Репозиторий Университета

© 2020 Elsevier Inc. Background: Severe von Willebrand disease (VWD) may be associated with chronic joint damage and may require prophylactic therapy. Emicizumab is a humanized bispecific antibody, which mimics the function of coagulation factor VIII (FVIII), and it has been approved for prophylaxis in hemophilia A. Methods: This is the first study assessing the potential future role of emicizumab as an alternative prophylactic treatment in patients with severe VWD, based upon a thrombin generation (TG) ex vivo analysis. We report 51 weeks of successful off label emicizumab prophylaxis in a child with severe VWD and recurrent hemarthroses and progressive arthropathy despite adherence to previous prophylaxis with replacement therapy. Results and conclusions: Our work demonstrated that ex vivo spiking with emicizumab increased TG in plasma from patients with type 3 VWD. Similar TG results were observed in our treated patient, whose therapy was well tolerated without any adverse events. Both in vitro and ex vivo TG data support sufficient hemostasis without exceeding the range seen in healthy volunteers. Further collaborative studies on the efficacy and safety of emicizumab prophylaxis in severe VWD is warranted.

© 2020 Elsevier Inc. Background: Severe von Willebrand disease (VWD) may be associated with chronic joint damage and may require prophylactic therapy. Emicizumab is a humanized bispecific antibody, which mimics the function of coagulation factor VIII (FVIII), and it has been approved for prophylaxis in hemophilia A. Methods: This is the first study assessing the potential future role of emicizumab as an alternative prophylactic treatment in patients with severe VWD, based upon a thrombin generation (TG) ex vivo analysis. We report 51 weeks of successful off label emicizumab prophylaxis in a child with severe VWD and recurrent hemarthroses and progressive arthropathy despite adherence to previous prophylaxis with replacement therapy. Results and conclusions: Our work demonstrated that ex vivo spiking with emicizumab increased TG in plasma from patients with type 3 VWD. Similar TG results were observed in our treated patient, whose therapy was well tolerated without any adverse events. Both in vitro and ex vivo TG data support sufficient hemostasis without exceeding the range seen in healthy volunteers. Further collaborative studies on the efficacy and safety of emicizumab prophylaxis in severe VWD is warranted.

© 2020 BMJ Publishing Group. All rights reserved. Introduction  Peutz-Jeghers syndrome (PJS) is an autosomal dominant hereditary hamartomatous polyposis with predominant localization in the jejunum and ileum and high risk of bowel perforation after traditional polypectomy. The modern enteroscopy is the only possible technique for visualizing and performing intraluminal endoscopic microsurgical manipulations in the deep sections of the small intestine. The study aims to develop an optimal method for the diagnosis and treatment of polyps in children with PJS. Materials and Methods  During 2015 to 2018 we conducted 30 comprehensive examinations of children with PJS in The Department of Endoscopic Research of the National Medical Research Center for Children's Health. We performed esophagogastroduodenoscopy and colonoscopy with removal of polyps more than 7 mm, then video capsule endoscopy and, guided by this, therapeutic single-balloon enteroscopy. Our technique for removal of polyps is general in all parts: (1) creating a resistant pillow; (2) electroexcision of polyp; (3) clipping the removal site. Results  Successfully performed electroexcision of polyps, which were located in the deep parts of the small intestine at a distance of 30 segments (one segment is 10 cm), reached a diameter of 2.5 cm, had a long pedicle. The postoperative period was uneventful. Conclusion  We have developed an optimal method of diagnostic and therapeutic measures, the observance of which allows us to avoid delayed perforations of the small intestine in the area of polypectomy in the postoperative period in children with PJS. Thanks to this technique, modern enteroscopy is becoming the only possible alternative to bowel resection in children with PJS.

