Репозиторий Университета

© 2020, LLC Science and Innovations. Pancreatic cancer (PC) is one of the most fatal types of oncological disease in the world and is an extremely aggressive cancer with a poor prognosis. The objective of this review was to analyze the domestic data of the incidence of PC in the Russian Federation and to analyze the protocols that are used for the management of this group of patients in Russian clinical centers. For the analysis of the literature sources, the data in the elibrary.ru database published in the period from 2015 to 2019 were used. The methodology that was used in each study was examined in order to ensure its reliability, and these data were selected as potential sources of evidence for the preparation of national recommendations. The study results influence the level of evidence assigned to the publication. Updates to the national recommendations are conducted at least once every three years, and these updates depend on new information about the diagnosis and management of patients with PC.

© 2020, LLC Science and Innovations. Pancreatic cancer (PC) is one of the most fatal types of oncological disease in the world and is an extremely aggressive cancer with a poor prognosis. The objective of this review was to analyze the domestic data of the incidence of PC in the Russian Federation and to analyze the protocols that are used for the management of this group of patients in Russian clinical centers. For the analysis of the literature sources, the data in the elibrary.ru database published in the period from 2015 to 2019 were used. The methodology that was used in each study was examined in order to ensure its reliability, and these data were selected as potential sources of evidence for the preparation of national recommendations. The study results influence the level of evidence assigned to the publication. Updates to the national recommendations are conducted at least once every three years, and these updates depend on new information about the diagnosis and management of patients with PC.

© 2019, MDPI AG. All rights reserved. Tuberculosis is known to be the biggest global health problem, causing the most deaths by a single infectious agent. Vaccine-development efforts are extremely important. This paper represents the results of the first-in-human trial of recombinant subunit tuberculosis vaccine GamTBvac in a Phase I study. GamTBvac is a new BCG booster candidate vaccine containing dextran-binding domain modified Ag85a and ESAT6-CFP10 MTB antigens and CpG ODN adjuvant, formulated with dextrans. Safety and immunogenicity of GamTBvac were estimated in an open-label clinical trial on 60 Mycobacterium tuberculosis uninfected (MTB-uninfected) volunteers previously-vaccinated with Bacillus Calmette—Guérin vaccine (BCG). The candidate vaccine had an acceptable safety profile and was well-tolerated. Three different vaccine doses with a double-immunization scheme were assessed for immunogenicity and induced a significant increase in IFN-γ in-house IGRA response and IgG ELISA analysis. Among them, the half dose vaccine group (containing DBD-ESAT6-CFP10, 12.5 μg; DBD-Ag85a, 12.5 μg; CpG (ODN 2216), 75 μg; DEAE-Dextran 500 kDa, 250 μg; and Dextran 500 kDa, 5 mg) provided high, early and stable in time immune response specific to both protein antigen fusions and is proposed for the further studies.

© 2019 Elsevier Inc. Over the last years, the experimental compound olesoxime, a mitochondria-targeting cholesterol derivative, has emerged as a promising drug candidate for neurodegenerative diseases. Numerous preclinical studies have successfully proved olesoxime's neuroprotective properties in cell and animal models of clinical conditions such as amyotrophic lateral sclerosis, Huntington disease, Parkinson disease, peripheral neuropathy and spinal muscular atrophy. The beneficial effects were attributed to olesoxime's potential impact on oxidative stress, mitochondrial permeability transition or cholesterol homoeostasis. Although no significant benefits have been demonstrated in patients of amyotrophic lateral sclerosis, and only the first 12 months of a phase II/III clinical trial showed an improvement in motor symptoms of spinal muscular atrophy, this orphan drug may still offer undiscovered potential in the treatment of neurological diseases. In our earlier preclinical studies, we demonstrated that administration of olesoxime in mouse and rat models of Huntington disease improved psychiatric and molecular phenotypes. Aside from stabilising mitochondrial function, the drug reduced the overactivation of calpains, a class of calcium-dependent proteases entangled in neurodegenerative conditions. This observation may be credited to olesoxime's action on calcium dyshomeostasis, a further hallmark in neurodegeneration, and linked to its targets TSPO and VDAC, two proteins of the outer mitochondrial membrane associated with mitochondrial calcium handling. Further research into the mode of action of olesoxime under pathological conditions, including its effect on neuronal calcium homeostasis, may strengthen the untapped potential of olesoxime or other similar compounds as a therapeutic for neurodegenerative diseases.

