Vol 49, No 3 (2021)

B7-H3, also called CD276, is a type I transmembrane glycoprotein that is encoded on human chromosome 15. It was discovered back in 2001. The original study described it as a positive co-stimulant, as it can stimulate T-cell response and IFN-y production. However, recent researches have shown that B7-H3 is involved in T-cell inhibition. A B7-H3 receptor has not been yet identified, and this may explain the complex immunomodulatory activity of B7-H3, as it can have more than one binding partner with different functions. Expression of the B7-H3 protein has been found on activated immune cells such as T-cells, NK cells and antigen presenting cells. Interestingly, it is overexpressed in a wide range of tumor cells and is associated with disease progression and outcome. The soluble form of this protein is also of particular interest. Increased sB7-H3 levels in the plasma of bone tumor patients might be their important diagnostic criterion.

Rationale: Ovarian cancer is the leading death cause in gynecological malignancies. More than 70% of the patients are diagnosed with progressing disease extending to outside the true pelvis. The 5-year survival of ovarian cancer patients remains low (about 47%) due to frequent relapses and drug resistance. Identification of markers for early diagnosis and relapse prediction could improve the outcomes of the disease.

Aim: To assess relative copy number of cancer-associated genetic loci c-Myc, CDK12, CDKN1B, PRPF19, ERBB2, DDB1, GAB2, COL6A3 in the tumor cells of ovarian cancer, in order to identify potential prognostic oncomarkers in ovarian cancer patients.

Materials and methods: The study included 50 women aged 27 to 70 years with ovarian cancer T1-3cN0-1M0-1, Gr. 2 (stages I—IV), who received their elective treatment in the National Medical Research Centre for Oncology in 2015 to 2019. The study was based on samples of genomic DNA from paraffinized blocks of tumor and “healthy” tissues. Relative copy numbers of 8 genetic loci (c-Myc, CDK12, CDKN1B, PRPF19, ERBB2, DDB1, GAB2, COL6A3) was assessed by RT-qPCR technique. Relative copy quantitation of a genetic locus was calculated as 2^-ΔCt. The dose of the locus studied was considered equal to diploid set (2n) if RCQ_{tumor/healthy} was about 1. If RCQ_{tumor/healthy} was > 1.5 or < 0.5, then the locus dose was considered increased (≥ 3n) or decreased (≤ 1n), respectively.

Results: For all genetic loci, an increase of relative copy quantitation in the ovarian tumor cells was observed compared to that in “healthy” tissues. There was a significant (р<0.05) aberrant copy quantitation of 4 genes: c-Myc (р = 0.001), DDB1 (р = 0.002), PRPF19 (р = 0.0001), and CDKN1B (р = 0.001). We identified differential thresholds for these genes that made it possible to predict an unfavorable disease course in the patients (р < 0.05). The strongest association with the risk of adverse outcomes was found for increased copy number of PRPF19 (odds ratio (OR) 7.3; р = 0.0001) and c-Myc (OR 6.8; р = 0.001).

Conclusion: In this study, we determined the prognostic value of 4 oncogenic drivers, namely, DDB1, PRPF19, CDKN1B, and с-Myc, whose increased copy number was associated with an adverse disease prognosis in ovarian cancer patients.

Aim: To assess clinical and epidemiological characteristics, as well as treatment results in COVID-19 pediatric patients hospitalized to the Department of infectious disease in the Moscow region. Materials and methods: We retrospectively analyzed medical records of 124 pediatric patients aged from 1 month to 17 years with confirmed (63.7%) and highly probable (proven epidemiological association with the infection source) COVID-19 infection. The children were hospitalized from March 25, 2020 to August 11, 2020. Among patients that were hospitalized during this time period, 43% had pneumonia and 30% had acute respiratory disorders. All cases of pneumonia were confirmed by computed tomography. The children were treated according to the standard Russian guidelines.

Results: The children had been infected with SARS-CoV-2 mostly from family members (75%; 95% confidence interval (CI) 66.4-82.3). In the families of the children with pneumonia, the number of pneumonia cases in their relatives was higher than in the families of the children with acute respiratory infections (1.7 ±1.0 vs. 1.1 ± 0.5 respectively; р < 0.001). The mean age of the hospitalized children was 8 years (7.4-9.6), with an even age distribution. The main COVID-19 signs and symptoms were as follows: fever (75.8%; 95% CI 67.3-83.0), cough (66.1%; 95% CI 57.1-74.4]), fatigues (38.7%; 95% CI 30.1-47.9), and hyposmia (33.9%; 95% CI 25.6-42.9). The severe disease course was rare (2.4%; 95% CI 0.5-6.9). The rates of positive reverse transcriptase polymerase chain reaction tests for SARS-CoV-2 were rapidly decreased at repeated tests: at day 3, 63.7% of the tests were positive, at day 7, 21.8% and at day 14, 5.6% (р < 0.001). The prevalence of pneumonia was 56.4% without any age differences, with mostly minimal areas of lung abnormalities (78.6%). The severity of pneumonia and duration of clinical manifestations in the patients treated with a III generation cephalosporin or its combination with a macrolide were similar. Cough duration in those, who were treated with ipratropium bromide / fenoterol inhalations including their combination with budesonide, was higher than in those who did not use inhalation treatment. Pyrexia of > 5 days duration can be a predictor of pneumonia in a pediatric patient with COVID-1 9 (odds ratio 4.55 (2.1-9.9), sensitivity 61.4%, specificity 74.1%).

