Complete blood count is one of the most accessible and common laboratory tests available today. In present-day healthy newborns, complete blood count levels differ from the normative values used in the 1970s, which may require critical analysis, clarification, further research, and revision of the concept of norm.

Objectives. To identify changes in the hematologic parameters of healthy newborns born in 2022 as compared to those reported in the 1930s and 1967–1970s.

Methods. A retrospective cohort study of neonatal records was conducted at the Neonatal Physiology Unit of the Perinatal Center of the Saint Petersburg State Pediatric Medical University (Ministry of Health of the Russian Federation). Eleven hematologic parameters were analyzed in 378 healthy full-term newborns (born in 2022) in their first three days of life with subsequent comparison of the obtained results with the data of 20th-century domestic publications, as well as with Russian and foreign scientific articles published in the last 15 years. The blood of all children was tested once using a Micros ES 60 automated hematology analyzer (HORIBA ABX S.A.S., France). Mathematical and statistical data processing was performed using Microsoft Office Excel 2021 (Microsoft, U.S.).

Results. A comparison of red blood cell and hemoglobin levels reported in newborns in their second and third days of life in 1970 and 2022 revealed statistically significant differences, with lower levels observed at present. Mean platelet counts are also significantly lower than those reported in the 1930 and 1970 studies but are almost the same as those reported by other authors in 2012–2019. The mean white blood cell count is slightly higher as compared to the 20th-century normative values. The dynamics of changes in the mean white blood cell count are similar in all studies presented in the article, revealing a marked decrease by the third day of life as compared to the first and second days; however, 20th century data reveals even lower levels on the third day of life. Noteworthy is the decrease in the relative numbers of lymphocytes and band neutrophils with an increase in segmented neutrophils in this study as compared to the 1930, 1970, and 2012 studies.

Conclusion. The current mean values and reference intervals of hematologic parameters in healthy newborn babies differ from those presented in scientific studies and medical articles of the 20th century. This fact requires repeat analysis and establishment of new norms due to the increased sensitivity of analysis, the emergence of new procedures, and higher accuracy of equipment, as well as, potentially, due to changes in the maturity criteria and physical development indicators for newborns in the 21st century.

Background. Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) represents a new global health challenge, potentially affecting all organs, including the kidneys. Renal pathology has been observed more frequently in younger children and individuals with comorbidities. Acute kidney injury has been reported in some patients with urinary tract pathology triggered by COVID-19 at the time of hospital discharge.

Objectives. To investigate critical aspects of the cytokine profile in serum and urine of children aged 9 to 14 years with acute pyelonephritis, both in the context of COVID-19 and without it.

Methods. The observational cohort retrospective clinical study involved 28 children diagnosed with acute pyelonephritis from the Nephrology Department, Samarkand Regional Children’s Multidisciplinary Medical Center, Uzbekistan. The control group consisted of 14 healthy children undergoing routine medical examinations according to their age and/or seeking medical advice in the outpatient clinic. Laboratory analyses of biological samples were conducted at the clinical diagnostic laboratory of the institution where the children were treated and monitored, as well as at international multidisciplinary medical center Innova Expert (Samarkand) and the Central Scientific Research Laboratory of the Institute of Immunology and Human Genomics, along with the laboratory of the Gunchamed clinic (Tashkent). Participants were selected for the study from January 2021 to December 2022. Children with acute pyelonephritis were included in the study upon hospitalization and were divided into two groups based on their COVID-19 history: Group 1 (n = 14) consisted of children with acute pyelonephritis without a history of COVID-19, while Group 2 (n = 14) included patients recovering from COVID-19 with a convalescent period ranging from 3 weeks to 3 months. The primary outcome consisted in the assessment of the cytokine profile (interleukin-4, interleukin-6, tumor necrosis factor-alpha, and interferon-gamma) in serum and urine. A secondary outcome comprised the evaluation of renal function based on the condition of proximal and distal tubules. Statistical analysis of laboratory results was performed using Excel (Microsoft Office, 2016, USA) and StatPlus version 7 (AnalystSoft Inc., USA). The differences were considered statistically significant at p < 0.05.

