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Vaginal delivery after a Caesarean section remains a controversial topic: there is a lack of reliable data to help doctors and women in labour to determine the best option for delivery during subsequent pregnancy. The review analyzed and summarized the results of the studies devoted to childbirth of pregnant women with scars on the uterus, considered the advantages and disadvantages of vaginal childbirth and repeat Caesarean section, the frequency of complications in the attempt of vaginal childbirth in women with scars on the uterus has been assessed. The modern medical literature available in open sources has been studied: Russian-language scientifc electronic libraries eLibrary and CyberLeninka, Englishlanguage database of medical and biological publications PubMed. It is necessary to consider the data of anamnesis and clinical-instrumental data when choosing the best management tactics of pregnancy and delivery for women with scars on the uterus. Attempting to deliver vaginally helps to reduce maternal and neonatal morbidity, and a large number of studies on this issue should help to reduce the number of unwarranted repeat Caesarean sections. Vaginal delivery after a Caesarean section is an opportunity to avoid severe abdominal surgery and negative consequences associated with repeated Caesarean sections.

The term «homocystinuria» combines a number of genetically determined nosological forms caused by defects of the metabolism of sulfur-containing amino acids (methionine, homocysteine), cobalamin and folate. The group of these diseases includes «classical» homocystinuria caused by insufficiency of cystathionine beta-synthase and forms associated with defects in methionine remethylation processes. More information is given about one of these forms — homocystinuria and megaloblastic anemia, type cblG, caused by MTR gene mutations. The results of observation of a child with this disease are presented. The clinical status includes: intellectual disability, autistic behavioral traits, stereotypes, nystagmus, visual impairment, macrocytic anemia, epilepsy in remission. Effective treatment requires the use of medications not registered in the Russian Federation — betaine and hydroxocobalamin.

Primary ciliary dyskinesia (PCD) (Online Mendelian Inheritance in Man - OMIM - #242650) is a rare hereditary disease, which is based on a defect in the ultrastructure of the cilia epithelium of the respiratory tract which leads to the motor function disorder. Data about health characteristics of patients with PCD in the Russian Federation are incomplete.The aim of the study was to investigate the clinical, laboratory, and instrumental characteristics of patients with PCD.Methods. The data of 90 patients (22 adults (24.4%) and 68 children (75.6%)) from several medical centers were studied. The following methods were used: medical history, spirometry, microbiological examination of the respiratory tract, video microscopic analysis of the functional activity of the nasal mucosa ciliated epithelium, transmission electron microscopy of the ciliated epithelium, and DNA testing.Results. The median age at diagnosis was 17.0 years for adults and 5.0 years for children. Kartagener syndrome was detected in 23 (27%) people, including 6 (26.0%) adults. Hearing loss was noted in 5 (26.3%) adult patients and 15 (26.8%) children. Light microscopy of the ciliated epithelium was performed in 14 (82.3%) children and 3 (17.7%) adults. In 12 patients, cilia motor activity was not registered at each of the magnifications (x 100, x 400, x 1,000). Transmission electron microscopy showed that absence ofinternal and external dynein handles (51%) and absence of internal dynein handles (17.9%) were the most common disorders. DNA testing was performed in 55 (61.2%) patients: 16 (29.1%) adults and 38 (70.9%) children. The most common genetic variants were found in the DNAH5 and HYDIN genes. Lung function was reduced in both adults and children, but a significant decrease was noted in adult patients. P. aeruginosa predominated in the culture and accounted for 21.3% (intermittent detection in 13.2%, persistent detection in 9%). It has increased resistance to antibiotics.Conclusion. The results correlate with the European data. Infection caused by P. aeruginosa with the increased resistance to antibiotics was prevalent in patienths with PCD.

