Исследования кишечного микробиома в настоящее время вызывают большой интерес у клиницистов. Это связано с тем, что результаты проведенных исследований показывают тесную взаимосвязь кишечного микробиома с развитием различных заболеваний. В статье представлены современные методы отбора проб для  исследований, охарактеризованы мультиомические методы исследования (метагеномика, метапротеомика, метатранскриптомика, метаболомика) и  возможности их применения в  клинической практике с  указанием их преимуществ и  недостатков. Описаны наиболее распространенные методы исследования (при этом особое внимание уделено изучению кишечного микробиома), в  которых можно получить оптимально объективные результаты и точность вычислительного анализа данных. Эти исследования будут способствовать развитию персонализированной медицины, которая будет применяться в самых различных областях — от точной идентификации патогенных штаммов для целенаправленного лечения до тщательного мониторинга дисбаланса микробных сообществ при заболеваниях и до персонализированного и рационального плана манипуляций с микробиомом. 

«Personalized» medicine is based on the belief that each person has unique molecular, physiological, environmental, and behavioral characteristics, and in case of disease, each patient should be treated taking into account these unique characteristics. This belief was to some extent confirmed by the use of the latest technologies, such as DNA sequencing, proteomics, imaging protocols and the use of wireless devices for health monitoring, which revealed large inter-individual differences. Literary sources (scientific articles) were searched, including those published in peer-reviewed journals indexed in PubMed, Wos, Scopus, and the Russian Science Citation Index. The review includes 49 articles on personalized medicine. It explores new technologies that make personalized medicine possible, new experiences, ways to test and apply individualized drugs, and potential treatments for people with fertility and infertility issues. It can be argued that the individualization of medical practice in certain cases is probably inevitable. Moreover, an individual approach to a patient becomes more efficient and cost-effective. 

The growth of late preterm labor in recent years and the increased frequency of neonatal complications in 34–36-week gestation newborns explain the interest of researchers in the problem of late prematurity. The loss of the last weeks of pregnancy by late prematurity interruptsthe formation of hierarchical connections between regulatory links and target organs, but the questionsremain open, how significant is the effect of late prematurity on the hormonal status of the newborn and what are the immediate and long-term consequences of hormonal disorders that occurred in the early neonatal period.

Purpose. This study analyzes the effect of hormonal status on cardio-respiratory adaptation of late premature newborns in the early neonatal period.

Materials and methods. The study included 105 newborns with a gestation period of 34–36 weeks. A comprehensive assessment of the early adaptation period was carried out, the levels of TSH, T3, T4 total, T4 free, cortisol were determined. Blood sampling was carried out immediately after birth from the umbilical cord vein and on the 4th day after birth from the subcutaneous veins. The concentration of hormones was determined by solid-phase enzyme immunoassay using standard sets (Alkor Bio, Russia).

Results. The  results of  the work established a relationship between the thyroostatic state, cortisol concentration and the course of cardio-respiratory adaptation in late premature newborns. Newborns in need of respiratory and cardiotonic therapy had reduced concentrations of T3, T4 free and cord blood cortisol. On the 4th day of life, newborns in  need of  respiratory therapy showed a decrease in free T4 and an increase in cortisol, children receiving cardiotonic support had a reduced concentration of free T4.

Conclusion. Hormonal maladaptation can be considered as an additional factor in the pathogenesis of respiratory disorders in late premature newborns along with a reduced gas exchange area in the lungs, immaturity of sodium pumpsin alveolocytes and surfactant deficiency. 

Purpose. This study is aimed at determining the predictive value of  the clinical assessment scale for premature newborns during pre-transport preparation in relation to the outcomes of treatment of newborns.

