Vol 14, No 4 (2023)

Congenital hyperinsulinism is a hereditary disease belonging to the orphan group, clinically manifested by the development of persistent hypoglycemia in the neonatal period. Neurological disorders resulting from persistent hypoglycemia, in most cases, are accompanied by dysfunction of the central nervous system, regression and delayed psychomotor and speech development. Congenital hyperinsulinism is characterized by heterogeneity of disease phenotypes, manifested by different severity of hypoglycemic syndrome, metabolic and neurological manifestations, which makes it difficult to verify the diagnosis, dictates the need for a comprehensive examination, including molecular genetic analysis in patients and their families. This allows timely appointment of insulinostatic therapy, thereby reducing the risk of severe neurological and metabolic complications. The article presents a description of three clinical cases of сongenital hyperinsulinism associated with homozygous variants in the ABCC8 gene and an autosomal recessive type of inheritance, which were included in the number of patients previously studied by us with variants in the ABCC8 and KCNJ11 genes. The results of this study were partially published by the authors earlier. The experience of monitoring these patients reflects the importance of early diagnosis of сongenital hyperinsulinism, including the use of molecular genetic testing, the timely administration of insulinostatic therapy, allows an objective assessment of the effectiveness of the treatment, and reduces the risk of developing severe metabolic and neurological complications.

BACKGROUND: According to Rosstat, respiratory diseases are the most common reason for children to seek medical help. Anatomical and physiological features of the child’s body and infectious factors predispose to the development of bronchial obstruction syndrome. The scientific literature describes that the presence of connective tissue dysplasia (CTD) worsens the course of bronchial obstruction syndrome. It is important to detect CTD in children with respiratory diseases, as they require more invasive examination methods. This group of patients has specific features of therapy, they need more careful dynamic monitoring.

AIM: Identification of CTD based on phenotypic signs and study of its features in patients of the pediatric pulmonology department with bronchial obstruction syndrome and chronic bronchial inflammation, assessment of the severity of the disease, analysis of examination methods and therapy.

MATERIALS AND METHODS: The article presents data from a one-stage cohort study of 380 patients with bronchoobstructive syndrome who received inpatient treatment in the conditions of the pulmonology department of the St. Petersburg State Medical Institution “K.A. Rauhfus Children’s City Clinical Center of High Medical Technologies”, in the period from 2019 to 2022.

RESULTS: Conventional therapy, which is used to treat bronchial asthma, is not always effective for patients with CTD. Pediatric patients with CTD and bronchial asthma who are being treated in the pulmonology department are subjected to greater radiation exposure and procedures with a higher level of invasiveness, including fibrobronchoscopy.

CONCLUSIONS: Children with CTD are characterized by a burdened anamnesis of bronchopulmonary pathology (complicated course of pneumonia, spontaneous pneumothorax), the absence of complicated heredity by atopy. In the group of children with CTD, the prevalence of severe bronchial asthma and obliterating bronchiolitis was revealed. Examination of patients with CTD requires expensive diagnostic studies (computed tomography of the chest organs, fibrobronchoscopy), in the acute period of the disease — the appointment of systemic glucocorticosteroids, humanized monoclonal anti-IgE drugs are used to treat the disease.

BACKGROUND: The problem of acute EBV-mononucleosis is one of the most urgent in pediatrics. In the structure of the incidence of infectious mononucleosis, the proportion of the child population is 70–80%, children 4–8 years old are more often ill. Maternal antibodies protect an infant only in the first months of life, primary infection may occur at 3 months of age, and a manifest form of acute EBV-mononucleosis may develop at 6 months of age.

AIM: The aim of the study was to analyze peculiarities of acute EBV-mononucleosis in children of different ages hospitalized in the infectious diseases hospital of the Saint Petersburg State Pediatric Medical University.

MATERIALS AND METHODS: The article presents data on 376 children aged 1 to 18 years with a diagnosis of Acute EBV mononucleosis, hospitalized in the period 2017–2020. In the infectious diseases department No. 1 of Saint Petersburg State Medical University. Etiological interpretation was carried out using ELISA (determination of IgM to VCA in the blood) and detection of EBV DNA in the blood by PCR.