Increasing the life expectancy of patients with CF is an urgent healthcare task all over the world. According to the Register of patients with cystic fibrosis in the Russian Federation (2020), the number of patients over 18 years of age is 26.5%. Assumably, cystic fibrosis can be used as a model of accelerated aging to study the aging process in general.Aim of the study was to analyze the number of rDNA copies in a sample of cystic fibrosis patients at different ages and with lethal outcome in relation to lung function, complications, and respiratory tract infections.Methods. We studied DNA samples isolated by the standard method from peripheral blood leukocytes of 277 patients diagnosed with cystic fibrosis. 998 DNA samples from healthy volunteers were used as a control group.Results. The study showed that the genomes of patients with CF contain more rDNA copies than those of control patients. The greatest number of copies of ribosomal genes was observed in DNA samples from deceased patients (p < 0.001) and was associated with more severe disease course. Among all CF patients, the largest number of rDNA copies in the genome was registered in patients with the lowest FEV1 values (less than 40%). It was found that patients with chronic Burkholderia cepacia complex infection had a significantly higher number of copies of ribosomal repeats than the total sample (p = 0.001) and the adults (p = 0.014). The number of ribosomal repeats did not differ between patients with other chronic respiratory tract infections.Conclusion. In the group of deceased patients, the patients with low respiratory function and Burkholderia cepacia complex infection had the highest number of rDNA copies in the genome, and the differences were significant. It can be assumed that the number of rDNA copies in the genome of CF patients is an additional prognostic marker that is associated with the patient’s life expectancy.

Purpose: to consider the modern possibilities of positron emission tomography combined with computed tomography (PET/CT) with FDG in the diagnosis of oncological formations in gynecology.Materials and methods. Search, selection and evaluation of existing foreign and domestic research included in the peer-reviewed E-library, PubMed, GoogleScholar, Scopus.Results. This article summarizes the existing evidence base to establish the clinical relevance and new possibilities for the use of FDG PET/CT in common gynecological malignancies.Conclusion. The use of FDG PET/CT can have a significant impact on patient management by improving cancer staging, influencing patient choice for treatment, and detecting early disease recurrence.

Angelman syndrome is a rare neurogenetic disease caused by the loss of the function of the maternal allele of the UBE3A gene on chromosome 15 (site 15q11.2–q13) and is characterized by severe mental retardation, lack of speech, epilepsy, microcephaly and a characteristic facial phenotype with a unique behavior in the form of frequent laughter. The combination of microcephaly, epilepsy, speechlessness and mental retardation poses a problem for differential diagnosis with many genetic diseases presenting with similar symptoms. Epileptic encephalopathy due to CDKL5 gene mutation and Rett syndrome have the greatest similarity. The hallmark of Angelman syndrome are laughter attacks and specific EEG changes. The authors have presented a table of the differential diagnosis of Angelman syndrome with some phenotypically similar genetic syndromes, indicating the most significant distinguishing features, which should facilitate for the pediatrician and neurologist the diagnostic path of establishing the correct diagnosis.

The objective was to evaluate the effectiveness and safety of video-assisted thoracoscopic surgery for closed chest trauma and to determine the most favorable terms for performing surgical intervention in case of complicated closed chest injury.METHODS AND MATERIALS. The study included 95 patients who underwent video-assisted thoracoscopy (VATS) for closed chest trauma. Group I – operated within the first 5 days from the moment of injury; group II – operated within 5–10 days after injury; group III – operated later than 10 days after injury.RESULTS. Performing thoracoscopic intervention within the first 5 days after the injury significantly reduces the incidence of complications such as pneumonia, pleurisy, empyema. VTS allows safely and effectively performing various surgical procedures in case of complicated closed chest trauma, and diagnosing diaphragm injuries.CONCLUSION. Indications for video-assisted thoracoscopy should be set as early as possible.

Assessment of motor development is an important part of the study of the neuropsychic development of children, which is carried out by a pediatrician during preventive examinations. To identify the causes of motor disorders, in addition to studying the anamnesis, it is necessary to conduct a physical examination of the child with the appointment of additional research methods. It is important to remember that developmental delay does not always indicate the presence of any disease but requires dynamic monitoring. However, if they progress, then these patients are more likely to be diagnosed with specific neuromuscular disorders. In this case, the pediatrician should pay attention to the neurological status of the child, assess visual acuity and hearing. At the same time, one should not forget that motor disorders are often combined with a general developmental delay (mental retardation) of the child. Fasciculation of the tongue, loss of motor skills, organomegaly, coarsening of facial features, increased levels of creatine phosphokinase (more than 3 times higher than normal), respiratory failure, in the presence of general weakness, a sharp deterioration in the child’s condition, accompanied by lethargy, vomiting, development of convulsive syndrome, disorders detected on MRI of the brain, are alarming symptoms that require urgent intervention by specialists (neurologist, genetics). Also, some hereditary (chromosomal and monogenic) diseases are often combined with the development of motor disorders. The best results are achieved if the early diagnosis of diseases accompanied by movement disorders is carried out using an interdisciplinary approach.

