Репозиторий Университета

AIM: To analyze long-term outcomes of tracheal transplantation. MATERIAL AND METHODS: There were 1128 patients with cicatricial tracheal stenosis who have been operated at the Petrovsky Russian Research Center for Surgery and the Sechenov First Moscow State Medical University for the period 1963-2015. RESULTS: Operations have become safer. Postoperative morbidity and mortality reduced from 41.4% (1963-1980) to 5.6% (2001-2015) and from 21.9% (1963-1980) to 0.5% (2001-2015), respectively. Tracheal transplantation was performed in 2 cases and fundamentally different tracheal structures were applied. Donor thyreotracheal complex with restored blood supply through thyroid vessels was used in the first case (2006). Perennial experimental trials preceded clinical application of this technique. In the second case (2010) we applied scientific results of foreign colleagues (cellular technologies and methods of regenerative medicine to create artificial trachea). Patients are still alive after 12 and 8 years, respectively. Restoration of blood supply of donor trachea is possible through thyroid collaterals. This technique is successful in long-term period. Tissue-engineered trachea cannot be considered true trachea due to no all tracheal components. However, such trachea provides air-conducting, evacuation and protective functions. Tracheomalacia requires further researches as one of the main problems of tracheal transplantation.

© 2018 Voprosy Sovremennoi Pediatrii - Current Pediatrics. All rights reserved. The lecture analyzes modern knowledge about etiology, key mechanisms of pathogenesis, clinical manifestations, types, diagnostic methods and treatment strategy of chordoma (tumor from notochordal cells). To assess the retention of the lecture material, a case problem and multiple-choice test questions are given.

© 2018 Izdatel'stvo Meditsina. All rights reserved. The right drug at the right dose administered to a patient in time is the goal which all medical specialists aim at when prescribing medicines to patients. Pregnancy is a condition when the principle of personalized pharmacotherapy is especially relevant. Due to the developing fetus and the occurring changes in the maternal organism, the selection of drug therapy during pregnancy is especially difficult for a clinician. This issue is tightly intertwined with clinical pharmacogenetics since the genetic code of a woman that determines the activity of the liver cytochrome, the fetus-placental barrier, and renal clearance contributes to the peculiarities of the drug metabolism during pregnancy. Additional data provides the opportunities to form therapeutic models and to determine the ways of personifying pharmacotherapy in pregnancy. The purpose of this review is to summarize the available data on the pharmacogenetics of antihypertensive drugs used during pregnancy.

© 2018 Media Sphera Publishing Group. All rights reserved. The role of modified low density lipoprotein in the activation of the classical pathway of the complement system and increasing expression C3 gene in human macrophages is described, role of these processes on the progression of atherosclerotic vascular lesions is considering.

© 2018 Pirogov Russian National Research Medical University. All Rights Reserved.  Rivaroxaban is a safer and more effective alternative to warfarin. However, there are reports of some cases of major hemorrhagic complications associated with rivaroxaban that significantly impair the patients' quality of life and can lead to a fatality. Personalized therapy, including pharmacogenetic testing, may help prevent such adverse events. This study aimed to investigate how ABCB1 3435C>T (rs1045642) and CYP3A5 6986A>G (rs776746) gene polymorphisms, when carried by a patient taking rivaroxaban to prevent thrombosis after total hip or knee replacement surgery, affect prothrombin time (PT). Sixty-five patients participated in the study. Their genotypes were identified by PCR in real time. To learn PT peculiar to each patient, we collected venous blood on the 5 th day of their anticoagulation therapy, 1 hour before they took rivaroxaban and 3 hours after. Having calculated %∆PT, we divided the patients into 2 groups: 1) %∆PT ≤ 0 (n = 7; 10.8%); 2) %∆PT > 0 (n = 58; 89.2%). Regarding the distribution of rs1045642 polymorphism, we determined the difference between the groups to be statistically significant (χ 2 = 6.64; p = 0.027). As for rs776746 polymorphism, the difference was insignificant (χ 2 = 0.101; p = 1.0). We discovered that rs1045642 polymorphism has a significant effect on PT variance in patients taking rivaroxaban to prevent thrombosis after total hip or knee replacement surgery.