© 2019 Elsevier B.V. Objective: Being increasingly faced with the problem of pediatric nasal septal perforations, we have found that the surgical management of nasal septal perforations in children is not widely described in the litrature. The objective of our study was to demonstrate the results of different surgical techniques, including two original endoscopic techniques, in the septal perforation repair in children. Methods: 24 children, ranging between 6 and 17 years of age, with nasal septal perforations were operated using different endoscopic techniques from February 2015 to May 2019 at the special tertiary referral clinic. Apart from well-known techniques, such as anterior ethmoidal artery flap, intranasal bipedicled advancement flap, sublabial flap, free temporal fascia graft, we used two original techniques – inverted edges technique and cross-septal returned flap. Results: The total rate of complete perforation closure was 79% (19 of 24 patients). Regarding the reduction of symptoms, the efficacy of surgery was approaching 100%. The combination of inverted edges technique and anterior ethmoidal artery septal flap demonstrated the best results with no reperforations in all 10 cases. Using cross-septal returned flap, we achieved complete closure of perforation in 5 (83%) of 6 patients. The remaining techniques were performed rare and showed relatively low rates of success. There were 2 cases of complications (oronasal fistula), both developed in patients with sublabial mucosal flap. Conclusion: Use of endoscopic assistance, vascularized mucoperichondrial flaps and bilateral closure demonstrates high effectiveness in septal perforation surgical repair in children. Level of evidence: 4.

© 2018 Ehlers-Danlos syndrome (EDS) is a heritable connective tissue disorder characterized by skin hyperextensibility, abnormal wound healing, and joint hypermobility with prevalence 1:20 000. Its incidence is probably underestimated due to unknown number of subjects having mild symptoms who may have never been diagnosed through entire life time. Classical EDS is characterized by pathogenic variants of genes encoding type V collagen. The biological effects and health risks of patients with EDS exposure to low doses of ionizing radiation is poorly understood. The aim of this study was to investigate biological effect of low doses of ionizing radiation in children with EDS. Background values of chromosome aberrations in children suffering from classical EDS were determined and compared with control subjects. The in vitro experiment was performed by γ-irradiation of blood lymphocytes from EDS patients and healthy subjects at low doses (0.1, 0.2 and 0.3 Gy). Results show a significant increase level of spontaneous and radiation-induced chromosomal aberrations in children suffering from EDS in comparison with the control subjects (p < 0.05). In conclusion, children with EDS express higher background chromosome aberration frequency and increased radiosensitivity. These findings suggest specific susceptibility of EDS patients and importance of future investigation on risks of diagnostics and therapy which include radiation and genotoxic agents.

© 2019 American Academy of Allergy, Asthma  &  Immunology Background: Mepolizumab is an anti–IL-5 antibody approved for the treatment of severe eosinophilic asthma. However, the prevalence of patients with severe asthma eligible for mepolizumab remains unknown, especially among children. Objective: To determine, in a population of patients with severe asthma from a tertiary referral center, the proportion of patients with an eosinophilic phenotype who would be eligible for mepolizumab, when stratified for the age of onset of asthma, and the prevalence of phenotypic features that favor mepolizumab therapy. Methods: An extensive database of 245 adults and children referred for severe asthma was used. The prevalence of severe asthma was estimated by using the European Respiratory Society/American Thoracic Society criteria. Patients with an eosinophilic uncontrolled phenotype qualified for mepolizumab. Results: In our cohort, 216 (88%) had severe asthma. Based on blood eosinophils of either greater than or equal to 150 cells/μL or greater than or equal to 300 cells/μL, 61%/41% had an eosinophilic phenotype, while 49%/34% were eligible for mepolizumab therapy. A greater percentage of adults (60%/47% of adults with asthma onset in adulthood [AoA] and 48%/26% adults with childhood-onset asthma [<18 years, CoA]) were eligible compared with children (33%/24%), for eosinophil counts of ≥150 and ≥300 cells/μL, respectively; P < .05. Compared with adults, children had a similar number of exacerbations while having better lung function (P < .05). Among adults, those with AoA were older, were more likely to have nasal polyps (28% vs 5%; P < .05), and had higher blood eosinophil counts (272 vs 150 cells/μL; P < .05) compared with those with CoA, with no difference in lung function noted between the 2 groups. Subjects showing greater than or equal to 500 eosinophils/μL, a strong indicator for mepolizumab therapy, had more nasal polyps, higher inhaled steroid dose, lower lung function, and AoA predominance than did those with less than 500 eosinophils/μL (P < .05). Conclusions: A smaller percentage of children with severe asthma were eligible for mepolizumab compared with their adult peers. Severe AoA has distinct phenotypic features that favor treatment with mepolizumab, including greater eosinophilia and nasal polyposis, in contrast to CoA, which appears to have fewer features of type 2 mucosal inflammation.