Materials and methods. The cohort study included data from 604 visits of the neonatal transport team to the newborn children hospitalized in the medical centers of the Sverdlovsk region from August 1, 2017, to December 31, 2018. Median birth weight [IQR] 2515 [1600; 3275] grams, median gestational age [IQR] 36 [32; 38] weeks. Primary medical documentation was used for scale assessment. Descriptive statistics tools: median and interquartile range, fraction, 95% CI for the proportion, error of the proportion, calculation of the area under the ROC curve, calculation of sensitivity, specificity, cut-off level, positive (PPV) and negative predictive value (NPV). The correlation analysis of quantitative data with an abnormal distribution is performed by Spearman’s test.

Results. The  scale demonstrated a high predictive value for lethal outcome (AUC  =  0.803 (0.734–0.872)), 7-day mortality (AUC  =  0.821 (0.743–0.899)), late neonatal sepsis (AUC  =  0.763 (0.697–0.830)), severe intraventricular hemorrhage (AUC = 0.784 (0.729–0.838)), and occlusive hydrocephalus (AUC = 0.802 (0.725–0.878)) in the total sample of newborns (fullterm and premature). The negative predictive value significantly prevails over the positive predictive value. Weak correlations were found between the score and the duration of intensive care (r = 0.305, p < 0.0001), duration of ventilation (r = 0.221, p >< 0.0001), duration of nCPAP (r = 0.214, p = 0.001), and hospitalization (r = 0.214, p >< 0.0001), both in the general sample and among the survivors. Conclusion. The scale has a high predictive value in relation to the outcomes of the hospital stage in newborns, but a weak correlation with quantitative outcomes. Key words: Newborns, interhospital transportation of newborns, neonatal transfer, severity assessment, tactical decision.>˂ 0.0001), duration of ventilation (r = 0.221, p ˂ 0.0001), duration of nCPAP (r = 0.214, p = 0.001), and hospitalization (r = 0.214, p ˂ 0.0001), both in the general sample and among the survivors.

Conclusion. The scale has a high predictive value in relation to the outcomes of the hospital stage in newborns, but a weak correlation with quantitative outcomes. 

Ранняя анемия недоношенных  — заболевание, характерное для  недоношенных детей, особенно с  экстремально низкой и очень низкой массой тела при рождении. Изучение новых механизмов ее формирования позволит своевременно проводить профилактические мероприятия и предотвратить формирование данной патологии в неонатальном периоде. Наше исследование было посвящено изучению инсулиноподобного фактора роста 1-го типа и белка-3, связывающего инсулиноподобный фактор роста, для  прогнозирования ранней анемии недоношенных и  ее тяжелого варианта. Проведено клинико-лабораторное обследование 65 новорожденных гестационного возраста до 32 нед с массой тела при рождении менее 1500 г. Содержание инсулиноподобного фактора роста 1-го типа и  белка-3, связывающего инсулиноподобный фактор роста, определяли в венозной крови на 3– 5-е сутки жизни. Выявлены новые предикторы формирования ранней анемии недоношенных: при содержании белка-3, связывающего инсулиноподобный фактор роста, на 3–5-е сутки жизни 0,766 мкг/мл или менее и при содержании инсулиноподобного фактора роста 25,9 нг/мл или менее прогнозируется формирование ранней анемии недоношенных у  глубоконедоношенных пациентов. Установлены предикторы формирования тяжелого варианта ранней анемии недоношенных, требующего гемотрансфузии на  основании уровня белка-3, связывающего инсулиноподобный фактор роста, с учетом антропометрических показателей ребенка при рождении. Разработаны и внедрены способы прогнозирования формирования ранней анемии недоношенных и ее тяжелого варианта, что дает возможность своевременно проводить профилактические мероприятия, чтобы предотвратить формирование заболевания и улучшить показатели здоровья и качества жизни глубоконедоношенных пациентов. 