As DNA sequencing techniques have been used more widely in clinical practice, there have been reports of a combination of hereditary diseases in a single patient. Cases of combining diseases with similar clinical symptoms present a particular difficulty for diagnosis. We observe a child who has been identified to have a combination of autosomal dominant diseases associated with connective tissue involvement — Marfan and Stickler type 1 syndromes. Common symptoms of both diseases were as follows: marfanoid habitus, arachnodactyly, kyphoscoliosis, chest deformity, involvement in the process of joints (hypermobile syndrome) and eyes. Marfan syndrome was evidenced by dissociation of mass-growth parameters at birth, tallstature, “Gothic” palate, crowded teeth, aortic dilation at the level of Valsalva sinuses and its ascending part. Type 1 Stickler syndrome was indicated by high-grade myopia, degenerative vitreous changes requiring vitrectomy, flat face, mandibular micrognathia, latent cleft of the soft and hard palate, grade 1 bilateral conductive hearing loss, mild cognitive failure. The diagnosis of both diseases was confirmed by the detection of de novo heterozygous mutations in the FBN1 gene (c.5060_5061 delGCinvAA, p. Cys1687) and COL2A1 gene (c.4074+1G>A). Establishing a final diagnosis is of great importance for predicting the course of the disease and genetic counseling of the proband and their relatives.

Evaluation of the effectiveness of bone metastasis therapy is an urgent problem for patients with prostate cancer, mainly due to the relationship between bone metastases, survival and quality of life, which directly depends on the correct interpretation of the results of treatment response. It is known that some patients may experience a multidirectional therapeutic effect in the form of a positive response of some bone metastases and the progression of others. In addition, there are now many new therapeutics with different action profiles and often extremely expensive, so it is important to quickly recognize whether true or pseudo-disease progression is occurring, and this is more evident in patients enrolled in clinical trials with fixed protocols, often requiring radiographic assessment early after the start of treatment. Therefore, the use of additional imaging modalities in clinical practice along with PSA assessment may help improve early prediction of outcome and monitor response to therapy in patients with metastatic CRPC, optimizing the use of this costly treatment.

Modern nuclear medicine is a rapidly developing field that includes various non-invasive molecular imaging techniques with the ability to examine the whole body.Inflammation is a frequent complication in surgical and traumatological practices, which is a complex, local and general pathological process that occurs in the body in response to injury. Having arisen under the influence of a damaging factor, inflammation is characterized by the development of a dynamic complex of changes. However, the search for inflammation foci of inflammation by traditional diagnostic methods in some cases is difficult even with a detailed clinical picture. In this case, nuclear medicine, which is able to visualize pathological processes, including those with a pathological increase in metabolism, may be the best option for finding the affected area.A wide variety of radiopharmaceutical drugs makes it possible to determine the localization of the inflammatory focus in a short time and with high accuracy and makes nuclear imaging methods a priority for the early diagnosis of pathophysiological reactions.This paper presents a review of domestic and foreign literature on the use of specific and nonspecific radiopharmaceuticals in the diagnosis of inflammation. Own cases is also presented.

Radiation therapy (RT) is one of the main methods of treatment of malignant tumors. More than 70% of patients with malignant tumors of various localizations require RT as part of their combination treatment. Cutaneous reactions can occur in up to 95% of patients during or after their treatment. Clinically, cutaneous radiation reactions are manifested by hyperemia, edema, burning and itching of the skin, which cause significant discomfort to patients and reduce their quality of life, especially if these processes are localized on the exposed parts of the body. Also in some localizations of malignant tumors together with RT are used antitumor drugs, which, in turn, increases the frequency of skin toxicity and worsens the clinical picture. Timely detection of the above symptoms, their adequate comprehensive therapy with the use of basic skin care products can significantly reduce or eliminate their manifestations. This article presents the clinical experience of using La Roche-Posay products during radiotherapy and chemoradiotherapy (the patients gave their informed consent for the publication of the clinical observations).

