[Peculiarities of blood coagulation disorders in patients with COVID-19].

AIM: To study the relationship of hemostatic disorders with inflammation and estimate their role in the course and outcomes of COVID-19. MATERIALS AND METHODS: We examined 215 consecutive patients with moderate and severe forms of acute COVID-19. The patients were on anticoagulants and immunosuppressive drugs. Hemostasis was assessed using the thrombodynamics assay, thromboelastography, fibrinogen and D-dimer levels, prothrombin time, and soluble fibrin-monomer complexes (ethanol gelation test). The hemostatic parameters were correlated with hematological and biochemical tests, including markers of inflammation (C-reactive protein, interleukins 6 and 8), as well as with the disease severity and outcomes. RESULTS: Laboratory signs of coagulopathy were revealed in the vast majority of the cases. Despite the use of low-molecular-weight heparins in the prophylactic and therapeutic doses, coagulopathy in COVID-19 manifested predominantly as hypercoagulability that correlated directly with the systemic inflammation and metabolic changes due to liver and kidney dysfunction. A direct relationship was found between the grade of coagulopathy and the severity of COVID-19, including comorbidities and the mortality. The chronometric hypocoagulability observed in about 1/4 cases was associated with a high level of C-reactive protein, which may decelerate coagulation in vitro and thereby mask the true inflammatory thrombophilia. Persistent hyperfibrinogenemia and high D-dimer in the absence of consumption coagulopathy suggest the predominance of local and/or regional microthrombosis over disseminated intravascular coagulation. CONCLUSION: The results obtained substantiate the need for laboratory monitoring of hemostasis and active prophylaxis and treatment of thrombotic complications in COVID-19.

[The use of the visuo-motor reaction training device for the improvement of the coordination in the eye-hand system of the children and adolescents following the completion of the antineoplastic treatment of brain tumours]. / Primenenie trenazhera zritel'no-motornoi korrektsii dlia uluchsheniia koordinatsii v sisteme glaz-ruka u detei i podrostkov posle zaversheniia protivoopukholevoi terapii novoobrazovanii golovnogo mozga.

The survivors among the children and adolescents with a brain tumour are likely to show evidence of the impairment of the most important cognitive functions, such as attention, visual-motor integration, and working memory, following the completion of the antineoplastic treatment. The basic characteristics of these functions compromised in the patients presenting with the most serious cognitive deficiency are the information processing rate and the time needed for carrying out any cognitive activity in the patients experiencing deficit of white matter in the brain. AIM: The objective of the present study was to demonstrate the possibility and the effectiveness of the application of the new method for the stimulation of the information processing activity of the brain, the enhancement of its effectiveness, and the improvement of the quality of the visual-motor coordination in the children and adolescents following the completion of the antineoplastic treatment of brain tumours. This paper reports the first experience of the application of the Dynavision d2 visuo-motor reaction training device which has been used for the visual-motor integration and the increase of the information processing speed. MATERIAL AND METHODS: The sample included in the study was comprised of a total of 46 children at the mean age of 10.6±3.34 years that had undergone the treatment of the brain neoplasm. Each patient participated in 5 to 8 sessions of exercises with the use of the the Dynavision d2 visuo-motor reaction training device during 21 days. RESULTS: All the treated patients exhibited the stable reduction of the mean time of the reaction from the first session to the last one. The comparison of the outcomes of the treatment between the children of different sexes has demonstrated better results (in absolute terms and in dynamics) in the girls in comparison with the boys. The exercises with the use of the Dynavision d2 visuo-motor reaction training device were not accompanied by any negative subjective sensations in the treated patients, nor did they induce the adverse somatic side effects. CONCLUSION: The results of the present study give evidence of both the applicability and the effectiveness of the application of the Dynavision d2 visuo-motor reaction training device for the diagnostics of the disturbances in the motor and visual coordination and the associated cognitive functions and for their correction in the children following the treatment of the neoplasm of the posterior cranial fossa.

[Humoral regulation of nutritional status in children].

