LEAD ARTICLE
This article is a review of modern ideas about human parechovirus infection in children. At this time human parechoviruses are a common cause of infectious diseases in childhood with clinical presentation of acute gastroenteritis, upper respiratory tract pathology, fever, and rash. Severe forms damaging the central nervous system or the development of sepsis are possible in newborns and infants and are almost exclusively associated with parechovirus A type 3 (HPeV-A3). The infection is transmitted mainly via food and droplet routes. The main method of infection diagnosis is the detection of viral RNA by real-time PCR in cerebrospinal fluid, blood, and feces. No treatment for the parechovirus infection has been developed so far.
REVIEWS
Low-birthweight and preterm infants have high risk of obesity and obesity-related diseases in the future. This review article identifies risk factors and endocrine biomarkers with greatest predictive value to the metabolic diseases development. Low concentrations of IGF-1 in low-birthweight children are associated with adipogenesis. Low leptin levels may be considered as a biomarker of catch-up growth. Long term programming effects of in utero exposure to leptin extend beyond infancy into early childhood. Adiponectin levels are positively correlated with obesity in early life, but not at ages older than three years. Rapid postnatal growth rate is associated with metabolic syndrome.
Conclusion. Specific features of endocrine regulation of growth and dynamics of plastic processes in premature infants and SGA children are associated with excessive accumulation of adipose tissue, which can function as a mechanism for metabolic programming of distant endocrine and cardiometabolic disorders.
Most children make a full recovery from a new coronavirus infection, but some of them have a variety of persistent symptoms for a long time. A wide range of symptoms that occur within weeks or months after infection with SARS-CoV-2 is referred to as a long COVID (post-COVID-19 syndrome). The review presents literature data on the duration and clinical features of post-COVID-19 syndrome in children. The paucity of studies on long COVID conditions does not allow us to draw unambiguous conclusions. However, it should be borne in mind that the consequences of a new coronavirus infection can have a significant impact on the health of children and their quality of life in the future.
Klebsiella pneumoniae is an important causative agent of nosocomial and community-acquired infections in children. The relevance of Klebsiella infection has increased in recent years due to the spread of multiresistant and hypervirulent strains that can cause invasive forms of infection (sepsis, meningitis, liver abscess, etc.). Strains of Kl. pneumoniae, producing extended-spectrum β-lactamase (ESBL), as well as carbapenem-resistant strains, are the cause of nosocomial outbreaks with high mortality. The choice of antibacterial drugs for the treatment of invasive forms of infection is limited and depends on the spectrum of sensitivity to antimicrobial drugs of Klebsiella clinical isolates circulating in the hospital and the age of the child. Due to the high rate of ESBL production, carbapenems are the drugs of choice in the empirical therapy of invasive forms of infection.
ORIGINAL ARTICLES
SARS-CoV-2 is known to be able to infect the gastrointestinal tract, causing a variety of symptoms. Practice shows that the clinical presentation of diarrheal syndrome with COVID-19 does not fit into the classic manifestations of osmotic diarrhea. Cases of lesions of the lower intestine are often reported.
Purpose. The study aims at evaluation of the features of clinical manifestations and laboratory parameters of diarrheal syndrome to determine the possible mechanism of gastrointestinal damage in children with COVID-19.
Material and methods. 80 subjects were examined on the basis of the Kazan Regional Clinical Hospital. 40 patients were selected for the main group with diarrhea and a confirmed diagnosis of COVID-19, 40 for the control group with rota- or norovirus infection.
The examination included a daily examination, laboratory tests to assess the clinical features of the course, etiological decoding, study of the pathogenetic mechanisms of diarrhea in COVID-19.
Results. COVID-19 differs from classical viral diarrhea in more pronounced catarrhal respiratory syndrome (p<0.001), pyretic fever (p=0.001). Vomiting is more typical for rota- and norovirus infections (p<0.001). SARS-CoV-2 is statistically significantly more likely to cause clinical scenario of distal colitis (p=0.034). Patients with increased levels of carbohydrates in the feces were observed more often in the viral diarrhea group, and calprotectin — in the COVID-19 group (p<0.05). A significant qualitative and quantitative imbalance of the intestinal microflora is more typical for patients infected with SARS-CoV-2.
Conclusion. The conducted study suggests a complex genesis of gastrointestinal lesions in children with COVID-19, which includes signs of both osmotic and exudative (invasive) mechanisms of diarrhea formation. Clearly, GI lesion in COVID-19 is a multifactorial process.
