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Introduction. Over the past 5 years, signifi cant progress has been achieved in the treatment of patients with Ph-negative acute lymphoblastic leukemia (ALL). Treatment results were compared between two protocols of the Russian multicenter studies «ALL-2009» and «ALL-2016», in which multicomponent high-dose consolidation was not used. The principle of continuity of treatment was observed with modifi cation of doses of cytostatic drugs depending on the depth of cytopenia.Aim – to compare the 5-year results of two studies and to determine the factors of unfavorable prognosis in the treatment of patients with ALL.Materials and methods. The studies were performed from April 2009 to April 2016 (ALL-2009) and from April 2016 to September 2021 (ALL-2016), and 596 patients were included: 330 in ALL-2009 and 266 in ALL-2016. The analysis was performed in March 2022. The median age of patients in ALL-2009 was 28 years (15–55), in ALL-2016 – 32.5 years (18–55). Cytogenetic studies were performed in 242 patients in ALL-2009 (73.3 %) and 236 patients in ALL-2016 (88.7 %). Patients in the ALL-2016 protocol underwent a centralized assessment of minimal residual disease (MRD) by fl ow cytometry on protocol +70 day (after completion of two induction phases), +133 and +190 days. Transplantation of allogeneic stem hematopoietic cells was performed in 7 % of patients in ALL-2009 and in 9 % in ALL-2016.Results. Overall, relapse-free survival (OS, RFS) and the probability of relapse for a period of 3 years from the moment of inclusion of patients in a particular study were 59 %, 63 % and 23 % for ALL-2009, and for ALL-2016 – 64 %, 59 % and 22 %, respectively. For patients with B-cell precursor ALL, two cytogenetic risk groups were formed, in which long-term survival rates differed signifi cantly: the standard group (hyperploid set of chromosomes and normal karyotype) – OS 63 %, RFS 70 %, and high cytogenetic risk (any abnormal karyotype, except for hyperploidy) – OS 49 %, RFS 52 % (р = 0.001, р = 0.0014). In T-ALL, cytogenetic markers had no prognostic value, but the immunophenotype of early T-cell precursor turned out to be an important predictor of poor prognosis (the probability of relapse was 52 % compared with 15 % for all other immunophenotypic variants). According to the results of centralized monitoring of MRD, it was determined that for B-cell precursor ALL, the signifi cant negative factors are the high cytogenetic risk group and positive MRD status at +70 day, and for T-cells, the early immunophenotype and positive MRD status at +133 day.

A solution is found by the method of perturbations with an accuracy up to values of the second order of smallness, which describes the state of an inhomogeneous elastoplastic thick-walled pipe under the action of compressive forces. Deviations of the contour of the cross-section of the pipe from the circumference and inhomogeneity of the material are characterized by independent small parameters. A condition is obtained under which, in the case of an experimental analysis of the pipe state, the average values of stresses and displacements will be close to those in the axisymmetric state.