© 2018 Media Sphera Publishing Group.All right reserved. Aim. To estimate association between disorders of salt-water homeostasis on admision and the remote one-year prognosis for patients hospitalized with decompensated CHF NYHA FC III-IV. Materials and methods. This prospective study was based on clinical amnestic data and results of one-year follow-up of 111 consecutive patients admitted for decompensation of CHF to the State Clinical Hospital No. 24 in January 2015-February 2016. Results. The relative risk of death within one year for patients hospitalized for decompensated CHF with disorders of water and salt homeostasis increased 1.43 times by the end of one-year follow-up compared to patients with normal blood levels of sodium and potassium on admission (RR=1.43; 95 % CI: 1.10-1.87; p<0.01). Furthermore, the relative risk of death within one year was significantly increased 1.4 times in the subgroup of patients with hypernatremia (RR=1.41; 95 % CI: 0.99-2.01; p<0.05, respectively) and 1.4 and 2.3 times in subgroups with hypo-/hyperkalemia respectively (RR=1.39; 95 % CI: 0.93-2.07; p<0.05 and RR=2.23; 95 % CI: 1.04-4.78; p<0.01) compared to patients with normal blood levels of sodium and potassium on admission. Conclusion. Disturbed water and salt homeostasis on admission of patients hospitalized for decompensated NYHA FC III-IV CHF is a predictor for an unfavorable remote prognosis.

© 2018 Ima-Press Publishing House. All Rights Reserved. Objective: to investigate the effectiveness of cognitive and motor training as an additional method to basic therapy in patients with Alzheimer's disease (AD) and vascular cognitive impairment (VCI). Patients and methods: The investigation enrolled 41 patients (15 women and 26 men; mean age. 73.59±6.3 years), including 32 patients with AD (mean age 74.94±5.15 years) and 9 patients with VCI (mean age, 72.31±4.98 years). Cognitive impairment (CI) corresponded to mild dementia in 15 patients (5 women and 10 men; mean age 74.6±2.8 years) and to moderate dementia in 29 (10 women and 19 men; mean age 72.1±3.2 years). The patients were randomly assigned to individual, group, and mixed (individual and then group) cognitive training groups. Quantitative scales were used to assess changes in CI and emotional and behavioral disorders after 1.5, 3, and 6 months of therapy. Results and discussion: During cognitive and motor training, all the groups showed a significant decrease in the severity of CI (p < 0.05), depression, anxiety, and apathy. The effectiveness of the training was further influenced by the severity of concomitant cardiovascular disease, the degree of apathy, adherence to the training, and the early initiation of basic symptomatic therapy. The greatest positive changes in anxiety and depressive disorders were noted in the patients receiving group cognitive and motor training. Conclusion: The results of the investigation allow group cognitive and motor training to be recommended as a mainstay in the therapy of patients with CI concurrent with emotional disorders.

© 2018 Ima-Press Publishing House. All Rights Reserved. The recently discovered glymphatic system (GS) ensures the efficient clearance of interstitialfluid and soluble compounds from the central nervous system into cerebrospinal fluid (CSF), which compensates for the lack of conventional lymphatic vessels in the brain parenchyma. This unique anatomical and physiological phenomenon had been unknown until 2012. GS lacks inherent proper vessels P the cuirent of CSF and interstitial fluid is carried out directly inside the arterial walls (the perivascular pathway) or near the walls of the cerebral arteries and veins (the paravascular pathway). Current biorheological technologies could establish a special role of aquaporin-4 in the filtration of CSF and interstitial fluid. The close link between GS and the CSF circulatoiy system allows the established views on fluid dynamics within the brain to be reconsidered. The discoveiy ofGS can contribute to our understanding of the pathogenesis of increased intracranial pressure and neurodegenerative diseases, as well as to the elaboration of new therapeutic approaches to their treatment.

© 2019, Privolzhsky Research Medical University. All rights reserved. The study of the epidermis and derma histogenesis, including its epigenetic regulation, is an actively developing field of histology and embryology. The results of the study can elucidate the mechanisms of pathogenesis of some skin diseases of unknown etiology. Wnt signaling is a key regulator of the main morphogenetic processes — cell proliferation and differentiation. Downstream of Wnt signaling is carried out by canonical and non-canonical pathways. Impairments of Wnt signaling in prenatal and postnatal development lead to degenerative and tumor diseases of the skin and hair. Clinical manifestations of the prenatal disorders of skin development epigenetic regulation in the period may appear long after the birth. Identification of factors that disturb the regulation of morphogenetic processes is an important task for investigators. It was found out that activation of the mother’s immune system in the early pregnancy resulted in the development of transient alopecia in the offspring of mice. There was the correlation established between the disorders of epidermal and dermal histogenesis and alopecia as well as the development of regional dysmorphogenetic changes in the skin, which indicate the need to study the rates and features of skin development in various parts of the body.