Conclusion: The results obtained are important to develop further treatment strategies for children with COVID-1 9.

Rationale: Cystic fibrosis is a common monogenic disease related to pathogenic nucleotide sequence variants in the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) (ABCC7) gene. The CFTR gene consists of 27 exons and is located in the 31.1 region on the long arm of chromosome 7 (7q31.1). The use of the sequencing method has led to the accumulation of new information about the diversity of genetic variants in cystic fibrosis. This information is important considering approaches to the development of targeted therapy for the disease, based on an individual genotype. No targeted therapy has been developed for the N1303K class II genetic variant. The function of the chloride channel in this mutation has not been compared with that in class II mutations like F508del.

Materials and methods: We have analyzed medical files of a patient with cystic fibrosis and F508del/N1303K CFTR genotypes, including the results of rectal biopsy samples. The assessments included measurement of the intestinal potential difference and forskolin-induced swelling assay (FIS) in rectal organoids, with the results being analyzed in relation to the clinical data.

Results: The results of intestinal current measurements (ICM) confirm that the N1303K genetic variant is “severe” and leads to the loss of the working CFTR protein, which is consistent with the clinical manifestations. The mean short circuit currency density (ΔISC) in response to amiloride (sodium channel stimulation) was -39 ± 1.22 µA/cm², to forskolin (chloride channel stimulation) 3.83 ± 1.43 µA/cm², to carbachol 6 ± 2.47 µA/cm², and to histamine 8.5 ± 3.02 µA/cm².

FIS results indicate that the VX-770 potentiator and the VX-809 corrector have a weak effect on the stimulation of organoids by forskolin in the genetic variant N1303K: organoid swelling was non-significant (about 20% from their baseline size).

Conclusion: The use of the ICM method and FIS assay in human intestinal organoids makes it possible to quantify the work of the CFTR protein and determine the in vitro effectiveness of targeted therapy in patients with cystic fibrosis. CFTR modulators are ineffective in patients with N1303K mutation in the compound-heterozygous condition with F508del, despite both pathogenic variants belong to class II.

Car accidents are the main cause of trauma during pregnancy. Even a non-severe accident is associated with a high risk of injury and unfavorable outcome for the fetus, especially in the event of placental abruption. Major agents leading to a trauma could also include safety belt and safety airbags. Blunt abdominal trauma during a car accident is associated with such type of intrauterine injury as fetal skull fractures and various intracranial hemorrhages. Despite a common viewpoint on relatively high death rates in this population, it is not infrequent that fetal trauma has a favorable outcome without any clinically significant neurological deficiency.

The paper presents an analysis of the main outcomes of intrauterine brain injury and associated factors. As an illustration, we describe a case of a car accident related brain injury to a fetus at 38 week of gestation, with skull fracture, brain contusion, and subarachnoidal, epidural and subdural, parenchymal and intraventricular hemorrhages induced by the safety belt, with the mother being virtually uninjured. After treatment, the patient was discharged from the hospital in a satisfactory state, without clinically significant neurological symptoms and signs. A 8-months follow-up of the infant showed some delay in brain maturation manifesting as benign epileptiform discharges of childhood and magnetic resonance imaging patterns.

It is highly likely, that the leading factors ensuring a favorable outcome of a intrauterine severe brain trauma (without fatal trauma to the mother and fetus) are as follows: correct obstetric strategy, late gestational age and absence of a massive parenchymal and/or intraventricular bleeding. After the short-term clinical recovery from a severe intrauterine brain trauma and in addition to it, proper follow-up of the child is essential because of a high risk of long-term cerebral and functional abnormalities, mostly paroxysmal, behavioral and cognitive.

Demyelinating diseases (DD) are autoimmune disorders that morphologically manifest mainly with myelin destruction in the central nervous system (CNS). Recently, there has been a continuous increase in DD of the CNS, including those in the pediatric population. Despite the active development of strategies for the diagnosis of DD and verification of its forms, the differential diagnosis of DD and other diseases associated with abnormalities in the brain white matter structure on magnetic resonance imaging continues to be problematic. We examined 123 patients with suspected DD CNS. The diagnosis was confirmed in 102 of them. The most common form of DD CNS was multiple sclerosis found in 79 of 102 subjects. Much less frequent were anti-MOG-associated disorders (5 patients), neuromyelitis optica spectrum disorders (3 patients), and acute disseminated encephalomyelitis (2 patients). The main clinical, laboratory and neuroimaging characteristics of each of these disorders and the main difficulties in the treatment of pediatric patients with DD CNS are described.