Currently, the main pathogenetic method for the treatment of paroxysmal nocturnal hemoglobinuria (PNH) is the treatment with recombinant monoclonal antibodies that block the C5 component of the complement system. Eculizumab is the first biotechnological drug, which is a monoclonal antibody, with proven clinical efficacy and safety for the treatment of patients with PNH, which is used in world clinical practice. In Russia, in the framework of the state program Development of the pharmaceutical and medical industry for 20132020 was developed Elizaria (JSC GENERIUM) the first biosimilar of the original drug eculizumab.To evaluate the pharmacokinetic and pharmacodynamic parameters, as well as safety and immunogenicity parameters of the drug Elizara in the induction phase of therapy in previously untreated patients with PNH.The study included 11 patients with PNH aged 26 to 75 years who had not previously received eculizumab. Each of the study participants was injected with the studied drug Elizaria at a dose of 600 mg intravenously once a week for 4 weeks.During the clinical study, it was noted that the concentration of the studied drug significantly increased by the time the infusion was completed and then gradually decreased to a minimum at the end of the dosing interval. The average concentration of eculizumab 5 minutes before the administration of the study drug at all visits exceeded 35 g/ml, the minimum concentration sufficient to completely inhibit intravascular hemolysis in patients with PNH. The pharmacodynamic efficacy of the drug Elizaria was confirmed by a decrease in the concentration of the membrane-attack complex (MAC) after the first infusion of the drug was maintained at stable levels until visit 5. A persistent decrease in the level of MAC and a four-fold decrease in the average values of lactate dehydrogenase to visit 5 from 1286.4 to 280.9 U/l demonstrated a marked decrease in activity and stabilization of the hemolytic process against the background of the induction of therapy with Elizaria at a dose of 600 mg once a week and confirmed the effecacy of the study drug. Among the 9 adverse events, only 5 had a relationship with the studied drug, including one serious adverse event in the form of an allergic reaction, which, according to the researcher, had a possible cause-effect relationship with the infusion of the studied drug. In 2 patients, low-titer binding anti-drug antibodies were detected without neutralizing activity during treatment with the studied drug, which may indicate its low immunogenicity.The study evaluated the pharmacokinetic and pharmacodynamic properties of the drug Elizaria in the regimen of induction therapy in previously untreated patients with PNH, confirming its efficacy. The study demonstrated the safety and low immunogenicity of the study drug.В настоящее время основным патогенетическим методом лечения пароксизмальной ночной гемоглобинурии (ПНГ) является терапия рекомбинантными моноклональными антителами, блокирующими С5-компонент системы комплемента. Экулизумаб первый биотехнологический лекарственный препарат, являющийся моноклональным антителом, с доказанной клинической эффективностью и безопасностью для лечения больных ПНГ, который используется в мировой клинической практике. В России в рамках реализации государственной программы Развитие фармацевтической и медицинской промышленности на 20132020 гг. разработан препарат Элизария (АО ГЕНЕРИУМ) первый биоаналог оригинального препарата экулизумаб. Цель. Изучение фармакокинетических и фармакодинамических показателей, а также параметров безопасности и иммуногенности препарата Элизария в фазе индукции терапии у ранее не леченных больных ПНГ. Материалы и методы. В исследование включены 11 пациентов с ПНГ в возрасте от 26 до 75 лет, ранее не получавших экулизумаб. Каждому из участников исследования вводили исследуемый препарат Элизария в дозе 600 мг внутривенно капельно один раз в неделю в течение 4 нед. Результаты. В ходе клинического исследования отмечено, что концентрация исследуемого препарата значительно увеличивается к моменту окончания инфузии и далее постепенно снижается до минимума в конце интервала дозирования. Средние значения концентрации экулизумаба за 5 мин до введения исследуемого препарата на всех визитах превышали 35 мкг/мл, минимальную концентрацию, достаточную для полного ингибирования внутрисосудистого гемолиза у больных ПНГ. Фармакодинамическая эффективность препарата Элизария подтверждалась снижением концентрации мембраноатакующего комплекса (МАК) после окончания первой инфузии препарата с поддержанием ее на стабильных уровнях до визита 5. Стойкое снижение концентрации МАК и четырехкратное снижение средних значений лактатдегидрогеназы к визиту 5 с 1286,4 до 280,9 Ед/л демонстрировало выраженное снижение активности и стабилизацию гемолитического процесса в результате индукции терапии препаратом Элизария в дозе 600 мг один раз в неделю и подтверждало эффективность исследуемого препарата. Из 9 нежелательных явлений только 5 имели связь с применением исследуемого препарата, включая одно серьезное в виде аллергической реакции, имевшее, по мнению исследователя, возможную причинно-следственную связь с инфузией исследуемого препарата. У 2 больных выявлены связывающие антилекарственные антитела в низком титре без нейтрализующей активности во время лечения исследуемым препаратом, что может свидетельствовать о его низкой иммуногенности. Заключение. В ходе исследования оценены фармакокинетические и фармакодинамические свойства препарата Элизария в режиме индукции терапии у ранее не леченных больных ПНГ, подтверждающие его эффективность. В исследовании продемонстрированы безопасность и низкая иммуногенность исследуемого препарата.