Significant economic damage is annually caused to agriculture by parasitic diseases of livestock animals. It is necessary to regular monitor the spread of endoparasites in small cattle on the territory of various subjects of the Russian Federation in order to subsequently improve control measures and ongoing therapeutic and preventive measures, as well as to detect resistance in various helminth species and genera to active ingredients of modern anthelmintics used. Research was carried out to study the endoparasite fauna of small cattle on the peasant farm and private subsidiary plots of the Podolsk, Voskresensk and Ramensk city districts of the Moscow Region. Feces were taken individually from each animal: 50 sheep, and goats (24 lactating goats and 9 baby goats kept together). Based on the studies, it was found that the sheep were infected with pathogens of gastrointestinal nematode infections as follows: 76% of the suborder Strongylata; 26%, the genus Nematodirus; 4%, the genus Trichocephalus spp.; 62%, protozoa of the genus Eimeria, and the milking and young goats by 87.8% pathogens of the suborder Strongylata and protozoa from the genus Eimeria (EI = 15.2%), which indicates a high infection rate of these pathogens in small cattle.

Introduction. Oncolytic virotherapy is one of the approaches in immunotherapy of solid brain tumors. Measles virus vaccine strains are prospective agents for the therapy of cancers such as neuroblastoma, mesothelioma, and glioblastoma multiforme. The hyperexpression of the CD46 and other receptors on the surface of malignant cells allows the measles virus to infect and lyse the tumor, thus inducing an immune response. However, widespread immunization of the population and the resistance of neoplasms to oncolysis present difficulties in clinical practice.Text. This review covers approaches to modifying the measles virus genome in order to increase specificity of virotherapy, overcome existing immunity, and enhance the oncolytic effect. It was shown that expression of proinflammatory cytokines on viral particles leads to tumor regression in mice and triggers a T-cell response. Several approaches have been used to overcome virus-neutralizing antibodies: shielding viral particles, using host cells, and altering the epitope of the protein that enables entry of the virus into the cell. Furthermore, the insertion of reporter genes allows the infection of target cells to be monitored in vivo. A combination with the latest immunotherapies, such as immune checkpoint inhibitors, demonstrates synergistic effects, which suggests the successful use of combined approaches in the therapy of refractory tumors.Conclusion. Measles virus attenuated strains appear to be an easy-to-modify and reliable platform for the therapy of solid brain tumors.

Angelman syndrome is a genetic disorder characterized by mental retardation and severe speech delay, movement disorders and ataxia, dysmorphic features, and behavioral disorders. Angelman syndrome is caused by the loss of the 15q11.2-q13 region of chromosome 15 received from the mother, which leads to a violation of the expression of the UBE3A gene.Purpose. To analyze clinical manifestations in children with Angelman syndrome to identify early-onset and characteristic clinical signs.Characteristics of children and research methods. The study included 60 children. In all cases, Angelman syndrome was diagnosed on the basis of international clinical criteria and the results of genetic testing. The researchers used clinical, functional and molecular genetic research methods.Results. 80-100% of children demonstrated delayed mental and motor development, lack of speech, affective behavior, ataxia, hand stereotypes, apraxia of hand movements, strabismus, sialorrhea. 72% of children had epileptic seizures; all patients (regardless of the presence / absence of epilepsy) had a pattern characteristic of Angelman syndrome on the electroencephalogram. Differential diagnosis was based on the gene / chromosomal syndromes characterized by similar clinical signs.Conclusion. The combination of such most frequent, early clinical symptoms as difficulties in feeding, strabismus, impaired muscle tone, delayed motor and psycho-speech development, affective behavior with frequent laughter, and sleep disorders may indicate Angelman syndrome in a child.

Chronic lung infection caused by Pseudomonas aeruginosa reduces respiratory function and life expectancy in people with cystic fibrosis. Up to 2/3 of hospitalized patients, have antibiotic-resistant strains of Pseudomonas aeruginosa, which presents significant difficulties in prescribing eradication antibiotic therapy, which in some cases is aggravated by undesirable side effects of antimicrobial chemotherapy. The nutritional status of patients with cystic fibrosis is directly related to the activity of chronic pulmonary infection and the frequency of pulmonary exacerbations. A clinical example discusses the tactics of prescribing an alternative inhaled antibiotic aztreonam lysine (Cayston (Aztreonam lysine), Gilead Sciences Inc.) active against carbapenemases, including metallobetalactamases, in a patient with multidrug-resistant Pseudomonas aeruginosa. The clinical case demonstrates the successful eradication of the multidrug-resistant biotypes of Pseudomonas aeruginosa, and, as a consequence, the improvement of respiratory function and nutritional status, including the normalization of the 25(OH)D level in the patient.