© 2019, Pediatria Ltd. All rights reserved. Acute kidney damage (AKD) is characterized by rapidly progressing organ dysfunction, which often results in development of chronic kidney disease. There are difficulties in diagnosing initial stages of kidney damage, which are usually reversible. Molecular diagnostics is a sensitive method that can detect early nephron changes that are not detectable by conventional methods (by assessing serum creatinine and urinary albumin in urine, diuresis) before renal filtration function decrease. The review examines markers of AKD development key stages: Ischemia (Kidney Injury Molecule-1 (KIM-1), Clusterin), hypoxia (Vascular Endothelial Growth Factor), Hypoxia Inducible Factor (HIF)), inflammation (Monocyte Chemoattractact Protein-1 (MCP-1), Interleukin 18 (IL18)), kidney tubule damage proximal (Beta-2-Microglobulin (B2M), Cystatin C, Neutrophil gelatinase associated lipocalin (NGAL)), distal (NGAL, Calbindin, Osteopontin). The study of these biomarkers in children's urine can be recommended for non-invasive screening, diagnosis and monitoring of AKD.

© 2019, Pediatria Ltd. All rights reserved. In the article the authors present relevant information on the criteria for assessing the activity of juvenile dermatomyositis (JDM) and modern approaches to its treatment. In clinical practice, various scales are currently used to assess the overall JDM activity and severity of damage to various organs, primarily muscles and skin. The article provides modern recommendations for JDM treatment: The use of glucocorticosteroids, disease-modifying antirheumatic drugs (methotrexate, calcineurin inhibitors, cyclophosphamide, mycophenolate mofetil, azathioprine, hydroxychloroquine, intravenous immunoglobulin), genetically engineered drugs (rituximab, infliximab, adalimumab, golimumab, certolizumab, etanercept), as well as promising new drugs and methods of maintenance therapy. The modern JDM treatment algorithm is described.

© 2019, Pediatria Ltd. All rights reserved. Skull computed tomography (CT), recognized as the «gold standard» in the diagnosis of craniosynostosis (CS), has a significant drawback associated with radiation exposure. The use of ultrasound in the imaging of cranial sutures is a possible research method, replacing CT. Objective of the research: To assess efficacy in CS diagnosis and postoperative observation of children after endoscopic cranioplasty. Materials and methods: The study includes analysis of ultrasound data of cranial sutures in 45 children aged 4,5±1,2 months (from 1,5 to 12 months), which were examined and treated at the Federal Center of Neurosurgery. Ultrasound of cranial sutures was performed on an expert class device. To assess cranial sutures condition authors developed a simple algorithm and an ultrasound protocol, according to which the study was performed. Additionally, all children underwent CT with skull volumetric reconstruction. Results and discussion: According to cranial sutures ultrasound, 14 children had positional plagiocephaly, 12 - metopic craniosynostosis, 18 - sagittal CS and one child had combined CS - a combination of metopic and right part of coronary sutures lesions. Thus, diagnostic imaging allowed to confirm metopic, sagittal and coronary sutures CS. Ultrasound was also performed in the postoperative period in the bone defect area to assess its and other cranial sutures fusion dynamics. The use of the algorithm and ultrasound protocol, in authors opinion greatly facilitates preoperative surgical planning and dynamic observation in the postoperative period. Conclusion: Cranial sutures ultrasound can be considered as an alternative method of instrumental CS diagnosis and patient postoperative management after endoscopic surgery. Described CS ultrasonic classification allows to use it for screening in the early stages of the disease.

