NEWS, DISCOVERIES AND EVENTS
The article is republished in order to expand the audience. The article was published earlier in the Akusherstvo i Ginekologiya (Russian Federation): Sukhikh GT, Serov VN, Artymuk NV, Andreeva MD, Bazina MI, Baranov II, Bashmakova NV, Bezhenar VF, Belotserkovtseva LD, Geppe NA, Dolgushina NV, Zaretskaya NV, Zakharova IN, Zubkov VV, Enkova EV, Yesayan RM, Katkova NYu, Kvashnina EV, Kogan IYu, Korsak VS, Krasnopolskaya KV, Kukarskaya II, Molchanova IV, Nazarenko TA, Pestova TI, Podzolkova NM, Saveljeva IV, Sazonova AI, Semenov YuA, Tapilskaya NI, Tetruashvili NK, Tiselko AV, Fadeev VV, Shamugia NL, Shakhova MA, Shikh EV, Yarmolinskaya MI. The safety of hormone therapy during pregnancy. Joint statement by experts in reproductive medicine, obstetrics and gynecology, endocrinology, clinical pharmacology, neonatology and pediatrics Akusherstvo i Ginekologiya (Russian Federation). 2024;(8):196–206. (In Russ.) https://doi.org/10.18565/aig.2024.201.
NEONATOLOGY
The article presents current information on vitamin D. It considers not only well-known recommendations for the administration of vitamin D in paediatric practice, but also the clinical aspects of the new guidelines – Vitamin D for disease prevention: a clinical practice guideline of the Endocrine Society 2024. The document was created using the results of the review of prioritized randomized placebo-controlled trials in general populations, taking into account systematic reviews of electronic databases of patients and their representatives (without an established indication for vitamin D treatment or 25[OH]D testing). The work assessed the effect of “empirical supplementation” defined as vitamin D intake at a dose that exceeds the Dietary Reference Intakes (DRI). This article considers two sections of above guidelines (obstetric and paediatric), alongside with the results of the analytical review, which present some scientific interest, deserve the attention of practicing physicians, confirm the importance of prevention in childhood, as well as indicate the need for further studies on the assessment of vitamin D status using long-term follow-ups and a personalized approach to the groups of children and adolescents that exact very careful attention. Apart from the new guidelines, attention is drawn to the urgency of the Russian National Program for Vitamin D Deficiency in Children and Adolescents of the Russian Federation: Modern Approaches to the Management, which outlines current treatment and preventive strategies for managing vitamin D deficiency in our country using the results of the multicenter study. It is important that Russian paediatricians have an evidence-based, specific and structured document with a brief look at the main strategic issues and operational decisions on the treatment and prevention of vitamin D hypovitaminosis in contrast to ongoing discussions in different countries of the world.
Bourneville-Pringle disease or tuberous sclerosis is a multisystem, genetically determined disease that manifests mainly in childhood and is manifested by the formation of benign neoplasms (hamartomas) in various organs and tissues. Tuberous sclerosis is a rare (orphan) disease. The prevalence of tuberous sclerosis among newborns ranges from 1:6000 to 1:10000. Tuberous sclerosis is inherited in an autosomal dominant manner. An analysis of a clinical case of a newborn child with tuberous sclerosis (Bourneville-Pringle disease) is presented. The peculiarity of the presented observation is the diagnosis of the disease during prenatal ultrasound screening in the third trimester with the identification of multiple space-occupying formations in the brain and heart of the fetus. Confirmation of the diagnosis in the early neonatal period is based on the presence of primary (major) diagnostic criteria: multiple cardiac rhabdomyomas, brain tubera and retinal hamartomas. The diagnosis was made primarily on the basis of data from echographic research methods, which have demonstrated their effectiveness in identifying typical signs of this disease in the perinatal period. Neonatologists should be wary of children with cardiac radbomyomas detected prenatally, due to the fact that this cardiac tumor is highly likely to be combined with tuberous sclerosis and is its diagnostic marker. In addition to heart damage, the early onset of the disease in the perinatal and postnatal periods manifests itself in damage to the central nervous system. Patients with tuberous sclerosis require lifelong monitoring from the first days of life by a multidisciplinary team of specialists with special attention to life-threatening complications (progressive hydrocephalus, status epilepticus, renal failure, respiratory failure). Managing a patient with this pathology is a complex multidisciplinary problem.
Introduction. Successful breastfeeding is possible if the child has a mature sucking reflex and coordination of sucking, swallowing and breathing. Violation of these coordinated functions can lead to a high risk of apnea, bradycardia, and aspiration.
Аim. To determine the factors influencing the transition from probe feeding to bottle feeding and breastfeeding in newborns. The study included 30 newborns of different gestational age and body weight.
Material and methods. To assess the activity of sucking, the Oral Feeding Scale was also used, proposed for premature infants, and reflecting the functional features of sucking, swallowing and breathing of sick newborns.
Results and discussion. The transition from tube feeding to bottle feeding with a nipple and the time required for successful transition to breastfeeding was longest in 5 children of gestational age (GA) 28–30 weeks, with perinatal hypoxic-ischemic CNS damage and infectious diseases, The second maturity level (PRO < 30% and RT ≥ 1.5 ml/min) was detected in 3 children aged 31–32 weeks with a similar combined pathology. The third maturity level (PRO ≥30% and RT <1.5 ml/min) was established in 3 children with combined perinatal pathology at GW 33–34 weeks. The most mature level of sucking is in full-term newborns and late preterm infants from 35 weeks of GA with PRO ≥ 30% and RT ≥ 1.5 ml/min.
Conclusion. The study of the rate of sucking and the proportion of nutrition sucked in 5 minutes, the total amount of absorbed nutrition and the number of days from the beginning to complete self-feeding are effective criteria for the transfer of sick newborns from probe feeding to breastfeeding, including those with neurological disorders, which allowed 83% of sick children to be transferred for breastfeeding.
BRONCHOPULMONOLOGY, OTORHINOLARYNGOLOGY
Introduction. Currently, much attention is paid to biregulatory therapy in the treatment of ARI, the goal of which is to improve the outcome of treatment by maintaining the body’s ability to autoregulate.
Aim. To study the effectiveness and safety of bioregulatory therapy using the multicomponent homeopathic drug in children with acute respiratory infections.