The article describes the principles of choosing parameters to be included into account registry of mandatory medical insurance system in 2019. The parameters should be applied for retrospective analysis of anti-neoplasm treatment of solid tumors in adults for accordance with clinical recommendations. It is proposed to extend account registries of mandatory medical insurance system with additional 13 parameters, reflecting both tumor type and course of disease and stages of medical care as well.

The characteristic feature of molecular medicine as medicine based on molecular structure of human genome data, is its individual character. It is focused on correcting pathological process in specific individual considering unique characteristics of its genome. The other most important feature is its expressed preventive direction. The complete genome information can be obtained well before the onset of disease. The appropriate preventive measures can completely eliminate or significantly prevent development of severe disease. The establishment of gene network of every multi-factorial disease, identification of central genes and genes-modifiers in it, analysis of association of their alleles with disease, development on this basis of set of preventive measures for specific patient constitute conceptual and methodological basis of predictive medicine. As a result of the examination, information can be obtained concerning particular risk of disease development. The physician, considering the results of molecular genetic analysis, elaborates tactics of pathogenetically justified preventive therapy, i.e. corrects congenital metabolic defect.

© 2018, The Author(s). Introduction: Trimetazidine (TMZ) has been shown to reduce angina symptoms and to increase exercise capacity in randomized clinical trials, but more extensive data would be useful to assess its effects in real-world clinical practice and in patients with different durations of disease. Methods: CHOICE-2 was a Russian, multicenter, 6-month, open-label, prospective observational study that assessed the effect of adding TMZ modified release 35 mg bid to antianginal treatment in a real-world setting. The present analysis of CHOICE-2 results explored the effects of adding TMZ to background antianginal therapies with regard to the duration of stable angina. Results: A total of 741 patients with known durations of disease were divided into four groups according to stable angina pectoris (AP) duration, ranging from less than 1 year to more than 9 years. Addition of TMZ led to a significant decrease in the frequency of angina attacks and in the use of short-acting nitrates in all groups. In patients with recently diagnosed angina (AP duration < 1 year), the average number of angina attacks per week decreased significantly from 3.75 ± 4.63 to 0.67 ± 1.51 and in those with advanced disease (AP duration > 9 years) from 5.63 ± 5.24 to 1.32 ± 2.07. Angina-free walking distance also improved significantly. Addition of TMZ also improved patient well-being. Results were achieved rapidly (within 2 weeks), were maintained over 6 months, and were obtained in all patient groups regardless of angina duration. Conclusion: TMZ added to other antianginal therapies proved to be effective for reducing angina attacks and short-acting nitrate use, increasing angina-free walking distance, and improving patient well-being in a real-life setting, irrespective of angina duration, including patients with recently diagnosed angina. This provides an opportunity for intensification of treatment early on in the disease process, with the aim of decreasing angina burden and improving patient quality of life. Funding: Servier. Trial Registration: ISRCTN identifier ISRCTN65209863. Plain Language Summary: Plain language summary available for this article.

The prevalence of habitual miscarriage varies depending on territories of the Russian Federation and other countries. The rate of premature delivery in the Moscow Zelenograd administrative okrug in 2013-2015 in average made up to 4.5%-4.7%. The percentage of habitual miscarriage made up to 3.6% that is a rather low indicator as compared with other Moscow okrugs and national average indices. The article considers three-level model of evaluation of medical, economic and social efficiency of obstetric gynecologic care support of population at the out-patient stage.

© 2018, Springer Science+Business Media, LLC, part of Springer Nature. Issues pertaining to determination of the pharmacokinetic parameters of calcium preparations are examined using their comparative bioavailability as an example. Pharmacokinetic parameters of calcium such as area under the concentration—time curve (AUC) and maximum concentration (Cmax) are calculated considering the background calcium contents in volunteers. Calcium excretion with urine is assessed as clearance of creatinine, a calcium elimination factor. The dynamics of the content of parathormone (PTH), the main hormone regulating calcium homeostasis, are studied. The results can be used to plan clinical trials for assessing the pharmacokinetics of drug analogs of endogenous compounds.