The purpose of the research was the investigation of the characteristics of insulin resistance, levels of adipokines, myokines and collagen metabolites type I in children in orphanages and social rehabilitation centers (SRC). The study involved 69 children aged 7-12 years. The first group consisted of 20 children from SRC, the second - 16 children living in orphanages, control group included 33 children (1-2 health groups) from wealthy families. The average length of stay of children in SRP was 1.0 (0.5-2.5) month, in orphanages - 38 (22-44) months. The groups were comparable in age and sex. Anthropometric indices were determined, in blood serum glucose concentration was measured by glucose oxidase method, blood serum level of insulin, cortisol, leptin, adiponectin, resistin, apelin, myostatin, collagen metabolites were determined by ELISA. Children from orphanages and SRC had significantly lower anthropometric indices in comparison with the control group. Particularly low parameters were observed in children from SRP, which in growth, body weight, chest circumference and body mass index significantly lagged behind the control group peers. The children from SRP as compared with the control group revealed higher insulin resistance index (3.33±0.49 vs 2.29±0.29, p<0.05) and cortisol level (405.21±38.21 vs 313.08±25.97 nmol/l, p>0.05). There were changes (p<0.05) in blood serum content of adipokines - reduced leptin level (5.35±1.55 vs 14.00±3.10 ng/ml) and increased apelin level (4.07±0.82 vs 2.19±0.41 ng/ml), as well as higher levels (p<0.05) of myostatin (183.95±16.3 vs 116.4±9.4 ng/ml) and C-terminal telopeptide of type I collagen (1.11±0.11 vs 0.72±0.08 ng/ml). The children in orphanages compared with the control group had lower levels of insulin (5.04±0.69 vs 11.3±1.12 µIU/ml), high insulin sensitivity - HOMA-IR was 1.01±0.16. The children in orphanages have even more pronounced reduction in leptin concentration (2.69±0.4 ng/ml), a decrease of resistin (4.99±0.32 vs 7.16±0.70 ng/ml, p<0.05), increased concentration (p<0.05) of apelin (3.53±0.67 ng/ml), myostatin (181.17±10.2 ng/ml) and C-terminal telopeptide of type I collagen (2.70±0.22 ng/ml). Features of hormone and cytokine regulation of metabolism make it particularly urgent to prevent disorders of eating behavior and to promote a healthy lifestyle among children left without parental care.

[Age-related characteristics of the efficacy of different glucocorticosteroids in the therapy of acute lymphoblastic leukemia].

AIM: To determine predictors for decision-making on a differential approach to choosing glucocorticosteroids (GCS) for children and adolescents with acute lymphoblastic leukemia (ALL). SUBJECTS AND METHODS: The analysis covered 1064 primary patients aged to 1 to 18 years with ALL who had been registered at the clinics of Russia and Belorussia in April 2002 to November 2006. Before induction therapy, the patients were randomized into a dexamethasone (DEXA) 6 mg/m2 group (n=539) and a methylprednisolone (MePRED) 60 mg/m2 one (n=525). RESULTS: The entire group showed no statistically significant differences in survival rates between the patients receiving DEXA or MePRED. However, an analysis of age groups revealed the benefits of DEXA in children younger than 14 years (the event-free survival (EFS) was 76±2 and 71±2%, respectively (p=0.048); the overall survival (OS) was 81±2 and 77±2%, respectively (p=0.046); therapy-induced mortality was 6.4% (DEXA) andl 1.1% (MePRED) (p=0.01 4); the rate of isolated extramedullary relapses was 1.5% (DEXA) and 4.4% (MePRED) (p=0.009). At the same time, EFS and OS in 14-to-18-year-old adolescents were statistically significantly higher than in those who used MePRED (EFS, 65±6 and 52±6%, respectively (p=0.087); OS, 72±6 and 61±6%, respectively; (p=0.l 7). CONCLUSION: The findings suggest that it is possible that the choice of a GCS for ALL therapy must be also based on a patient's age. There is a need for further studies of this matter in prospective randomized multicenter trials in children and adolescents.

[Quality of life and socio-medical consequences in adolescent and young adult survivors following treatment for Hodgkin's lymphoma].

Between 1997 and 2008, 97 adolescents and young adults with a median age 18.9 years (range, 15.0-33.6) with all stages Hodgkin's lymphoma (HL) were treated by a pediatric protocol DAL-HD-90m. The 12-year event-free survival and overall survival was 73.4 ± 4.8% and 81.5 ± 4.7% respec- tively. The frequency of secondary malignancies was 2.1%. In the study of quality of life (QOL), 47 patients were included with duration of complete remission at least 5 years who had no relapses and other adverse events. The median age of the patients at the time of testing was 28.0 years (range, 23.2- 41.0). Reference values of age-adjusted 85 healthy volunteers were used for comparison. The QOL was measured through the questionnaire EORTC QLQ-C30. In total, the QOL of survivors was comparable to that of our control and reference values of EORTC. The only factor that influenced the QOL of long-term survivors was the presence or absence of their children. Among patients who did not have their own children was increased activity of the fatigue (+14.4 points; p = 0.035), insomnia (+25; p = 0.003) and anorexia (+16.7; p = 0.009). The deficit on the overall QOL score was -14.6 points (p = 0.005).

