EDITORIALS
ORIGINAL ARTICLES
Background. The genetically engineered biological drug dupilumab, which blocks the IL-4 and IL-13 signaling pathways, has demonstrated high efficacy in the treatment of Atopic Eczema (AE) in children and adults. However, there are no studies in Russia that evaluate the clinical response and the dynamics of biomarkers in children of different ages with a multimorbid atopic phenotype who receive therapy with this drug. The aim of the study is to evaluate the efficacy and safety of dupilumab, as well as to analyze the dynamics of inflammation biomarkers in children with a multimorbid atopic phenotype, including patients with moderate to severe AE.
Methods. A prospective observational study included 15 children aged 6 months to 17 years 11 months. All patients received dupilumab for at least 16 weeks. Clinical efficacy was assessed using the SCORAD and EASI scales (with SCORAD-50/75/90 and EASI-50/75/90), quality of life (CDLQI), and control of concomitant diseases (ACT, VAS). Biomarkers (periostin, VEGF, DPP4, eosinophils, and FeNO) were determined before and 16 weeks after the start of therapy.
Results. By the 16th week, all patients had reached SCORAD-50 and EASI-50, 80% had reached SCORAD-75, 100% had reached EASI-75, 60% had reached SCORAD-90, and 87% had reached EASI-90. During the treatment, there was a decrease in the levels of periostin (median change of –8%), VEGF (–9.7%), and a tendency towards a decrease in the number of eosinophils and FeNO, while the levels of DPP4 remained stable. The quality of life improved in most patients, and the accompanying manifestations (bronchial asthma, allergic rhinitis) were under full control. Side effects were limited to local reactions and conjunctivitis.
Conclusion. Dupilumab therapy in children with a multimorbid atopic phenotype, including patients with moderate to severe AE, provides rapid and persistent clinical improvement, a decrease in the severity of inflammatory markers, and an improvement in quality of life. The data obtained confirm the efficacy and safety of the drug and indicate the prospects for using biomarkers to predict the individual response to therapy.
Background. Functional gastrointestinal disorders (FGID), accompanied by abdominal pain, are among the most common gastrointestinal issues (GI) in pediatric practice. Despite the large number of epidemiological studies conducted on functional disorders of the GI in children, data on the actual prevalence of these conditions remain uncertain. This is due to the fact that different methods were used in different studies, which led to heterogeneous results.
The aim of the study is to determine the prevalence and study the structure of FGID occurring with abdominal pain among children aged 8–17 years.
Materials and methods. On the basis of the children’s polyclinic of the Dolgoprudny Central City Hospital, a cross-sectional study of the prevalence of FGID occurring with abdominal pain in children was conducted according to electronic medical records. Electronic medical records of children aged 8–17 years, whose main or concomitant diagnosis is functional dyspepsia, biliary dysfunction, irritable bowel syndrome and functional abdominal pain, were selected. Based on the data obtained, the prevalence index was calculated, the structure, age and gender characteristics of FGID with abdominal pain in children aged 8–17 years were studied.
Results. The study involved 13,907 children aged 8 to 17 years inclusive. The prevalence of FGID with abdominal pain among schoolchildren of this age was 13.6%. When analyzing the structure, the authors revealed that functional dyspepsia is the most common form of digestive disorders in children in this age group. An analysis of the age distribution showed that the frequency of these disorders is higher in older children. These disorders are also prevalent in girls in most age groups.
Conclusion. The prevalence of FGID with abdominal pain in children aged 8 to 17 years corresponds to the literature data. Primary care physicians still have a number of difficulties when working with children suffering from FGIS with abdominal pain.
The aim of the study is to evaluate the diagnostic information value of direct serological biomarkers — hyaluronic acid (HA), collagen types I and III (COL1, COL3), growth differentiation factor-15 (GDF-15), monocyte chemotactic factor-1 (MCP-1) and extracellular matrix protein 1 (ECM1) — for noninvasive stage identification hepatic fibrosis (HF) in children.
Material and methods. The study included 60 patients (average age 10.2 ± 4.7 years) with chronic liver diseases of various etiologies, including autoimmune hepatitis (16), primary sclerosing cholangitis (11), glycogen disease (10), Wilson’s disease (6), and unspecified HF (17). All children underwent ultrasound examination of the abdominal organs with two-dimensional shear wave elastography (2D-SWE) and quantitative determination of the above markers in the blood serum. The concentrations of HA in the blood serum of patients were determined by enzyme-linked immunosorbent assay (ELISA); COL1, COL3, ECM1, GDF-15 and MCP-1 were determined by sandwich ELISA.