© 2018 Izdatel'stvo Meditsina. All Rights Reserved. Nerve damage is a common severe trauma caused by a complete or partial disruption of the integrity of the nerve trunk and appropriate dissociation of the CNS and denervated tissue. «Golden standard» in the treatment of extensive injuries of peripheral nerves is the use of autografts of nerve fibers, but when they are used, pathological disturbances appear in the donor zone and the results of surgical treatment are not always satisfactory. Currently, an alternative to the traditional method is the use of nerve conduits (conductors) for directed regeneration of axons. In this work, the results of the application of nerve conductors from various materials and with various biologically active components in preclinical and clinical studies, as well as conduits used in clinical practice, were analyzed. The efficiency of regeneration was compared, on the basis of the analysis the conductor most suitable for successful nerve regeneration was selected, including approaches for creating innervated tissue engineered constructs. In this work, we have collected research on nerve conductors from various materials with various prescribed properties using certain factors used to treat damage to the peripheral nervous system, showing all the advantages and disadvantages of their use, which makes it possible to develop and create a conduit that meets all the requirements of modern regenerative medicine.

In a study of 537 patients with chronic generalized periodontitis and metabolic syndrome (MS) depending on age and gender, it was found that the increase of TNF-α and IL-6 in the content of periodontal pockets correlated with the severity of chronic generalized periodontitis and MS. For these cytokines, there was a clear gender relationship: women had higher levels in periodontal pocket content than men. For IL-1β and IL-4 cytokines, there is no coupling between the severity of the damage and the level of cytokines in the periodontal pocket. The developed model for calculating the risk of chronic generalized periodontitis depending on the level of TNF-α in the patient's periodontal pockets allows predicting and monitoring the dynamics of the disease.

© 2018 Russian Association of Endocrinologists. The prevalence of cholelithiasis, its close pathogenetic connection with metabolic syndrome, high frequency of surgical intervention, significant economic losses put forward this comorbid pathology in a number of leading problems of modern clinical medicine. The factors associated with the metabolic syndrome not only increase the risk of developing cholelithiasis, but also form the basis of non-drug and drug therapy. Metabolic syndrome often determines the occurrence of three common and potentially life-Threatening complications of cholelithiasis: Acute cholecystitis, acute cholangitis and biliary pancreatitis. Therefore, the solution of this problem is associated with the need for early detection of additional risk factors for cholelithiasis, optimization of the early diagnostic and prognostic model of existing multi-organ pathology with the aim of reducing the progression of the disease and its complications. The data obtained in recent years on the human genome with metabolic syndrome and cholelithiasis make it possible to predict the development of comorbid pathology and to fully ensure the effectiveness of primary prevention.

© 2018 Voprosy Sovremennoi Pediatrii - Current Pediatrics. All rights reserved. Background. Insufficient efficacy or intolerance of the first TNF-α inhibitor in patients with juvenile idiopathic arthritis (JIA) is an indication for the appointment of a second inhibitor. Golimumab is a new TNF-α inhibitor registered for treating JIA under pediatric indications. Clinical Case Description. At an early age, the patient had an onset of polyarticular JIA. Due to the aggressive and rapidly progressive course, failure of therapy with nonsteroidal anti-inflammatory drugs, methotrexate and glucocorticosteroids for intra-articular administration, infliximab was prescribed to the patient, with a positive effect. Subsequently, the patient developed a secondary resistance to infliximab, inflammatory changes in the joints relapsed; thus, a second TNF-α inhibitor (golimumab) was prescribed. In the course of therapy, pain and signs of arthritis in the patient were reversed, and the range of motion in the affected joints increased. After one year of therapy, JIA remission was ascertained. At the same time, the child was not administered oral glucocorticosteroids. The duration of remission of the joint syndrome was 5 years. Adverse events were not serious and did not constitute a basis for drug discontinuation. Conclusion. Switching to a second TNF-α inhibitor (golimumab) was effective in a patient with a secondary resistance to the first TNF-α inhibitor.