The features of polymorphism of genes characterizing the functional state of the vascular wall in newborns born to mothers with preeclampsia were studied. 150 children were examined, the main group consisted of 100 newborns born to mothers with preeclampsia (PE), the control group included 50 children born to women without preeclampsia. Single-nucleotide polymorphisms were determined in the blood of newborns: ADD1 G1378T (rs4961), AGT T704C (rs699), AGT C521T (rs4762), AGTR1 A1166C (rs5186), AGTR2 G1675A (rs1403543), CYP11B2 –344 C/T (rs1799998), GNB3 C825T (rs5443), NOS3 –786 T/C (rs2070744), NOS3 G894T (rs1799983) using the real-time polymerase chain reaction method with the DTprime 5 device (DNA-Technology, Russia) and the Cardiogenetics kit (DNA-Technology, Russia). The genetic analysis revealed that newborns born to mothers with PE were significantly more likely to have unfavorable genotypes АDD1 1378 G/T, AGT 704 T/C, AGT 704 C/C, AGTR2 1675 A/A, NOS3 (-786) C/C, NOS3 894T/T and alleles АDD1 1378T, AGT 704 C, AGTR2 1675A, NOS3 (-786) C, NOS3 894T. In newborns from mothers without PE, genotypes homozygous for the “wild type” alleles were significantly more common: АDD1 1378 G/G, AGT 704 T/T, CYP11B2 (-344) C/C, NOS3 (-786) T/T, NOS3 894 G/G and the NOS3 (-786) T allele. The revealed changes in newborns born to mothers with PE indicate an increased risk of developing disorders of the cardiovascular system. 

The problem of  the combination of  tuberculosis and chronic nonspecific diseases of  the bronchopulmonary system in  children and adolescents has not been sufficiently studied to date and remains relevant.

Purpose. The study aims at determination of predictors of tuberculosis infection to identify groups at high risk of developing tuberculosis among children with chronic nonspecific pathology.

Materials and research methods. A prospective study of children and adolescents (n = 158) with isolated respiratory tuberculosis and its combination with various forms of chronic obstructive pulmonary disease (lung defects, chronic bronchitis, bronchial asthma) was conducted. These two groups were compared in respect of the medical history and physical examination data, as well as computed tomography findings.

Results. The predictors of the development of tuberculosis included cases of pneumonia at an early age, acute respiratory infections 3 or more times a year, and the early age of children infected with Mycobacterium tuberculosis.

Conclusion. These conditions increase the risk of developing active tuberculosis in children and cause its more severe course. In addition, chronic nonspecific lung diseases associated with tuberculosis often complicate the course of a specific process and are often characterized by recurrent attacks. 

The combination of gastroesophageal reflux disease with dyspepsia syndrome in a particular patient is designated as overlap syndrome, the problem of which is widely discussed.

Purpose. To study the regional characteristics of the association of gastroesophageal reflux disease with dyspepsia syndrome in Siberian schoolchildren with gastrointestinal complaints.

Materials and methods. Schoolchildren of  Siberia 7–17 years old were examined: in  Tyva (1535 children), Buryatia (790 children), and Evenkia (1369 children). Information about gastroenterological complaints was collected. By the method of random selection, children with gastroenterological complaints underwent esophagogastroduodenoscopy in Tyva, 283 children, in Buryatia, 110 children, and in Evenkia, 205 children. The studies were approved by the ethics committee and the consent of the patients and their parents was obtained.

Results. In Siberian schoolchildren, the prevalence of GERD and DS overlap syndrome was 4.7%. In Tyva, the overlap of gastroesophageal reflux disease with dyspepsia syndrome in  schoolchildren was found most often: 6.9%, which was significantly higher than in Buryatia (3.7%; p = 0.0016) and in Evenkia (2.8%; p = 0.0001). regional features have been established in the distribution of clinical variants of dyspepsia associated with gastroesophageal reflux disease in schoolchildren. So, in the children of Buryatia and Evenkia, the dominant association was gastroesophageal reflux disease with postprandial distress syndrome, in Tyva — with epigastric pain. Among endoscopically examined schoolchildren in the absence of erosive and ulcerative diseases, similar associative relationships between gastroesophageal reflux disease with dyspepsia syndrome and its clinical variants were determined.