[Efficacy and tolerance of coamoxiclav in community-acquired lower respiratory tract infections in children]. / 'Effektivnost' i perenosimost' amoksitsillin/potassium klavulanata pri lechenii detel s vnebol'nichnol infektsiel nizhnikh dykhatel'nykh putel.

Amoxyclav (amoxycillin/potassium clavulanate, A/PC) was used in the treatment of 55 children with acute bronchitis and pneumonia. The drug was administered in a dose of 20-40 mg/kg body weight a day in 3 portions. The treatment course was 4 to 10 days. The treatment was performed under careful clinicoroent-genologic control. The clinical picture of the disease in the children was characterized by a moderate process which made it possible to treat the children as outpatients. The clinical efficacy amounted to 90.5 per cent. The isolates of Streptococcus pneumoniae, Streptococcus pyogenes, Staphylococcus aureus and Haemophilus influenzae proved to be susceptible to A/PC. It may be used as the 1st class agent in the treatment of children with lower respiratory tract infection.

Low Density Mononuclear Cells from Umbilical Cord Blood as a Target for Retrovirally Mediated Gene Transfer.

Umbilical cord blood has been intensively studied as a source of hematopoietic stem cells for transplantation as well as the target for gene therapy. In this study we used a single step density separation to obtain a light density mononuclear cells. The isolated cell population was significantly enriched with progenitor cells. The population also contained sufficient number of primitive hematopoietic stem cells, allowing expansion of cells in serial culture with the addition of IL-6, G-CSF, Epo and kit-ligand and long-term hematopoiesis on preliminary formed stromal layer. Addition of cytokines resulted in a significant increase of cell proliferative activity that is a susceptible target for retrovirally mediated gene transfer. Retroviral transduction with a mutated human dihydrofolate reductase gene assured a significant increase in metatrixate resistance of CFU-GM and selective growth advantage for the transduced cell population. Our data indicate that enriched mononuclear cell population from cord blood can reach high level of metatrixate resistance and is capable of generating a high amount of both drug-resistant progenitors and mature cells.

Beta-thalassemia alleles and unstable hemoglobin types among Russian pediatric patients.

A recently initiated collaboration between Russian and American institutions has resulted in the characterization of several known or new beta-thalassemia alleles and unstable hemoglobin types. Nine known beta-thalassemia alleles were present which have also been found in Mediterranean, East Asian, and Black populations; the possibility of independent mutations for some of the rare alleles should be considered. Hb Durham-N.C./Brescia with a codon 114 (CTG-->CCG; Leu-->Pro) change was present in six members of two families. This condition and two new variants have the characteristics of a dominant type of beta-thalassemia heterozygosity with moderate anemia, Heinz body formation, splenomegaly, etc. One new beta-thalassemia allele is a frame-shift at codon 124 (-A), while another is characterized by the introduction of an extra proline residue (codon: CCA) between residues Thr (beta 123) and Val (beta 126) to give the sequence -Thr-Pro-Pro-Pro-Val-.

Long-term remission in acute lymphoid leukemia patients on maintenance chemoimmunotherapy.

Comparative effectiveness of maintenance chemo- and chemo-immunotherapy with Soviet strain of BCG vaccine was studied on 75 children with acute lymphoid leukemia (ALL). The patients were divided in two groups: I -- 25 patients received maintenance chemotherapy plus BCG; II -- 50 patients were given sole form of maintenance chemotherapy. Median duration of remission in the group I -- 36.3 +/- 4.2 months; in the group II -- 13.8 +/- 1.9 (p less than 0.001); median duration of life -- 45.1 +/- 3.7 and 23.9 +/- 3.3 (p less than 0.001) respectively. In 6 out of 25 patients (group I) the first complete remission continues for more than 6 years (median duration of remission -- 82.5 and life -- 85.3 months). In the group II the first remission continues only in 1 patient out of 50.