Results. The concentrations of HA and GDF-15 in blood serum increased statistically significantly with the progression of HF (p < 0.001; p = 0.001, respectively). To determine the threshold values of HA depending on the stages of HF, high sensitivity (90%) and specificity (up to 100%) were obtained, and the best values of the area under the ROC-curve were used to distinguish the late stages of fibrosis (AUC up to 0.965). The concentrations of GDF-15 in serum are characterized by maximum sensitivity when determining cut-off values to determine the stage of severe fibrosis and its initial manifestations, the specificity for close stages was lower (up to 70%). The concentrations of COL1, COL3, MCP-1, and ECM1 did not show significant differences between the HF stages (p = 0.108; p = 0.455; p = 0.158; p = 0.058, respectively). Direct correlations were found between serum levels of COL1 and COL3 (p = 0.341, p = 0.008), HA and GDF15 (p = 0.592, p < 0.001), MCP-1 and COL3 (p = 0.443, p < 0.001), as well as HA and GDF-15 with the results of 2D-SWE (p = 0.534, p < 0.001; p = 0.505, p < 0.001, respectively).
Conclusion. Determination of HA and GDF-15 concentrations can be considered as a valuable prognostic tool for noninvasive HF stratification in children. The usage of these indicators as part of diagnostic algorithms can help to more accurately determine the stage and dynamics of fibrosis, allowing in some cases to abandon invasive methods such as biopsy.
Objective. The aim of the study is to evaluate diagnostic significance of human leucine-rich alpha-2 glycoprotein (LRG) for noninvasive diagnosis of inflammatory bowel disease (IBD) activity in children.
Methods. The study included 60 patients with IBD (Crohn’s disease — 33, ulcerative colitis — 27) who were examined in 2023–2025. The average age was 9.7 ± 4.9 years. Serum LRG levels were measured via enzyme-linked immunosorbent assay (ELISA), “sandwich method”, AssayPro kit, USA. Disease activity was evaluated with specific pediatric indices PUCAI and PCDAI. We have additionally analyzed several immunological markers (anti-Saccharomyces cerevisiae antibodies (ASCA), IgG, IgM, IgA), as well as standard clinical and laboratory parameters. All the data is presented as median, lower, and upper quartiles (Q1; Q3). We have used Kruskall – Wallis test for comparison of three or more groups, Dunn test with Holm correction for post hoc comparisons, Mann – Whitney U test for comparison of the two groups. The correlation between variables was estimated via Spearman’s rank correlation coefficient (ρ); differences at p < 0.05 were considered statistically significant.
Results. Serum LRG levels were statistically significantly higher in patients with high inflammatory activity compared to mild to moderate IBD activity according to PUCAI (p = 0.038) and PCDAI (p = 0.021) scales. The most profound differences were revealed when stratified by the degree of disease clinical activity. Statistically significant positive correlations were also mentioned between serum LRG levels and PUCAI (ρ = 0.556, p = 0.021) and PCDAI (ρ = 0.902, p = 0.001) activity indices, as well as with serum ASCA levels (ρ = 0.314, p = 0.039).
Conclusion. Serum LRG level is obviously an informative laboratory marker of IBD activity in children and can be recommended for implementation in comprehensive laboratory diagnostics and monitoring of therapy efficacy along with generally accepted indices and immunological indicators.
Background. Robotic mechanotherapy is one of the most relevant and promising areas in modern neurorehabilitation. The possibilities of using exoskeletons in the rehabilitation of children of early and preschool age are currently insufficiently studied.
The aim of the study is to evaluate the effectiveness of using exoskeletons to correct motor stereotypes and form walking patterns in children of early and preschool age with motor disorders. Materials and methods. The patients were divided into 3 groups: group I consisted of 29 patients with cerebral palsy of preschool age who received traditional rehabilitation procedures, group II — 29 preschool children with cerebral palsy, whose rehabilitation complex included trainings with the ExoAtlet Bambini exoskeleton, and group III — 14 toddlers, whose rehabilitation program included training with a small ExoAtlet Sofia exoskeleton. To analyze the data, modern scales, tests, and hardware and software data were used to assess changes in biomechanical parameters and performance indicators of a particular muscle group.
