Introduction. Cystic fibrosis (CF) is an autosomal recessive hereditary disease resulting from the presence of pathogenic nucleotide variants (NVs) in the CTFR gene, encoding a regulator of the transmembrane transport of chloride ions. CF is characterized by an impaired secretory function of the epithelial cells of exocrine glands and, as a consequence, a number of systemic progressive pathological changes in the functioning of the gastrointestinal tract, respiratory system, etc. CF might be accompanied by a number of comorbidities (CMs), including those leading to the development of mutual burden, affecting the diagnosis or choice of therapy. At the same time, of CMs repertoire in CF may vary in different ethnic groups and populations, especially geographically isolated ones. Thus, for more informed approach to the diagnosis and treatment of CF in certain ethnic groups and populations, it is necessary to determine the CMs repertoire characteristic of these groups.

Materials and methods. The study included one hundred twenty five 2 months to 17 years and 11 months patients with a confirmed diagnosis of CF. The children were divided into groups according to ethnicity: residents of the Chechen Republic (71 patient), residents of the Karachay-Cherkess Republic (23 patients), residents of the Republic of Ingushetia (9 patients), the Republic of Dagestan (16 patients), the Republic of North Ossetia — Alania (6 patients).

Results. The frequencies and spectrum of comorbidities (CMs) in CF children from ethnic groups living in the North Caucasus Federal District differ from those previously described for CF patients from other populations and ethnic groups. The most common CMs identified in this study are adenoid hypertrophy (n = 51; 40.8%), chronic gastritis (n = 47; 37.6%), lactase deficiency (n = 38; 30.4%), gastroesophageal reflux disease (n = 30; 24%), development retardation (n = 22; 17.6%), allergies of various origins (n = 21; 16.8%), and consequences of perinatal damage to the central nervous system (n = 11; 8.8%).

Conclusion. For the early differential diagnosis of CMs and further clinical management of pediatric CF patients, it is necessary to implement an interdisciplinary approach using of medical genetic methods, as well as additional monitoring by several medical specialists. First and foremost, the decision on which medical specialists should be involved in a clinical management of such patients should be based on the CMs repertoire prevailing in a given population or ethnic group. When performing a clinical monitoring of the CF children from the ethnic groups living predominantly in the North Caucasus Federal District, it is advisable to choose the therapeutic approach that takes into account the ethnic-specific features of CMs, identified in our work.

Compliance with ethical standards. The work was carried out as part of the implementation of the state task and the research work “Study of the etiological features of rare diseases with pathogenetic therapy” № 1220032300501-0, approved by the Ethics Committee (Protocol No. 10 of 06.10.2022) of the National Medical Research Center for Children’s Health.

Contribution:
Simonov M.V. — concept, research design, research coordination, material collection and data processing, review of publications on the topic, article editing;
Simonova O.I. — concept and design of the article, writing the text, editing;
Chudakova D.A. — review of publications on the topic, writing the text, editing;
Gorinova Y.V. — review of publications on the topic, concept and design of the article;
Kondakova O.B. — concept and design of the article;
Demyanov D.S. — editing, molecular genetic research;
Pushkov A.A. — editing, writing, molecular genetic research;
Savostyanov K.V. — concept design of the article and editing.
All co-authors — are responsible for theintegrity of all parts of the manuscript and approval of its final version.

Acknowledgements. The study had no sponsorship.

Conflict of interest. The authors declare no conflict of interest.

Received: April 25, 2024
Accepted: June 14, 2024
Published: July 31, 2024

Aim. To analyze anamnestic, clinical and paraclinical indicators in patients with Duchenne muscular dystrophy (DMD) receiving pathogenetic therapy with a drug for correcting nonsense mutations in the dmd gene — ataluren (translarna), to evaluate the safety of therapy and the dynamics of motor disorders in real clinical practice against the background of use drug.