© 2019, Pediatria Ltd. All rights reserved. Pyelonephritis treatment in children with neurogenic bladder (NB) has a number of peculiarities, which include incomplete bladder emptying after self-urination and causing difficulties in determining treatment tactics for primary care pediatricians. Residual urine is a risk factor for development and relapse of chronic pyelonephritis, and urinary incontinence is also a medical and social problem. The article presents an example of observing an 8-year-old girl after 2 years of ineffective treatment for chronic pyelonephritis with mistakes in primary diagnosis. It provides the analysis of 3 months treatment and examination of the child with NB, including monitoring of urination functional productivity. The scheme of combined correction of inflammatory process and urinary tract dysfunction is presented. A systematic step-by-step approach to diagnosis and treatment of recurrent pyelonephritis in children with NB allows to increase therapy efficacy and improve patient's quality of life. The presented clinical case differs because bladder dysfunction manifested itself at the age of 8 years with an increase of bladder residual volume. Peculiarity of pathogenetic mechanisms of this pathology development in the described observation is a combination of delayed mature urination formation and manifestation of acute pyelonephritis, which required a non-standard approach to diagnosis and treatment.

© 2019, Pediatria Ltd. All rights reserved. The question of the methodology for assessing the physical development (PD) of the child population remains debatable. An analytical, prospective, cohort study (8300 children) was performed. A comparative evaluation of 4 methods of PD assessment based on informativity criterion is presented. The ratio of methods and content of regulatory documents of the Ministry of Health of the Russian Federation is shown. Advantages of the complex technique were revealed, which is important for pediatricians, since the stated deviation in child's PD allows to determine the amount of diagnostic, preventive, and health-improving measures and recommendations for a healthy lifestyle. Within the confines of Decade of Childhood, it is necessary to eliminate the existing contradictions in normative base of the Ministry of Health of the Russian Federation, medical statistics, and medical personnel training.

© 2019, Pediatria Ltd. All rights reserved. The article presents main pathogenetic factors of enuresis formation in children without malformations and diseases of the spine and spinal cord. 48 children were treated with cognitive and behavioral methods, based on formation of an age-related physiological regimen of fluid intake and urination. The drug of choice for drug therapy was desmopressin (Antikva Rapid) 120 mcg, efficacy was evaluated after 6 weeks of treatment by the number of night bedwetting per week. If its number was reduced by 50% or more from the original, then the drug dose remained the same. For children, whose proportion of night bedwetting was more than 50%, the desmopressin dose was increased by 60 mcg/ day. The total treatment course was 3 months. Treatment efficacy at the end of the course was evaluated by the “dry” period duration. If it was less than 14 days, a similar repeat course was planned. A correlation was found between the volume of nocturnal diuresis (ND) and the number of enuresis episodes per week, a decrease of these indicators by 32% at the stage of 1,5-month treatment and by 67% at the end of 3-month treatment was noted. DD showed a statistically significant increase, and ND a statistically significant decrease following the results of 1,5 and 3 months of treatment. After a 3-month course, a dry period of 14 days was observed in 16 children (33%). 2/3 of patients (67%) required a second course of treatment.

© 2019, Pediatria Ltd. All rights reserved. Brain–lung–thyroid syndrome (BLTS) is a rare genetic disease associated with mutations in the NKX2.1 gene encoding thyroid transcription factor 1. The most common manifestations of this syndrome are benign hereditary chorea, hypothyroidism and respiratory distress syndrome, however, mutations in the NKX2.1 gene can also cause other pathologies of nervous, respiratory systems and thyroid gland. The article describes 4 patients with mutations in the NKX2.1 gene observed by authors. Based on the analysis of the observations of 168 patients with BLTS presented in the world literature from 1998 to 2019, current information on the genetics, pathogenesis, clinical X-ray manifestations, outcomes and treatment of the syndrome are summarized.

