsening entailed greater risk of IHD, especially in a group of 30-39-year-olds.

The paper presents the results of clinical and labour examinations of 51 drivers with cardiac arrhythmia. Long-term postinfarctional ECG monitoring was attempted in 30 drivers in the course of driving. The frequency of arrhythmia episodes correlated with the presence of extrasystole in acute and subacute period of the disease, anginal functional class, the size and time of myocardial infarction. Single episodes of ventricular extrasystole registered in the course of driving did not interfere with professional activities because such extrasystoles did not imply the risk of more severe arrhythmia. Labour prognosis in drivers with frequent, polytopic ventricular extrasystoles or fibrillation was much worse.

The paper is concerned with phenotyping of alpha 1-antitrypsin using a method of isoelectric focusing in the polyacrylamide gel with ampholine (pH-4-6) in 1000 healthy persons and 583 patients with chronic bronchitis. Phenotype M was registered in 96 and 95.71% of the cases, respectively. The occurrence of heterozygous phenotypes was practically similar among the healthy persons as well as among the patients (4.0 and 4.29%, respectively). It was concluded that the heterozygous carrying of an alpha 1-antitrypsin deficit gene was of no particular importance in the development of chronic bronchitis.

The paper is concerned with the results of a study of efficacy of rehabilitation of 1174 patients with chronic nonspecific pulmonary diseases in sanatoria. On the basis of clinical criteria and the results of bicycle ergometry 4 clinicofunctional groups of patients were defined. A tactical approach to the differentiated use of different types of therapeutic, physical and psychic rehabilitation was worked out for these groups. An index method for assessment of the efficacy of rehabilitation based on 5 groups of symptoms was proposed. Therapeutic efficacy in different clinicofunctional groups varied from 89.6% in the 1st group to 71.8% in the 4th group; it was higher among the patients with chronic nonobstructive bronchitis (from 89 to 98%) than among the patients with chronic obstructive bronchitis and bronchial asthma (from 70 to 80%).

The paper is concerned with the results of a special study of the deontological potential of students prior to and after subinternship. Their attitude to occupation, the knowledge of the fundamentals of deontology, motivation of behavior in specific deontological situations and the reasoning of their actions and opinions were determined. A considerable gap between a high level of correct theoretical (declarative) ideas of deontology rules and inability to use them in everyday clinical practice was observed. Experience of the correction of graduates' deontological disposition was presented. The dialectic unity of inductive and deductive methods in mastering the fundamentals of deontology was stressed. Methods of the verification of deontological training of students in medical institutes were specified.

The paper discusses the efficacy of rehabilitation of 108 patients with rheumatic fever with the use of radon baths, of them in 36 in conjunction with homologous immunoglobulin. The patients were treated in a local balneological hospital. Balneotherapy has been shown to have a beneficial effect on the humoral and cellular immune response, and on factors of the body non-specific resistance in patients with unstable clinicolaboratory characteristics after the treatment for protracted rheumocarditis with minimal activity and latent course. The number of relapses and intercurrent infections were found to be decreased, and the working ability to be improved. The most pronounced effect was recorded in a group of patients who received radon baths and homologous immunoglobulin.