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Background: The pathogenesis of acne is multifactorial, and it was traditionally believed that four different processes play a decisive role in the development of the disease: the increased production of sebum, changes in keratinization processes leading to the formation of comedones, bacterial colonization of hair follicles by Cutibacterium acnes (C. acnes; formerly called Propionibacterium acnes), and synthesis of pro-inflammatory mediators in the pilosebaceous unit. The role of genetic factors in the development of acne has been repeatedly discussed and continues to be the subject of discussion among scientists. The currently available data from various studies on genetic associations in acne are contradictory, which makes it relevant to address the problem of searching and analyzing the molecular mechanisms of the influence of regulatory genes in the pathogenesis of acne. The aim of this study was to identify and analyze SNPs in the regulatory genes (GATA1, GATA2, GATA2-AS1 [GATA2 Antisense RNA 1], NFKB2, NFKBIA, and NFKB1) in patients with severe acne. Methods and Results: A prospective, open, non-randomized, single-center comparative study was conducted between 2017-2020. The study included 50 (29 men and 21 women) patients (the main group [MG]) with severe acne aged from 15 to 46 years (the median age of 23.2 years) and 20 (13 men and 7 women) apparently healthy individuals (the comparison group [CG]) aged from 16 to 40 years (the median age of 19.4 years). Molecular genetic diagnostics was performed using high-throughput DNA sequencing—next-generation sequencing (NGS). The results of our study made it possible to identify SNPs in regulatory genes (GATA1, GATA2, GATA2-AS1 [GATA2 Antisense RNA 1], NFKB2, NFKBIA, and NFKB1) associated with the development of severe acne. Conclusion: The revealed SNPs within the GATA1, GATA2, GATA2-AS1 [GATA2 Antisense RNA 1], NFKB2, NFKBIA, and NFKB1 genes in patients with severe acne probably indicate the involvement of regulatory transcription factors in the pathogenesis of acne.

Background: At the present moment, an urgent and unresolved problem is the search for a method to diagnose disorders of the hemostasis system in patients with the new coronavirus infection. The integral tests, in particular, the thrombodynamics test, will presumably make it possible to monitor changes in blood clotting, and predict the course of the disease in patients with COVID-19. Aims: To comparatively assess the plasma hemostasis parameters and results of the thrombodynamics test in patients with COVID-19 viral infection of different severity. Methods: The study included 96 patients with a confirmed diagnosis of COVID-19, admitted to a hospital for infectious diseases on the base of the V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology, and Perinatology in the period from April 23, 2020, to June 20, 2020, and discharged at the end of treatment. SARS-CoV-2 was identified by PCR. The patients were stratified by the severity into 3 groups: mild course (n=25), moderate course (n=54), severe course (n=17). The diagnostics and treatment of patients were carried out in accordance with the Temporary Methodological Recommendations of the Ministry of Health of the Russian Federation for the prevention, diagnosis and treatment of the new coronavirus infection, versions 5, 6, 7. In the course of the treatment, the patients were assessed for APTT, prothrombin %, prothrombin time (PT) and thrombin time, fibrinogen, D-dimer, platelet count, and the thrombodynamic test parameters (V/Vi/Vst, Tlag, Cs, D). Results: Significant differences were observed in the thrombin time, D-dimer, platelet count, and the thrombodynamic parameters of V/Vst, Cs, and D taken before admission and a week after admission. We found a relationship between the parameters of hemostasis (fibrinogen concentration, PT, prothrombin %, APTT, Tlag, D) and the duration of hospital stay. There was a positive relationship between the content of fibrinogen and D (r=0.6307, p 0.0001) and a strong positive relationship between PT and Tlag (r=0.7499, p 0.0001). Conclusions: The thrombodynamics test can be recommended as a potential tool for a personalized approach to monitoring the hemostasis system and treating patients with COVID-19.