Materials and methods. 42 children with acute respiratory infections from 3 months to 7 years were examined. Main group: 22 children receiving, as part of complex therapy, the multicomponent homeopathic drug in the form of rectal suppositories as an antipyretic and anti-inflammatory agent. Comparison group: 20 children receiving the antipyretic and anti-inflammatory drug paracetamol. All patients were prescribed symptomatic therapy, which did not differ in the compared groups.
Results. It was revealed that the administration of the multicomponent homeopathic drug leads to a more rapid decrease in temperature (in the main group 1.70 ± 0.14 day; in the comparison group – 3.78 ± 0.17 day, p < 0.05) against the background of the disappearance of myalgia, headache, relief of symptoms of discomfort and intoxication, as well as manifestations of the local inflammatory process (sore throat, hyperemia of the pharynx, nasal congestion, rhinorrhea, cough), which led to a reduction in the duration of the disease by 3.4 days and reducing the need for antibiotics by 3.3 times. No side effects from the use of the multicomponent homeopathic drug were identified.
Discussion. The results of the study are comparable with the literature data. Thus, foreign authors have shown that the drug multicomponent homeopathic drug meets all the requirements for effective, but at the same time practically risk-free therapy for febrile anxiety, influenza infections, and pain.
Conclusions. The prescription of the multicomponent homeopathic drug as part of the complex therapy of ARI in children leads to faster relief of all symptoms and a reduction in the duration of the disease than with the use of paracetamol, with a better safety profile.
Asthma is the most common chronic respiratory disease of childhood worldwide with around 10% of children and young adults affected. Despite the high prevalence, paediatric asthma treatment outcomes are inadequate, and there are several avoidable deaths each year. Uncontrolled asthma in the paediatric population remains a major challenge worldwide, continues to impose a significant economic burden, and has a negative impact on the quality of life (QOL) of patients and their families. Effective asthma management involves a holistic approach addressing both pharmacological and non-pharmacological management, as well as education and self-management aspects. Working in partnership with children and families is key in promoting good outcomes. Education on how to take treatment effectively, trigger avoidance, modify risk factors and actions to take during acute attacks via personalised asthma action plans is essential. There is uncertainty about the best treatment option for children/ adolescents with uncontrolled asthma despite the fact that inhaled corticosteroids are the treatment of choice. This article presents clinical case reports that consider therapies reducing asthma exacerbations and symptoms in patients with uncontrolled asthma aged < 6 years, who receive inhaled corticosteroids. The first case is the treatment of a 5-year-old child with a hereditary loading from the mother: bronchial asthma; allergic anamnesis: sensitization to food products (cow’s milk protein), household (house dust mites, cat hair) and pollen (birch) allergens was identified. The second case is a 4-year-old child with a history of recurrent bronchitis and bronchial obstruction due to acute respiratory infections since the age of 2 and a diagnosis of bronchial asthma established at the age of 2.5 years.
Introduction. Intracranial complications (IC) of sinusitis and acute otitis media (AOM) in children are rare but life-threatening phenomena. Both intracranial and extracranial complications require early diagnosis and timely interdisciplinary approach to treatment. The article considers data on the prevalence of otorhinogenic complications in children, the possibilities of their early diagnosis, treatment and prognosis at the present stage.
Aim. To study the prevalence of otolaryngogenic complications, the possibility of their early diagnosis and prediction of the occurrence of complications in children.
Materials and methods. A retrospective analysis of medical records of patients aged ≤ 18 years who were treated in the pediatric otolaryngology department of the Tyumen Regional Clinical Hospital No. 2 from 2013–2023 was performed. A patient database was created, the prevalence of intracranial complications was studied, the significance of clinical, laboratory parameters, and integral blood indices was assessed, and a model for predicting otolaryngogenic intracranial complications was created based on the logistic regression method.
Results. A total of 21 495 people were treated over the past period, 233 (1.1%) had verified otogenic complications, 55 (0.3%) had intracranial complications, and 178 (0.8%) had extracranial complications. The average age of children with otogenic intracranial complications (OIC) was 6.3 ± 4.1 years, and rhinogenic intracranial complications (RIC) was 11.3 ± 4.5 years. With Ht ≤ 34.2 and ISL ≥ 3.98, OIC is diagnosed, and with ISL ≥ 4.75, RIC is diagnosed, requiring surgical treatment by an ENT doctor and a neurosurgeon. Using logistic regression, a model for predicting complications was created, the sensitivity of which was 97.6%, specificity – 94.0%, and efficiency – 95.6%. The first-line antibiotic therapy used was penicillin group drugs, including combination drugs with clavulanic acid, as well as cephalosporins.
Conclusions. The prevalence of otorhinogenic intracranial complications in children of the Tyumen region was 0.3%. Early diagnostics, prognosis, otorhinogenic complications using integral blood indices and logistic regression is a modern and informative method in pediatric practice. The use of amoxicillin in the form of dispersible tablets as a starting antibacterial therapy in children with uncomplicated acute otorhinolaryngitis has good efficiency due to high bioavailability.
In outpatient practice, both pediatrician and otorhinolaryngologist, acute rhinosinusitis is the most common infectious disease of the upper respiratory tract. The formation of sinusitis against the background of acute respiratory viral infection (colds) in children is facilitated by the unjustified administration of antibiotics, decreased immunity, allergies, changes in the structure of the nose and paranasal sinuses, metabolic disorders, beriberi, chronic diseases, adverse environmental factors. The administration of systemic antibiotics for viral infections of the upper respiratory tract leads to a violation of the immune response of the mucous membranes and does not prevent the development of bacterial complications. Mucociliary transport is the main mechanism for cleaning the nasal cavity and paranasal sinuses from mucus and pathogens, preventing the development of inflammation. Violation of mucociliary transport against the background of viral infections leads to the development of acute sinusitis, which can be complicated by acute otitis media, eustachiitis, adenoiditis. Sometimes intracranial and orbital complications develop. The article presents a clinical case of a 12-year-old patient with complaints of difficulty in nasal breathing, mucopurulent nasal discharge, discharge from the back of the throat, unproductive cough, especially disturbing at night, periodic facial pain on the right, pain and congestion in the right ear. An endoscopic examination of the nose, nasopharynx and ear, as well as a computed tomography scan were performed. When prescribing complex treatment, including a combined mucolytic drug, a complete recovery was achieved on the 7th day of treatment. The use of the topical mucolytic drug (acetylcysteine, tuaminoheptane) in children improves the rheology of discharge from the nose and paranasal sinuses and prevents the development of complications of acute rhinosinusitis.