RESULTS: In 89.6% of cases, the disease was of moderate severity. Acute onset of the disease was noted in 69.7% of cases, more often in children from 1 to 10 years old. Intoxication syndrome was observed with the same frequency in all age groups. Febrile fever was observed in 96.0% of patients. The syndrome of acute tonsillitis, lymphadenitis was detected in all patients. The phenomena of adenoiditis and hepatomegaly were more pronounced in younger children. Splenomegaly was recorded in 74.5% of cases, more often than hepatomegaly. Cytolysis syndrome was observed in every second child. In older age groups, there was a higher level of hyperenzymemia and a pronounced mononuclear reaction in the hemogram.

CONCLUSION: All the analyzed patients had a typical clinical picture of acute EBV mononucleosis with a characteristic syndrome complex. In most cases, the disease was of moderate severity, severe severity was recorded in 8.2% — mainly in older children. Involvement of the liver and spleen in the pathological process simultaneously took place in every second patient. In older age groups, there was a higher level of hyperfermentemia and a pronounced mononuclear reaction in the hemogram.

BACKGROUND: Nephrotuberculosis is characterized by the accumulation of extracellular matrix proteins, the regulation of which is carried out by matrix metal propriets (MMP).

AIM: To study the dynamics of the MMP / inhibitors of the blood in the treatment of experimental nephrotuberculosis using mesenchymal stem cells (MSC).

MATERIALS AND METHODS: Among the 20 rabbits with nephrotuberculosis caused by the Mycobacterium tuberculosis, the group 1 compiled by untrue animals; group 2 — with anti-tuberculosis therapy; group 3 — with anti-tuberculosis therapy and mesenchymal stem cells. The development of nephrotuberculosis was confirmed by the reaction with Diaskintest. In the blood serum, the levels of MMP (MMP-1,-9), their tissue inhibitor-TIMP-1, cystatin C (CC), creatinine (KR), albumin (AL), ceruloplasmin (CP), neutrophilic elastasis (NE) and adenosin deaminase (ADA) were determined. A histological examination of the kidneys was carried out. Used Statistica 7.0.

RESULTS: The presence of specific inflammation in the kidneys by 2.5 weeks in all groups was confirmed by increased levels of ADA, CP and a decrease in the body weight of animals, but was not accompanied by changes in the MMP-1,-9, TIMP-1, CC and KR. By the 21^st week after infection in all groups, an increased level of ADA, NE and the KR was preserved, and the concentrations of CP and AL were normalized. In group 1 alone, high levels of MMP-9 and CC, foci of specific inflammation and distinct glomerulus changes were noted. The differences between the groups 3 and 2 were associated with lower values of the area of interstitial fibrosis and collagen (p = 0.03). A discriminant function based on the values of the MMP-1,-9, TIMP-1, NE, KR and CC, characterizing significant differences between three groups has been obtained.

CONCLUSIONS: 1. Nephrotuberculosis in rabbits infected with the Mycobacterium tuberculosis 5582 Beijing genotype, after 2.5 weeks was characterized by an increase in the blood of ADA, NE, CP and a decrease in AL, and the lack of changes in the MMP-1,-9 and TIMP-1, KR and CC. 2. The processing of nephrotuberculosis was accompanied by an increase in the blood of concentrations of hell, NE and KR, MMP-9 and CC, but not MMP-1 and TIMP-1. 3. The therapy of the anti-tuberculosis and mesenchymal stem cells normalized the levels of the MMP-9 and the CC, but not ADA and NE. 4. The complex from MMP-1,-9, TIMP-1, NE, KR and CC, allows you to differentiate groups with different vephrotuberculosis activity.

BACKGROUND: Dislocation syndrome is characterized by a displacement of the median structures in brain and is a consequence of a progressive increase in intracranial volume in vascular accidents, traumatic brain injury, and neoplasms. Lateral dislocation of the median structures leads to their gross dysfunction, as well as to compression of the cortical sections, which leads to violations of the mechanisms of generation of bioelectrical activity. In acute cerebral insufficiency in conditions of scarcity of clinical symptoms, the analysis of changes in the bioelectrical activity of the brain becomes an important part of the diagnosis and prognosis of the course of a critical condition.

AIM: The aim of this study is to characterize the electroencephalography (EEG) patterns recorded in patients with lateral dislocation in the acute period of traumatic brain injury and hemorrhagic stroke.

