NEONATOLOGY
HEALTHY CHILD
Introduction. Vitamin D plays a fundamental role in the regulation of calcium and phosphorus homeostasis, and in recent decades its non-calcemic effects have been intensively studied.
The aim of the work was to analyze the patterns of vitamin D availability in young children against the background of prolonged use of an aqueous solution of cholecalciferol in preventive doses.
Materials and methods: 192 children of the first three years of life were examined (Arkhangelsk – 77 (40.1%), Moscow – 38 (19.8%), Stavropol – 77 (40.1%) children). Assessment of vitamin D availability was carried out by the level of serum calcidiol (25(OH)D). Based on the initial vitamin D supply, patients were divided into groups, and participants used cholecalciferol preparations for 30 days.
Results. The baseline vitamin D supply was 26.0 (19.5–35.4) ng/ml. Median 25(OH)D in children in the Moscow region is higher than in Arkhangelsk and Stavropol (p<0.0001). After using vitamin D in therapeutic doses, the median 25 (OH) D in Arkhangelsk was 46.7 (32.3–64.5) ng/ml, in Moscow – 52.6 (40.2–64.9) ng/ml, in Stavropol – 51.4 (41.3–69.8) ng/ml. According to the results of taking the prophylactic dose (1000 IU/day), satisfactory vitamin D was detected in 105 (54.7%) patients, insufficiency (from 20 to 30 ng/ml) – in 70 (36.5%), deficiency (from 10 up to 20 ng/ml) – in 17 (8.8%) children. Among children who had a 25(OH)D level of more than 30 ng/ml at the end of the study, the use of vitamin D preparations of 50–100 IU/kg and in 42 (41.0%) was effective in 62 (59.0%) children – in a dose of 100–150 IU/day, and in the group of patients with a level of 25(OH)D less than 30 ng/ml – a dose of 50 to 100 IU/kg was used in 69 (79.3%) patients, and a dosage of 100–150 IU/kg in only 18 (20.7%) children (p < 0.0005).
Conclusion. The used prophylactic dosage of 1000 IU/day of an aqueous solution of cholecalciferol was effective in most compliance children. The elimination of deficiency and the prevention of vitamin D deficiency is most effective when used for 6 months or more.
ACTUAL
BRONCHOPULMONOLOGY, ENT
Introduction. Mucolytic drugs are included in treatment standards and clinical guidelines for the management of children with respiratory diseases.
Target. To study the effectiveness of mucoactive therapy through its comparative evaluation in pediatric practice with respiratory pathology.
Materials and methods. A total of 48 patients (mean age 8.6 ± 4.1 years) with respiratory diseases were examined. They received conventional therapy and were divided into groups: the main one took Ambroxol (26) in syrup 15 mg/5 ml three times a day 4 days; comparison – a complex cough syrup with marshmallow (22) three times a day – 7 days. Dynamic control of clinical symptoms through statistical analysis and on special scales, accounting for clinical symptoms were evaluated out on the 1st, 3rd, 5th, 7th and 10th day from the start of mucoactive therapy.
Results and discussion. The reception of ambroxol was accompanied by a pronounced muco-regulatory effect. On the 2nd day of treatment: significant relief of sputum discharge (p = 0.0002), dry cough stopped faster (p = 0.0007), wet cough remained in the recovery period for a short time (p = 0.003); by the 4th–6th day of treatment, a significant decrease in sputum volume and its production period (p = 0.017), shorter duration of dry (3.82 ± 0.84 and 1.79 ± 0.18 days; p = 0.022) and wet rales in the lungs (3.57 ± 0.78 and 1.61 ± 0.21 days; p = 0.024), the severity of dry cough in the main group by 5–7 days in children with allergopathology was less (p = 0.0001). On the 7th day, the severity of wet rales in patients of the main group was 0.08 ± 0.05 points, and in the comparison group 0.18 ± 0.07 points (p = 0.0003), the duration of wet cough (4.4 ± 0.23 against 5.71 ± 0.38 points), sputum discharge (4.63 ± 0.38 against 5.74 ± 0.35 points) and rhinorrhea (2.69 ± 0.57 against 4.42 ± 0.32 points) (p < 0.05).