In recent decades, there has been significant progress in the diagnosis, prevention and treatment of acute respiratory viral infections (ARVI), including influenza. The authors summarized the current literature data regarding the clinical effectiveness of the antiviral and immunomodulatory drug inosine pranobex in the prevention and treatment of frequent recurrent respiratory infections in children. The results of recent studies have shown that during the COVID-19 pandemic, non-drug restrictive measures influenced the typical seasonal patterns of circulation of various respiratory viruses and bacteria. Continuous monitoring of these viruses is necessary to take preventive measures and improve forecasting, in particular, to optimize the use of antiviral drugs, especially among children with frequent episodes of SARS, as well as those at risk of their severe course. Resistance to pathogens can be achieved by specific vaccination (against influenza, pertussis, pneumococcal, hemophilic infection, etc.), the introduction of immunoglobulins, monoclonal antibodies (for the prevention of respiratory syncytial virus (RSV) infection). However, the specific prevention of highly pathogenic and highly virulent viral infections (influenza, SARS-CoV-2) has its limitations due to the high variability of these viruses. Therefore, the focus of therapeutic and preventive measures against ARVI is increasingly shifting towards non-specific prevention based on the use of safe and effective antiviral drugs, drugs that can prevent the development of the disease and at the same time affect its course, ensuring a favorable outcome. One of the drugs of choice in the prevention and treatment of ARI is inosine pranobex, especially in children with a burdened premorbid background and in cases where a complex antiviral and immunomodulatory action is required. In the absence of the effect of preventive measures for 3 months, an in-depth examination of the child in a polyclinic or hospital and an individual selection of appropriate treatment are shown.
Acute cough in children is a very common problem, especially in young children. Approximately 4.7 to 23.3% of all causes for visiting primary care physicians and up to 60% of all consultations are related to cough in children. Cough is more common in preschool children than in older children. Acute respiratory viral infections/acute bronchitis is the most common cause of acute cough in children. About 75% of children aged 0 to 4 years with acute respiratory infections have a cough. The therapeutic approach of a primary care paediatrician is to assess the symptoms of the disease causing the cough. Infections that can cause complications, such as pneumonia, should be excluded. In most children with acute cough, the etiology is associated with an acute respiratory viral infection and only requires symptomatic therapy (antipyretics, fluid regimen, and nasal irrigation with saline solutions). Over-the-counter cough suppressants have shown to be ineffective in treating acute cough and can cause side effects, so they should be prescribed with caution in children under 2 years of age. Herbal medicines in paediatrics are agents of great interest today. They have proven efficacy and safety in the treatment of acute cough, for example, Hedera helix L.-based preparations (ivy leaf extract). The 2015 Cochrane review of 71 randomized clinical trials on herbal medicines (pelargonium, echinacea, ivy, thyme, primrose, essential oils, andrographis paniculata, etc.) used for the treatment of cough in children with colds, demonstrated substantial evidence of the effectiveness of ivy-based preparations in reducing the frequency and severity of cough symptoms (OR 1.40, CI 95% 1.23–1.60; p < 0.00001).
Cough is one of the most common symptoms in pediatric practice. It can manifest itself in children as a mild cough, which has almost no effect on the general condition and behavior, or, on the contrary, have a severe and debilitating character, disrupting sleep and worsening the child’s quality of life. Cough is a multifunctional problem caused by a variety of causes, which creates certain difficulties in diagnosis, especially in case of prolonged (subacute) and chronic cough, and in choosing the appropriate treatment. It can be associated with various diseases, which requires a careful approach from the doctor and selection of adequate therapy taking into account the causes of cough, response to treatment, patient’s age and other indicators. This article discusses the etiology, as well as diagnosis and treatment of respiratory pathology in children, where the main symptom is a prolonged cough. The advantages of mucoactive therapy of subacute cough using a combination drug containing salbutamol, guaifenesin and bromhexine in pediatric practice are considered.
Introduction. Currently, nonsteroidal anti-inflammatory drugs with anti-inflammatory, analgesic, and antipyretic effects are widely used in clinical practice.
Aim. To obtain additional data on the efficacy and safety of paracetamol and ibuprofen in children with acute respiratory infections accompanied by fever.
Materials and methods. A single-center (observational) study was conducted involving 32 children (5.2 ± 1.8 years) with fever due to acute respiratory disease. At temperatures above 38.5 °C, an antipyretic in the form of forte was prescribed in an age-specific dosage according to the instructions for a course of 3 days. Patients of the first group (n = 16) were prescribed paracetamol against the background of standard therapy for the underlying disease according to the nosology, children of the second group – ibuprofen forte in syrup without fragrances, dyes and flavor additives. The average daily temperature, frequency and duration of taking the study drugs, the development of adverse reactions, a score of satisfaction with parents/legal representatives of the use of antipyretics and quality of life were taken into account.
Results. The result of therapy was clinical improvement: normalization of temperature (below 37.2 °C) over time with analysis of average daily values after 1, 4 hours, 1, 2, 3 days. The patients of both groups did not need to take antipyretics after 10 hours in 47.1% of cases, after 18 hours – in 53.8%. Noted the absence of adverse drug and allergic reactions and drug rejection by children, which confirms their safety. The average satisfaction rating of parents/legal representatives was 4.87 ± 0.23 (96.2% rated the effects of the studied drugs as “satisfied” and “completely satisfied”). The quality of life improved significantly with normalization of temperature by the end of the 3 days (1.92 ± 0.07).
Discussion. The drugs ibuprofen and paracetamol are safe for use in pediatric practice if the dosage rules are followed and are approved for use by the World Health Organization, the FDA and other expert organizations. In addition, the emergence of new forms of release of these drugs is most important in pediatrics.
Conclusions. The study conducted allows us to state the effectiveness of paracetamol and ibuprofen in the form of tablets and forte without fragrances, dyes and flavors, when taken in the correct dosage, which resulted in the relief of fever against the background of acute respiratory infections and an improvement in the quality of life.
ENDOCRINOLOGY
Introduction. Obesity is a multifactorial disease that arises through the joint actions of multiple genetic and environmental factors. Identification of genetic markers of obesity, including their polymorphisms, especially in children of early and preschool age is an important field of diagnosis and prevention of the disease.
Aim. To study the prevalence of single-nucleotide polymorphisms of the gene (AGT: с.174C>T, p.T174M (rs4762) and AGT: с.235T>С, p.M235T (rs699)) in children with obesity.