Materials and methods. The study included 24 patients with DMD receiving ataluren who were hospitalized at the Center for Pediatric Psychoneurology of the National Medical Research Center for Children’s Health of the Ministry of Health of the Russian Federation for the period from January 2019 to February 2024. An analysis of anamnestic data, the most common clinical manifestations and paraclinical indicators, assessed the safety of the drug by the presence of serious adverse events leading to discontinuation of therapy, and the effectiveness of treatment using functional scales of motor activity: the “North Star” scale and the 6-minute walk test.

Results. The age of onset of independent walking was 14.3 ± 2.6 months, the age of onset of the disease was 3.3 ± 2.6 years, the age of visiting a doctor was 4.25 ± 2.00 years, the age of diagnosis was 5.3 ± 2,3 years, age of initiation of glucocorticosteroids (GCS) — 6.3 ± 1.8 years. GCS in an adequate dose and regimen was taken by 13 (56%) patients. Cognitive, emotional-volitional and behavioral disorders were registered in 17 (70.8%) patients, excess body weight — in 6 (25%), and stiffness of the ankle joints — in 9 (37.5%).Pulmonary function was analyzed in 16 (66.6%) patients, of which a decrease was detected in 1 boy. No patient experienced a serious adverse event leading to discontinuation of ataluren. When assessing the effectiveness of treatment in a group of patients under 7 years of age (n = 11), 10 (91%) children showed improvement or stabilization of their condition according to the 6-minute walk test; in 6 (54.5%) — improvement in motor skills when analyzing scores on the “North Star” scale; in 5 (45.5%) the condition was stabilized. the group of patients over 7 years of age (n = 13), according to the 6-minute walk test, 4 (30.8%) children showed stabilization of the condition, 7 (53.8%) had disease progression, 2 (15.4%) the child entered the non-ambulatory stage. When analyzing scores on the “North Star” scale, 1 (7.7%) child showed improvement in performance, 6 (46.1%) — stabilization, 4 (30.8%) — decrease, 2 (15.4%) — loss outpatient.

Conclusion. Early diagnosis of the disease and timely initiation of therapy in compliance with all standards of management of patients with DMD are crucial for maintaining motor function. Pathogenetic therapy with ataluren increases the duration of the outpatient stage, improving and/or stabilizing the motor skills of patients.

Compliance with ethical standards. Voluntary informed consent was obtained from the legal representatives of all patients.

Contribution:
Popovich S.G. — concept and design of the article, text writing, editing;
Kuzenkova L.M. — concept and design of the article, text writing, editing;
Uvakina E.V. — concept and design of the article, editing;
Podkletnova T.V. — editing;
Kozhevnikova O.V. — editing;
Bushueva T.V. — editing;
Zvonkova N.G. — editing.
All co-authors — approval of the final version of the article, responsibility for the integrity of all parts of the article

Acknowledgment. The study had no sponsorship.

Conflict of interest. Popovich S.G., Kuzenkova L.M., Uvakina E.V., Podkletnova T.V. are lecturers receiving honoraria from the pharmaceutical company PTC Therapeutics LLC.

Received May 31, 2024
Accepted June 20, 2024
Published July 31, 2024

Introduction. Developmental and epileptic encephalopathy are severe developmental disorders of the nervous system, characterized by recurrent epileptic seizures that begin over the neonatal period or childhood, accompanied by psychomotor retardation and intellectual disability. Massively parallel sequencing is a technology used to determine the complete nucleotide sequence of DNA or RNA. The technology is characterized by the high productivity and speed, marking the beginning of the golden age of genetics, allowing large volumes of DNA to be sequenced quickly and efficiently at lower costs. The aim of this study is to evaluate the effectiveness of whole-exome sequencing as a first-line genetic test in patients with developmental and epileptic encephalopathy and detect the structure of identified variants in the Russian population.

Materials and methods. Patients with drug-resistant seizures, onset in neonatal and early childhood, hospitalized in the Psychoneurological Department during 2017–2023. All patients underwent clinical and genealogical analysis, video-EEG and MRI of the brain, and whole-exome sequencing.