Findings. The clinical effectiveness of secretolitics is confirmed by reliably quick relief of dry and wet cough, sputum production intensity.
GASTROENTEROLOGY
ESPGHAN EXPERT CLUB
Introduction. Coeliac disease is a genetically determined disease associated with the HLA-DQ2 and DQ8 genes. According to European data, these alleles are detected in more than 95% of patients. The results of earlier studies in various regions of the Russian Federation and the constituent republics have shown a lower incidence of HLA-DQ2/DQ8 in children with coeliac disease (60–80%). These data served as a basis for discussion about regional genetic features and the potential for disease development in a significant proportion of patients without DQ2/DQ8 alleles.
Methods. Genetic screening was conducted on 275 children with coeliac disease. According to the results of the study, the patients were assigned to genetic risk groups.
Results. HLA-DQ2/DQ8-alleles were detected in 274 children (99.6%), with 86.9% of patients having DQ2 molecule in genotype and 12.7% having DQ8 molecule. Among 239 DQ2-positive patients, 33.5% were DQ2 homozygous. The remaining DQ2-positive patients had the following HLA-DR-DQ allele distribution: DR3-DQ2/DR5-DQ7 – 8.7%, DR7-DQ2/DR5-DQ7 – 13.4%, DR3-DQ2/ DRx-DQx – 22.2%, DR7-DQ2/DRx-DQx – 2.2%. In five children the incomplete DQ2 molecule was determined, represented by DQA1*0501 allele, while in four patients DQA1*501 was associated with DQB1*0301 allele forming DR5-DQ7 molecule. We found high and significant risk alleles in 29.1% and 22.2% of cases, while moderate and low risk alleles were found in 27.3% and 21.4% of cases respectively.
Conclusions: In Russian children with coeliac disease the prevalence of HLA-DQ2/DQ8 alleles corresponds to European data. Low detection frequency of HLA-DQ2/DQ8 molecules in Russian coeliac patients, which was reported earlier, may be due to peculiarities of the approach to the disease diagnostics, which do not correspond to modern Russian and international recommendations.
ALLERGOLOGY AND IMMUNOLOGY
The article provides a clinical example of the use of an amino acid-based mixture in a child with allergies to cow’s milk protein, gastrointestinal and skin symptoms, and no effect on the mixture based on highly hydrolyzed protein. When applying of an amino acid-based mixture a mixture (Neocate) and subsequent observation of the child after 1, 2 and 4 weeks, were noted normalization of the stool, a decrease in gas formation, the disappearance of skin manifestations, a decrease in the level of eosinophilic neurotoxin in the stool and a decrease in the time of anxiety of the child while maintaining normal rates of physical development. During the evaluation of the general blood test parameters in dynamics a decrease of eosinophilic concentration was shown from 0.62 x 109/l to 0.28 x 109/l (p < 0.01), normalization of eosinophilic neurotoxin level in stool – 93 ng/g of stool (p < 0.01) was observed.
Introduction. The intestinal microbiome is an integral part of the health of its owner and performs several important functions: metabolic, coordinating, protective, epigenetic, which are closely interactive. In conditions of dysbiosis, disturbances of these functions contributes to different disorders.
The intestinal immune system closely interacts with the microbiota. It is represented by all cells: T- and B-lymphocytes, T-regulatory, dendritic cells, macrophages. Micropresentation of antigens occurs through M-cells located between enterocytes. Toll-like receptors that recognize bacterial patterns are presented on the epithelial membrane. Dendritic cells present these antigens to T-cells and direct a further adaptive immune response.
The immune system matures as a result of colonization of the intestine with microbiota, which is confirmed experimentally in gnotobiotic animals. Under physiological conditions, the immune system provides tolerance to its own microbiota through Tr-cells. Tolerogenic effects decrease in dysbiotic conditions, as a result, inflammation develops.
The state of the intestinal barrier. The intestinal barrier is maintained by microbiota, which stimulates the synthesis of mucin and claudine. In dysbiosis, permeability increases, and the immune system is attacked by microbes and their metabolites, which contributes to inflammation.
