Outcomes of pediatric extracranial germ cell tumors: A single center experience in a developing country.

The purpose of this study was to analyze the outcomes of extracranial GCT in children in a developing country and to assess prognostic factors. The data on 141 children (<18 years old) with extracranial GCT, confirmed histopathologically, collected over the past 9 years (from February 2013 to June 2022) were retrospectively studied. The patients underwent the same therapy with platinum-containing chemotherapy regimens. In the malignant GCT group, OS and EFS were 81.0 ± 4% and 73 ± 5%, respectively. OS and EFS in the teratoma group were 90 ± 5% and 85 ± 6%. In univariate analysis, parameters like stage of disease, tumor localization, AFP level ≥10,000 ng/mL, serum AFP kinetics and resection status were found to be statistically significant prognostic factors. In the multivariate analysis, the significant adverse factors were the resection status, initial AFP level ≥10,000 ng/mL and serum AFP kinetics slow down (p = .000). Good survival rates can be achieved in developing countries with adequate compliance with treatment protocols. The analysis demonstrates high efficacy of platinum-containing chemotherapy regimens. In our opinion, the protocol used in high-income countries can be implemented in low-income countries with the financial support from the government. The qualification of specialists is also important.

Application of microRNAs in the diagnosis and monitoring of pediatric germ cell tumors: Kazakh experience.

GCT is characterized by specific biochemical markers expression, such as human chorionic gonadotropin (hCG) and alpha-fetoprotein (AFP), which are the main tools in the diagnosis and monitoring of GCT treatment. They are expressed in 15-20% of cases of seminoma and in 60-80% of cases of non-seminoma. MicroRNA profiling allows to identify a number of microRNAs that are superior to classical serum tumor markers in the diagnosis of primary tumors, as well as in subsequent monitoring and prediction of recurrence. We analyzed the expression of 9 microRNAs (microRNA clusters 302/367 and 371-373, microRNA375) in the blood serum of 20 children with extracranial GCT at different stages of therapy and showed their usefulness and informativeness in early detection of events. Taking into consideration the high sensitivity and specificity, serum microRNAs 367,371,372,373,302d are of great interest for clinical use in malignant GCT. Significant expression of miR 375-3p was not detected either in malignant GCT or in teratomas.

Long-term outcomes and immune profiling in children with multisystem inflammatory syndrome (MIS-C).

BACKGROUND AND AIM: Existing follow-up data after MIS-C is limited. PURPOSE OF THE STUDY: to investigate the long-term consequences in children who have undergone MIS-C. METHODS: The retrospective study included 93 children. The identified changes were divided into the following periods: occurred within first 6 months, 1 year, 2 years, and more than 2 years after MIS-C. Besides, 31 children underwent prospective immunophenotyping of peripheral blood and the determination of cytokines during the acute period of the disease and after discharge. RESULTS: Outpatient monitoring events included pneumonia (9.6%), somatic disorder syndrome (11.8%), visual impairment (7.5%), joint damage (6.6%), weight changes (2.2%), and MIS-C recurrence (2.2%). A study of the cardiovascular system showed a statistically significant decrease in the frequency of the right and left heart dilatation, left ventricular dysfunction, pericarditis, pulmonary arterial hypertension, coronaritis, mitral regurgitation. But at the same time an increase in pulmonary and tricuspid valve regurgitation and arrhythmias compared with the acute period was detected. Most of the changes took place within first year of observation. Immune profiling showed reconstitution of CD3, CD4 T-lymphocytes, NK-cells, maintenance of a high relative value of CD8, reduction of CD19+ B-cells, expression of CD3-HLA-DR+, CD25, CD279, CD95. CONCLUSIONS: After the history of MIS-C, children in the long-term follow-up had various somatic disorders and disease recurrence. Most patients (64.1%) showed subclinical signs of myocardial involvement within first year of observation. Low expression of CD95 may justify an certain role in the pathogenesis of the disease.

Genes of Predisposition to Childhood Beta-Cell Acute Lymphoblastic Leukemia in the Kazakh Population.