IntroductionThe J Project (JP) physician education and clinical research collaboration program was started in 2004 and includes by now 32 countries mostly in Eastern and Central Europe (ECE). Until the end of 2021, 344 inborn errors of immunity (IEI)-focused meetings were organized by the JP to raise awareness and facilitate the diagnosis and treatment of patients with IEI.ResultsIn this study, meeting profiles and major diagnostic and treatment parameters were studied. JP center leaders reported patients’ data from 30 countries representing a total population of 506 567 565. Two countries reported patients from JP centers (Konya, Turkey and Cairo University, Egypt). Diagnostic criteria were based on the 2020 update of classification by the IUIS Expert Committee on IEI. The number of JP meetings increased from 6 per year in 2004 and 2005 to 44 and 63 in 2020 and 2021, respectively. The cumulative number of meetings per country varied from 1 to 59 in various countries reflecting partly but not entirely the population of the respective countries. Altogether, 24,879 patients were reported giving an average prevalence of 4.9. Most of the patients had predominantly antibody deficiency (46,32%) followed by patients with combined immunodeficiencies (14.3%). The percentages of patients with bone marrow failure and phenocopies of IEI were less than 1 each. The number of patients was remarkably higher that those reported to the ESID Registry in 13 countries. Immunoglobulin (IgG) substitution was provided to 7,572 patients (5,693 intravenously) and 1,480 patients received hematopoietic stem cell therapy (HSCT). Searching for basic diagnostic parameters revealed the availability of immunochemistry and flow cytometry in 27 and 28 countries, respectively, and targeted gene sequencing and new generation sequencing was available in 21 and 18 countries. The number of IEI centers and experts in the field were 260 and 690, respectively. We found high correlation between the number of IEI centers and patients treated with intravenous IgG (IVIG) (correlation coefficient, cc, 0,916) and with those who were treated with HSCT (cc, 0,905). Similar correlation was found when the number of experts was compared with those treated with HSCT. However, the number of patients treated with subcutaneous Ig (SCIG) only slightly correlated with the number of experts (cc, 0,489) and no correlation was found between the number of centers and patients on SCIG (cc, 0,174).Conclusions1) this is the first study describing major diagnostic and treatment parameters of IEI care in countries of the JP; 2) the data suggest that the JP had tremendous impact on the development of IEI care in ECE; 3) our data help to define major future targets of JP activity in various countries; 4) we suggest that the number of IEI centers and IEI experts closely correlate to the most important treatment parameters; 5) we propose that specialist education among medical professionals plays pivotal role in increasing levels of diagnostics and adequate care of this vulnerable and still highly neglected patient population; 6) this study also provides the basis for further analysis of more specific aspects of IEI care including genetic diagnostics, disease specific prevalence, newborn screening and professional collaboration in JP countries.

Background: Acne is a multifactorial disease, in the pathogenesis of which one of the leading factors is the excessive effect of androgens on the hair follicles (HFs) and sebaceous glands (SGs), along with hypersecretion of sebum, pathological follicular hyperkeratosis and an inflammatory response. The search for genotypic markers in patients with varying severity of acne is a difficult task due to the multifactorial pathogenesis and the role of trigger factors in the formation of acne. The aim of this study was to determine SNPs within 3 genes involved in steroidogenesis (MVK, ARPC1B, and CA2) in patients with severe acne. Methods and Results: The study included 70 patients (42 men and 28 women) aged between 15 and 46 years (the median age - 22.1 years). The main group (MG) included 50 patients (29 men and 21 women) with severe acne. The control group (CG) consisted of 20 apparently healthy individuals (13 men and 7 women). Molecular-genetic diagnostics was carried out by the method of high-throughput DNA sequencing (next-generation sequencing). Our study showed that severe acne is associated with 12 polymorphic loci of the MVK gene (4 SNPs in exons and 8 SNPs in introns), 7 SNPs of the ARPC1B gene (2 SNPs in exons and 5 SNPs in introns), and 9 SNPs of the CA2 gene (3 SNPs in exons and 6 SNPs in introns). Conclusion: The revealed features of the SNPs within the MVK, ARPC1B, and CA2 genes in patients with severe acne probably indicate a hereditary determination of steroidogenesis in acne.