We present a case report of a middle-aged patient with a rare sinus venosus atrial septal defect (ASD) and ischemic stroke that developed due to paradoxical embolism. Occlusion of the anterior cerebral artery led to a stroke with cognitive impairment, acalculia, and apraxia. Diagnostic ultrasound features of this anomaly in suspected cases are discussed. In the presented case, verification of the stroke cause became possible due to the contrast-enhanced computed tomography of the heart. ASD detection made it possible to refer the patient to the surgical treatment necessary to prevent both recurrent cerebral accidents and the progression of pulmonary hypertension, and the prevention of the development of right ventricular heart failure.

For the first time, a comparative study of haplotype and nucleotide diversity, genetic differentiation, and phylogeny of Tuvan woolly (two populations, n = 34) and Mongolian cashmere goats (five populations, n = 94) was carried out on the basis of polymorphisms of the hypervariable region of the mtDNA D‑loop and the SRY gene. An intrabreed, including interpopulation, analysis was carried out in comparison with the reference sequences of goats of other breeds. A high level of genetic diversity of the studied samples was revealed. The assessment of molecular variance showed that the main contribution to the genetic diversity of the studied breeds is made by intrapopulation diversity (98.84%) and only 1% is due to interbreed differences. The most common among Mongolian and Tuvan goats was haplogroup A of mtDNA; individuals belonging to haplogroups C and F were also found; other haplogroups (B, D, and G) were not found in these samples. Most of the males of the Mongolian breed on the basis of the SRY gene polymorphism had haplotypes Y1A (66.7%) and Y2A (25%); in the populations of Altai Ulaan and Three Beauties, individuals with a rare haplotype Y2B (8.3%) were identified. All studied males of the Tuvan breed of goats belonged to the Y2A haplotype.

Speech and language are the most important means of communication between a child and the outer world. Currently in the Russian Federation there is no reliable data on the prevalence of speech and language disorders in children. According to foreign authors, speech disorders are diagnosed in 3,4–6,4% in the population of preschool children, and language disorders are diagnosed in 8–10% of cases. Early identification of the causes of speech and language development disorders in children is a complex interdisciplinary problem. The authors have developed an algorithm for diagnosing speech and language developmental disorders in preschool children, where the district pediatrician plays the leading role. It is district pediatrician who can assess the speed of the child’s speech skills development, based on age norms, analyze the history data, risk factors, carry out a physical examination of the child, develop an individual program for conducting basic laboratory and instrumental studies and consult specialists. Dynamic observation of this category of children is important.

The development of modern society is characterized by an increase in the volume and changing forms of information presentation. In the works of Russian and foreign gerontologists, it is noted that the perception and analysis of the flow of relevant data today causes difficulties for a significant part of citizens of older age groups, which is due, among other things, to the deterioration of their psychophysiological state. The lack of the ability to use the necessary information negatively affects the quality of life, the level of social adaptation and professional competence. This problem is particularly significant for population groups and professional communities, whose life and activities require the actualization of certain sectors of the information field. Typical examples of such groups are citizens of retirement age who continue professional activities related to the mobilization of intellectual and creative potential, in particular, university teachers. The use of gerontotechnologies contributes to solving the problem, which provides for the development of effective methods for correcting the functional state of elderly citizens, in particular, increasing the ability to perceive information and the level of vital activity. This publication presents the results of an experimental study of the effectiveness of the combined use of peptide bioregulators and massage on the level of professional performance of elderly teachers of a pedagogical university.Развитие современного общества характеризуется увеличением объемов и изменением форм подачи информации. В работах российских и зарубежных геронтологов отмечается, что восприятие и анализ потока актуальных данных сегодня вызывает затруднение у значительной части граждан старших возрастных групп, что обусловлено в том числе ухудшением их психофизиологического состояния. Отсутствие возможности использования важной информации негативно влияет на качество жизни, уровень социальной адаптации и профессиональные компетенции. Особо значима эта проблема для популяционных групп и профессиональных сообществ, жизнь и деятельность которых требует активизации отдельных секторов информационного поля. Типичные примеры таких групп — граждане пенсионного возраста, продолжающие профессиональную деятельность, связанную с мобилизацией интеллектуального и творческого потенциала, в частности преподаватели вузов. Использование геронтотехнологий способствует решению проблемы, что предусматривает разработку эффективных методов коррекции функционального состояния и работоспособности пожилых граждан, в частности повышение способности восприятия информации и уровня жизненной активности. Настоящая публикация представляет результаты экспериментального исследования влияния сочетанного использования пептидных биорегуляторов и массажа на уровень профессиональной работоспособности у пожилых преподавателей педагогического вуза.