Results. The main result obtained in the study analysis of patients who underwent whole exome sequencing for the period of 2017-2023 was the detection rate of variants in genes associated with developmental and epileptic encephalopathy (21.7%; 71/331). Of these, 35/71 (49.3%) had pathogenic and probably pathogenic variants of the nucleotide sequence. Based on the results of whole exome sequencing patients were selected for the most effective targeted antiepileptic drugs.

Conclusion. The use of whole-exome sequencing as a first-line molecular genetic test in patients with developmental and epileptic encephalopathy has been shown to be highly effective. Making an accurate genetic diagnosis is a fundamental background for precision therapy. Personalized medicine, that is, the attempt to personalize prevention, diagnosis, and treatment as much as possible according to the characteristics and needs of the patient, should be the main goal of clinical research and a new direction of modern medicine.

Compliance with ethical standards. Patient management was carried out according to the principles of the Declaration of Helsinki of the World Medical Association (2013). Informed consent was obtained from the parents of patients to conduct a genetic study (whole exome sequencing).

Contribution:
Kozhanova T.V. — concept, writing text;
Zhilina S.S. — concept, editing;
Meshcheryakova T.I. — editing;
Abramov A.A. — editing;
Ayvasyan S.O. — editing;
Zavadenko N.N. — editing;
All co-authors — are responsible for the integrity of all parts of the manuscript and approval of its final version.

Conflict of interest. The authors declare no conflict of interest.

Acknowledgment. The study had no sponsorship.

Received: April 23, 2024
Accepted: June 14, 2024
Published July 31, 2024

Introduction. The high morbidity and mortality in premature infants, neurological and somatic disorders leading to disability, determine the search for early markers and predictors of developmental disorders at an early age and the development of a system of preventive measures, medical rehabilitation and habilitation, depending on the gestational age in the premature infant at birth. The purpose of the study is to compare neonatal risk factors for the development of neurological disorders at an early age in premature newborns taking into account the gestational age at birth.

Materials and methods. A retrospective-prospective study was performed. The study included two hundred twelve premature babies born between 26^th and 37^th week of gestation. There were formed four groups depending on the gestational age at birth: up to 28 weeks (n = 36), 28–31 weeks (n = 51), 32–33 weeks (n = 55), 34–36 weeks (n = 70).

Statistical processing of the research results was carried out using the R system, developed at the Department of Statistics at the University of Auckland, is available under the GNU GPL license and is distributed in the form of source codes and applications.

Results. A high incidence of intrauterine infection in premature infants (90.1%) was revealed. Significant differences and dependence of the frequency of encephalopathy of prematurity (ENPP) on the degree of prematurity were established (p< 0.001), while even with late prematurity (34–36 weeks) ENPP was observed in 12.9%. Data analysis showed the presence of ENPP in the neonatal period in premature infants to increase the likelihood of disability at an early age according to the class of nervous diseases by 22 times compared with the disability rate in premature infants without ENPP, Fisher’s p < 0.001.

Conclusion. Risk factors for delayed neurological disorders in premature infants vary significantly and depend on gestational age, must be taken into account when developing preventive habilitation programs.

Compliance with ethical standards. Research work for the academic degree of Doctor of Medical Sciences “Neurological disorders in premature infants: early diagnosis, prediction of outcomes, habilitation”, order of the rector of the Belarusian Medical Academy of Postgraduate Education No. 1301-ob dated October 31, 2019 on enrollment in doctoral studies Zhauniaronak I.V. The study was approved by the ethics committee of the Belarusian Medical Academy of Postgraduate Education, protocol No. 5 dated March 29, 2022.

Contributions:
Zhаuniaronak I.V. — development of research design and concept, data collection and processing, statistical processing, writing the text of the article, text editing;
Smychek V.B. — text editing.
All co-authors — are responsible for the integrity of all parts of the manuscript and approval of its final version.

Acknowledgements. The study had no sponsorship.

Conflict of interest. The authors declare no conflict of interest.