BACKGROUND: Today, acute lymphoblastic leukemia is one of the most common malignant diseases of the hematopoietic system. The genetic predisposition to ALL is not fully explored in various ethnic populations. OBJECTIVE: The study aimed to conduct a comparative analysis of the population frequencies of alleles and genotypes of polymorphic gene variants: immune regulation GATA3 (rs3824662); transcription and differentiation of B cells: ARID5B (rs7089424, rs10740055), IKZF1 (rs4132601); differentiation of hematopoietic cells: PIP4K2A (rs7088318); apoptosis: CEBPE (rs2239633), tumor suppressors: CDKN2A (rs3731249), TP53 (rs1042522); carcinogen metabolism: CBR3 (rs1056892), CYP1A1 (rs104894, rs4646903), according to genome-wide association studies analyses associated with the risk of developing pediatric beta-cell acute lymphoblastic leukemia (B-cell ALL), in an ethnically homogeneous population of Kazakhs with studied populations. METHODS: The genomic database consists of 1800 conditionally healthy persons of Kazakh nationality, genotyped using OmniChip 2.5-8 Illumina chips at the deCODE genetics as part of the InterPregGen 7 project of the European Union (EU) framework program under Grant Agreement No. 282540. RESULTS: High population frequencies of single nucleotide polymorphism (SNP) minor alleles identified for immune regulation genes - GATA3 rs3824662 - 42.5%; transcription and differentiation of B-cells genes - ARID5B rs7089424 - 33.1% and rs10740055 - 48.5%, which suggests their significant genetic contribution to the risk of development and prognosis of the effectiveness of B-cell ALL therapy in the Kazakh population. The significantly lower population frequency of the minor allele G rs1056892 CBR3 gene - 38.6% in the Kazakhs suggests its significant protective effect in reducing the risk of childhood B-cell ALL and the smaller number of cardiac complications after anthracycline therapy. CONCLUSION: The obtained results will serve as a basis for developing effective methods for predicting the risk of development, early diagnosis, and effectiveness of treatment of B-cell ALL in children.

Clinical and immunological features in children with multisystem inflammatory syndrome associated with SARS-CoV-2.

BACKGROUND AND AIM: MIS-C is characterized by intense immune activation and increased production of cytokines. The aim of our study was to analyse the changes of cellular and humoral immune responses in children with MIS-C, depending on the severity of the disease. METHODS: To conduct the study, the results of clinical, hematological and immunological parameters in children with severe and extremely severe MIS-C were compared. A total of 50 patients participated in the study, which were divided into 3 groups, of which: 20 children with extremely severe MIS-C treated in the ICU (MIS-C ICU "+"); 15 children with severe MIS-C, but without the need for hospitalization in the ICU (MIS-C ICU "-"); 15 children who had COVID-19 and absence MIS-C (MIS-C "-") made up the control group. RESULTS: In patients with MIS-C hospitalized in the ICU, heart and liver damage, hematological changes, and the development of severe complications such as edematous syndrome, polyserositis, DIC, and cardiogenic shock were statistically more common. Both groups of children with MIS-C had CD3+ T-cell lymphopenia and a decrease in CD95 expression. In the group of children with MIS-C hospitalized in the ICU, a significant increase in the relative number of B-lymphocytes, CD3-HLA-DR+ and CD25 and decrease of NK-cells was observed. CONCLUSIONS: The risk of hospitalization in the ICU in children with MIS-C is associated with more profound immune dysregulation, as evidenced by our data. (www.actabiomedica.it).

Pediatric Extracranial Germ Cell Tumors: Expression of microRNA.

BACKGROUND: Germ cell tumors (GCTs) may occur from the neonatal period to late adulthood, characterized by extensive clinical and pathologic heterogeneity. MicroRNAs are a family of small noncoding RNAs that regulate a wide array of biological processes including carcinogenesis. MicroRNAs may be used for many purposes in clinical diagnostics. Numerous studies have proven the diagnostic value of microRNA371-373 and microRNA302/367 expression in malignant GCT. The diagnostic value of microRNA375 is disputable, because while its value is confirmed by some research data, there are still others denying it. METHODS: The results of our own research on the relative expression of 10 microRNAs, including microRNA375, associated with GCT in the tumor tissues of 84 children and adolescents are presented. RESULTS: In our research, overexpression of microRNA 371-373, 302/367 detected in the group of malignant GCT subtypes. Statistically significant expression of microRNA375 have been defined not only in the group of malignant GCT subtypes, but also in the group of immature teratomas. Among malignant GCTs, high expression of microRNA375 is specific for yolk sac tumors. In the group of seminomas, embryonic carcinomas, and mature teratomas expression of microRNA375 was observed imperceptible, even so the results were statistically insignificant. CONCLUSION: Expression of microRNA 371-373, 302/367 is representative of malignant GCT subtypes. Statistically significant and high expression of microRNA375 attributable for yolk sac tumors and immature teratomas.