© 2018, Pediatria Ltd. All rights reserved. Clinical guidelines for the selection and use of antibiotics (AB) for common and most important community-acquired infections are aimed at increasing the treatment efficacy and overcoming growth of bacterial pathogens resistance to AB. They are based on the principle of positive ratio of «benefit/risk» of AB and selection of primary and alternative drugs. The article presents Russian and foreign data on pediatricians preferences in the choice of AB for ARI in children, on the level of Streptococcus pneumoniae resistance to penicillins and macrolides and other respiratory bacterial pathogens to macrolides in Russia (including the pediatric population) and abroad, which led to similar changes in grouping of AB in the Eurasian clinical recommendations and WHO recommendations. It demonstrates a significant coincidence of the AB choice for community-acquired pneumonia and acute bacterial rhinosinusitis in children in comparable recommendations with the recognition of amoxicillin as the first choice drug and the general tendency to restrict the use of macrolides. It also points on the need to control the AB use.

© 2018 Aisanov et al. The high prevalence of COPD together with its high level of misdiagnosis and late diagnosis dictate the necessity for the development and implementation of clinical practice guidelines (CPGs) in order to improve the management of this disease. High-quality, evidence-based international CPGs need to be adapted to the particular situation of each country or region. A new version of the Russian Respiratory Society guidelines released at the end of 2016 was based on the proposal by Global Initiative for Obstructive Lung Disease but adapted to the characteristics of the Russian health system and included an algorithm of pharmacologic treatment of COPD. The proposed algorithm had to comply with the requirements of the Russian Ministry of Health to be included into the unified electronic rubricator, which required a balance between the level of information and the simplicity of the graphic design. This was achieved by: exclusion of the initial diagnostic process, grouping together the common pharmacologic and nonpharmacologic measures for all patients, and the decision not to use the letters A–D for simplicity and clarity. At all stages of the treatment algorithm, efficacy and safety have to be carefully assessed. Escalation and de-escalation is possible in the case of lack of or insufficient efficacy or safety issues. Bronchodilators should not be discontinued except in the case of significant side effects. At the same time, inhaled corticosteroid (ICS) withdrawal is not represented in the algorithm, because it was agreed that there is insufficient evidence to establish clear criteria for ICSs discontinuation. Finally, based on the Global Initiative for Obstructive Lung Disease statement, the proposed algorithm reflects and summarizes different approaches to the pharmacological treatment of COPD taking into account the reality of health care in the Russian Federation.

© 2018, Media Sphera Publishing Group. All rights reserved. This publication was designed to report the experience gained by the Department of ear, nose and throat diseases at I.M. Sechenov First Moscow State Medical University in the matters concerning professional medical education in the framework of the clinical residency. The main factors that contribute to the adequate shaping of the future ENT-doctor are considered. These include the continuity of generations and conservation of the traditions in the combination with the development of the leading areas of scientific, clinical and educational work.

© 2018 Voprosy Sovremennoi Pediatrii - Current Pediatrics. All rights reserved. The problem of dosing drugs at an early age is conditioned by specific metabolism of medicinal products (MP) in the child's body. Currently, there are a few clinical trials on the study of physiological characteristics in different periods of childhood and systematised data. It is still relevant to understand the characteristic differences that affect the bioavailability, distribution and excretion of MP, especially in children over one month of life. The results of such studies are necessary in order to formulate the recommendations for use of MP in children taking into account their age and compensate for the lack of data from direct clinical trials in pediatrics. The possibility of using a dose calculation method regarding the fat content of the body in different periods of childhood and the chemical properties of the substance has been discussed.

