Pleuropulmonary blastoma (PPB) is the most common primary lung tumor of infants and young children and is known to be associated with pathogenic variants in the DICER1 gene. In addition to PPB,  DICER1-associated conditions include a variety of other benign and  malignant tumors including cystic nephroma and Wilms tumor, ovarian  Sertoli-Leydig cell tumor and gynandroblastoma, multinodular goiter  and thyroid carcinoma and certain childhood brain tumors among  others. Early identification of individuals most at risk for DICER1- associated conditions may allow family education, targeted surveillance  and identification of DICER1-related tumors and conditions in their  earliest and most curable form. Given the rarity of these conditions, international collaboration is underway and encouraged.

The multicentre prospective open uncontrolled study investigated efficiency and safety of national recombinant factor IX (rFIX, nonacog alfa, Innonafactor®, JSC “Generium” for preventive  treatment of 15 patients at the age of 12 years and older with  severe (n = 10, FIX activity < 1 %) and moderate (n = 5, FIX  activity 1–2 %) hemophilia B. Patients included to the study were 8  adolescents from 12 to 18 years and 7 adults at the age of 18 years  and older. Innonafactor was administered at a dose of 40–50 IU/kg  (in patients at the age of 12–18 years) and at a dose of 40–46 IU/kg (in patients at the age of 18 and older) twice a week with an interval of 72–96 h. The duration of preventive therapy was 26 ± 1 week  (not less than 50 days of administration of drug study). The average value of increasing the FIX activity (K-value) in 30 min after administration of Innonafactor was 1.38 ± 0.34 IU/dl of IU/kg in the  whole group of the patients, 1.26 ± 0.11 IU/dl of IU/kg in  adolescents, 1.53 ± 0.46 IU/dl of IU/kg in patients at the age of 18  years and older (p = 0.165). The average value of the recovery  degree of the FIX activity was 60.38 ± 13.44 % in all 15 patients,  62.91 ± 18.71 % – in adults, 58.17 ± of 7.03 % – in adolescents (p  = 0.563). During preventive treatment with the Innonafactor drug  18 hemorrhagic episodes were registered in 7 (46.7 %) patients.  Hemorrhagic episodes were registered mainly among adolescents, 17 (94.4 %) of the cases. The average number of bleeding episodes in 15 patients for the whole observation period was 1.2 ± 1.7, in  adolescents – 2.1 ± 1.9. 13 (72.2 %) episodes among 18  hemorrhagic episodes were post-traumatic, 5 (27.8 %) –  spontaneous (all have been observed in adolescents). The average  number of spontaneous bleeding episodes that occurred within 72 h  after administration of the Innonafactor, during the entire period of  the study (the main criterion of efficiency) in all 15 patients was 0.3 ± 0.8, and in adolescents – 0.6 ± 1.1. All registered hemorrhagic episodes were mild (8, or 44.4 %) or moderate (10, or 55.6 %). Among spontaneous bleeding 2 (40 %) episodes were mild and 3  (60 %) – moderate (additional criterion of efficiency). 6 (33.3 %)  hemorrhagic episodes (2 mild and 4 moderate) required additional  drug administration for the relief, 10 (55.6 %) of hemorrhagic  episodes (6 mild and 4 moderate) were stopped after 1 injection of the Innonafactor, 2 (11.1 %) episodes of moderate severity took 3 drug administration. 3 (60 %) spontaneous hemorrhagic episodes (1 mild and 2 moderate) did not require additional administration of the drug for relief, the remaining 2 (40 %) episodes (1 mild and 1  moderate) were treated with a single injection of the Innonafactor.  The average amount of drug Innonafactor injected in all patients  during the period of preventive treatment, was 134.3 ± 33.1  thousand IU, in adolescents – 122.4 ± 36.0 thousand IU, in adult  patients – 147.9 ± 25.4 thousand IU. The total amount of drug  Innonafactor injected in all 15 patients (additional criterion of efficiency), was 2014 thousand IU, in adolescents – 979 thousand IU, in adult patients – 1035 thousand IU. During the 2nd and 4th  visits in all 10 (100 %) patients with severe hemophilia B residual  FIX activity in 72–96 h after administration of the Innonafactor was  1 % or more (additional criterion of efficiency), during the 3rd visit  there were 9 (90 %) such patients. Among patients with moderate  hemophilia B the number of patients with residual FIX activity of 2 % or more in 72–96 h after administration of the Innonafactor (additional criterion of efficiency) during the 2nd, 3rd and 4th visits was 80 % (4 of 5). During the study 5 adverse events (AES) were registered, 2 (40 %) events were laboratory and 3 (60  %) events – clinical. All AES were mild severу and, according to  clinical investigator, were not related to the study drug.  Thromboembolic complications and immunogenic reactions were not  registered. Thus, the obtained data demonstrate the efficiency and  safety of the drug Innonafactor both to prevent and stop bleeding in  patients at the age of 12 years and older with severe and moderate hemophilia B.