Comparative Analysis of Clinical and Laboratory Data in Children with Multisystem Inflammatory Syndrome Associated with SARS-CoV-2 in the Republic of Kazakhstan.

Background and Objectives: Data with more severe mutations of the SARS-CoV-2 virus, compared with the original wild-type strain of COVID-19 disease, were reported worldwide. The study aims to describe the clinical and laboratory manifestations of a multisystem inflammatory syndrome in children (MIS-C) associated with SARS-CoV-2 in the Republic of Kazakhstan and to compare the severity of the disease depending on the time of the circulating variant of SARS-CoV-2 virus. Material and methods: A retrospective, multicentre, nationwide study of 89 children with MIS-C who received inpatient treatment from August 1, 2020, to December 1, 2021. The patients were allocated into two groups: 1(2020) - 45 children and 2 (2021) - 44 children. Study periods were characterized by the circulation of different strains of the SARS-CoV-2 virus. Results: In children with MIS-C in 2021, acute renal failure, disseminated intravascular coagulation syndrome, and shock were statistically more frequently found, which led to fairly common admittance to the intensive care unit. When comparing laboratory data, the children with MIS-C in 2021 had higher values of inflammation markers: ferritin, procalcitonin, erythrocyte sedimentation rate, leukocytes, and neutrophils. Furthermore, these children had a lower level of lymphocytes than children with MIS-C in 2020. Conclusions: MIS-C is a severe, life-threatening systemic disease characterized by multiple organ damage and important inflammatory changes in laboratory parameters. A more aggressive clinical course of MIS-C in 2021 may be associated with the emergence of new SARS-CoV-2 strains.

Current issues of gastro-oesophageal reflux disease surgical treatment in children.

Gastro-oesophageal reflux (GER) disease is one of the most common diseases amongst a wide range of chronic inflammatory diseases of the gastrointestinal tract in children of all ages, significantly impairing the quality of life of the child and posing a serious threat to the health of the patient. From 2008 to 2019, 134 patients aging from 6 months to 12 years were hospitalised at the Scientific Center for Pediatrics and Pediatric Surgery including 69 (51%) infants. Of them, 51 (38%) were the patients with persistent manifestations of regurgitation, despite an outpatient course of conservative therapy; 29 (22%) patients with recurrent reflux-associated pneumonia; also, 35 (26%) children with GER in the structure of the main pathology of the central nervous system, as well as 19 (14%) patients after surgery of the anastomosis of the oesophagus with its atresia. One hundred and seven (79.8%) patients underwent surgery. Nissen oesophagofundoplication was traditionally performed in 41 (38%) patients, in combination with Stamm gastrostomy in 14 (34%), with Mikulich pyloroplasty in 9 (22%) and in combination with gastrostomy and pyloroplasty in 12 (29%) children. Laparoscopic Nissen oesophagofundoplication was used in 16 (15%) cases. Thall oesophagofundoplication was performed in 48 (45%) patients, while in two (2%) cases, Boerema gastropexy was conducted. The immediate results were studied in all 107 patients. Complications in the form of gastric distress syndrome were revealed in four (3.7%) patients who did not undergo pyloroplasty, which in two (1.9%) cases required additional surgery of the stomach draining, whereas in the other two (1.9%) patients, the distress syndrome was stopped conservatively. A dumping syndrome was identified in two (1.9%) patients. Timely recognition of the pathological process, its nature and prevalence determines the indications for the use of various methods of operation, which are based on an individual approach to each patient.

Current issues of GERD surgical treatment in children.