Conclusion. Regional differences were established, both in the prevalence of overlap syndrome and the severity of the association of gastroesophageal reflux disease with variants of the clinical course of dyspepsia syndrome. It is not unlikely that overlapping disorders are united by a single leading pathomechanism in their formation. 

Reference ranges of blood parameters adapted for young athletes are necessary for proper assessment and timely detection of deviations in the state of health.

Purpose. A comparative analysis of the reference ranges of some biochemical blood parameters calculated on a sample of thousands of athletes under 18 years old, members of Russian national teams, versus similar indices of children not engaged in sports obtained in the framework of projects carried out in Canada and in Scandinavian countries.

Results. Differences in the width of reference ranges, their minimum and maximum values between the compared groups for several indicators of protein and lipid metabolism, cortisol and testosterone aredescribed. The authors discuss the expediency of further development of reference ranges of blood parameters, which consider sex, age of athletes, and specifics of sports.

Conclusion. The specified data on reference ranges of blood indices are necessary for clearer differentiation and objective evaluation of adaptational transformations arising against the background of physical loads, as well astimely detection of pathological deviations in the functional state of juvenile athletes’ organism and prognosis of their further development. 

Purpose. The study is to analyze tobacco smoking among girls aged 15–17 years according to the data of the all-Russian epidemiological monitoring conducted in 2019–2020 and to identify the main aspects and directions of tobacco smoking prevention among girls.

Materials and methods. In 2019–2020, on the basis of a multi-stage selection from 12 constituent entities of the Russian Federation (6 Federal Districts), secondary schools were selected by random sampling from urban areas, in which a continuous anonymous survey of students in grades 9–11 was conducted. The total number of respondents was 14084 teenagers (6535 boys and 7549 girls).

Results. The data analysis showed that the prevalence of tobacco smoking among girls did not differ significantly from that of boys. Girls started smoking later than boys, but the intensity of initiation at the age of 13–14 years is higher than among boys. The structure of the motives of the first smoking test in boys and girls is the same. However, girls who tried smoking for the first time significantly outperformed boys by the motive «out of curiosity», and boys — «to feel like an adult» and «to please someone.» For most of the main reasons for smoking, girls did not differ significantly from boys, but girls smoked more often to «calm down,» and boys — «to seem more mature.» Awareness of the dangers of smoking among girls is slightly higher than among boys, and their sources of information are more reliable and scientifically based.

Conclusion. In 2019–2020 the prevalence of tobacco smoking among girls for the first time in 20 years of monitoring has become the same as among boys, and in some surveyed cities — even higher. In our opinion, this is due to the fact that society’s attitude towards women smoking has changed. Tobacco smoking among women has become less condemned and quite acceptable. However, this working hypothesis requires further, more detailed study. 

Purpose. To identify the aspects of suicide mortality of the child population of the Russian Federation and to propose directions for its prevention.

Materials and methods. An analysis of official data on the incidence of suicide deaths and injuries with uncertain intentionsin children of various age groups and in the context of the Russian Federation constituent entities was carried out. Special attention of suicide death age structure was paid to adolescents aged 15–17 years. The proportion of suicides among children due to external causes of death was determined.

Results. The incidence of suicide in children and adolescents depends on age, gender, and place of residence: in general, boys and urban residents dominated among the dead; suicide cases were recorded starting from the age group 5–9 years, more than two thirds of them were in the 15–17 age group; suicide rates among external causes of child death increased with age, were higher in girls and in rural areas; all the indicators studied had regional characteristics. Suicide mortality of children higher than the all-Russian level was recorded in the Volga, Siberian and Far Eastern, and at the age of 15–17 years — in the Southern, North Caucasus and Ural Federal Districts.

Conclusion. The characteristics of suicide mortality of children its social conditionality should be taken into account in the preventive measures’ formation. An analysis of inaccurate and unspecified causes of children death is important; intensive development of medical and social assistance and introduction of modern technologies of medical and social support for children and adolescents; using the principles of intersectoral and interdepartmental interaction to identify and strengthen State control over improper parenting; raising the social responsibility of parents. 