Results. A clinical assessment against the background of a complex of rehabilitation measures using an exoskeleton by the end of rehabilitation showed a significant improvement in vertical posture, walking, and postural control in general. Correlation analysis conducted at the end of rehabilitation revealed statistically significant relationships between the total number of exoskeleton training sessions, the dynamics of the Hauser index (p = 0.033 in group II, p = 0.045 in group III), and the dynamics of the timed “Up and Go” test (p = 0.038 in group II, p = 0.49 in group III).
Conclusion. The usage of an exoskeleton leads to a statistically significant improvement in the postural control of patients in the study who received a full course of individualized comprehensive rehabilitation using an exoskeleton. The results of the comparative analysis demonstrated not only the higher efficiency of exoskeleton-assisted rehabilitation in toddlers and preschool children compared with traditional methods, but also allowed us to identify key factors predicting the success of this technology for this category of patients.
Background. The prevalence of structural brain abnormalities among Russian children remains unknown, which hinders effective planning for the prevention of severe neurological and neurosurgical complications. The significance of a number of conditionally pathological findings that are accidentally detected by magnetic resonance imaging (MRI) in clinical practice also remains debatable.
The aim of the study is to determine the frequency of macrostructural changes in the brain among primary school— age children, detected by MRI of the brain, and to assess their clinical significance in relation to disorders from the group of mild cognitive impairment (MCI) and attention deficit hyperactivity disorder (ADHD).
Methods. All participants, 7–8 year old children from Chelyabinsk and Moscow, underwent an MRI scan of the brain, representatives of the Moscow cohort of children additionally underwent an in-depth clinical and psychological examination: consultation with a neurologist/psychiatrist, neuropsychological and speech therapy testing, and Wexler intelligence assessment.
Results. 162 children of the combined (Chelyabinsk and Moscow) population sample and 114 Moscow children of the pathology group — ADHD, MCI and their combined variants were examined. A subgroup of 30 neurologically healthy children was also isolated from the Moscow population cohort. The most common findings in the population group were ventricular asymmetries (35.8%), dilation of perivascular spaces (11.1%), epiphysis cysts (4.3%), and an increase in the size of the large brain cistern (4.3%). According to the survey results, 2.5% of the children were referred for in-depth examination in connection with the findings. Conditionally pathological findings in general and specifically perivascular space dilation and arachnoid cysts are significantly more common among children with MCI and combined pathology of MCI + ADHD compared with neurologically healthy children and the general population of children.
Conclusion. Continuous screening of Russian children using MRI can identify about 2.5% of children with suspected serious abnormalities requiring specialized monitoring. In addition, some findings that are considered insignificant may signal mild neuropathology.
CLINICAL RECOMMENDATIONS
Gastroesophageal reflux disease (GERD) is a chronic condition with recurrent retrograde flow of gastric contents to esophagus due to impaired lower esophageal sphincter function. It leads to typical symptoms such as heartburn, regurgitation, and dysphagia, as well as non-specific manifestations such as cough, sore throat, retrosternal pain. Implementation of modern diagnostic methods and personalized therapeutic strategies can significantly reduce symptoms, prevent complications, and improve quality of life of patients with GERD. The presented clinical guidelines describe integrated approach to diagnosis including history taking, physical examination, and imaging studies. Differential diagnosis with other diseases with similar symptoms is crucial as well. GERD management should be systemic and include non-pharmacological measures: lifestyle correction and drug therapy (antacids, proton pump inhibitors, and prokinetics). Particular attention is paid to complications prevention. These guidelines are the basis for timely and comprehensive management for GERD patients.
REVIEW
Autism spectrum disorders (ASD) are a group of psychological development disorders characterized by high heterogeneity of phenotypical and underlying biological mechanisms. To this date, there is no single concept of ASD etiology and pathogenesis; however, many studies discuss complex impact of genetic, epigenetiс, and exposomal factors on impaired neurodevelopment in children. Currently therapeutic approaches for ASD are symptomatic despite the dynamic research of autism issue. The high degree of etiopathogenetic and clinical differences dictates the need to find new methods for studying autism. Increasing number of people with ASD worldwide in recent decades, challenging early diagnosis, timely diagnosis and therapy require deeper, comprehensive study of ASD with innovative research methods. This review focuses on multi-omics — integrative approach to analysis of data obtained via high-tech omix studies (genomics, transcriptomics, epigenomics, proteomics, metabolomics, and microbiomics). Its implementation will provide the opportunity for better understanding of etiopathogenetic mechanisms and development of personalized strategies for autism diagnosis and management.