Materials and methods. A total of 180 children aged 5–17 years were examined in a clinical case-control study. The case group included 120 obese subjects, of whom 60 were aged 5–10 years old and 60 were aged 11–17 years old. The control group included 60 subjects with normal body weight, of whom 30 were aged 5–10 years old and 30 were aged 11–17 years old. The subjects underwent measurement of physical development, carbohydrate metabolism, and lipid status, as well as daily blood pressure monitoring, and molecular genetic testing, in particular, gene polymorphisms (AGT: p.174C>T, p.T174M (rs4762) and AGT: p.235T>C, p.M235T (rs699)). Odds ratios (OR) and their 95% confidence intervals (CI) were calculated to assess the impact of polymorphisms on the development of obesity and obesity-associated conditions.
Results. No association was established between the AGT gene polymorphism: c.174C>T and obesity and dyslipidemia in children aged 5–17 years old. We found an association between the AGT gene polymorphism c.235T>C and obesity and dyslipidemia in children aged 5–17 years old (OR 3.1 [0.1; 3.9], p = 0.000001; OR 1.6 [0.9; 3.3], p = 0011). An association between both polymorphisms and the development of arterial hypertension (AH) in children and adolescents with obesity (OR 1.2 [0.4; 2.7], p = 0.000025; OR 2.2 [0.5; 2.4], p = 0.00002) was established.
Discussion. Numerous works performed by foreign authors demonstrated the association between the AGT gene polymorphism: p.235T>C and the development of obesity and related comorbid conditions in adults. There is no information on the effect of the AGT polymorphism: p.174C>T.
Conclusion. The renin-angiotensin-aldosterone system (RAAS) gene polymorphisms contribute to the development of obesity, dyslipidemia and hypertension in childhood.
Introduction. Patients with diabetes mellitus perform blood glucose measurements daily using their personal glucose meters. The procedure of disinfecting the place of blood sampling with antiseptic solutions or washing hands with soap and drying them thoroughly is recommended to the patients to prevent infections. However, the effects of used antiseptics on the accuracy in blood glucose measurement using glucose meters have not been evaluated.
Aim. To evaluate the effects of antiseptic solutions on the accuracy in blood glucose measurement using a personal glucose meter. Materials and methods. We mixed several drops of the control solution (CS) with low “L” or high “H” concentrations, which were developed for the Contour Plus glucose meter, and a drop of one of five antiseptic solutions: chlorhexidine bigluconate (Chlorhexidine), benzyl dimethyl[3-(myristoylamine)-propyl] ammonium chloride monohydrate (Miramistin), salts of fatty acids (liquid soap), ethyl alcohol, hydrogen peroxide. Thereafter, the blood glucose levels were measured with a glucose meter. The results obtained were compared with the reference range for the CS with appropriate concentration.
Results. Chlorhexidine solution had no effect on the blood glucose measurements in the CS. Adding Miramistin solution (1/5 of the sample with CS “L” and “H”) and liquid soap (4/5 of the sample with CS “L” and 2/5 of the sample with CS “H”) resulted in underestimating blood glucose measurements. Alcohol solution had no effect on the blood glucose measurements in the CS “L”, but the glucometer failed to measure the blood glucose concentration in half of the cases, requiring the test strip to be replaced (“E11” error); when mixed with CS “H”, the measurements were overestimated in 2/5 of samples. Adding hydrogen peroxide solution (4/5 of the sample with CR “L” and “H”) resulted in overestimating the blood glucose measurements.
Discussion. Getting fruit juice on the hands, applying hydroquinone-containing cosmetics to the skin affects the accuracy in glucose measurements. Correct use of alcohol-containing disinfectants does not affect results of the blood glucose measurement using a personal glucose meter.
Conclusion. The results of the blood glucose measurement using a glucose meter can be significantly distorted if antiseptic gets into the sample. Traces of antiseptic should be removed before obtaining the sample that will be used to measure the blood glucose level with a glucose meter. Hydrogen peroxide should not be used as antiseptic solution when using a glucose meter.
Introduction. The analogue of glucagon-like peptide-1 (GLP-1), liraglutide, has been shown to be effective in reducing body weight. Its effect on lipid and carbohydrate metabolism is still being studied.
Aim. To assess the dynamics of body weight, carbohydrate metabolism and lipid profile in obese children using liraglutide.
Materials and methods. A single-center, prospective study was conducted to evaluate the use of liraglutide in children aged 12 to 18 years with constitutional exogenous obesity over a period of 12 months. The decrease in body weight, the standard deviation of the body mass index (SDS BMI) and the dynamics of laboratory parameters (glucose, insulin, lipid profile) were evaluated. Results. A decrease in SDS BMI by 0.25 or more was noted in 23 children (71.8%, group 1). Weight loss in group 1 patients was observed from 1 to 8 months of therapy. In group 1 patients, there was a significant decrease in glucose values from 5.0 ± 0.4 to 4.6 ± 0.5 mmol/l (p < 0.0001), fasting insulin from 13.0 ± 7.6 to 8.3 ± 5.7 mMU/l (p = 0.004), HOMA-IR insulin resistance index from 3.4 ± 2.0 to 1.9 ± 1.5 (p = 0.0008). In group 2 patients, who did not experience weight loss, there was a significant reduction in serum cholesterol levels from 4.4 ± 0.8 mmol/l to 3.3 ± 1.6 mmol/l (p = 0.02) and low-density lipoprotein cholesterol levels from 2.1 ± 0.6 mmol/l to 1.7 ± 0.6 mmol/l (p = 0.014).
Discussion. In our study, as in previous studies, there was no effect of gender, age, and degree of obesity on the effectiveness of treatment. The obtained significant changes in carbohydrate metabolism and lipid profile in obese children after liraglutide therapy had not been previously observed.
Conclusions. In the group of children who did not lose body weight, there was an improvement in lipid metabolism, which requires an additional assessment of the effect of GPP-1 agonists on metabolism. More research is needed to identify factors that affect the effectiveness of liraglutide treatment.