INTRODUCTION: Gastroesophageal reflux disease is one of the most common diseases among a wide range of chronic inflammatory diseases of the gastrointestinal tract in children of all ages, significantly impairing the quality of life of the child and posing a serious threat to the health of the patient. MATERIALS AND METHODS: From 2008 to 2019, 134 patients aging from 6 months to 12 years were hospitalized at the Scientific Center for Pediatrics and Pediatric Surgery, including 69 (51%) infants. Of them, 51 (38%) were the patients with persistent manifestations of regurgitation, despite an outpatient course of conservative therapy; 29 (22%) patients with recurrent reflux-associated pneumonia; also, 35 (26%) children with gastroesophageal reflux in the structure of the main pathology of the central nervous system, as well as 19 (14%) patients after surgery of the anastomosis of the esophagus with its atresia. One hundred and seven (79.8%) patients underwent surgery. Nissen esophagofundoplication was traditionally performed in 41 (38%) patients, in combination with Stamm gastrostomy in 14 (34%), with Mikulich pyloroplasty in 9 (22%), and in combination with gastrostomy and pyloroplasty in 12 (29%) children. Laparoscopic Nissen esophagofundoplication was used in 16 (15%). Thall esophagofundoplication was performed in 48 (45%) patients, whereas in two (2%) cases, Borema gastropexy was conducted. RESULTS: The immediate results were studied in all 107 patients. Complications in the form of gastric distress syndrome were revealed in four (3.7%) patients who did not undergo pyloroplasty, which in two (1.9%) cases required additional surgery of the stomach draining, whereas in the other two (1.9%) patients, the distress syndrome was stopped conservatively. A dumping syndrome was identified in two (1.9%) patients. CONCLUSION: Timely recognition of the pathological process, its nature, and prevalence determines the indications for the use of various methods of operation, which are based on an individual approach to each patient.

COVID-19 in the paediatric population of Kazakhstan.

Background: To date, there have been no studies of COVID-19 infection in children in Central Asia, particularly the Republic of Kazakhstan. This report analyses the epidemiological data on COVID-19 infection in children in Kazakhstan.Methods: The study included 650 paediatric patients diagnosed with COVID-19. Demographic and epidemiological data and the symptoms and radiological evidence of complications were collected and analysed. Children were sub-divided into four groups: neonates/infants, young children, older children and adolescents.Results: All of the 650 children were under 19 years of age, 56.3% of whom were male, and 122 (18.8%) were newborns and infants. The majority of cases (n = 558, 85.8%) were asymptomatic and only four cases were severe (0.6%). The symptoms were as follows in descending order: cough (14.8%), sore throat (12.8%), fever (9.1%) and rhinorrhoea (5.5%). Diarrhoea (2%), dyspnoea (1.8%) and muscle pain were rare (1.1%). Only three children required intensive care, including invasive ventilation. One patient had acute respiratory distress syndrome. There were no deaths.Conclusion: Most cases of COVID-19 infection in children in Kazakhstan were asymptomatic or the symptoms were mild. Only three patients required intensive care.

Respiratory Dysfunction in Children and Adolescents with Mucopolysaccharidosis Types I, II, IVA, and VI.

Mucopolysaccharidosis (MPS) is a rare genetic disease involving active storage of glycosaminoglycans (GAGs). Accumulation of GAGs in the connective tissues of airways leads to progressive pulmonary dysfunction. Studies conducted in Taiwan revealed mainly restrictive pulmonary dysfunction, whereas the same studies in Egypt and California revealed obstructive pulmonary dysfunction. The contradictory results and lack of studies of respiratory system in patients with MPS in Asian populations are an indication to study pulmonary impairment in patients with MPS in Kazakhstan. The prospective study of respiratory system in patients with MPS was conducted in the Scientific Centre of Paediatrics and Paediatric Surgery. Patients with MPS (n = 11) were examined for respiratory function. Different types of pulmonary dysfunction were present in MPS patients, they were mainly of a restrictive pathology. One patient with MPS II had obstructive dysfunction. Enzyme replacement therapy was provided for an average duration of four years, leading to improvements in respiratory function in two patients with total normalization in one. All observed patients had respiratory dysfunction, mainly of the restrictive type. Pulmonary impairment in patients with MPS is the main reason for death. Thus, it is necessary to follow up with pulmonary function assessments in children with MPS.