Introduction. The Problem of the use of recombinant activated factor VII (rFVIIa) in hemophilia patients with inhibitors is the complexity of the laboratory evaluation of the therapy. After rFVIIa  administration standard clothing tests are changing, however, are not normalized.

The aim of this study was to investigate the possibility of using standard clothing tests (activated partial thromboplastin time (APTT) and prothrombin time (PT)) to assess the efficiency of hemostatic  therapy with rFVIIa in hemophilia patients with inhibitors. The aim of this work is to investigate the possibility of using standard clothing  tests (activated partial thromboplastin time (APTT), prothrombin time (PT)) to assess the efficiency of hemostatic  therapy with rFVIIa in patients with inhibitory hemophilia.

Materials and methods. 20 male hemophilia patients with inhibitors were included in the study. At the time of study inclusion  none patients had signs of bleeding. Plasma levels of FVIII were < 1  %, FVIII inhibitor titers were from 5 BU/ml to 463 BU/ml. All  patients received rFVIIa (Coagil-VII) at a dose of 90 μg/kg. Before  the administration of rFVIIa and then in 15, 30 and 60 min, 2 and 24 h the APTT, the PT, the endogenous thrombin potential (ETP) and thromboelastography (TEG) parameters (reaction time – R, maximum amplitude – MA) were evaluated.

Results. Before rFVIIa administration all patients had prolonged APTT. 15 min after administration of rFVIIa APTT shortened and remained shorter than baseline level, but 2 times longer than  normal ranges during 2 hours. The PT also significantly decreased in  15 min after the rFVIIa administration. Prior to treatment patients had minimal to no clotting detectable by TEG. Administration of rFVIIa led to normalization of TEG traces in the most of the patients  in 15 min. Elevated by TEG hemostatic effects persisted for 2 h. The  ETP increased in 15 min after rFVIIa administration. This increase of  ETP persisted for 60 min. There were strong correlations between R  and APTT (r = 0.74; p = 0.001), between MA and APTT (r = 0.70),  between PT and R (r = 0.79; p = 0.01), PT and MA (r = 0.76; p =  0.01). There were no correlations between ETP and APTT, and  between ETP and R. The shortening of the APTT after rFVIIa administration for 17 s and more or for 22 % and more from the baseline levels were associated with the normalization of R and MA.  Changes of the PT poorly allowed to discriminate normal values of  TEG.

Conclusion. Shortening of the APTT after rFVIIa administration in hemophilia patients with inhibitor for 17 s and more or for 22 % and more from the initial value can be used to assess the hemostatic efficiency of rFVIIa therapy.

Timing is extremely important for movement and speech, and understanding the neurobiological basis of rhythm perception and reproduction can be helpful in addressing motor and cognitive recovery after brain lesions.

The aim of the present study was to investigate temporal abilities in children treated for a malignant tumor in cerebellum. Children with a diagnosed medulloblastoma and astrocytoma and age-paired  control children were given an audio-motor synchronization task:  tapping according to the metronome sounds at 40, 60 and 120 beats per minute. Additionally correlations between timing accuracy and  variability and working memory and processing speed were  calculated (for executive functions assessment the Cambridge  Neuropsychological Test Automated Battery (CANTAB) was used). The performance in the audio-motor synchronization task (both accuracy and variability) was significantly poorer in children with  cerebellum tumors than in controls. A linear correlation was revealed between timing accuracy and variability: the more accurately, the  less variable the rhythm will be produced. Finally, it was shown that  successful timing performance associated with fine spatial working memory, high processing speed and visual spatial span.

A third of patients with localized (non-metastatic) forms of tumors of the Ewing sarcoma family (ES) have resistance to modern systemic therapy regimens, which leads to a relapse of the disease. Forecasting such cases for the purpose of timely intensification of treatment is possible by studying the biology of the tumor process  and in particular angiogenesis (AG) – the process of formation of the tumor by the own vascular network. Earlier, we found that the level of AG markers (TFPI2 mRNA expression (tissue factor inhibitor) and the ratio of VEGFA165/VEGFA189 vascular endothelial growth factor  isoforms) in the tumor tissue prior to treatment can differentiate  patients. Previously we have established the ability to predict poor  outcome based on mRNA expression levels of both TFPI2 (tissue  factor pathway inhibitor 2) and VEGFA165/VEGFA189 (vascular endothelial growth factor isoforms) ratio in pretreatment tumor tissue, it makes it possible to differentiate patients from localized ES into groups of favorable and unfavorable outcome of the disease.