Results. A statistically significant increase in the concentrations of interleukin-6, interleukin-4, tumor necrosis factor-alpha, and interferon-gamma was observed in urine samples. In Group 1, tumor necrosis factor-alpha levels were found to be 4.9 times higher and interferon-gamma levels were 11.0 times higher compared to the control group. In Group 2, these values exceeded those of healthy children by 8.8 and 14.8 times, respectively. Additionally, interleukin-4 levels in urine exceeded those of the control group by 4.7 times for Group 1 and by 5.6 times for Group 2. The analysis results indicate a significant role of interleukin-6 as an aggressive factor in the development of tubulointerstitial renal diseases, with its level in urine being increased by 37.9 times in children from Group 1 and by 47.1 times in patients from Group 2 compared to healthy children. A substantial growth in interleukin-6 levels even with less pronounced tubulointerstitial injury and a rise in its values as the tubulointerstitial injury grows suggest an increased cytokine excretion in urine due to tubular function impairment caused by SARS-CoV-2, leading to proximal tubular damage.

Conclusion. Controlling the course of latent lesions of tubular functions (screening study) in patients who have undergone COVID-19 implies studying the level of cytokines (interleukin-6, interferon-γ, tumor necrosis factor-α, interleukin-4) in urine, in order to determine the degree of proliferative changes in the tubulointerstitial tissue of the kidneys and forming risk groups of patients for chronicity of the process.

Background. Functional gastrointestinal disorders are highly prevalent among young children and pose a significant burden on outpatient healthcare services. Functional disorders of the gastrointestinal tract may be caused by increased intestinal permeability. Markers characterizing the transcellular pathway are currently being studied. Intestinal fatty acid-binding protein (I-FABP) serves as a marker of intestinal mucosal integrity, represents a cytosolic protein that plays a crucial role in intracellular transport and metabolism of fatty acids in enterocytes, and is released upon their death.

Objectives. To evaluate the diagnostic value of the intestinal fatty acid-binding protein as a marker for enteral tolerance in neonates with gestational ages ranging from 33 to 41 weeks.

Methods. A cross-sectional cohort study involved 115 newborns admitted to the second-stage care units of Voronezh Regional Children’s Clinical Hospital No. 1 from maternity facilities in Voronezh Oblast between March 2023 and May 2024. The cohort included boys n = 72, 62.6%; girls n = 43, 37.4%. The participants were divided into two groups: Group 1 consisted of term neonates (gestational age 37–41 weeks, n = 80), while Group 2 included preterm neonates (gestational age 33–36 weeks, n = 35). The age of term patients accounted for 5.0 [4.0; 7.0] days, while the age of preterm neonates was 7.0 [4.0; 8.0] days. I-FABP concentration was measured once using the Human IFABP/FABP2 ELISA kit on a Multiskan Go analyzer. Based on the presence of symptoms indicating impaired enteral tolerance during the neonatal period, the groups were further subdivided into Subgroups 1A (n = 39) and 2A (n = 10) without symptoms of reduced enteral tolerance, 1B (n = 41) and 2B (n = 25) with symptoms of reduced enteral tolerance. Statistical analysis was performed using StatTech v. 4.3.2 (Stattech, Russia). The differences were considered statistically significant at p <0.05.

Results. The circulating intestinal fatty acid-binding protein level in term neonates accounted for 1.130 [0.796–1.911] ng/ml, while in preterm neonates, it was 1.134 [1.050–1.614] ng/ml, showing no dependence on the type of feeding (p > 0.05). In term newborns without gastroenterological symptoms in the neonatal period, the concentration of I-FABP amounted to 0.920 [0.695–1.160] ng/ml, compared to 1.900 [0.965–2.564] ng/ml in those with gastrointestinal symptoms, (p < 0.001). A similar  tendency was observed in preterm neonates: those without clinical signs of reduced enteral tolerance had an I-FABP concentration of 1.002 [0.867 to 1.073] ng/mL versus 1.312 [1.102 to 1.972] ng/mL in neonates with gastroenterological symptoms (p = 0.002). The level of intestinal fatty acid-binding protein was associated with the degree of enteral tolerance: the highest values were noted in newborns with all three symptoms, measuring 2.802 [1,641–3.402] ng/ml.

Conclusion. Circulating intestinal fatty acid-binding protein during the neonatal period is independent of gestational age and feeding type but increases in neonates with gastrointestinal symptoms, suggesting that intestinal fatty acid-binding protein may serve as a biomarker for assessing enteral tolerance in neonates. Further investigation of intestinal fatty acid-binding protein may contribute to the development of decision-making tools for complex clinical situations, including the initiation and expansion of enteral nutrition in extremely preterm neonates or following an enteral pause, as well as in the differential diagnosis of early stages of surgical gastrointestinal pathology in newborns.