© 2018 Voprosy Sovremennoi Pediatrii - Current Pediatrics. All rights reserved. Abstarct:-Background. An important goal of treating patients with juvenile idiopathic arthritis (JIA) is to achieve the best quality of life associated with health. Objective. Our aim was to assess the impact of methotrexate plus etanercept therapy on the quality of life of patients with early and late JIA. Methods. The prospective study included patients with early and late JIA without systemic manifestations. The patients' quality of life was assessed with the help of questionnaires for children and parents: the Pediatric Quality of Life Inventory (PedsQL) Generic Core Scale, the Pediatric Quality of Life Inventory (PedsQL) Rheumatology Module, and the Health Utilities Index Mark 3 (HUI3). The quality of life was assessed prior to the therapy and after one, six, and 12 months of treatment. Results. 150 children with JIA aged 5.1 (2.0; 17.7) years; 50 children aged 4.0 (2.3-11.4) years in the group of etanercept monotherapy, 50 children aged 5.0 (3.2-9.0) years in the group of methotrexate monotherapy, and 50 children aged 9.9 (6.4-13.0) years in the group of methotrexate plus etanercept combination therapy. All groups showed low scores on all questionnaires before treatment, compared to healthy children. In the course of therapy, there was a tendency for score increase to almost 1.0 according to the HUI3 questionnaire in all groups. After one year of etanercept therapy, the parameters of the quality of life of children with early JIA did not differ from healthy children; the score increased from 56 to 90 p = 0.942 according to the physical functioning scale and from 60 to 85 p = 0.889 according to the emotional functioning scale. In the 2nd group, there was a tendency for score increase, but a statistically significant difference was found across all scales of the questionnaire. After 12 months of etanercept plus methotrexate combination therapy in patients with late JIA, the questionnaire analysis showed that the responses of healthy children and children with JIA differed with probability p = 0.001 for the physical functioning scale, p = 0.001 for the social functioning scale, p = 0.001 for role functioning, and p = 0.001 for the total score. The score increase from 60 to 85 p = 0.789 was noted for emotional functioning scales. Conclusion. The use of questionnaires to assess the quality of life in children with severe chronic diseases can significantly improve the efficacy of treatment and ensure its control.

© Group of authors, 2018. The article presents literature data on the methods of correction of linear atrophy of the skin (striae). This pathology is widespread in both sexes. The decline in the quality of life in this disease occurs largely due to the presence of a cosmetic defect. To date, there is no universal therapeutic approach for the correction of stretch marks. In this article available literature data on the problem of linear atrophy of the skin has been summarized.

© 2018, Media Sphera Publishing Group. All rights reserved. The review of the literature deals with the participation of Clara cells now called club cells (CCs) of the epithelium in the respiratory and terminal bronchioles in the pathogenesis and morphogenesis of chronic inflammatory diseases, precancer, and cancer of the lung, which develop in the respiratory segments. The review summarizes data on the histophysiology of CCs and their participation in the pathogenesis and morphogenesis of chronic interstitial lung diseases, pneumoconiosis, chronic obstructive diseases, adenomatosis, and adenocarcinoma of the lung. In this area, there is a bronchioloalveolar junction area (BAJA), one of the most important stem cell niches. CCs are located in the BAJA; they are progenitor tissue stem cells and play an important role in the regeneration of the epithelium of the respiratory bronchioles and alveoli. Pathology of CCs in the BAJA leads to the maintenance of chronic inflammation, to the destruction of the lung elastic frame, and to impaired epithelial regeneration, interstitial fibrosis, and adenomatosis. In this case, decompensated inflammation, pathological regeneration, and fibrosis develop, which, along with the action of carcinogenic agents, can contribute to the accumulation of mutations and epigenetic rearrangements in the CCs, which subsequently results in atypical adenomatous hyperplasia and adenocarcinoma of the lung.

Traditionally, Parkinson's disease (PD) is associated with the lesion of the substantia nigra and dopamine system dysfunction. However, current studies show the involvement of other CNS regions, which extend far beyond the substantia nigra, in the pathogenesis of PD. The prevalence of altered α-synuclein in PD leads to the dysfunction of several neurotransmitter systems including the orexin system located in the hypothalamus. The involvement of this system in the neurodegenerative process explains some symptoms of PD including daily drowsiness and eating disorders. The authors consider the pathophysiology of the orexin system and its role in the pathogenesis of PD.