Dysbiosis predisposes to the development of inflammatory bowel diseases, colorectal cancer, metabolic syndrome and obesity, food allergies. In these diseases, the microbiota loses its diversity and richness and has a predominantly pro-inflammatory effect.
The effect of probiotics on the immune system. Probiotics, due to adhesion to the mucous layer, enhance barrier functions, interact with the immune system, affect dendritic cells, promoting the formation of Tr and inhibiting the activation of NF-kB. Commensal metabolites (butyrate) increase the involvement of Tr cells in the colon, exerting a tolerogenic effect.
Indications for the appointment of probiotics. Enterococcus faecium and Bifidobacterium longum have proven their activities similar to normal microbiota, and effectiveness in treatment of dysbiosis in children and adults.
Up to 22% of the population in the world suffer from bronchial asthma according to the data from different regions and sources. This is about 358 million people. At the same time, accurate figures for the prevalence of this disease cannot be obtained. Despite the many ongoing studies of this disease, developed treatment options, asthma hasn’t become a fully controlled disease. The problem of control and treatment of the disease as well as patient compliance is of great concern to modern clinicians. Every year GINA releases new documents and makes changes in the treatment and diagnosis of this chronic bronchopulmonary disease. Children’s asthma has become not only the most common chronic disease, but also the most common cause of children hospitalization.
This article provides an overview of the international randomized clinical trials results and expert opinions regarding the treatment of uncontrolled bronchial asthma in children and adolescents. The results of 2017–2020 meta-analyzes regarding the use of tiotropium in children and adolescents are described. The use of basic therapy schemes is disclosed, including the use of tiotropium bromide in accordance with the recommendations of the Russian Respiratory Society and GINA.
The authors also presented a clinical case of difficultly controlled bronchial asthma in a child of 12 years old. The use of tiotropium bromide in this patient is described in detail and the effectiveness of this drug is demonstrated.
CLINICAL CASE/PRACTICE
Introduction. Glycemic control in patients with diabetes mellitus type 1 (DM1) can be held using glucometer with mobile application, continuous glucose monitoring (CGM), and intermediately scanned CGM (isCGM). isCGM do not need calibration with glucometer as CGM, but its usage in children and adolescents is recommended only together with glucometer.
Aim: to study characteristics of glucometer usage in real clinical practice in a patient which utilizes glucometer with mobile application and is CGM simultaneously.
Materials and methods. A 17-year-old girl with diabetes mellitus type 1 was advised to use isCGM together with glucometer Contour Plus One (ISO 15197:2013) and mobile application Contour Diabetes.
Results. The first three months, while insulin dose titration and education, the patient used glucometer 1–9 times a day (3.0 (2.0; 4.0)), filled in diary. These led to decrease of glycaemia (10.7 (5.5; 14.7) – 7.8 (5.2; 9.5) mmol/L) and variability (56–45%), increase of percent of measurements within range (38–57%), according to glucometer; decrease of mean glycaemia (11.8–8.5 mmol/L) and increase of time in range (TIR) (14–59%), according to isCGM. The next three months, while diabetes mellitus type 1 compensation, according to glucometer (glycaemia 6.9 (4.9; 9.7) mmol/L, variability 48%, percent of measurements within range 71%) and isCGM (mean glycaemia mean glycaemia 7.3 mmol/L, TIR 67%), the patient stopped to fill in diary, decreased number of measurements by glucometer to 1.0 (1.0; 2.0) times a day. Mean month glycaemia was 5.5–9.8% lower according to glucometer than isCGM. The patient used glucometer in cases with relatively high risk of hypoglycemia more often.
Conclusion. Usage of glucometer with mobile application can increase adherence to treatment. If glucometer and isCGM used simultaneously the patients measure glycaemia with glucometer in cases of decompensated diabetes mellitus type 1 and while insulin titration more often. Mean month glycaemia according to glucometer, if used every day, corresponds with isCGM data. We must discuss with patients circumstances when they use glucometer because this can influence glycemic control indicators in mobile application reports.