A vertically integrated management system in the health care sector in the Russian Federation is based on the model of functioning of national centers. One of the key components in achieving success is the interaction of national center with a leading national professional society. The aim of the article is to present the experience of joint work of the National Society of Pediatric Hematologists and Oncologists (NSPHO) with the leading centers of excellence in pediatric cancer care in Russia in the field of development of pediatric oncology-hematology in Russia. In order to accomplish the task of building a system of pediatric oncology-hematology care, a comprehensive development program was implemented, which included collecting data on the structure of the regional services and improvement of these services. Experience of creating of professional standards and the concept of a unified approach of training in pediatric oncology and hematology using the technology of continuing medical education are reflected. Other projects of NSPHO are represented too.

For the first time, the influence of COVID-19 on blood microrheology was studied. For this, the method of filtering erythrocytes through filters with pores of 3.5 μm was used. Filterability was shown to significantly decrease with the increasing severity of the patient’s condition, as well as with a decrease in the ratio of hemoglobin oxygen saturation to the oxygen fraction in the inhaled air (SpO2/FiO2). The filterability of ≤ 0.65, or its fast decrease during treatment, were indicators of a poor prognosis. Filterability increased significantly with an increase in erythrocyte count, hematocrit and blood concentrations of hemoglobin, albumin, and total protein. The effect of these parameters on the erythrocyte filterability is directly opposite to their effect on blood macrorheology, where they all increase blood viscosity, worsening the erythrocyte deformability. The erythrocyte filterability decreased with increasing oxygen supply rate, especially in patients on mechanical ventilation, apparently not due to the oxygen supplied, but to the deterioration of the patients’ condition. Filterability significantly correlates with the C-reactive protein, which indicates that inflammation affects the blood microrheology in the capillaries. Thus, the filterability of erythrocytes is a good tool for studying the severity of the patient’s condition and his prognosis in COVID-19.

Introduction: Primary immunodeficiencies (PID) are a group of rare genetic disorders with a multitude of clinical symptoms. Characterization of epidemiological and clinical data via national registries has proven to be a valuable tool of studying these diseases.Materials and Methods: The Russian PID registry was set up in 2017, by the National Association of Experts in PID (NAEPID). It is a secure, internet-based database that includes detailed clinical, laboratory, and therapeutic data on PID patients of all ages.Results: The registry contained information on 2,728 patients (60% males, 40% females), from all Federal Districts of the Russian Federation. 1,851/2,728 (68%) were alive, 1,426/1,851 (77%) were children and 425/1,851 (23%) were adults. PID was diagnosed before the age of 18 in 2,192 patients (88%). Antibody defects (699; 26%) and syndromic PID (591; 22%) were the most common groups of PID. The minimum overall PID prevalence in the Russian population was 1.3:100,000 people; the estimated PID birth rate is 5.7 per 100,000 live births. The number of newly diagnosed patients per year increased dramatically, reaching the maximum of 331 patients in 2018. The overall mortality rate was 9.8%. Genetic testing has been performed in 1,740 patients and genetic defects were identified in 1,344 of them (77.2%). The median diagnostic delay was 2 years; this varied from 4 months to 11 years, depending on the PID category. The shortest time to diagnosis was noted in the combined PIDs—in WAS, DGS, and CGD. The longest delay was observed in AT, NBS, and in the most prevalent adult PID: HAE and CVID. Of the patients, 1,622 had symptomatic treatment information: 843 (52%) received IG treatment, mainly IVIG (96%), and 414 (25%) patients were treated with biological drugs. HSCT has been performed in 342/2,728 (16%) patients, of whom 67% are currently alive, 17% deceased, and 16% lost to follow-up. Three patients underwent gene therapy for WAS; all are currently alive.Conclusions: Here, we describe our first analysis of the epidemiological features of PID in Russia, allowing us to highlight the main challenges around PID diagnosis and treatment.