Ultra-short celiac disease is one of the phenotypes of common celiac disease, it is characterized by hyper-regenerative atrophy and/or intraepithelial lymphocytosis in duodenal bulb along with no mucosal damage in distal duodenum, serological positivity, the presence of HLA-DQ2. However, seropositivity and classical HLA-DQ2 haplotypes frequency differs from usual celiac disease, thus, there are significant difficulties in differential diagnosis. Data on prevalence, clinical manifestations, histological lesions, genetic features, and outcome of ultra-short celiac disease is insufficient and should be accumulated. This review focuses on analyzing the studies results about ultra-short celiac disease and describes the clinical, immunological, and genetic features of this disease phenotype.
Autism spectrum disorders (ASD) are neurodevelopmental disorders of polyetiological nature. The leading role in their development belongs to genetic and environmental factors. Nowadays, the main treatment landscapes are methods of psychological and pedagogical correction. Over the past decades, there has been an active search for biological causes and pathogenetic mechanisms in order to develop additional treatments approaches. One of the methods of hardware neuromodulation used in ASD is transcranial magnetic stimulation (TMS). This article provides the analytical review of modern research on TMS implementation in ASD. Neurobiological hypotheses of ASD pathogenesis that underlie the use of hardware neuromodulation, are considered. Special emphasis is paid to targeted approach in using TMS according to the clinical signs of patients. The purpose of this review is to analyze and summarize modern scientific studies on TMS usage in ASD in various clinical groups, as well as to determine further research directions. Analysis of 39 publications, including double-blind, placebo-controlled studies, has shown TMS safety and good efficacy in patients with autism. However, there is no uniform approaches in selection of stimulation protocols, in definition of clinical groups of ASD patients, as well as in methods for monitoring the dynamics of clinical indicators. The profound clinical and biological heterogeneity of ASD, as well as indicated heterogeneity in studies, lead to the absence of TMS protocols that can be included in clinical guidelines, which necessitates further research.
SOCIAL PEDIATRICS AND HEALTH CARE
Background. The health-related quality of life (HRQL) in children with inflammatory bowel diseases (IBD) is one of the key criteria for evaluating the effectiveness of therapy and the organization of medical care. To date, Russia has lacked validated tools for a standardized comprehensive assessment of HRQL in pediatric patients with gastrointestinal tract pathology, which limited the comparability of domestic data with international studies.
The aim of the study is to verify the reliability, validity and sensitivity of the Russian-language version of the module of gastrointestinal symptoms of the general PedsQL questionnaire and to determine its suitability for assessing HRQL in children with IBD of different age groups.
Patients and methods. The study included 346 patients aged 2 to 18 years with confirmed diagnoses of ulcerative colitis and Crohn’s disease. In the cross-sectional part, HRQL in children with IBD was evaluated simultaneously, in the cohort part, the dynamics before and after surgery. To analyze the psychometric properties of the module, the Cronbach’s alpha coefficient, an assessment of the constructive and convergent validity, as well as the sensitivity of the instrument were used.
Results. The Russian-language version of the module of gastrointestinal symptoms of the general PedsQL questionnaire showed high internal consistency of scales (Cronbach’s alpha from 0.721 to 0.983), reliable validity (the tool differentiates groups of patients with different stages of the disease), as well as sensitivity (statistically significant improvement in HRQL after surgical treatment).
Conclusion. The Russian-language version of the module of gastrointestinal symptoms of the PedsQL general questionnaire has satisfactory psychometric characteristics and can be successfully used to assess HRQL in children with IBD in Russian clinical and scientific practice. The tool expands the possibilities of medical monitoring, makes it possible to objectify the effectiveness of therapy and form personalized approaches to the management of patients in this category.
SHORT REPORT
The consumption of vegetables and fruits containing increased amount of fibers and phytochemicals has beneficial effect on human health. Typically, adherence to high plant-based diets shows its efficacy in reducing the risk of cardiovascular diseases, obesity, and type 2 diabetes development. In return, there are complex interactions between diet, intestinal microbiota, and immune homeostasis. One of the mechanisms of dietary factors affecting the body is change in intestinal microbiota composition and short-chain fatty acids production. To this date, there are only single clinical studies on the effect of high plant-based diets on intestinal microbiota. Their results have shown that switching to high plant-based diets can increase diversity of healthy intestinal bacteria. It has beneficial effect on immune processes, intestinal motility, and has anti-inflammatory effects.
NEWS OF PEDIATRIC PHARMACOLOGY
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