Received: May 25, 2024
Accepted: June 14, 2024
Published: July 31, 2024

Sialorrhea in children is a complex medical problem and leads to the development of a large number of complications. Sialorrhea also negatively affects the social aspects of the patients’ lives and their families. All this leads to a deterioration in the quality of life both in the child and his relatives. In mucopolysaccharidosis (MPS) type II, the main cause of sialorrhea is pseudobulbar syndrome, which forms gradually as the neurodegenerative process progresses. This can reach a significant degree of manifestation, leading to continuous salivation, the need for constant change of clothes and evacuation of saliva from the mouth and pharynx.

One of the most effective modern approaches in the treatment of sialorrhea in children is the use of botulinum toxin type A (BTA) preparations. Unlike cerebral palsy, in which the practice of treating sialorrhea with BTA drugs is already becoming routine, therapy of this problem in patients with MPS is not widespread. This publication presents three clinical cases of successful therapy of chronic sialorrhea in patients with MPS type II. All patients were observed at the National Medical Research Center for Children’s Health of the Russian Federation Ministry of Health for many years.

The procedure was performed in all patients according to the recommended standard scheme — injection of the product BTA — Xeomin (international name incobotulinumtoxinA) into the parotid and submandibular salivary glands on both sides under ultrasound control, depending on the child weight. To assess the severity of sialorrhea and its course after injections of Xeomin, “The Drooling Impact Scale” was used.

The results of our observations show the use of the drug Xeomin to allow obtaining a significant effect in reducing the severity of sialorrhea in MPS patients type II for at least 3 months. Using this product in the recommended doses and administration regimen, effective and safe treatment can be carried out, which, with repeated injections, can be used to achieve long-term improvement in chronic sialorrhea in children with MPS type II.

Contribution:
Kurenkov A.L. — concept and design of the study, writing the text, editing;
Podkletnova T.V. — concept and design of the study, writing the text, editing;
Bursagova B.I. — editing.
All co-authors — are responsible for the integrity of all parts of the manuscript and approval of its final version.

Acknowledgements. The study had no sponsorship.

Conflict of interest. The authors declare no conflict of interest.

Received: February 21, 2024
Accepted: April 24, 2024
Published: July 31, 2024

Introduction. Over 2023, in vascular centers of the Krasnoyarsk Territory thrombolysis operations were performed in five hundred ninety six cases with ischemic stroke, which amounted to 7.7% of all admitted patients and corresponds to the recommended federal indices. Nevertheless, due to the length and sparsely populated territory, there remains a part of patients who live in territories remote from the PVD and Regional Vascular Centers (RVC), when the transport leg significantly exceeds the “therapeutic window”, and therefore reperfusion therapy becomes impossible for them. The solution to this problem was the management of tele-PVD in a number of territories of the Russian Federation on the basis of district hospitals with the availability of Multispiral Computer Tomography (MSCT) in the Krasnoyarsk Territory.

Results. The first results of performing 20 thrombolysis in the tele-PVD showed the effectiveness and safety of the technique. Hemorrhagic transformations according to the control MSCT were no observed. There were no fatal outcomes among the patients who underwent thrombolytic therapy (TLT). Regression of neurological deficit occurred in 55% of cases, 75% of patients were discharged in Rankin 1–2 state. The results of thrombolytic therapy correspond to the indices of regional and urban vascular centers.

Conclusion. Performing thrombolytic therapy in tele-PVD under the telemedicine supervision of RVC specialists is a safe and effective procedure and allows increasing the number of reperfusion interventions in patients with ischemic stroke.

Contribution:
Shnyakin P.G. — concept, analysis and interpretation of data;
Halo N.V. — data collection, analysis and interpretation;
Grigoriev E.A. — data collection, analysis and interpretation;
Gavrilova A.O. — text analysis and editing.
All co-authors — are responsible for theintegrity of all parts of the manuscript and approval of its final version.

Acknowledgements. The study had no sponsorship.

Conflict of interest. The authors declare no conflict of interest.

Received: April 23, 2024
Accepted: June 14, 2024
Published: July 31, 2024