© 2018; Pediatria Ltd. All rights reserved. Among the leading forms of socially significant pathology is chronic kidney disease (CKD), which has a variety of causes and often originates in early childhood. Risk factors and causes of CKD in children are associated with congenital anomalies in urinary tract (UT) development, accompanied by a persistent chronic infection, urodynamic disorder, remodeling of renal blood flow. Kidneys homeostatic functions disorder causes morphofunctional changes in various organs and tissues, incl. dentoalveolar system (DAS). The negative effect of CKD on the formation of maxillofacial region in children is studied. The data on disorders of jaw bones structures, temporomandibular joint (TMJ) and its function, oral cavity mucous membrane pathology, periodontal diseases, quantitative and qualitative changes in saliva, the defects of teeth hard tissues, pulp calcification caused by this pathology are systematized. The lack of a holistic view of DAS abnormalities development mechanisms in children with kidney damage makes it difficult for the dentist to conduct a timely diagnosis and combine work with doctors of other specialties, such as a pediatrician and a pediatric nephrologist. An integrated approach to managing children with CKD would allow to personify patient management tactics and improve treatment and rehabilitation results.

© 2018; Pediatria Ltd. All rights reserved. Congenital uropathies (CU) are anomalies associated with impaired patency of the upper and lower urinary tract and include congenital hydronephrosis, megaureter, primary vesicoureteral reflux (VUR), infravesical obstruction with prevalence in the pediatric population up to 1,4-2,8%. The most dangerous complication of CU is the development of kidney fibrosis in 30-60% of children combined with a persistent urinary system infection (USI). The lack of effective methods for early diagnosis and evaluation of renal parenchyma fibrosis treatment efficacy dictates the need for further search for molecular indicators of kidney injury. The article describes the study of inflammation biomarkers (interleukin 6 (IL6), inertleukin 8 (IL8), interleukin 10 (IL10)) and fibrosis (monocyte chemoattractant protein 1 (MCP1), transforming growth factor Β1 (TGFΒ1), vasculoendothelial growth factor (VEGF)) in urine in children with CU for diagnosis, monitoring and predicting the course of pathology. The study included 255 patients with various variants of CU (congenital hydronephrosis - 75, VUR - 169, infravesical obstruction - 11). The mean age of the patients was 4,3±3,2 years. The comparison group included 20 almost healthy children stratified by sex and age without USI. Biomarkers were determined by the method of enzyme immunoassay (ELISA) in the dynamics of pathology. All patients had an increase in urinary levels of proinflammatory cytokines (IL6, 8), even without clinical picture of USI. The increase in the concentration of MCP1 and TGFΒ1 in the urine is proportional to the degree and duration of VUR before its treatment, their content increased after 6 months after the correction of VUR and indicated the persistence of latent pyelonephritis and fibrosis progression. Molecular diagnosis of inflammation and fibrosis markers n the urine is a promising noninvasive method for assessing the pathological process in kidneys, the effectiveness and adequacy of the treatment.

© 2018; Pediatria Ltd. All rights reserved. Chronic pathology of the urinary system (US) among children is widespread. Continuously relapsing course of the disease significantly reduces the quality of life (QOL) of patients and their caregivers. Objective of the research - to analyze the necessity of QOL study of children with US chronic pathology. The article presents modern methods, approaches to the assessment of QOL of children of this group. It explains the need to study the evaluation of QOL in children in pediatric practice. QOL indicators of children with chronic diseases are presented as a criterion for assessing the effectiveness of their treatment and socialization. The revealed flaws of QOL of children of different medical and social groups testify to the need to include this indicator in their survey program to optimize medical care for these patients.