The present report illustrates efficacy of rituximab (RTX) in granulomatosis with polyangiitis (GPA) with severe lung involvement. Female patient, 45 years old, was ill since March 2016, her disease manifested at the onset with fever, recurrent epistaxis, otitis media, mastoiditis, conjunctivitis and arthritis. Thoracic CT scan showed multiple decaying pulmonary infiltrates. The presence of PR3-ANCA confirmed the diagnosis of GPA. Induction therapy included high doses of glucocorticoids, cyclophosphamide (total dose 4 g), with following azathioprine and mycophenolate mofetil. Lung disease continued to progress with emerging extensive infiltrates and forming a giant cavity with air-fluid level in the right lung. Further treatment included antibiotics followed by surgical draining of lung cavity in December 2018. Fever, necrotic rhinitis and otitis persisted despite treatment, lab findings included red blood cells in the urine, C-reactive protein 90 g/l, thrombocytosis 740×109/l, anemia (Hb 80 g/l). RTX 2 g and intravenous immunoglobulin were initiated in December 2018, a second course of RTX (0.5 g) was administered 4 months later. Patient’s condition was gradually improving, CT scan at 6 months after RTX treatment showed fibrous tissue in the area of former cavity. One year later, total RTX dose was 3.5 g, further regression of changes and GPA remission were achieved. There were no adverse reactions. Anti-B cell therapy with RTX is a safe and highly effective option in GPA patients with severe destructive lung disease, potentially curative even in cases of giant pulmonary cavities.

MicroRNAs epigenetically regulate physiological and pathological processes. Previously, we found that miR-204-5p is expressed at low levels in melanoma cells, and an increase in its level leads to a change in proliferation, migration, and invasion of these cancer cells. Now, using bioinformatics analysis, it has been shown that the target of miR-204-5p is FOXC1 transcription factor, which is implicated in carcinogenesis. Using the luciferase reporter assay, it was found that miR-204-5p suppresses expression of the FOXC1 gene by binding to its 3' non-coding region. Transfection of small interfering RNA (siRNA) targeting FOXC1 into melanoma cells caused a decrease in miR-204-5p levels, which is consistent with the generally accepted concept of feedback regulation of miRNA expression by target genes. According to the results of the MTT test and fluorescence microscopy, the proliferation level of melanoma cells under the influence of siRNA to FOXC1 decreased 72 h after transfection. Changes in the ratio of cells by cell cycle phase were analyzed using flow cytometry. Regulatory relationships between FOXC1 and miR-204-5p, and an inhibitory effect of FOXC1 knockdown on melanoma cell proliferation were revealed. Based on the results, it can be assumed that miR-204-5p regulates proliferation of melanoma cells by affecting FOXC1 expression.

The article presents a case of periodic fever (PF) in a 35-year-old patient, who did not have hereditary and proven genetic factors of the disease, which was characterized by an atypical course with variable in duration and frequency severe abdominal pain and febrile fever attacks, increased acute phase reactants and ineffectiveness of colchicine intake. Differential diagnosis with a wide range of febrile conditions was performed. Daily subcutaneous therapy of interleukin 1 inhibitor (iIL1) at a dose of 100 mg was used as a diagnostic marker to confirm the diagnosis of PF. As a result of the therapy, a rapid (within a few hours after injection) relief of the current attack of the disease, normalization of serum CRP levels, and further complete control over the disease (no relapses) were achieved. Our observation shows that a positive response to iIL1 therapy can serve as a diagnostic marker of PF.