Background. Approximately 11.1% of children are born prematurely each year. Advances in modern neonatal care technologies have significantly improved the survival rates of newborns, including preterm infants, over the past few decades. However, despite the annual decrease in infant mortality, high risks of developing central nervous system pathologies among preterm infants still exist, including motor impairments, with cerebral palsy among them. Currently, the options for specific treatment of hypoxic perinatal lesions of the central nervous system in preterm infants are limited. Consequently, drawing up rehabilitation programs for preterm infants who have undergone neonatal resuscitation, taking into account diagnostic criteria, remains a pressing issue. 

Objectives. To determine the incidence of motor impairments in late preterm infants requiring neonatal intensive care by 18 months of corrected age, considering the levels of matrix metalloproteinase-2 (MMP-2) in serum at 40 weeks postmenstrual age.

Methods. A prospective cohort study was conducted on the basis of Children’s Regional Clinical Hospital, Krasonodar, Russia. Out of 215 preterm neonates born at 34–36 weeks of gestation who required intensive care after birth, 136 children with either high or low levels of matrix metalloproteinases-2  at 40 weeks postmenstrual age were included in the study. Group 1 consisted of 44 children with a matrix metalloproteinase-2 level greater than 350 ng/mL, while Group 2 comprised 92 children with a matrix metalloproteinase-2 level less than 160 ng/mL. The study assessed pregnancy history, delivery, neonatal period, neurological status, and neuroimaging data (neurosonography). At 18 months of corrected age, motor development was evaluated based on the Infant Neurological International Battery (INFANIB) score.

Results. No significant differences were observed in the course of pregnancy, delivery, neonatal period, or symptoms of perinatal lesions of the nervous system between the study groups, except for the incidence of chronic fetoplacental insufficiency (Group 1 — 81.8%, Group 2 — 42.4%, p < 0.05). No significant differences in neurological status at 40 weeks postmenstrual age were noted between the groups. Neurosonography revealed periventricular ischemia in all cases, while intraventricular hemorrhages and periventricular leukomalacia were more frequently recorded in Group 1 (intraventricular hemorrhages: Group 1 — 63.6%, Group 2 — 32.6%, p < 0.05; p < 0.05; periventricular leukomalacia: Group 1 — 40.9%, Group 2 — 15.2%, p < 0.05). Significant differences in motor development levels were identified by 18 months of corrected age. Cerebral palsy (68 points or fewer on the INFANIB scale) developed in 25% of Group 1 and in 3.3% of Group 2 (p < 0.05). Delayed motor development (69–81 points) was observed in 54.6% of Group 1 and in 27.2% of Group 2 (p < 0.05), while normal motor development (82 points or more) was recorded in 20.4% of Group 1 and in 69.5% of Group 2 (p < 0.05). Additionally, a statistically significant inverse correlation was of moderate strength according to Cheddok (ρ = –0.366; p < 0.001). In late preterm infants requiring intensive care after birth, those with high levels of MMP-2 at 40 weeks postmenstrual age were seven times more likely to develop cerebral palsy by 18 months of corrected age compared to those with low levels of MMP-2; they also experienced twice the incidence of delayed motor development and three times less frequent normal motor development.

Conclusion. The determination of matrix metalloproteinase-2 levels in serum at 40 weeks postmenstrual age will support the strategy for early intervention in cases of elevated matrix metalloproteinase-2 levels. This strategy will include dynamic monitoring by a neurologist and a comprehensive set of intensive rehabilitation measures (early initiation of active and passive kinesiotherapy, physiotherapy interventions, and, if necessary, pharmacological correction).

Background. Kikuchi-Fujimoto disease, also known as histiocytic necrotizing lymphadenitis, is characterized primarily by regional benign lymphadenopathy. The disease can occur at any age; however, it is more commonly observed in individuals aged 30–40. The exact etiology of the disease remains elusive. The cervical lymph nodes appear most frequently affected, while involvement of other lymph node groups is exceedingly rare. Diagnosis is confirmed through histological and immunohistochemical analysis of lymph node biopsy specimens. The differential diagnosis of Kikuchi-Fujimoto disease includes infectious lymphadenitis of various etiologies, autoimmune disorders, and lymphomas. A lymphadenopathy generally obtains favorable prognosis. Treatment primarily involves symptomatic therapy and, rarely, glucocorticosteroids.

A case report. The paper presents a clinical case of Kikuchi-Fujimoto disease in an 11-year-old girl with involvement of the mesenteric lymph nodes. The girl was hospitalized with the abdominal pain syndrome. Due to suspicion of acute appendicitis, a diagnostic laparoscopy was performed, revealing a conglomerate of enlarged mesenteric lymph nodes. Initial histological analysis of the lymph node biopsy suggested Hodgkin lymphoma. However, as the patient exhibited no typical clinical manifestations of lymphoma, a review of the biopsy material was conducted, leading to the diagnosis of Kikuchi-Fujimoto disease. Over six months following the discharge from the surgical department, the patient’s condition remained satisfactory, with no recurrence of abdominal pain syndrome and no new symptoms noted. Continued follow-up with a hematologist was recommended.