GASTROENTEROLOGY
The article provides an overview of the current knowledge on the use of fermented milk products (FMPs) in the children’s nutrition and FMP contribution to the health and development of children. The benefits of FMPs due to the fermentation process underlying their production are considered. The article presents the findings of clinical studies emphasizing the favourable properties of FMP, including gut microbiota modulation, as well as immunostimulating, antibacterial, anticancer, antiallergenic and antioxidant effects; the outcomes of prospective cohort studies that identified a reverse association between the consumption of milk products in early childhood and blood pressure values in adolescence. The assortment of liquid FMP and drinks taking into account the regional nutritional characteristics of the population is described. A differentiated approach to defining the FMP type according to the milk raw materials, the starter composition, and the functional components is presented. The current FMP types produced using various starter cultures (lactic acid bacteria, yeast, acetic acid bacteria) and various fermentation methods that largely affect their taste and nutritional value are characterized. The distinctive features of probiotic FMPs are shown. Special mention is made of FMPs that are considered traditional for the Russian Federation, in particular kefir, which has a probiotic potential due to the composition of bacteria. The main methods used to produce FMPs, the biochemical processes during fermentation of products, their characteristics according to the starter cultures and the type of fermentation are described. The processing flow-charts for the liquid non-adapted curdled milk products and special requirements for the production of specialized FMPs for baby nutrition are considered. National guidelines for the introduction of FMPs to infant nutrition are discussed.
NEPHROLOGY / UROLOGY
The development of Russian clinical guidelines for the treatment of children with recurrent urinary tract infection and cystitis was almost completed by 2019. But the high level of complications of viral and infectious nature during the coronavirus pandemic has made significant adjustments to the diagnostic and therapeutic complex of management of such patients. Clinical recommendations are presented for urinary tract infections in children, which include both cystitis and pyelonephritis. Exclusively for cystitis, there are only clinical recommendations “Cystitis in women”. Cystitis is classified according to various signs: etiology, course, primary lesion and complicated forms. In determining acute cystitis in clinical recommendations for urinary tract infection in children, the bacterial origin of inflammation is indicated. It is assumed that the most common causative agents of cystitis are E. coli and other representatives of the intestinal group. In the practice of a pediatric urologist, there are observations when patients with complaints characteristic of cystitis are treated against or after viral infections (respiratory viral, and in recent years, including against the background of a new coronavirus infection). At the same time, with a few exceptions, normal results of urine tests are revealed in patients, and in observations when the diagnostic process comes to cystoscopy, hyperemia and hyperplasia of the epithelium, not characteristic of the bacterial etiology of cystitis, is detected on the mucosa (usually in the lower part of the Lieto triangle and in the neck of the bladder). Taking into account the peculiarities of the structure of the bladder wall in children, we consider it important to understand the etiology of cystitis. The article describes the features of cystitis caused by various viruses: herpes simplex virus, cytomegalovirus, papillomavirus infection, polyomavirus and coronavirus. For the final revision of clinical recommendations for the treatment of children with cystitis and the prevention of complications from the upper urinary tract in bacterial, viral and other infectious diseases, the experience of urologists and surgeons should be analyzed.
Regulation of immune and inflammatory processes of the body is necessary to limit the pathogenic process induced by uropathogenic E. coli in the bladder and kidneys while limiting damage to epithelial barriers. This review presents modern ideas about the features of innate immunity of the epithelium of the urinary system (urothelium) as the first barrier to infectious agents. As the nature of immune responses in the urinary tract becomes clearer, this knowledge can be used to develop new and effective strategies for the treatment and/or prevention of urinary tract infection. Some of these strategies are aimed at enhancing innate immune responses, and some at adaptive immune responses. However, the effectiveness of these strategies is based almost exclusively on data obtained from experimental mouse models. Overall, these recent results continue to better illuminate the processes in the body that increase susceptibility to urinary tract infections and their severity. In addition to the isolation and characterization of the uropathogen, a key requirement in the diagnosis of urinary tract infection may be to determine the nature of a defect in the local urinary tract immune system. This information can eventually serve as a basis for the development of new possible therapeutic approaches to the treatment of acute and recurrent urinary tract infections and allow in the future to adapt treatment methods for individual patients in such a way that they are pathogenetically justified, as individualized as possible and reduce the risks of recurrence and chronization of urinary tract infections.
DERMATOLOGY
Treatment of atopic dermatitis remains a serious challenge due to the prevalence of the disease, significant impact on the quality of life of patients and their families, as well as the risk of sensitization and triggering the “atopic march” in young children. It is known that the development of the disease is associated with a violation of the epidermal barrier; approximately half of the patients have defects in the production of filaggrin protein; in 30%, dermatosis is associated with allergic diseases, most often with food allergies. The course of atopic dermatitis is chronic, often persistently relapsing, and worsens in childhood. First of all, this is due to the peculiarities of the structure and functioning of the skin of children, which predisposes to disruption of its barrier functions, increased transdermal water loss and increased resorptive properties. The above factors determine the need for a particularly careful selection of drugs for external therapy of atopic dermatitis, which can not only cope with the acute period of the disease, achieve remission and control, but also have a sufficient level of safety and good tolerability. Topical corticosteroids remain one of the most commonly used basic therapy, the use of which is recommended by leading Russian and foreign experts. Most often in clinical practice, drugs with strong anti-inflammatory activity are used, one of which is methylprednisolone aceponate 0.1%, approved for use from 4 months of life. Extensive experience has been accumulated in the use of medicines containing this active substance, confirming its effectiveness and minimal side effects. The article presents our own experience of using methylprednisolone aceponate in the form of Comfoderm K cream (with ceramides as a base) in young children (up to 2 years), the results of which are consistent with the data on the high level of safety and effectiveness of the drug obtained earlier.
ALLERGOLOGY AND IMMUNOLOGY
Creation of a legal framework for immunodiagnosis of tuberculosis in paediatric practice in our country began in 1923, when the 2nd All-Russian Tuberculosis Congress and the 2nd All-Union Congress of Paediatricians were held. These congresses were known to approve the medicinal product label for the first tuberculosis diagnostic product Koch's alt-tuberculin. The product continued to improve; hence the method of tuberculin diagnosis has changed overtime. Starting from 2017, medical screening for TB in the paediatric population has been determined in Russia. TB is identified using various tuberculosis allergens according to the age group: a) immunodiagnostic examination of children aged 1–7 years is performed using a bacterial allergen with 2 tuberculin units of purified protein derivative-standard solution; b) immunodiagnostic examination of children aged 8–14 years is performed using the recombinant tuberculosis allergen derivative-standard solution; c) immunodiagnostic examination of children aged 15 through 17 years is performed using recombinant tuberculosis allergen derivative-standard solution or chest X-ray fluoroscopy. This review describes in detail the formation and development of the legal framework for screening for TB in the paediatric population in Russia. Detailed information on the current requirements for immunodiagnosis of TB in children and adolescents in accordance with the current legislation of the Russian Federation is presented. Issues of sanitary legislation, interdisciplinary interaction between primary health care facilities and anti-tuberculosis institutions are highlighted. Answers to the most frequently asked questions on the screening for TB in paediatric practice are provided.