Bronchoesophageal Fistula (BEF) is an uncommon condition related to complex thoracic surgery. The development of BEF is usually an indication of the progression of bronchial or lung cancer; whereas the etiology of this illness being recorded as benign is much rarer – not exceeding 4 - 6%. [1, 2]. Surgery is the main method for treating patients who have benign BEF, allowing for the reliable result. At the same time, similar operations are extremely traumatic and are fraught with the development of post-operation complications, especially when concerning patients with genetically determined coagulopathy. Factor V Leiden mutation is a hereditary coagulopathy in which there is a point mutation in the gene that encodes blood coagulation factor V. Factor V Leiden mutation is the most common cause of the hereditary disposition to thrombosis, heart attacks, strokes in Europeans. The frequency of occurence among the population of the USA is 4 – 6% [3]. We present our own observation of successful endoscopic surgery to treat BEF in a patient with Factor V Leiden mutation and chronic pulmonary embolism.

Objective: to analyze the safety of rituximab (RTM) in children with various rheumatic diseases.Materials and methods. The retrospective study included 81 pediatric patients with a confirmed diagnosis of rheumatic disease. Data on the safety of RTM were analyzed for all patients who received at least one infusion of the drug. All patients underwent a standard clinical, laboratory and instrumental examination in accordance with the verified diagnosis before the appointment of RTM therapy. The dose of RTM for administration was calculated based on 375 mg/m 2 of body surface area, the drug was administered once a week for 1 to 4 consecutive weeks, depending on the number of CD19 lymphocytes determined after the infusion, and the tolerability of therapy.Results. Among the patients included in the study, 38 (46.9%) were with systemic lupus erythematosus (SLE), 16 (19.75%) – with juvenile idiopathic arthritis (JIA), polyarticular variant (14 (87,5%) of them – RF-positive), 9 (11,1%) – with juvenile idiopathic arthritis with systemic onset (sJIA), 6 (7.4%) – with systemic sclerosus (SSc), 5 (6.2%) – with primary Sjogren’s syndrome, 2 (2.5%) – with juvenile dermatomyositis, 4 (4.9%) – with mixed connective tissue disease, and 1 – with livedoid vasculopathy. 53 (65.4%) patients underwent more than one course of RTM therapy, with a maximum of 10 courses. The total number of infusions was 198. The median time between each course was 182 [156–315] days. RTM was effective in 67 (95%) patients, ineffective in 2 (2.5%) patients with sJIA, 2 (2.5%) patients with SLE and macrophage activation syndrome (MAS).Adverse reactions (AE) of mild to moderate severity were reported in 23 (28.4%) patients, including upper respiratory tract infections – in 7 (8.6%), urinary tract infections – in 2 (2.5%), mild infusion reactions that did not require discontinuation of therapy – in 2 (2.5%), clinically insignificant neutropenia (I–II degree) – in 4 (4.9%), a decrease in IgG levels – in 14 (17.5%) patients (median – 5.5 [4.0; 6.9] g/l). Two patients with sJIA had persistent hypogammaglobulinemia for 3 and 5 years after the last RTM infusion, respectively. The incidence of infections in patients with low IgG levels was 35.7%, and no cases were registered in patients with neutropenia. Serious AE was reported in 16 (19.7%) patients: sepsis – in 4 (4.9%), pneumonia – in 3 (3.7%), herpes zoster – in 1 (1.2%), serious infusion reactions – in 2 (2.5%), serious postinfusion reactions within 3–10 days – in 4 (4.9%) (in 3 patients (3.7%) – MAS, in 1 (1.2%) – hemorrhagic vasculitis); death was registered in 2 cases of SLE and MAS (therapy of RTM was inefficient). In general, various AE were reported in 55.6% of patients with sJIA, 52.6% of patients with SLE, 50% of patients with SSc and juvenile dermatomyositis, and 80% of patients with primary Sjogren’s syndrome. Discontinuation of therapy due to serious AE was observed in 15 (18.5%) patients.Conclusion. Our study demonstrated that RTM therapy is highly effective with an acceptable safety profile in children with rheumatic diseases. The safety data obtained indicate the need for careful monitoring of therapy, primarily taking into account the risk of infection, despite the fact that in this study the frequency of infectious complications was not high. A decrease in IgG level was observed in a small proportion of patients and did not correlate with the incidence of infections.