MATERIALS AND METHODS: The work was based on the analysis of the EEG amplitude-frequency parameters recorded in 74 patients (52 men, 22 women, mean age 53.3 ± 12.5 years) who were treated at the Dzhanelidze Research Institute for Emergency Medicine. The cause of acute cerebral insufficiency in 42 cases was a traumatic brain injury, in 32 cases — a hemorrhagic stroke. Inclusion criteria: 1) lateral dislocation more than 4 mm according to the results of computed tomography; 2) level of consciousness Coma 1 or Coma 2; 3) the outcome of the disease was determined within 23 days from the moment of injury or stroke. 24 observations had a favorable outcome.

RESULTS: According to the results of computed tomography, lateral displacement of the brain structures (Me 9 [6; 16] mm) was revealed in all patients, but without signs of their compression or infringement. Recorded EEG variants were divided into three groups: 1) focal and diffuse disturbances without signs of persistent epileptiform activity of a high index (30%); 2) dominance of gross epileptiform disorders included in the syndromic structure of non-convulsive status epilepticus (59%); 3) isoelectric “silence” of the brain (11%). The degree of lateral dislocation reached its maximum values when registering the bioelectric “silence” pattern. With a favorable outcome of acute cerebral insufficiency, there was practically no correlation between the severity of EEG disturbances and the degree of dislocation. With unfavorable outcomes, dislocation syndrome was a factor that determined the severity of EEG disturbances (r = 0.36). An analysis of the distribution of favorable and unfavorable outcomes showed that the formation of non-convulsive status epilepticus complicates the course of acute cerebral insufficiency, but is not an unambiguous predictor of an unfavorable outcome (χ² = 0.589, p = 0.44).

CONCLUSIONS: Thus, the bioelectrical activity of the brain recorded in patients with acute cerebral insufficiency complicated by lateral dislocation, reflects both general cerebral and focal changes. In 60% of patients with lateral dislocation of the midline structures of the brain on the EEG, patterns are formed corresponding electrographic patterns of nonconvulsive status epilepticus.

BACKGROUND: It is traditionally believed that the mortality of children operated on in the first days of life depends on the severity of congenital malformation and gestational age.

AIM: The aim of the study was to analyze the causes of death of children in the neonatal period, after surgical interventions performed in the perinatal period, in order to develop a set of measures to reduce mortality.

MATERIALS AND METHODS: A retrospective study was conducted between two groups: the main group included 77 newborns who underwent surgery in the Perinatal Center of St. Petersburg State Pediatric Medical University in the perinatal period (the first 168 hours of extrauterine life) and died in the first 28 days of life, the control group included 287 children operated on in the perinatal period and survived 28 days.

RESULTS: It has been established that the cause of death in more than half of the newborns operated on in the perinatal period are infectious agents (viruses, bacteria and their combinations). The infectious process aggravates the course of the postoperative period and increases the number of complications of the underlying disease, which, as a result, leads to the death of the child in the neonatal period. Significant contributors include: chlamydial infection, toxoplasmosis, cytomegalovirus infection, and infection caused by Herpes simplex 1, 2. The most common causes of death in newborns in the postoperative period were microorganisms of the Staphylococcaceae family, the genus Mycoplasma, as well as Klebsiella pneumoniae and Enterococcus faecalis.

CONCLUSIONS: The cause of death in more than half of newborns operated on during the perinatal period is infectious agents (viruses, bacteria and their combinations). The infectious process makes the postoperative period more difficult and increases the number of complications of the underlying disease, which ultimately leads to the death of the child in the neonatal period. The high prevalence rate in the population, infection of the placenta, tissues and organs of the fetus, as well as the high role in the genesis of death in newborns, indicate the need for examination for Human herpesvirus 1 and 2, Chlamydia trachomatis, Toxoplasma gondii and Cytomegalovirus in pregnant women with prenatally diagnosed congenital malformations and in newborns requiring surgical treatment in the perinatal period.