Comorbid conditions in pediatric and adolescent phthisiology determine the need for interdisciplinary collaboration between healthcare professionals in different areas of expertise both at the stage of disease diagnosis and during tuberculosis treatment. This review is aimed to systematize the knowledge of pediatricians in different areas of expertise about comorbid conditions in tuberculosis (causes, risk factors for their development, options for timely diagnosis, impact of forced polypharmacy on the development of drug complications). The data of available methodological documents and published articles on the issue are systematized. The article presents groups at high risk for developing TB disease among patients with somatic pathology, the possibilities of modern diagnostic techniques based on a comprehensive medical examination with due account for the diagnostic algorithm and treatment regimen for a particular disease. If there is a reason to suspect tuberculosis in primary health care facilities and prior to prescribing immunosuppressive drugs, the minimum mandatory diagnostic examination in risk groups is set forth. The importance of key techniques for the detection and diagnosis of tuberculosis in children and adolescents including those with immunocompromised diseases is emphasized: Mantoux test using 5 tuberculin units (TU) of purified protein derivative (PPD)-L, a test with recombinant tuberculosis allergen (RTA), diagnostic tests assessing release of interferon gamma by T-lymphocytes in vitro during selective screening), computed tomography, detection of Mycobacterium tuberculosis in any diagnostic samples. Attention is paid to the impact of forced polypharmacy on the drug complications and treatment failures in patients with comorbidities, which requires collaboration between healthcare professionals in different areas of expertise to provide adequate selection of anti-tuberculosis therapy taking into account comorbidities. This approach to the management of patients with chronic somatic pathology allows for the prevention or early detection of tuberculosis.
PRACTICE
Breastfeeding affects infant’s health over the shortand long-term horizon. Components of breast milk such as immune cells, cytokines, chemokines, lipids, hormones and enzymes play an important role in protecting breastfed infants and contribute to the development of the immune system. The gut microbiome is one of the important role-players in the development of immunity. Its formation is influenced by many factors, and breastfeeding is considered one of the most significant. The gut microbiota composition significantly differs in breastfed and formula-fed infants. It may explain the reduced risk of many infectious and non-infectious diseases in breastfed infants. The main goal of formula manufacturers is to ensure not only healthy physical development of infants, but the same indicators of cognitive development, as well as protection from infections, which are observed in breastfed infants. When choosing a baby formula due to failure to breastfeed, it is important to choose a quality product that has a stimulating effect on the maturation of immunity and the formation of the infant's microbiota. Goat milkbased infant formulas are becoming popular in the world as an alternative to cow's milk-based infant formulas and can be the first choice for optimal nutrition. This review compares the various effects of breast milk and goat milk-based formulas on the formation of infant’s immunity.
DIFFICULT DIAGNOSIS
Sitosterolemia (phytosterolemia) is an inherited metabolic disorder characterized by the accumulation of plant sterols (phytosterols). The disease is caused by loss-of-function genetic mutations in sterolin proteins, which play an important role in selective excretion of plant sterols. Patients exhibit increased serum levels of phytosterols, total cholesterol and low-density lipoprotein cholesterol, which is accompanied by the risk of pre-mature atherosclerosis. Patients can have severe sitosterolemia when xanthomatosis develops as early as in infancy. Hematological disorders in the form of macrothrombocytopenia, stomatocytosis, episodes of hemolysis are reported in patients with sitosterolemia, which can be the only manifestation of the disease and are often interpreted as a manifestation of immune thrombocytopenia or primary hemolytic anemia. Hepatoand splenomegaly, acute liver failure, arthralgia may also be seen. Due to the similarity of clinical phenotypes, sitosterolemia can be misdiagnosed as familial hypercholesterolemia. It is vitally important to perform differential diagnosis to distinguish it from such diseases as lecithin-cholesterol acyltransferase deficiency, Tangier disease, cerebrotendinous xanthomatosis, familial dysbetalipoproteinemia, lysosomal acid lipase deficiency, primary biliary cirrhosis, storage diseases. The treatment of sitosterolemia in children includes the use of the intestinal cholesterol/phytosterol absorption inhibitor ezetimibe and bile acid sequestrant cholestyramine. The effective use of the combination of these drugs is described. The partial bypass of the distal ileum where the absorption of cholesterol, phytosterols, and reabsorption of bile acids mainly occurs can be used in severe cases. For patients with advanced vascular atherosclerosis and resistance to the standard treatments, LDL-C apheresis could be considered. The article describes our own clinical observation of a five-year-old patient suffering from sitosterolemia.
Introduction. Diagnosing cervical lymphadenopathy in children with a history of oncological or immunopathological conditions is challenging, often resulting in overtreatment. This study analyses ultrasound-based differential diagnostics for lymphadenopathy in this patient group.
Aim. To improve diagnostic accuracy for cervical lymphadenopathy in children with a history of oncological or immunopathological conditions.
Materials and methods. A retrospective analysis was performed on clinical and demographic data from 217 paediatric patients diagnosed with cervical lymphadenopathy. These patients underwent excisional lymph node biopsy and/or lymphadenectomy between December 2017 and December 2022. The cohort was divided into Group A (benign lymphadenopathy; n = 92) and Group B (malignant lymphadenopathy; n = 125).
Results. Significant predictors of malignant lymphadenopathy were identified, including “Lymph Node Configuration Index ≤ 2” (increasing the odds by 4.4–5.1 times), “Short Axis of Lymph Node > 10 mm” (OR 2.5–2.8), “Specific Therapy Prior to Lymph Node Removal” (OR 6.9–7.2), “Absence of Lymph Node Differentiation” (OR 2.2–2.4), “Presence of Intranodal Microcalcifications” (OR 14.1–16.3), “Increased Vascularisation of the Lymph Node” (OR 2.0–2.6), “Overall Hypoechogenicity” (OR 2.4), and “Formation of Conglomerates” (OR 3.6). Predictive models integrating these factors demonstrated strong accuracy, with an informational capacity of 81.1% (p < 0.001), sensitivity between 79.3% and 82.6%, and specificity from 80.0% to 82.4%.