The aim of this study was to intensify treatment by blockade of AH for patients with an adverse outcome predicted by the level of AH markers. VEGF-blockade was used to enhance the therapeutic effects for patients with a predicted adverse outcome. 29 patients with  localized forms ES included in the study. For patients with adverse prognosis (51.7 %) standard chemotherapy has been strengthened through bevacizumab (VEGF inhibitor). 5-years Event-free survival  (EFS) for patients with adverse prognosis was 66.7 % for patients  with good prognosis – 100 %, for all patients EFS rate was 82.4 %.  EFS of the combined cohort of patients was 82.8 %. It was shown  that anti-angiogenic therapy can be effective in patients with  localized forms of ES with a predictable (based on the level of AH markers) adverse outcome of the disease.

An urgent issue of pediatric oncology is the search for new methods of therapy for patients with malignant rhabdoid tumors (MRT), a type of  rare malignant neoplasms of childhood. Insufficient knowledge,  difficulties in diagnosis lead to the fact that the diagnosis is confirmed in the most common stages of the process and is in most cases fatal.  The review of the literature presents modern ideas about the origin of  MRT, approaches to diagnosis and therapy of patients.

NUT midline carcinoma (NMC) is a very rare, highly malignant disease with a specific cytogenetic abnormality t(15;19)(q14;p13.1). This tumor can occur throughout life, unfortunately, most cases are  characterized by the presence of metastases at the time of  diagnosis. There are clear cytogenetic and molecular-biological  criterias for diagnosis. There are no specific standards of therapy  that provide effective treatment of this pathology in the world.  However, the presence of a chimeric oncogene characterizing the  tumor is promising in terms of targeting drug research in the  framework of international cooperation. It is also necessary to collect information about this rare disease to analyze it and to identify the  most effective therapy method. This article presents an analysis of  the clinical case of NMC, first diagnosed in a child of 9-yearsold in the Republic of Belarus.

Patients’ survival with nephroblastoma improved dramatically with a multimodal treatment. Wilms tumour (WT) relapses occur during 18  months of follow up in a tumour bad or/and in lungs in most cases.  Herein we present a case of patient with a late nephroblastoma recurrence locally, in irradiated field, and with  metastasis in a right liver lobe. Primary treatment included: urgent  surgery (nephrectomy), irradiation of a tumour bad, paraaortic  lymph nodes, a left abdominal flank (29–33 Gr); and chemotherapy  (vincristine, actinomycin D and adriamycin) according the protocol  SIOP WT 2001 recommendations for stage III. A boy was 5 years old when WT was diagnosed. The patient developed relapse 18 months  later a primary surgery. A tumour’s volume has been decreased  dramatically after 3 courses (ICE – ifosfamide, carboplatin,  etoposide) of neoadjuvant chemotherapy. A left retroabdominal mass, a left ureteral stump and a right liver lobe (V, VI, VII) were  removed during a surgery followed by 2 courses of adjuvant  chemotherapy (ICE). The radiotherapy was avoided because of a primary irradiation. After 18 months of follow up the patient is in a second remission.

One of the fundamentals of high-tech therapy in immunology, neurology, hematology-oncology and other areas of medicine is the use of immunological drugs isolated from the blood plasma of healthy donors. It is known that the indications and the routes of drug administration (in particular, immunoglobulins) are based on  numerous studies of its efficiency in various diseases, traditionally  the attention of physicians is precisely focused on it. However, in the  21st century, the safety and convenience for the patient and medical personnel are no less important. The article presents a modern  manufacturing enterprise of blood plasma preparations and data on  its application in the field of immunology, hematology-oncology and  neurology according to the First Intercontinental Academy on Immunology and Congenital Angioedema.

The authors present the analysis of the development of the regional specialized pediatric hematology and oncology health-care in the Chelyabinsk region (CHR), which has common pathway both for  the country and the region over the past 55 years: the  establishment of clinical departments and centers on the basis of  multi-specialty children’s hospitals, the creation of a team of well- trained physicians, who had internships in the federal clinics, close  cooperation with Russian and foreign researchers. The results of the  Regional Oncohematological Center for Children and Adolescents  named by prof. Heryne of the Chelyabinsk Regional Children’s  Clinical Hospital are comparable with the best clinics in the country,  infant mortality rates among the I and II categories of diseases in  the CHR were 2.88 per 100,000 children. The cancer cause by the year of 2016 went to the 7th place in the structure of the causes of death among infants and children in the CHR, while in other regions  it occupies the 2nd and 3rd places. Research and clinical activities of  the medical team of the Center in cooperation with the Department  of Pediatrics of the South Ural State Medical University, Dmitry  Rogachev National Medical Research Center under the leadership of  General Director Alexander G. Rumyantsev, MD, PhD ensured the  completion of more than 16 dissertations. The results of the  treatment of patients in CHR confirm the consistently high level of  availability and quality of specialized and high-tech medical care for children with oncological and hematological diseases.