There is an opinion that COVID-19 may be the cause of the reactivation of herpesviruses.
Purpose. To study the state of the cellular link of adaptive immunity in the combined course of herpesvirus infections and COVID-19, to describe the clinical and laboratory characteristics of such conditions.
Material and methods. In 2022–2023 a cross-sectional study was conducted. 71 patients aged from 1 month to 16 years were selected. Inclusion criteria: presence of signs of acute respiratory disease associated with SARS-CoV-2 and/or mononucleosis-like syndrome associated with active herpesvirus infection. All patients underwent a standard laboratory examination, determined by nosology, and an additional assessment of the cellular link of adaptive immunity (CD3+, CD4+, CD8+, CD3+HLA-DR+, CD3- CD16+CD56+ and CD20+) on a flow cytometer using monoclonal antibodies.
Results and conclusion. The clinical pattern of the combined course of herpesvirus infection and SARS-CoV-2 differs little from monoinfections. Only at the first encounter with the Epstein-Barr virus, lymphoproliferative syndrome and hepatomegaly were more often recorded (p<0.05). Comparing the nature of the cellular immune response in patients with COVID-19 and herpesvirus infection, we observed pronounced differences. In patients with primary herpesvirus infection, the T-cell immune response was an order of magnitude higher than in acute COVID-19, herpesvirus reactivation, and co-infection, and this was true for all studied lymphocyte subpopulations. With SARS-CoV-2, a decrease in the total number of T-lymphocytes, T-helpers, and cytotoxic lymphocytes was observed. This condition, of course, cannot be called immunosuppression, but some parallel is clearly traced. And even with the combined course of SARS-CoV-2 and herpesvirus infection, the absolute values of T-cell immunity indicators do not reach the same indicators in patients without COVID-19. It is likely that this reason underlies the phenomenon of reactivation of persistent herpesviruses in patients infected with SARS-CoV-2.
Of particular interest is the study of colonization resistance of the oral cavity as a physiological phenomenon that reflects the ability of the microbiota and macroorganism in cooperation to protect the ecosystem of the oral cavity from pathogens.
Purpose is to evaluate the significance of indicators of colonization resistance of buccal epithelial cells as a marker of homeostatic resources of mucosal immunity in recurrent respiratory diseases in children.
Material and methods. 232 (5–16 years old) children were examined, including 56 children with acute bronchitis, 73 with recurrent bronchitis, 103 with community-acquired pneumonia. The control group included 31 apparently healthy children of the same age and sex. Used: conventional paraclinical and laboratory-instrumental methods, etiological verification of viruses and bacteria, colonization index and artificial colonization of buccal epitheliocytes, antiadhesive activity of saliva.
Results. 64.38% of children with recurrent bronchitis and 72.82% of children with community-acquired pneumonia were born from an aggravated pregnancy and already at 3 months had signs of acute respiratory diseases. Viral antigens were detected in 63.36% of children. An inverse relationship was found between the indicators of artificial colonization and adhesion of Candida albicans on buccal epithelial cells — the lower the values of artificial colonization, the more often pneumonia and recurrent bronchitis were recorded. A significant decrease in saliva antiadhesion was found in recurrent bronchitis and community-acquired pneumonia, significantly different not only from the control, but also from patients with acute bronchitis. This contingent of patients finds itself in extremely unfavorable conditions due to the disruption of the adaptive reserves of the mucosal defense of the body.
Conclusion. A decrease in the index of colonization, antiadhesive activity of saliva against the background of increasing parameters of artificial colonization in children with recurrent bronchitis and community-acquired pneumonia indicate deep dysbiosis. The high significance of screening approaches in assessing the homeostatic resources of mucosal protection of the oral cavity in children with bronchopulmonary pathology has been proven.
Dysfunction of the lower urinary tract is a fairly common consequence of perinatal lesions of the nervous system. Dysfunction of the bladder and muscles of the urogenital diaphragm in this group of children can be accompanied by severe urodynamic disorders and, in some cases, can lead to complications such as chronic recurrent urinary tract infection, vesicoureteral reflux, nephrosclerosis, kidney atrophy, chronic renal failure.
Purpose. To study uronephrological complications in children with various forms of neurogenic bladder dysfunction and suggest methods for their prevention and pathogenetic treatment.
Material and methods. 67 children with neurogenic bladder dysfunction were examined. All children underwent comprehensive uronephrological and neurological diagnostics using objective neuroimaging, electrophysiological and functional research methods.