Discussion. The comprehensive analysis of predictive factors for malignant lymphadenopathy in patients with a history of oncological or immunopathological diseases suggests that no single ultrasound risk factor should be the sole basis for differential diagnosis, supporting earlier findings.
Conclusion. The predictive models provide a standardised, robust approach for assessing malignant lymph node involvement, improving diagnostic accuracy in paediatric patients with oncological or immunopathological histories.
PEDIATRICIAN SCHOOL
Introduction. Vitamin D plays an important role in anti-tuberculosis immunity, and the reduction level of this vitamin in the body is critical.
Aim. To estimate the probability of diagnosis of active tuberculosis in children with positive ATR-test and/or IGRA test results and different vitamin D status.
Materials and methods. A prospective study was conducted in 46 children aged 1–14 years from 2021 to 2023 in the Tuberculosis Department of St. Petersburg Children’s Infectious Diseases Hospital No. 3. Exclusion criteria comprised severe immunodeficiency diseases. The examination methods included the complex phthisiological examination and determination of serum calcidiol concentrations (inactive, main form of vitamin D).
Results. 93.5% of the examined patients had low levels of this vitamin. The mean calcidiol level in all examined children was 14.60 ± 1.30 ng/ml. The clinical examination identified residual changes after earlier rickets in 80.4% of patients. Moreover, most children had normal blood macroelement concentrations: calcium – in 87.0%, phosphorus – in 67.4%, magnesium – in 84.8% of cases. The probability that active tuberculosis may be diagnosed in children with positive ATR-test and/or IGRA test results and vitamin D deficiency (level less than 20 ng/ml) was higher than in children with vitamin D deficiency and normal level (OR = 10.13 CI [2.32–44.17] Se = 0.75, RR = 2.66 CI [1.16–6.10] Se = 0.42; F = 0.0017; χ2 = 11.060 (p < 0.001); φc = 0.49). Among children with vitamin D deficiency (level less than 20 ng/ml) and active tuberculosis, the proportion of complicated and disseminated forms was 48.1%, while among children with vitamin D deficiency and normal concentration, it was not observed. Discussion. The mean calcidiol level in all examined children was 14.60 ± 1.30 ng/ml, which indicated the absence of active manifestations of rickets during examination, and therefore the prevalence of decreased immune system function due to vitamin D insufficiency.
Conclusions. Vitamin D deficiency is a significant endogenous factor contributing to the development of tuberculosis.
The article is devoted to an urgent medical and social problem of recurrent respiratory infections in children. In domestic pediatric practice, there are currently no unified approaches to diagnosis, prophylactic medical examination and rehabilitation of a group of sickly children. This article presents an adapted version of the Inter-society Consensus developed by the Italian Medical Associations in the field of pediatrics, pediatric infectious diseases, allergology, immunology, and otorhinolaryngology. The consensus includes an algorithm of a differentiated approach to determining the risk of recurrent respiratory pathology in children in different age groups, markers for additional examination to exclude genetic pathology and chronic diseases. The low effectiveness of prevention of recurrent acute respiratory infections in children creates prerequisites for the search of methods to improve the rehabilitation potential of patients. Over the past few years, the study of the human gut microbiome as a separate extracorporeal organ that affects all body systems is promising. In the case of propensity to frequent respiratory diseases, the most important attention is paid to the “intestine-lung” axis, since this axis is bidirectional and represents the cross-relationships of the respiratory and digestive systems. The presence of this axis is due to the structural homology of the intestine and lungs from the point of view of histology and embryology and confirmed by experimental and clinical studies. The article presents the results of domestic and foreign studies devoted to find the changes in a gut microbiome and microbiome of upper respiratory tract. There is a numberof systematic reviews and meta-analyses demonstrating the presence of interrelated and interdependent changes in the gut microbiome duringrecurrent respiratory infection process, which allows to consider the prospect of using probiotics in sickly children.
Christ – Siemens – Touraine syndrome is a genetically determined disease, mainly of males, the female is carriers of the pathogenic gene. The incidence of the disease has not been precisely established, according to modern data 1 case on 5 000–10 000 newborns, in female carriers 17 cases 100 000. Usually, the syndrome is inherited linked to gender, but autosomal and spontaneous forms are possible. There is a mutation of the EDA1 gene encoding the synthesis of ectodysplasin-A. As a result, epithelial and mesenchymal interactions are disrupted, leading to a lack of regulation of the formation of epithelial appendages. There are phenotypic specific features: thick lips, triangular lower jaw, wide saddle-shaped bridge of the nose and deformed low-set ear, wide cheekbones, fine wrinkled and hyperpigmented skin around the eyes, agenesis of the mammary glands in women. A clinical triad of signs is characteristic: hypotrichosis/atrichosis (thin, light, dry hair); hypodontia/anodontia (conical teeth); hypohidrosis/anhidrosis (a condition that threatens the death of a child due to hyperthermia). The authors presented a clinical case of hereditary Christ – Siemens – Touraine syndrome in a newborn child. The documentation was used when writing the article, we was used the medical history of the department of pathology of newborn children and young children of Tyumen regional clinical hospital No. 2 and was analyzed scientific articles about this theme in the open scientific databases, such as PubMed, Elsiver, Springer and Russian scientific electronic library. The presence of specific phenotypic and clinical signs makes it possible to diagnose the syndrome immediately after birth. Based on the datas of medical history, a burdened genealogical history, the initial the patient examination allowed to identify numerous stigmas of dysembriogenesis and malformations that confirmed the rare hereditary Christ – Siemens – Touraine syndrome. Christ-Siemens-Touraine syndrome is a risk factor for skin diseases, respiratory system and teeth, which must be taken into account for early diagnosis and determination of further patient management tactics by a pediatrician, dermatologist and dentist.
Introduction. The population strategy of modern healthcare is aimed at preventing obesity and its complications. The study of the spectrum of fatty acids is a progressive direction of lipidomics in the diagnosis of metabolic disorders.
Aim. To evaluate the possibilities of calculated fatty acid indices in determining the risk of metabolic disorders in obese adolescents.