© 2018; Pediatria Ltd. All rights reserved. Search for biomarkers, reflecting the severity of inflammation and damage to kidney tissue in children with pyelonephritis is very important. Objective of the research - to study clinical significance of lipocalin 2 associated with neutrophil gelatinase (uNGAL) in urine as a marker of renal parenchymal lesion severity in children with pyelonephritis debut. Study materials and methods: 73 children with pyelonephritis debut hospitalized in the nephrologic department were examined. Children were divided into 2 groups: 1st group - 41 children with acute pyelonephritis (without USO abnormalities), 2nd group - 32 children with acute pyelonephritis combined with various abnormalities of urinary system organs. In all patients, the levels of urea, creatinine, cystatin C, procalcitonin, renal concentration capacity, uric excretion of lipocalin 2 associated with neutrophil gelatinase (uNGAL) were assessed. Results: the study revealed that the level of uNGAL/Cr excretionat the admission in children of both main groups did not differ significantly. A positive correlation was found between uNGAL/Cr value and cystatin C level in patients of the 2nd group. All children had a direct correlation between the duration of febrile fever from the onset of antibiotic therapy and the uNGAL/Cr excretion level. The study also revealed a correlation between uNGAL/Cr excretion level in the acute period of the disease and the degree of renal parenchymal lesion in children from the first and second groups confirmed by static DMCA nephroscintigraphy. Conclusion: a high urinary excretion of uNGAL/Cr in patients with acute pyelonephritis indicates a marked renal parenchyma lesion and requires static nephroscintigraphy with further observation, but not earlier than 6 months after the normalization of clinical-laboratory indicators.

© 2018; Pediatria Ltd. All rights reserved. An expert analysis of lectures and reports at the XIX Congress of the European Union of School and University Medicine and Health (Belgium, Leuven, 2017) presents issues of school and university medicine: modern approaches to assessment of children’s health; ensuring equal access of all children, adolescents and youth to medical care during the period of education in accordance with the Convention on the Rights of the Child, regardless of socioeconomic status, ethnicity and cultural level; the effectiveness of health services, friendly to students, assessment of medical care for students quality; the role of parents in organizing medical care for students; the role of the media in shaping the identity of children in the process of growth and development. The concept of «positive health» focuses on positive and healthy aspects, and not only on medical treatment. The main elements of «positive health» include: physical functioning, daily routine, mental health, social activity, intentions, quality of life. In Europe prevails a program approach to prevention based on targeted work with relevant groups of children and adolescents. There is a need for assessing the impact of environmental factors, access to care and education for children with special needs, providing preventive care for vulnerable children, infants and their families, promoting healthy behavior among students, special approaches to providing mental health to students through available health services and various programs, incl. based on the welfare of children and interventions in the early stages of emotional problems considering risk factors that can be identified in educational institutions. Modern main directions of research in the field of health protection and promotion of students in educational organizations are due to large-scale changes in the environment (pronounced urbanization), the new way of life and quality of life for children and adolescents, their life conditions in a rapidly changing world combined with unfavorable trends in health and development indicators of the growing up generation of Russians.

© 2017 Elsevier B.V. Background: A major role of the innate immunity in the defence of mucosal tissue is well established. However, a balance between the main components of the immunity such as toll-like receptors (TLRs) and defensins in the pathology of upper respiratory tract in children has not been addressed yet. Our aim was to investigate the gene expression of some TLRs as well as alpha and beta-defensins in children suffered from adenoid hyperthrophy in comparison with healthy children. Methods: Samples (nasal epithelium and adenoids) from patients with hypertrophic adenoids (n = 77) and control group (n = 33) were investigated. Quantification of HBD-1 and 2 mRNA, alpha-defensin-HNP1 and toll-like receptors (TLR) 2, 4 and 9 mRNA expression was performed by real-time polymerase chain reaction (PCR). The detection of TLR4 and TLR9 was performed by immunohistochemistry. Results: The main finding of the study is a dramatic up-regulation of TLR2 and TLR4 expression (but down-regulation of TLR9) along with a significant reduction in the expression of the defensins in children with adenoid hyperthrophy. Conclusion: The data suggest that one of the mechanisms of mucosal involvement in the pathogenesis of upper respiratory tract infection might by a disbalance between TLRs and defensins revealed in our study.

© 2018, Pediatria Ltd.. All rights reserved. The article presents data of a systematic review of observational and interventional studies on possible associations between the level of macro-and micronutrients consumption by lactating mothers and their breast milk composition. Authors present the results of a 3-week prospective medical observation in assessing the tolerability of specialized products for lactating mothers, as well as the dynamics of the physical development of their children who are exclusively breastfed.