Introduction. One of the causes of sudden cardiac death in children is inherited arrhythmias. In view of the links between the increase in body temperature and the manifestation of some inherited cardiac arrhythmias (including typical electrocardiographic changes), the frequency of inherited cardiac arrhythmias in children with infectious diseases have been analyzed.
The relevance of the study: is initiated by the necessity of timely diagnosis of inherited cardiac arrhythmias and conduction in children in order to prevent sudden cardiac death in them.
The purpose of the study: to determine the frequency of inherited arrhythmias in children with infectious diseases based on clinical and electrocardiographic analysis.
Materials and methods: 3584 electrocardiograms (ECGs) of children with infectious diseases (average age 8.5 ± 5.3 years old; boys – 57.5%, girls – 42.5%) hospitalized in the Pediatric Research and Clinical Center for Infectious Diseases were analyzed. Patients with changes in the ECGs were given additional examination depending on the intended diagnosis (inherited arrhythmias): 24-Hour Holter ECG monitoring, stress test, echocardiography. The family history was also clarified, and the parents’ ECG was analyzed.
Results and conclusions. ECG changes, which are typical for Brugada syndrome (type 1), were detected in two children (0.05%) at first. Long QT syndrome was also detected in two children (0,05%). Mutations in the SCN5A gene were identified in children with Brugada syndrome, and in the KCNQ1 gene with long QT syndrome. An episode of monomorphic ventricular tachycardia was recorded at night in a 5-year-old girl with atrioventricular block 1 degree, hypoadaptation of the QT interval with repeated Holter ECG monitoring during sleep. Cases of life-threatening ventricular arrhythmias have previously been described in the literature in patients with Brugada syndrome. An increase in body temperature leads to disruption of the sodium ion channels which underlie the development of this syndrome, thereby, on the one hand, increasing the risk of life-threatening arrhythmias and sudden cardiac death, on the other hand, to the clinical manifestation of the disease, allowing the diagnosis to be made in time. In the cases of long QT syndrome, in our study, the increase in the corrected QT interval (QTc) is most likely due to a change in heart rate rather than a direct effect of an increase in body temperature on the ion channels.
PEDIATRICIAN SCHOOL
The prevention and treatment of osteoporosis in children is an urgent problem of pediatrics and pediatric endocrinology. This is due to the need for preventive measures for the formation of adequate bone mass and bone strength, the duration of rehabilitation during the development of the disease and the occurrence of fractures, as well as the requirements for optimizing the treatment of this pathology in childhood.
Bone tissue is a dynamic and constantly updated system. The main regulators of osteogenesis include trace elements (calcium, phosphorus, zinc, fluorine, etc.), vitamin D, hormones (parathyroid hormone, calcitonin, growth hormone, corticosteroids, etc.), growth factors (IRF-1, IRF-2, ERF, FRF, etc.), local bone-resorbing factors (IL-1, IL-6, TNF, PGE, etc.) and mechanical stress. Remodeling processes continue throughout life, but are most intense until 18 years of age.
The most important risk factors for developing osteoporosis are a history of prematurity and / or IUGR, rickets, low intake of protein, calcium and vitamin D, weight deficiency, periods of active growth, low physical activity, endocrine diseases (diabetes mellitus, growth hormone deficiency, hypogonadism, etc.), somatic pathology (chronic diseases of the kidneys, liver, malabsorption), taking certain medications (GCS, anticonvulsants, cytostatics, etc.). Clinical manifestations of osteoporosis in children include signs of tissue calcium deficiency (trophic changes in the nails, hair and tooth enamel, paresthesia, pain in the calf muscles) and a decrease in bone mineralization (impaired posture, slowed growth, pain in the spine and large joints, pathological low-energy fractures) Measures to prevent osteoporosis in childhood include regular physical activity, a balanced diet, adequate insolation, and the identification and treatment of somatic pathology. Additional pharmacological correction is carried out in risk groups – the recommended course use of preparations containing vitamin D, calcium and other osteotropic minerals.