This study was aimed to systematize magnetic resonance imaging (MRI) presentation of toxic leukoencephalopathy, to find the correlation between method of central nervous system (CNS) leukemia prevention and changes on MRI, to find relationship between existence leukoencephalopathy on imaging and neurocognitive deficits in pediatric patients after anti-leukemic therapy. Brain MRI data of 48 children, who underwent a therapy course according to the ALL-MB intermediate risk protocol, was evaluated. In accordance with two arms of this protocol, they received either radiation therapy, or additional intrathecal administration of chemotherapeutic agents as a prevention of CNS leukemia. Also, neurocognitive tests were performed. According to the results of the performed investigation, 10 (50%) out of 20 children, who received cranial irradiation and 18 (66.6%) out of 27 patients, who received only intrathecal therapy demonstrated abnormal brain changes (leukoencephalopathy) according to MRI data. Leukoencephalopathy was mostly presented by diffuse zones and localized predominantly in the frontal and temporal lobes. There was no correlation between method of CNS prevention and the existence of leukoencephalopathy on MRI. The analysis of our data did not show significant differences in brain damage and severity of cognitive impairment depending on the type of prevention of CNS leukemia. Moreover, in this study no statistical correlation was found between leukoencephalopathy on MRI and neurocognitive impairment according to clinical tests data. Further long-term prospective studies and examinations should be performed to assess late neurotoxic effects.

COVID-19 patients with acute respiratory distress syndrome (ARDS) have an immune imbalance when systemic inflammation and dysfunction of circulating T and B cells lead to a more severe disease. Using TREC/KREC analysis, we studied the level of mature naive T and B cells in peripheral blood of COVID-19 patients and its relationship with clinical and laboratory data. TREC/KREC analysis was performed by multiplex real-time quantitative PCR on a sample of 36 patients aged 45 years or younger. The reduced TREC/KREC level was observed in ARDS patients compared with non-ARDS patients, and similar results were found for the deceased patients. During days 6 to 20 of hospitalization, a higher neutrophil-to-lymphocyte ratio (NLR) was detected in ARDS patients compared with non-ARDS patients. TREC/KREC negatively correlated with NLR; the highest correlation was recorded for TREC per 100,000 cells with the coefficient of determination R2 = 0.527. Thus, TREC/KREC analysis is a potential prognostic marker for assessing the severity and outcome in COVID-19.

Background: Premature infants have a high risk of bacterial infections facilitated by the immaturity of their immune system.Objective: Our aim was to study the expression of Fc-gamma receptors of neutrophils and the possibility of its modulation in preterm infants (with a low, LBW, very low, VLBW and extremely low, ELBW, birth weight) with bacterial infection.Methods: We examined cord blood samples, as well as peripheral venous blood samples of newborns taken at 28–30th day of life. The flow cytofluorometry method was used to determine the level of surface expression of Fc-gamma receptors by neutrophils (CD64, CD32, CD16), phagocytic activity and oxygen burst of granulocytes stimulated with fluorescently labelled Escherichia coli. Results: We examined blood samples of 10 full-term infants, 20 preterm infants with LBW, 18 preterm infants with VLBW and ELBW. CD64 expression in preterm infants at birth was higher than in full-term children and made 6.0 (5.3; 9.8), 7.1 (5.1; 11.5), and 4.27 (2.4; 5.8) MFI respectively (p = 0.013). CD16 expression in preterm infants, in contrast, was lower: 99.7 (71.3; 126.0) and 80.9 (58.7; 114.8), and 125.3 (95.5; 144.1) MFI respectively (p = 0.021). By the end of the 1st month of life, CD16 expression of peripheral blood neutrophils in preterm infants increased to 126.6 (110.1; 129.0) MFI in children with LBW and to 118.5 (99.5; 132.2) MFI — in children with VLBW/ELBW. CD32 expression in compared groups did not differ. A correlation between the intensity of the oxygen burst of neutrophils and gestational age was established (r = 0.67; p