© 2018 by the authors; licensee Modestum Ltd., UK. Objective: Arterial hypertension (AH) is one of the most common and socially significant diseases worldwide. Despite years of experience gained in studying hypertension, the problems concerning selection of antihypertensive therapy with pleiotropic organ-protecting effects are still of current importance. The purpose of the study was to assess therapeutic efficacy and pleiotropic organ-protective capability of third-generation calcium antagonist lercanidipine in patients with stage 2-3 hypertension. Method: Our study enrolled a total of ninety-two 31-to-84-year-old patients. Of these, 72 patients diagnosed as having stage 2 or 3 AH composed the Study Group and 20 apparently healthy subjects were included into the Control Group. At baseline and after 6 months, all patients of the Study Group underwent examinations consisting in measuring biochemical parameters [total cholesterol (TCH), triglycerides (TG), low-density lipoprotein cholesterol (LDL CH), uric acid, urea, creatinine, glucose], 24-hour ambulatory BP monitoring, echocardiography (EchoCG) in order to assess the dimensions and volume of the cardiac chambers, thickness of the left ventricular posterior wall (LVPW) and left-ventricular myocardium mass index (LVMMI), studying microalbuminuria (MAU), a known marker of endothelial dysfunction and early renal lesion; assessing the state of the vascular wall by the ankle-brachial index (ABI) and pulse pressure (PP). Antihypertensive therapy consisted in lercanidipine alone taken at a dose of 10-20 mg/day, failure to thereby achieve the target BP level was followed by additionally prescribing an angiotensin converting enzyme (ACE) inhibitor, enalapril, given at a dose of 5-20 mg twice daily. Results: All patients by the end of the study achieved the target level of AP (p<0.05), also demonstrating significantly improved (p<0.01) parameters of endothelial dysfunction and an early marker of renal damage (MAU), indices of elastic properties of the vascular wall ABI (p<0.05) and PP (p=0.01). Significantly positive dynamics was observed for the following parameters: decreased creatinine concentration (p<0.001), increased GFR (p<0.001), decreased levels of TCH (p<0.01) and LDL CH (p<0.001). Conclusion: Lercanidipine therapy of patients with stage 2-3 AH proved highly efficient, well tolerated, metabolically neutral with pleiotropic organ-protecting properties in the form of improved condition of the vascular wall, correction of endothelial dysfunction, nephroprotective action.

© 2018 Russian Transplant Society. All rights reserved. Aim. To establish the ability of the total RNA extracted from the body’s bone marrow cells (BMCs), in which liver tissue was damaged, to serve as a carrier of targeted regenerative signals to this organ. Materials and methods. By method of adoptive transfer in rats (n = 37) the mitotic and proliferative activity of liver and kidney cells were studied in intact recipients after intraperitoneal injection: the mononuclear BMCs – 2,5×106; 5,0×106; 3,5×107 cells – group 1 and the total RNA of the same BMCs (30μg/100g of weight) – group 2 from donors in 12 hours after 70–75% of hepatectomy; in group 3 (control), a saline solution was injected. RNA from BMCs was extracted by the method developed by the «Evrogen» firm (Russia) with the reagent Extract RNA. Results. In group 2 in 48 and 72 h. there was the increasing of mitotic and proliferative cell activity in the liver, but not in the kidneys (control of the specificity of regenerative signals); in group 1 there was no transfer of regenerative signals to these organs. Conclusion. The authors believe that the total RNA from BMCs, activated by hepatectomy, accumulates targeted (hepatospecific) regeneration signals, but they are perceived only when RNA has been obtained by the damaged tissue.

© 2018 Stolichnaya Izdatelskaya Kompaniya. Синдром такоцубо - это остро развивающаяся и, как правило, обратимая дисфункция миокарда левого желудочка. Наиболее часто синдром такоцубо проявляется локальной гипокинезией апикальных сегментов миокарда левого желудочка в ответ на эмоциональные или физические триггеры. Синдром такоцубо составляет около 2% от всех госпитализаций с подозрением на острый коронарный синдром. Диагностика синдрома такоцубо остается затруднительной. Клиническая картина острой фазы синдрома такоцубо зачастую не отличима от симптомов острого коронарного синдрома с подъемом или без подъема сегмента ST. Заболевание также сопровождается повышением маркеров по- вреждения миокарда, которое, однако, отличается от такового у пациентов с инфарктом миокарда с подъемом сегмента ST. Наиболее рас- пространенными для постановки диагноза являются модифицированные критерии клиники Mayo. Патогенез заболевания также мало изучен и представлен различными теориями, в которых главную роль играют катехоламины и их воздействие на миокард. На основании описанных семейных случаев синдрома такоцубо нельзя исключить генетическую предрасположенность к развитию заболевания. Несмотря на обратимую дисфункцию миокарда, почти в половине случаев синдром такоцубо осложняется развитием острой сердечной недостаточности, а госпитальная летальность сопоставима с таковой при инфаркте миокарда с подъемом сегмента ST. Вопрос о лечении синдрома такоцубо на сегодняшний день малоизучен. Проспективных клинических исследований каких-либо препаратов не проводилось. Считается, что тактика ведения пациентов с синдромом такоцубо, госпитализированных с подозрением на острый коронарный синдром, должна соответ- ствовать протоколу ведения больных с инфарктом миокарда, пока острая коронарная патология не исключена. На сегодняшний день забо- левание требует дальнейшего изучения.