The treatment of osteoporosis in children and adolescents is actively debated. A mandatory component of therapy are calcium salts in combination with vitamin D. The possibility of using bisphosphonates is being examined, the effect of monoclonal antibodies (denosumab), somatropin and anabolic steroids on bone metabolism is being studied. In addition, non-pharmacological methods are prescribed - orthopedic correction for fractures, exercise therapy, gymnastics, therapeutic swimming and massage.
DIFFICULT DIAGNOSIS
Introduction. Liver lesion in congenital syphilis in infants in the first months of life is clinically observed in 74–86% of children in the form of enlargement and thickening during palpation. Pathological and anatomical studies reveal in 100% of cases typical changes in the liver, which are mainly due to diffuse round-cell infiltration, expansion of connective tissue and formation of gummas.
Purpose of research. To analyze the indicators of ultrasound examination of the liver and spleen with the assessment of organ blood flow in children born to women with syphilitic infection and to identify the most significant signs associated with early congenital syphilis in the neonatal period.
Materials and methods. The paper analyzes the data of a comprehensive survey of 397 newborns who were under observation from birth to 1 month of life, included in the study with the indication of the fact, born to women with a history of documented confirmed syphilitic infection.
On the basis of the total sample, three groups of children from birth to 28 days of life were formed, taking into account the Federal clinical guidelines for the management of patients with syphilis (Moscow, 2015).
The results of the study and their discussion. In 1 and 2 study groups found a significant increase in the oblique vertical size of the right lobe was 74.3 ± 0.7 mm (p < 0.05) and 73.9 ± 0.4 mm (p < 0.05), vs. 68.8 ± 0.3 mm in the control, as well as the thickness of the left lobe of the liver is 35.3 ± 0.4 mm (p < 0.05) and 34.8 ± 0.6 mm (p < 0.05), compared to 31.4 ± 0.7 mm in the control group. Along with this, in these groups, a higher index of the maximum blood flow velocity in the portal vein was noted, which in these 1 and 2 groups was 0.26 ± 0.02 m/s (p < 0.05) and 0.25 ± 0.02 m/s (p < 0.05), respectively, against 0.20 ± 0.02 m/s in the control. Along with sonographic signs, there was a significant prevalence of hyperbilirubinemia in groups 1 and 2 of newborns – 24.1% (p < 0.001) and 19.9%, respectively, against 9.0% in the control group (neonatal hepatitis was diagnosed in 11.4% of newborns with early congenital syphilis).
Conclusion. The ultrasound features of the liver and early congenital syphilis include an increase in size, structural changes in the liver (only in PBC with symptoms) and hemodynamic features, characterized by increased blood flow by increasing the absolute value of linear velocities (maximum systolic and minimum diastolic) with a reduced resistance index.
From a long time ago to the present day, measles remains one of the leading health problems in the world. The main reason for this is high mortality from measles – 1/500. Despite the availability of an effective and safe vaccine, which was discovered in 1963, there are still epidemic outbreaks of measles. According to WHO, there were 413,308 confirmed cases in 187 countries and 764 deaths during 2019. Most measles deaths are due to complications associated with the disease.
Complications are most common in children under five or in adults over 30 years of age. The most serious complications include blindness, encephalitis leading to cerebral edema, severe diarrhoea and associated dehydration, purulent otitis and severe lower respiratory tract infections such as pneumonia. In a study from 2019, Michael J. Mina and colleagues showed that after measles in the group of unprivileged people, 11 to 73% of previous immune memory is “erased”. Currently, there is no specific etiotropic therapy for measles. One of the pathogenetic links in therapy is the use of interferon replacement therapy. According to the Federal Clinical Recommendations and WHO recommendations, the use of recombinant interferon α-2B and vitamin A is recommended. The effectiveness of interferonotherapy for measles was first shown in 1992 by the Leopardi R team. This study showed that the secretion of measles virus in human peripheral blood mononuclear cells was gradually reduced by increasing the concentrations and blocked at the concentration of interferon α-2B in 1000 units/ml. Moreover, at the XXIV World Congress of Neuroscientists (WCN) it was noted that the safest and most effective method of treatment of subacute sclerosing panencephalitis, one of the severe complications of measles, is recombinant human α-2B interferon.
TESTS/TASKS
ISSN 2658-5790 (Online)