Results. Complications leading to somatic health disorders in patients were diagnosed. These included chronic cystitis — in 13 (19.4%) patients, chronic pyelonephritis — in 57 (85.1%), vesicoureteral reflux — in 25 (37.3%), chronic renal failure — in 8 (11.9%) children. Therapy for neurogenic bladder dysfunction consisted of basic therapy of the central nervous system lesion, as well as symptomatic therapy aimed at normalizing the functional state of the bladder. In the vast majority of cases of neurogenic bladder dysfunction complications, their relief occurred within a year in the process of curing the underlying disease. In some cases, in children with severe neurological disorders (myelodysplasia, meningoradiculocele), along with medication and physiotherapy, surgical manipulations (periodic bladder catheterization) and surgical interventions (epicystostomy) were performed.
Conclusion. In children with detrusor hyperreflexia and mild «high» lesions of the nervous system, clinical symptoms of neurogenic bladder dysfunction were usually noted, worsening only their quality of life. In children with a significant neurological deficit and a rather severe lesion of the lumbosacral spinal cord, complications developed that worsened the somatic health of this group of patients.
The study of the characteristics of carnitine metabolism in representatives of certain sports makes it possible to study the effect of physical loads of various nature on the body of a young athlete, and also makes it possible to assess the competitive potential and predict the tolerance of long-term and intense loads.
Purpose. This study is to investigate the characteristics of carnitine metabolism in young athletes of various specializations.
Material and methods. The study included athletes aged 14 to 18 who had been engaged in intense physical exercise for at least 12 hours per week forthe past 12 months or more. The control group consisted of healthy children aged 14 to 18 who were not involved in sports. In the blood serum of all study participants, the concentration of free carnitine, acetylcarnitine and acylcarnitines was determined. Based on the data obtained, ratios were calculated reflecting the activity of lipid beta-oxidation enzymes.
Results. We found that the content of free carnitine in the representatives of all the studied groups was within the normal range. At the same time, the level of free carnitine in the blood of athletes involved in field hockey was significantly lower than that of athletes-swimmers and representatives of the control group (p<0.001). It was also studied that, compared with athletes-swimmers and the control group, athletes-hockey players have significantly higher functional activity of carnitine palmitoyltransferase 1 (p<0.05) and lipid beta-oxidation enzymes (p<0.001).
Conclusion. In our work we have demonstrated that athletes involved in team sports (field hockey) have a more pronounced shift towards fatty acid oxidation compared to aerobic sports (swimming). A possible reason for the identified changes may be a more significant effect of alternating aerobic and anaerobic loads on lipid metabolism compared to exclusively aerobic activity.
CLINICAL CASES
The article presents a unique case of a transient myelodysplastic syndrome characteristic of children with trisomy 21. This condition has non-specific clinical manifestations and a specific hematological picture similar to those of acute leukemia. The uniqueness of transient myelodysplastic syndrome lies in the spontaneous resolution within a few weeks or months after birth and/or the development of acute myeloid leukemia after spontaneous regression in the first 4–5 years of life. A prerequisite for the development of myelodysplastic syndrome is the presence of a blast clone of trisomy of the 21st chromosome and a mutation in the GATA1 gene in the cells.
Congenital bullous epidermolysis is a severe hereditary disease, the main manifestation of which is bubbles that occur after minor mechanical action on the skin and mucous membranes due to congenital violation of the coding of dermo-epidermal proteins. The difficulty in making a diagnosis of congenital bullous epidermolysis is associated with the rarity of pathology and a small number of scientific publications.
The article presents a clinical case of a child with a perinatal form of Niemann–Pick disease type C. The clinical manifestations were cholestasis syndrome, cytolysis, hepatosplenomegaly, muscle hypotension. Differential diagnostics was performed with toxic, cytomegalovirus, viral hepatitis, alpha-1-antitrypsin deficiency, autoimmune liver diseases, aminoacidopathies, Alajille syndrome. After Cholestasis panel genetic testing, a mutation in the NPC1 gene was detected. Biochemical diagnostics showed an increase in the concentration of lysosphingomyelin-509 and increased activity of chitotriosidase in dry blood spots. According to the Sanger sequencing of the NPC1 gene, a nucleotide substitution of chr18:21131617G>A was detected in a child in a homozygous state. According to vital indications (“off-label use”), the patient was prescribed substrate-reducing therapy with Miglustat. Relief of cholestasis syndrome, minimal cytolysis syndrome after administering the drug for 1 month may indicate good tolerability and effectiveness of therapy.