Materials and methods. Single-center observational single-stage comparative study. The study sample consisted of 155 adolescents aged 10–15 years. The main group was represented by 101 participants – 45 boys and 56 girls with diagnosed obesity of exogenous constitutional type, 1–2 degrees (SDS BMI +2,0–+3,0 ). The control group included 54 healthy children with -1<SDS BMI <1: 28 girls and 26 boys. The calculation of SDS BMI was carried out using the WHO computer program “Anthro Plus” for the age category from 5 to 19 years. The levels of fatty acids in the blood serum were determined by chromatomass spectrometry.
Results. Significantly lower levels of polyunsaturated fatty acids and higher content of some monounsaturated ω-7 and ω-9 fatty acids, as well as the main representatives of the saturated fatty acid family, were observed in obese adolescents. The values of the ω-3 index, both for whole blood and for erythrocyte membranes, were statistically significantly reduced in the main group. Subintimal inflammatory reaction risk index and PUFA % index/%NLC had high values in boys and girls of both groups. The ω-6/ω-3 index on the background of obesity was increased only in boys. The activity of delta-6-desaturase did not differ statistically significantly between the groups.
Conclusions. The presented indices (ω-3 index, risk index of subintimal inflammatory reaction, ω-6/ω-3 index, polyunsaturated/saturated LC index, ω-6 desaturase activity index) require additional study and specification of application conditions, reference values and interpretation rules, especially in the pediatric population.
Introduction. Childhood obesity is one of the most pressing problems in modern pediatrics. The serious attention of specialists is attracted by numerous reports on changes in the composition of the intestinal microbiota (IM) in obese patients.
Аim. Тo find the relationship between the metabolic complications of obesity in children and the diversity of IM.
Materials and methods. A single-stage prospective controlled study was conducted, which included 133 children with exogenous constitutional obesity and 23 healthy children of the control group. All children underwent an examination aimed at diagnosing metabolic complications of obesity. An additional research method was the assessment of the microbiome of the luminal contents of the large intestine with the identification of microorganisms by MALDI-ToF mass spectrometry.
Results. The study revealed a high incidence of metabolic complications of obesity in the examined patients: arterial hypertension (AH, 22.7%), impaired carbohydrate metabolism or type 2 diabetes mellitus (25.1%), dyslipidemia (25.6%), impaired purine metabolism (46.4%) and metabolically associated fatty liver disease (49.3%). When assessing the microbiological profile, a decrease in the frequency of excretion of bifidobacteria and streptococci in patients with hypertension was revealed, and the relationship of individual microorganisms with some complications of obesity was also found.
Discussion. According to the literature, the frequency of excretion of bifidobacteria in obese patients is reduced, as in our case. This can be considered as a potential therapeutic target for the correction of metabolic disorders. The issue of reducing the diversity of IM in patients with hypertension is also being discussed in the scientific community, which this study also shows, proving the relationship of changes in IM with complications of obesity. It turned out to be interesting that certain bacteria associated with colorectal cancer were isolated from obese patients, which requires further study of the issue, given the higher prevalence of oncopathology in this group of patients.
Conclusions. The results of the study demonstrate a high incidence of metabolic complications of obesity in children, as well as their relationship with IM, which dictates the need for further study of this area and the search for possible ways to influence IM in order to influence metabolic disorders in obese patients.
Introduction. Despite the availability of modern, effective antibiotics and vaccines, up to 825 000 children under five years of age worldwide suffer from severe pneumococcal infection every year.
Aim. To study the prevalence and manifestation of asymptomatic carriage of St. pneumoniae in unvaccinated preschool children.
Materials and methods. The study design was a prospective cohort study that began before the inclusion of pneumococcal vaccination in the National Preventive Vaccination Calendar of Uzbekistan (2015). The microbiota of the nasopharynx was studied in 236 practically healthy children, of which children attending preschool, from 3 to 5 years old – 143 (60.6%), unorganized children from 1.5 to 3 years old – 93 (39.4%). According to standard methods, a bacteriological analysis (bacterial culture) was carried out to detect St. pneumoniae in a nasopharynx smear.
Results and discussion. Asymptomatic nasopharyngeal carriage of St. pneumoniae was detected in 40.7% of those observed, which was higher than the detection rate of H. influenzae – 22.0% (52/236), as well as Moraxella catarrhalis – 13.6% (32/236), and in children attending kindergartens, the detection rate was two times higher (50.4% versus 25.8%), compared to unorganized children. According to two-year observations, a more aggressive effect of pathogens was noted in young children (unorganized children). Repeated episodes of pneumonia were noted in 29.2%, which is 5.2 times more than in children from the second age group (5.6%). The data obtained indicate a high incidence of children under three years of age with St. pneumoniae carriage.
Conclusion. Among unvaccinated children under five years of age, asymptomatic nasopharyngeal carriage of St. pneumoniae was 40.7%, and the transition of asymptomatic carriage to invasive respiratory diseases reached 97.9%, which indicates the need for family doctors to organize and conduct effective vaccination of children before their admission to preschool institutions.
Paroxysmal nocturnal hemoglobinuria in children is an acquired orphan disease that has not yet been sufficiently studied. Diagnostic errors with delayed diagnosis of paroxysmal nocturnal hemoglobinuria are common, due to the diversity of the clinical picture and insufficient awareness of doctors about this rare disease. Using the example of a clinical case of a patient with paroxysmal nocturnal hemoglobinuria to show the features of the manifestation and course of this disease. A 14-year-old patient, due to anemia, was hospitalized in the oncology department of the Regional Children’s Clinical Hospital named after N.N. Silishcheva (Astrakhan). During the examination, the diagnosis was made: severe iron deficiency anemia. Copious menstruation of the puberty period. Microhematuria and leukocyturia were noted in the urine analysis. Systemic connective tissue diseases and oncological pathology were excluded. Studies have been performed to diagnose autoimmune diseases. Survey results. As the patient was monitored, the diagnostic and therapeutic concepts changed. Given the presence of anemia, moderate hyperbilirubinemia, negative Coombs test and microhematuria, paroxysmal nocturnal hemoglobinuria is suspected. During cytofluorometry, an APG clone was detected – determined on erythrocytes (12.49%), granulocytes (93.7%) and monocytes (91.1%); ADAMTS13 91%, which confirmed the diagnosis of Paroxysmal nocturnal hemoglobinuria. Classical paroxysmal nocturnal hemoglobinuria in the practice of a pediatrician is extremely rare, the use of routine research methods leads to improper treatment and the development of complications. Timely specific diagnostics and therapy provided positive dynamics of clinical and laboratory symptoms of the disease and a favorable prognosis for health.
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