Conclusion. The presented clinical case illustrates the complexity of diagnosing a very rare form of lymphadenopathy due to the lack of experience in managing such patients and the specific histological features observed in the lymph node biopsy. At the clinic the patient presented an isolated lymphadenopathy of the mesenteric lymph nodes, while systemic inflammatory response, weight loss, hepatosplenomegaly, and alterations in peripheral blood analysis remained absent. Consequently, the diagnosis of Hodgkin lymphoma was questioned, thereby preventing unnecessary and aggressive treatment from being conducted.

Background. Hypersensitivity pneumonitis refers to a rare interstitial lung disease that requires differential diagnosis with a large spectrum of nosologies. However, the prevalence of hypersensitivity pneumonitis in the population remains unclear, partly due to low awareness among healthcare professionals of various specialties regarding this condition, as well as diagnostic challenges. Many authors emphasize the necessity of a detailed analysis of professional and environmental factors affecting the patient as one of the crucial steps in diagnosing hypersensitivity pneumonitis. The prognosis for hypersensitivity pneumonitis in children is more favorable than in adults, with complete clinical and functional recovery possible in most cases if the causative antigen is eliminated.

Case description. The paper presents data from a six-year observation of a 9-year-old girl. Within six months prior to her consultation, she developed respiratory complaints (shortness of breath, respiratory distress, fits of dry coughing), poor tolerance to physical exertion, and chronic weakness. She was monitored and treated for bronchial asthma by a pulmonologist without significant clinical improvement. Subsequently, specialists at a regional center conducted extensive work on differential diagnosis and verification of the disease through meticulous collection of anamnesis and clinical data and the use of modern laboratory and instrumental resources. Effective treatment was selected, and recommendations were given in order to correct influencing factors (change of residence and living conditions). A clear improvement in clinical, laboratory, and instrumental data was demonstrated over the observation period, with significant effects achieved within a year from the start of therapy. Improvements were noted in both volume and flow parameters on spirometry, with no restrictive disorders observed; the most indicative changes were revealed in the dynamics of high-resolution computed tomography.

Conclusion. The presented clinical case demonstrates the necessity of paying special attention to thorough history-taking and identifying potential causal factors. A distinctive feature of the disease consists in reversible symptoms, sustained remission, and a favorable prognosis under conditions of timely diagnosis, treatment, and removal of the causal factor.

Background. Type 1 diabetes mellitus refers to one of the most prevalent chronic diseases. In recent years, a steady growth in this nosology has been registered in the Russian Federation, as well as globally, particularly among children and adolescents. Consequently, the number of children and adolescents classified as disabled by type 1 diabetes mellitus is also rising, prompting the global medical community to focus on mitigating these issues. The primary treatment for type 1 diabetes mellitus involves insulin replacement therapy combined with self-monitoring of blood glucose levels. Currently, insulin pumps and devices for continuous glucose monitoring have been developed and implemented in clinical practice, enhancing the effectiveness of type 1 diabetes mellitus treatment and significantly improving the quality and expectation of lives. However, even hybrid closed-loop systems (a combination of continuous subcutaneous insulin infusion and continuous glucose monitoring) fail to achieve physiological regulation of blood glucose levels and to completely eliminate the risk of long-term complications.

Objectives. To explore the history of alternative preventive therapeutic methods for type 1 diabetes mellitus based on data from both Russian and international research literature.

Methods. A comparative analysis of literature from both Russian and international authors addressing the issues of therapy and prevention of type 1 diabetes mellitus was conducted using the scientometric database eLibrary. ru and the biomedical search engine PubMed.

Results. The search for alternative therapeutic methods that can prevent or delay the onset of the diabetes remains relevant. These therapeutic methods can be conditionally divided into conservative and surgical approaches,  primarily aimed at protecting pancreatic β-cells from immune-mediated destruction. Notable immunotherapeutic agents include antiproliferative agents, systemic immunomodulators, T-cell inhibitors, monoclonal antibodies, autoantigens, various types of stem cells, dendritic cells, and microbiota therapy.

Conclusion. The paper presents several experimental methods of preventive therapy for type 1 diabetes mellitus and the results of studies conducted in this area, describes the proposed mechanisms for establishing immunological tolerance. A brief overview of completed and ongoing clinical trials is provided.