It is well known that herpesviruses are pantropic, hence herpetic infections are characterized by a diverse clinical pattern. Often one of the syndromes of various «herpetic nosologic forms» is the exanthema syndrome. Traditionally, this is a vesicular rash accompanying the infection caused by herpes simplex virus, which occupies a fairly limited area, but the rashes can be completely different in nature, quantity, and localization. The article discusses a relatively rare variant of herpetic infection, called: Kaposi’s varicelliform eruption (eczema herpeticum), or Kaposi–Juliusberg varioliform pustulosis, characterized by the severity of clinical manifestations, often an unfavorable outcome, diagnostic and therapeutic difficulties. Photo documents of the dynamics of the skin process and laboratory parameters against the background of antiviral therapy are presented.
Early diagnosis of the cystic fibrosis remains an urgent problem, despite ongoing nationwide neonatal screening. The uniqueness of the presented clinical case lies in the atypical onset of cystic fibrosis in a young child with clinical manifestations of acute kidney injury. The suddenly developed severe general condition in a child was due to manifestations of acute renal injury of the third stage (severe lethargy, anuria for 14 hours, an increase in blood creatinine to 121 µmol/L, a decrease in glomerular filtration rate to 17.4 mL/min), decompensated metabolic alkalosis with hypokalemia, hyponatremia, hypocalcemia (pH 7.6, K+ 2.6 mmol/L, Na+ 118 mmol/L, Ca2+ 0.96 mmol/L, HCO3 – 35.5 mmol/L). The observed disturbances in acid-base status and electrolyte metabolism were manifestations of the pseudo-Bartter syndrome. For the prevention of acute kidney injury in a patient with cystic fibrosis, timely electrolyte and fluid management is important to prevent the development of pseudo-Bartter’s syndrome, exsicosis and hypovolemia.
The article describes a clinical example of the development of sarcopenic obesity in a child with type IXa glycogen disease. The reasons for the development of sarcopenic obesity were, on the one hand, the lack of control over the child’s nutrition: excess consumption of easily digestible carbohydrates, fats and lack of protein in the actual diet and inactivity due to a child’s motor activity restriction in view of surgical interventions for Perthes’ disease, on the other. The article provides practical recommendations on the example of prescribing diet therapy to a child with a complex combination of type IX glycogenosis, sarcopenic obesity, Perthes disease, and eosinophilic esophagitis.
Dilated cardiomyopathy is one of the leading causes of heart failure in children with a variety of clinical characteristics. A 12-year-old patient with dilated cardiomyopathy and heterozygous familial hypercholesterolemia, who underwent surgical treatment for implantation of the Abbott HeartMate III Left Ventricular Assist Device as a bridge to donor heart transplantation, is presented. Establishing an accurate diagnosis in the presented observation became possible thanks to the use of a modern molecular genetic method — whole genome DNA testing by next generation sequencing (NGS). The description of this case will help expand the range of possible clinical manifestations of dilated cardiomyopathy and reminds us of the importance of dynamic monitoring of children with cardiac arrhythmias.
Moyamoya disease is a progressive cerebrovascular disease characterized by bilateral stenosis of the supraclinoid (proximal) part of the internal carotid arteries and the initial segments of the anterior and middle cerebral arteries, with subsequent involvement of the vertebrobasilar basin and accompanied by the development of a basal network of anastomoses. The disease most often manifests itself at the age of 5 to 30–40 years, which makes this pathology an actual and significant cause of functional disorders in children and young people. Diagnosis of moyamoya disease can be difficult because of the polymorphism of its clinical manifestations. This disease must be taken into account in the differential diagnosis of symptoms of cerebral ischemia, since early detection and therapeutic intervention can improve the prognosis by preventing irreversible brain damage. The article presents its own clinical observation of a 6-year-old child with moyamoya disease with a predominant lesion of the right internal carotid artery basin.
Mucocutaneous lymph node syndrome (Kawasaki syndrome/disease) is an acute systemic disease characterized by a predominant lesion of medium and small arteries (arteriitis), the development of destructive proliferative vasculitis. The most serious manifestations of Kawasaki disease are coronaritis and the formation of aneurysms of the coronary arteries, which can be a potential cause of acute coronary syndrome in children. The article presents our own clinical observation of a 7-month-old child with a complete form of Kawasaki disease with the formation of aneurysms of the coronary arteries, complicated by acute coronary and hemophagocytic syndromes. Kawasaki syndrome should be considered in all children with persistent fever ≥ 5 days, and the combination of persistent fever with 2–3 typical features of Kawasaki syndrome should be an absolute indication for echocardiography with mandatory visualization of the coronary arteries.