Hereditary connective tissue diseases are among the most common genetic syndromes. In most cases the studies of children with Ehlers–Danlos syndrome are devoted to the clinical manifestations of the disease. Insufficient information on the features of emotional, personal, and behavioral spheres in this category of children creates the need to perform targeted psychological research. Objective. To study the features of the emotional and personal sphere in adolescents with Ehlers–Danlos syndrome of 12–16 years old. Material and methods . The study involved 24 boys and 22 girls from 12 to 18 years old with a clinical diagnosis of Ehlers–Danlos syndrome. The study used multidirectional diagnostic methods of emotional, personal and behavioral spheres. Results. The emotional features of adolescents with Ehlers–Danlos syndrome are manifested in the form of depressive, anxiety states, which are associated with frustrated needs for self-affirmation. The study revealed the heterogeneity and originality of the picture of emotional and personal characteristics of patients with Ehlers–Danlos syndrome. The degree of awareness of the individual characteristics of a teenager affects the personal development of the child as a whole.

Vemurafenib revolutionized the treatment of melanomas which harbor mutations in BRAF oncogene whereas BRAF-negative tumors are resistant to its antitumor effects. Meanwhile tumor chemoresistance is associated with the presence of quiescent, resting-dormant (G0-positive, Ki-67-negative) cancer cells in the heterogeneous cancer cell population. In order to test if BRAF-inhibitor can stimulate quiescence in melanoma cells, two melanoma cell lines (BRO and SK-MEL-2) were treated with the antitumor drug vemurafenib, and populations with G1/G0 cell cycle arrest were obtained. The latter were confirmed by negative staining with Ki-67 antibodies, and changes in the gene expression of cell cycle regulatory proteins, such as CDK4, CCND1 and CDKN1B.

The article presents current data on synovitis (inflammation of the synovial membrane), which is often the only clinical manifestation of osteoarthritis (OA), and considered to be one of the risk factors for the OA development. Synovitis severity correlates with the severity of OA symptoms. The assessment of the prevalence of synovitis presents significant difficulties and depends on the nature and severity of the disease, the cohort in question, diagnostic method, and therapy. The classification based on etiological, clinical and histological characteristics of synovitis is presented. Examination of synovial tissue characteristics and its changes during inflammatory response can significantly expand the possibilities for therapy and prognosis. The use of symptomatic delayed-action drugs (SYSADOA) is considered as the basic treatment of OA. Chondroitin sulfate (Chondroquard®) is one of the well established drugs, it has symptom- and structural-modifying properties. The article presents the results of studies confirming its effectiveness in reducing the severity of knee synovitis.

Veltischev Researchand Clinical Institutefor Pediatricsofthe Pirogov Russian National Research Medical University, Moscow, Russia The article presents modern data on the most common monogenic connective tissue disease – Ehlers–Danlos syndrome. The authors describe two previous classifications of the syndrome: Berlin (1988) classification, which distinguishes 11 types of the disease, and Beyton (1998) classification, which includes 6 types of the syndrome and takes into account the results of molecular genetic studies. Particular attention is paid to a new classification, proposed by the International Consortium in 2017. This classification is based on the clinical and molecular genetic data and unites 13 types of Ehlers–Danlos syndrome, divided in 7 groups (A–G), depending on the main molecular defect. This defect determines the violation of various collagen structures (primary, spatial, cross-linking) and others constituents of the connective tissue (myomatrix, glycosaminoglycans, complement component, etc.). The classification provides general clinical symptoms for all types of the disease and comprehensive information on the specific signs of each of the 13 types of the syndrome.The authors discuss approaches to the pathogenetic therapy of the syndrome, the possibilities of symptomatic treatment, including both medications of different spectrum of action, and physiotherapeutic measures, exercise therapy. The complex of the listed therapeutic measures is aimed at stabilizing the main pathological process, preventing complications, improving the patient’s quality of life and social adaptation. The authors emphasize that correct patient management, targeted medical supervision and medical genetic counseling requires molecular genetic verification of the diagnosis.