Epidemiology, clinical, biochemical and molecular genetic characteristics of gangliosidoses, genetically heterogeneous group of autosomal recessive diseases caused by hereditary deficiency of lysosomal glycohydrolases involved in the catabolism of GM1-, GM2- and GA2-gangliosides, are presented. Three clinical forms of GM1 gangliosidosis are caused by hereditary deficiency of lysosomal β-galactosidase, one of the activities of which is the release of galactose from carbohydrate complexes. As a result, GM1-ganglioside and, to a lesser extent, keratan sulfate accumulate in the lysosomes of neurons and other cells. Three genetically heterogeneous forms of GM2-gangliosidosis are associated with dysfunction of hexosaminidase activity. Tay–Sachs disease, or GM2 ganglioside variant B, is caused by mutations in the hexosaminidase alpha chain HEXA gene. Sandhoff’s disease is associated with mutations in the HEXB gene for the hexosaminidase beta chain. In this case, there is a deficiency of the A and B components of the enzyme — the null variant of GM2 gangliosidosis. In variant AB, or juvenile GM2 gangliosidosis, all hexosaminidase components are present, but the activating factor is defective due to mutations in the GM2A gene. All types of gangliosidosis are characterized by progressive retardation of psychomotor development and early death of patients, most often under the age of 3 years. The frequency of various types of gangliosidoses in different populations does not exceed 1 : 300,000. An exception is the ethic group of Ashkenazi Jews, in which the incidence of Tay–Sachs disease, reaches 1 : 3000, which makes total screening of heterozygotes and prenatal diagnosis of the disease in high-risk families economically justified. The article highlights the importance of experimental models for studying the molecular basis of pathogenesis and developing various therapeutic approaches, such as bone marrow transplantation, enzyme replacement therapy and substrate reducing therapy, gene therapy, and genome editing. Clinical examples of patients with gangliosidosis are given to improve the efficiency of diagnostics of these rare diseases by clinicians.

Autoimmune pancreatitis is a specific peculiar and rather new form of chronic pancreatitis (ChP) that has been intensively studied by pancreatology specialists of the whole world for the last years. Autoimmune pancreatitis does not have any individual specific clinical features. This condition was described for the first time in adults and it often mimics pancreas cancer. Autoimmune pancreatitis can involve some organs, synchronously or metachronously, and is rarely identified in children. Autoimmune pancreatitis is a systemic fiber-inflammatory condition with poorly understood pathophysiological mechanism, affecting different parts of the body. In case of the treatment absence the disease can lead to fibrosis and irreversible impairment of the organs. However, the combination of the findings of serologic, histologic, and instrumental methods of investigation characteristic for аutoimmune pancreatitis allows to identify its presence. IgG4-associated disorder has been mainly described in adults, therefore pediatricians usually do not know much about it. We underline the complexity of the diagnosis of autoimmune pancreatitis / IgG4-associated disorder, in children. The article presents two clinical cases of children diagnosed with autoimmune pancreatitis. Both children had the symptoms of abdominal pain and/or mechanical jaundice combined with focal pancreas enlargement, roughness of the basic pancreas duct and distal narrowing. According to our data, the diagnosis of autoimmune pancreatitis in children can be made on the basis of the combination of specific clinical symptoms at admission and various results of imaging. Both timely made diagnosis and administered treatment provide a favorable prognosis for further course of the disease and complication development.

In August 2023, Vladimir Nikolaevich Timchenko, dean of the pediatric faculty of the St. Petersburg State Pediatric Medical University of the Russian Ministry of Health, and head of the Department of Infectious Diseases in Children named after Vladimir Nikolaevich, turned 70 years old. Professor M.G. Danilevich, Doctor of Medical Sciences, Professor, Honored Doctor of Russia, Chief freelance specialist in infectious diseases in children of the Northwestern Federal District of the country. V.N. Timchenko after graduating from LPMI with honors in 1978, he entered clinical residency at the Department of Infectious Diseases in Children. Between 1980 and 1983 studied full-time graduate school at the same department. In 1983 he successfully defended his candidate’s dissertation, and in 1989 — his doctoral dissertation. He has headed the department since 1997. Under the leadership of the head of the department, comprehensive studies of infectious diseases in children have been conducted for many years. Vladimir Nikolaevich is the scientific supervisor of ten candidate dissertations, the scientific consultant of one doctoral dissertation. He regularly gives lectures and reports in children’s clinics, at congresses, conferences, and symposiums. Consults seriously ill patients from the Leningrad, Novgorod, Pskov, Kaliningrad Regions, the Republic of Karelia and other regions of the country. Author of more than 530 scientific papers. The administration, public organizations, staff and students of the University wish the professor further great creative success in the training and education of young doctors, good health and personal well-being, inexhaustible energy and prosperity.