Mastocytosis belongs to a group of rare diseases in which there is a pathological accumulation of mast cells in tissues. In childhood, it is more often limited to skin lesions. A clinical case of a bullous form of severe cutaneous mastocytosis, with the onset of the disease at 3.5 months, is presented. Cutaneous manifestations with a positive Darier–Unna symptom and a high level of tryptase in the blood, the exclusion of systemic lesions allowed diagnosing cutaneous mastocytosis and choosing treatment tactics.
Despite the availability of current Russian clinical guidelines for the management of eosinophilic esophagitis, this disease is a difficult diagnostic and therapeutic problem. The article presents a clinical observation of a teenager with recurrent eosinophilic esophagitis. The importance of clarifying the patient’s compliance with an emphasis on adherence to the regimen and the adequacy of the dose of the therapy used is emphasized. Despite the ongoing complex therapy administered to the patient with eosinophilic esophagitis, including an elimination diet, proton pump inhibitors and topical steroids, the patient has relapses of the disease, confirmed endoscopically and morphologically. The absence of a regulated duration of therapy with topical steroids, the need for endoscopic and morphological monitoring of the effectiveness of treatment also complicates the management of this group of patients.
SHARING EXPERIENCES
Neuroblastoma (NB) is a malignant extracranial solid tumor of childhood. The peak incidence occurs in the first year of life. In 50% of cases, the disease already has signs of metastasis at the time of diagnosis. The clinical picture in neuroblastoma is varied; the symptoms are not specific and depend on the localization. The diagnosis is confirmed by histological examination of the biopsy of the primary tumor and metastasis. A specific method for the topical diagnosis of neuroblastoma is 123I-labeled metaiodobenzylguanidine scintigraphy, which makes it possible to detect the primary tumor, the presence of regional and distant metastases. Combinations of high-dose chemotherapy and transplantation of autologous stem cells and differentiating agents, as well as immunotherapy with anti-GD2 monoclonal antibodies, can increase the life expectancy of patients.
The article provides a view on the problem of chronic venous disease syndrome in children, summarizing the pediatric and vascular surgical approaches. Varicose veins in children are a combination of problems of varicose veins in the legs, a cosmetic defect, and the task of management by pediatric specialists in outpatient settings. The article reflects many years of experience of the authors in the treatment of patients with venous diseases. The purpose of the article is to present the features of managing patients with chronic venous diseases in primary care medical institutions. The modern level of diagnosis and treatment of the disease is reflected. Peculiarities in children related to the development of complications, the formation of chronic venous insufficiency and the need for surgical interventions are shown.
Conclusions: the role of an outpatient pediatrician is important in the identification and verification of children with chronic venous diseases; further examination and management of the patient is carried out in strong relationship between the pediatrician and the pediatric (pediatric vascular) surgeon. To achieve satisfactory results, timely and selective surgical and laser interventions and an ongoing individual conservative treatment program are required.
GUIDELINES FOR THE PRACTITIONER
Calprotectin is a calcium- and zinc-binding protein belonging to the S100 protein family. This protein is found mainly in the cytoplasm of neutrophils, and, to a lesser extent, in monocytes and macrophages, which can be found in any human organs, but mainly in blood, cerebrospinal fluid, feces, saliva, and synovial fluid. Calprotectin is an effective tool forthe differential diagnosis of inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS). There is a connection of fecal calprotectin (FC) with the endoscopic activity of IBD, however, the available literature shows significant differences in the sensitivity and specificity of FC for predicting the endoscopic activity of the disease. In addition, FC can be considered as a predictor of histological mucosal healing and as a marker for assessing the response to treatment, including surgical, but there is still no consensus on the threshold value of a biomarker for these purposes. Conflicting data are presented in reports on FC as a predictor of IBD recurrence. FC seems to be effective for detecting relapse, however, there is no specific threshold value, therefore, the marker cannot completely replace endoscopic examination methods. In addition, there is intraindividual variability in the concentration of FC in patients, depending on age, type of feeding in the first year of life, taking medications, which significantly complicates the interpretation of the results.
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