The objective of the research was to elaborate experimental-theoretical and clinic-bacteriological rationale for the application of laser diagnostic for identification of main pathogens of purulent-inflammatory processes in maxillofacial area. For germs identification by giant Raman scattering effect SERS-substrate with nano silver metallic balls, reference strains (Ps. aeruginosa 27853 and S. aureus 25923) and clinical cultures of Staphylococcus, Bacillus and Escherichia coli were used. Using an example of purulent inflammation pathogens we considered that each of bacterial species is characterized by individual spectral lines of Raman scattering, which allows to identify them in short term (1-2 min). Moreover the proposed method is highly sensitive (105-106 CFU/ml). Creation of germs library and device portability makes use of laser diagnostic for express-indication purulent infections possible directly in clinical conditions. Thus, analytical capability, quick result, high sensitivity and peculiarity, economical effectiveness due to lack of necessity to use growth medium and to transport it to microbiological lab gives an opportunity to consider laser diagnostic as a perspective universal express-method of clinical microbiology.

Literature data devoted to transplantation of Langerhans cells have been analyzed. The main stages, indications, dissection of islets, immunosuppressive therapy, complications and data of the latest clinical trials were discussed.

© 2018 Media Sphera Publishing Group.All Rights Reserved. In the modern clinic of internal diseases, the specific gravity of the infectious pathology, manifested by various clinical syndromes, is increasing. Infectious pathology is represented by diseases of the respiratory system, heart disease (infective endocarditis, cardioimplant infections, viral myocarditis), infectious arthropathies, extrahepatic manifestations of viral hepatitis, cytopenic syndromes, various manifestations of sepsis and some other conditions.In most cases, the diagnosis and management of such patients is the responsibility of the internist, who must be able to suspect the infection and carry out its verification. In the process of diagnostic search and management of patients, close interaction of the internist with a clinical microbiologist, clinical pharmacologist and other related specialists is necessary.

© 2018 Voprosy Sovremennoi Pediatrii - Current Pediatrics. All rights reserved. Background. Infections are the main cause of death for patients with autoimmune rheumatic diseases. In adult patients with rheumatoid arthritis (RA), mortality caused by respiratory infections is 2-5 times higher than in the population. One of the frequent infectious complications in the course of treatment with tocilizumab, the first-choice drug for treating systemic juvenile idiopathic arthritis (sJIA), is pneumonia characterized by a poor clinical picture, normal values of laboratory indices of the disease activity (ESR, C-reactive protein) with pronounced changes in the lungs revealed by computed tomography. In case of acute respiratory infection in children with systemic JIA, immunosuppressants and genetically engineered biological preparations (GEBP) are discontinued. This often leads to an exacerbation of the underlying disease and the progression of a pathological process. At present, vaccination against pneumococcal infection in Russia is not included in the standard for managing patients with rheumatic diseases. Studies of the safety and efficacy of vaccination with 13-valent pneumococcal conjugate vaccine (PCV) in patients with sJIA receiving genetically engineered biological preparations were not conducted. Clinical Case Description. The article shares the experience of vaccination of a girl aged 9 years with a 13-valent PCV that was conducted in the course of a scientific investigation, which studied the efficacy and safety of vaccination of children with systemic JIA prior to prescription of GEBP tocilizumab. Vaccination did not cause a deterioration in the course of the main disease (1 month), led to a reduction in the incidence of acute respiratory infections (from 4 to 1 time within 6 months before and after vaccination), and discontinuation of antibacterial drugs within 6 months after vaccination. Conclusion. The safety of a 13-valent PCV in a child with sJIA and a decrease of the incidence of respiratory diseases after vaccination, their complications, and the use of antibacterial drugs have been shown.

© 2018 Limited Liability Company KlinMed Consulting. All Rights Reserved. In this article we have described clinical pharmacology and data of clinical studies of an innovational drug valsartan + sacubitril in patients with chronic heart failure (CHF). The use of supramolecular complex valsartan + sacubitril allows to elevate quality of life and improve prognosis of patients with CHF. High efficacy of valsartan+sacubitril relative to impact on composite primary end-point (cardiovascular death + hospitalization due to CHF) was demonstrated in the clinical trial PARADIGM-HF in which it was compared with angiotensin converting enzyme inhibitor enalapril. Advantages of the use of valsartan + sacubitril for the budget were demonstrated in pharmacoeconomic studies. These advantages are maximally realized at long-term administration. Cost-efficacy of the use of valsartan+sacubitril in pharmacotherapy of CHF is comparable with that of statins in the treatment of ischemic heart disease or implantation of a cardioverter-defibrillator in prevention of sudden cardiac death. Thus, introduction of the drug into practice can be expected to reduce budget expenditures.