A new coronavirus infection (COVID-19, Corona Virus Disease 2019) is a disease caused by the SARS-CoV-2 virus, presenting as both a mild acute respiratory viral infection and a severe form, with damage to various organs and systems. In children under 16 years of age infected with SARS-CoV-2, the vast majority of cases were mild, without marked neurological manifestations.

This paper describes a case of acute disseminated encephalomyelitis in a five-year-old child associated with SARS-CoV-2, which caused difficulties in the differential diagnosis with demyelinating diseases and hereditary pathology. The disease was diagnosed in a family where both parentswere diagnosedwith COVID-19 by polymerase chain reaction (PCR).The CNSlesionwasrepresented by severe central hemiparesis, involvement of some cranial nerves, with impaired pelvic organ function. During the treatment there was a positive dynamicsin the somatic and neurologicalstatus. The patient was discharged for outpatient treatment with satisfactory rehabilitation potential.

SARS-CoV-2 lesions of the nervous system in children can lead to life-threatening and fatal conditions. Timely diagnosis and a comprehensive approach to the management of a child with encephalomyelitis made it possible to avoid adverse effects of the disease and improve the rehabilitation prognosis. 

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. 

Clinical observations of three cases of hypertrophic cardiomyopathy caused by mutations in the PRKAG2 gene with a debut in early childhood are presented. The  sisters whose father suffered from a severe form of  hypertrophic cardiomyopathy in  combination with Wolf—Parkinson—White syndrome and died at a young age from progressive heart failure are described. Early manifestation of  the disease is characteristic, while there was a combination of  ventricular preexitation syndrome and myocardial hypertrophy with rapid progression to extreme values. Hypertrophy was concentric symmetrical and biventricular. The main clinical symptom in  the first observation was frequent paroxysms of supraventricular tachycardia. New atrioventricular fenestrations were detected during dynamic observation, insufficient effectiveness of radiofrequency ablation, recurrence of supraventricular tachycardia, and a good response to propafenone were noted. The third clinical case is sporadic, a long-term follow-up for 15 years is presented and clearly reflects the progression of  the increase in myocardial hypertrophy and cardiac arrhythmias. The disease debuted from an early age in the form of hypertrophy in combination with severe bradycardia, which made drug therapy difficult. Due to the high risk of sudden cardiac death against the background of extreme myocardial hypertrophy, a cardioverter defibrillator was implanted. Signs of mitochondrial insufficiency according to skeletal muscle biopsy are described. 

Neurogenic detrusor overactivity is a dangerin terms of the formation of vesicoureteralreflux, pyelonephritis, and chronic kidney disease. The standard treatment for neurogenic detrusor overactivity is intermittent catheterization of the bladder in combination with M-cholinoblockers, which is not always sufficient. In the article, the authors briefly outlined the physiological basis of intradetrusor injections of botulinum toxin in neurogenic detrusor overactivity in patients with myelodysplasia who underwent surgery for spinal hernias, tumors of the spinal canal, as well as patients with spinal trauma. The technology of intradetrusor injections of botulinum toxin is shown, possible complications are described. The effectiveness of intradetrusor injections of botulinum toxin is shown by a specific clinical example — a description of the medical history of a child who has a history of surgical treatment for a spinal hernia in the newborn period. After the operation, neurogenic detrusor overactivity was revealed, insensitive to treatment with M-cholinoblockers. Complications were vesicoureteral reflux and recurrent pyelonephritis. The results of cystometry before and after double administration of botulinum toxin are shown. Detrusor hypertension was stopped, pyelonephritis remission was achieved, trabecularity of the bladder mucosa was stopped. Simultaneously with the introduction of botulinum toxin, endoscopic correction of vesicoureteral reflux was performed. 

