Management of functional gastrointestinal disorders in children. Focus on restoring intestinal microenvironment and motility

Functional gastrointestinal disorders in children are one of the most common reasons why parents visit a pediatrician. Functional gastrointestinal disorders include various persistent combinations of chronic or recurrent gastrointestinal symptoms in the absence of any organic pathology in the gastrointestinal tract (structural abnormalities, inflammatory changes, infections, or tumours) and metabolic disturbances. The article presents details on the mechanisms of development, clinical manifestations, diagnostic criteria and approaches to the treatment of functional gastrointestinal disorders. Clinical manifestations of functional gastrointestinal disorders vary depending on age and characteristics of physical and intellectual development. In more than half of children, they are observed in various combinations, less often as one isolated symptom. The drug therapy should consider the main components of pathogenesis and facilitate the solution of the following issues: improvement of digestion; restoration of intestinal microenvironment and motility; reduction of visceral hypersensitivity. Special attention is paid to the management of motor disorders and restoration of intestinal microenvironment using symbiotics. When choosing a supplement, it is advisable to focus on the composition of probiotic strains, which should comply with the WGO global guidelines (Bifidobacterium bifidum, Lactobacillus acidophilus, etc.).Prescription of peripheral δ-, μ- и κ-receptor agonists – trimebutine and pre- and probiotics combinations to children with functional gastrointestinal disorders results in decreased signs of functional disorders of the digestive tract. By acting on the enkephalinergic system, trimebutine regulates the bowel activity, improves motility, and reduces visceral hypersensitivity. Trimebutine is included in the Russian guidelines for the diagnosis and treatment of functional disorders of the digestive tract in children, as well as in the clinical guidelines for the treatment of irritable bowel syndrome, functional dyspepsia, and functional abdominal pain

Genetic and Clinical Features of Shwachman-Diamond Syndrome in Russian Population: Prospective Study

Background. Shwachman-Diamond syndrome (SDS) is the rare genetic autosomal recessive disorder with pathogenic variants in SBDS gene. The spectrum of SBDS gene variants in patients with SDS and features of disease course have not been studied before in Russian population.Objective. The aim of the study was to describe all the variants of SBDS gene and clinical and laboratory abnormalities in children with SDS. Methods. In this prospective study exocrine pancreatic function was estimated by amylase and lipase activity in blood, steatorrhea presence and stool elastase levels during the initial hospitalization. Haematological disorders were analysed by complete blood count. Bone abnormalities were diagnosed via X-ray imaging. Growth delay was established due to anthropometry indicators and percentile curves. Molecular genetic testing was performed with using next generation sequencing and Senger sequencing.Results. Pathogenic variants in SBDS gene (8 in general) were revealed in 25 (89%) out of 28 children with SDS. The most common variant (in 23 patients, 82%) was с.258+2T>C, and in 18 cases it was in compound heterozygous state with c.183_184delTAinsCT. Two patients had с.653G>A (p.Arg218Gln) variant and for one patient for every of the following variants: c.258+1G>A, c.107delT, с.356G>A, c.297_300delAAGA, c.338C>T. All children with SDS had growth delay, in 11 (39%) cases we revealed bone abnormalities. In blood samples of 24 (86%) children we revealed neutropenia and less frequently anemia and thrombocytopenia. The stool elastase I decreased activity (< 200 pg/g) was revealed in 26 (92%) patients. 21 (75%) children had cytolysis syndrome.Conclusion. Pathogenic variants of SBDS gene were revealed in majority of Russian children with SDS. The most frequent are c.258+2T>C and c.183_184delTAinsCT variants. Clinical signs of Shwachman-Diamond syndrome manifest since birth with growth delay, steatorrhea and haematological disorders

Safety and Immunogenicity of Inactivated Whole Virion COVID-19 Vaccine CoviVac in Clinical Trials in 18–60 and 60+ Age Cohorts

We present the results of a randomized, double-blind, placebo-controlled, multi-center clinical trial phase I/II of the tolerability, safety, and immunogenicity of the inactivated whole virion concentrated purified coronavirus vaccine CoviVac in volunteers aged 18–60 and open multi-center comparative phase IIb clinical trial in volunteers aged 60 years and older. The safety of the vaccine was assessed in 400 volunteers in the 18–60 age cohort who received two doses of the vaccine (n = 300) or placebo (n = 100) and in 200 volunteers in 60+ age cohort all of whom received three doses of the vaccine. The studied vaccine has shown good tolerability and safety. No deaths, serious adverse events (AEs), or other significant AEs related to vaccination have been detected. The most common AE in vaccinated participants was pain at the injection site (p p 1:256, the rate of fourfold increase in nAB levels was below 45%; the participants who were seropositive at screening of the 2nd vaccination did not lead to a significant increase in nAB titers. In conclusion, inactivated vaccine CoviVac has shown good tolerability and safety, with over 85% NT seroconversion rates after complete vaccination course in participants who were seronegative at screening in both age groups: 18–60 and 60+. In participants who were seropositive at screening and had nAB titers below 1:256, a single vaccination led to a fourfold increase in nAB levels in 85.2% of cases. These findings indicate that CoviVac can be successfully used both for primary vaccination in a two-dose regimen and for booster vaccination as a single dose in individuals with reduced neutralizing antibody levels