© 2018, Dynasty Publishing House. All rights reserved. The objective. To offer a clinical and laboratory characteristic of coronavirus infection in hospitalised children. Patients and methods. The group of study included 50 children, who were diagnosed with coronavirus infection by polymerase chain reaction (PCR). Mono-coronavirus infection was found in 40 children (80%), mixed virus infection conditioned by a combination of two or three viruses - in 10 children (20%). Results. In all examined children with coronavirus infection disease had an acute onset and took a mild or moderate course. In general, the clinical picture of disease was manifested by cough, signs of rhinitis (stuffy nose, mucus discharge from the nose), febrile fever (in 52.5% of patients with mono-infection and in 80% of children with mixed infection), laryngotracheitis with laryngeal stenosis grade 1 (in 52.5% with mono-infection and in 80% with mixed infection). In 10% of children with monoinfection and in 50% of children with mixed infection gastrointestinal dysfunction was noted in the form of repeated vomiting to 2-6 times, diarrhoea to 1-4 times daily without pathological admixtures. Haematological parameters did not show any characteristic specificities in any child in both mono-infection and mixed infection. Cclusionon. Catarrhal inflammation is the leading clinical syndrome in mono- and mixed coronavirus infection; disease was manifested by cough, often - elevated body temperature, signs of stenosing laryngitis; part of children developed gastrointestinal dysfunction.

© 2018 Dynasty Publishing House. All rights reserved. The objective: The purpose of the study is to establish the role of infection with herpes simplex viruses type I and II in the pathogenesis of urogenital infection in pregnant women. Patients and methods: 89 patients of I, II trimester gestation, aged 18 to 35 years (average age of 27.5 ± 5.6 years) were examined. The design of the research and the methodology of verification of the UGI pathogens of pregnant women are presented in previously published materials. The establishment of character of pregnancy course (urgent delivery, premature birth, termination of pregnancy and mis-carriage), the presence or absence of infection and/or clinical manifestations of infectious and inflam-matory diseases, as well as evaluating the gene expression of TLR-2, TLR-3, TLR-4, TLR-8 (in relative units - RU) was conducted according to manuals. Results: It is established, that in UGI in pregnant combined viral-bacterial infection is registered. Viral component of UGI pathogens in pregnant women is presented by the association of viruses from the Herpesviridae family - herpes simplex viruses, Cytomega-lovirus, Epstein-Bar virus. Against the background of polyfactorial mechanisms of the pathogenesis of abortion, extra maximum activation of gene expression of TLR (22-23 RU or more) additional external factors, for example, infections can be an aggravating pathogenetic factor of miscarriage. Reduced expression of genes of TLR2, TLR4, TLR3 and TLR8 in the mucous membrane of the cervical canal in UGI of pregnant women in infection with herpes simplex virus due to the oppressive effect of pregnancy on the reaction of TLR, combined with the immunodepressive effect of the virus itself. With the violation of cellular part of immuno-logical reactivity of the body under the influence of adverse endogenous and exogenous factors on the process of pregnancy is activated the infectious process caused by the bacte-rial-viral pathogens association, which is accompanied by hyper reaction and increased reaction from the expression of genes of TLR, determines the pathological development of pregnancy. It is established that in the UGI of pregnant gene expression levels of TLR2-21.2 and above, TLR4-23.0 and above, TLR8 - 26.0 and above (the level of gene expression of TLR8 above 28 is the predictor of the onset of abortion and miscarriage) testify to the acute infectious process with the clinical manifestations of the UGI, and also indicates the possible interruption of pregnancy and miscarriage; levels of gene expression of TLR2 below 21.2, TLR4 below 23.0, TLR8 below 26.0, in-dicated a decrease in the severity of the infectious process and its chronicity, as well as the possibility of direct microbial damage to the tissues of UGT, placenta, and fetus. Conclusion: Verified in preg-nant women in 61% of cases clinical manifestations of the infectious process are necessarily associated with the verification of the association of herpes simplex viruses I and II type - triggers of infectious process deterioration, determining the prognosis and outcome of the development of the UGI in preg-nant.