Patients with idiopathic anaphylaxis account for up to 1/3 of the total number of patients with anaphylactic reactions. In the case of idiopathic anaphylaxis, even in the presence of a typical clinical picture, difficulties often arise in its diagnosis due to the absence of a trigger, which determines a long period of time from the first episodes of systemic reactions to the verification of the diagnosis and the proper treatment prescription. In this article we describe a case report of diagnosis and management of a patient who had recurrent episodes of severe systemic reactions since the age of 9 year, and only at the age of 11 years in our department he was first diagnosed with idiopathic anaphylaxis and given the necessary recommendations for the use of epinephrine. 

The few foreign papers of the last decade have shown the relationship of various pathogenic variants of the ELAC2 gene to heterogeneous phenotypic manifestations, for which the unfavorable prognosis is common, caused by severe cardiomyopathy in the first year of life. The article presents the first clinical observation of a rare variant of the hypertrophic phenotype cardiomyopathy with a fatal outcome in the first year of life, and variants c.887T>C, p.L296P and c.1979A>T, p.K660I of the ELAC2 gene in Russia.

The purpose of the work is to present clinical observation of a child with an early manifestation of a hypertrophic phenotype of cardiomyopathy caused by pathogenic variants of the ELAC2 gene. 

The lecture is devoted to the role of mitral valve prolapse in children and adolescents, in the population and in the formation of health. Particular attention is paid to the mechanisms of its formation, the evolution of the mitral valve prolapse criteria. The reasons for its overdiagnosis,risk factors, as well asthe high frequency of complications are explained. The interrelation of this pathology with connective tissue dysplasias and the inappropriateness of classifying the defect as a group of minor heart anomalies are emphasized. Primary mitral valve prolapse is an independent disease. There is no proven basis to consider it a marker or «affiliation” of systemic connective tissue dysfunction. An algorithm of modern treatment and prevention of mitral valve prolapse for modern pediatric practice is presented. 

Vitamin D-dependent rickets type 1 is a rare autosomal recessive disorder caused by mutation of the CYP27B1 gene, that further leads to a decrease in the activity of 1A-hydroxylase and vitamin D metabolic disorder. The disease manifests itself by means of rickets-like changes, alike to the symptoms of vitamin D-deficiency rickets, what inhibits both the early diagnosis and timely appointment of an adequate pathogenetic therapy with the usage of active vitamin D metabolites. Etiology, pathogenesis, diagnosis, differential diagnosis, and treatment of vitamin D-dependent rickets type 1A issues are presented in this article. Using the example of the clinical case, it shows the principles of selecting an adequate dose of replacement therapy. 

Congenital heart disease occurs in the population with a frequency of 8 per 1000 live births. Information on the incidence of various congenital heart defects in newborns in connection with the widespread introduction of prenatal ultrasound diagnostics and an increase in its accuracy allows for planning pregnancy and management of newborns with critical heart defects. The aim of this study wasto retrospectively study the incidence of various congenital heart defects according to echocardiographic studies among newborns in the framework of the experience of one clinic over the period from 2009 to 2019. In the clinic of the Science Research Institute of Cardiology, echocardiographic studies were performed in 34298 children aged 1 day to 17 years, the average age was 3.68 years, the median 2.0 years. The newborns accounted for 4.6% of them (n = 1607). The results of echocardiographic studies were analyzed in 1607 newborns aged from 1 to 27 days. In 247 (15.3%) of the examined no congenital defects were detected, 1360 newborns had various congenital heart diseases. It was found that the most common anomaly in  newborns were interventricular septal defects (37%), more than 60% of all interventricular septal defects were clinically insignificant small muscle defects. It has been shown that the incidence of congenital heart defects in newborns with complex prenatal diagnosis (coarctation of the aorta, double outlet right ventricle) has increased in recent years. A decrease in the incidence of atrioventricular septal defect was observed over the past five years. The possibilities of neonatal cardiac surgery in a particular clinic influenced the structure of the occurrence of individual congenital heart disease due to prenatal pregnancy planning and surgical tactics. 

Theses of the XXI Russian Congress "Innovative technologies in pediatrics and pediatric surgery" with  international participation.