The correct determination of the blood types of the recipient and the donor is very importante for the choice of blood components for transfusion. As a result of the study, it was established that 18.0% of patients, admitted to the hematology clinic, have difficulties in interpreting of the results of immunohematological tests. Most often, a double population of red blood cells was detected when determining antigens of the Rhesus system (10.9%), auto- (3.9%) and alloantibodies (2.8%). The proposed algorithm for the selection of donor red blood cells in difficult diagnostic cases helps to prevent the development of post-transfusion complications.

Aim. To analyze the regularities of the prevalence of allergic diseases in patients of different age groups. Materials and methods. Epidemiological indices of allergic diseases were studied in children, adolescents, adults and elderly persons using official statistical data. Results. The general and primary morbidity, allergopathology structure and its dynamics were evaluated in patients of different age groups. The data, obtained in Perm Krai and the Russian Federation, were compared. Conclusions. The level of atopic dermatitis (AD) is the highest in children, allergic rhinitis (AR) – in adolescents, bronchial asthma (BA) – in adolescents and elderly persons. The cases of BA prevail in the structure of allergopathology in all age groups, besides children. Among children AD cases make 50.5 % of all allergic diseases. In dynamics, AD has a tendency to reduction of general morbidity in all age groups, BA – in children; a tendency to elevation is typical for AR in children and adolescents, BA – in adolescents, adults and elderly persons.

The medical personnel of mobile teams of emergency medical care are exposed to factors of working environment that affect health state and results in development of occupational diseases. The purpose of study is to analyze morbidity of medical personnel of mobile teams of emergency medical care according data of temporary disability and results of medical check-ups. The analysis was made according information from certificates of incapacity for work and the final acts of periodic medical examinations for five-year period. The study established significant increase of rate and duration of primary and general morbidity with increase of age and length of service of workers, higher susceptibility to diseases of physicians as compared with paramedics and employees of pediatric teams and specialists of other clinical profiles. In the structure of morbidity according to results of medical examinations, diseases of the eye and its accessory apparatus, the circulatory system and the musculo-skeletal system prevailed.

The issues of diagnosis and management of allergic rhinitis (AR) in pediatric patients are considered on the basis of the current Russian clinical guidelines. The article presents the paediatrician tasks on the collection of anamnesis, the assessment of clinical symptoms, the setting of a preliminary diagnosis, the development of a diagnosis and therapy plan taking into account the modern medical care quality criteria. It also discloses the general principles of AR treatment, approaches to emergency symptomatic therapy using a combined intranasal drug Vibrocil (dimethindene + phenylephrine). The paper provides recommendations for the management of patients with allergic rhinitis in the district covered by child health care.

A case of Norwegian scabies is described in a patient of 19 years with a lesion of the scalp, face, trunk, upper and lower extremities that occurred against the background of acute lymphoblastic leukemia. A good effect was obtained from conducting etiotropic, pathogenetic and symptomatic therapy in combination with specific treatment of the underlying disease.

Using data obtained from domestic and foreign sources, we formed a set of primers and fluorogenic probes for analyzing twenty-six specific sequence polymorphisms and one reference gene. In the course of evaluating the effectiveness of real-time PCR, using the example of one of the markers (S01a), we obtained the optimal amount of DNA per reaction (70 ng), providing a resolution of at least 0.1% of the method with the ability to estimate linear chimerism. Formed panel of primers for genetic polymorphisms - InDel has a high degree of informational content for donor-recipient pairs of Russia. From January 2018 to June 2019, a quantitative assessment of the level of linear (CD3 +, CD34 +) and general chimerism was carried out for 28 patients of the clinic of the Institution. Finally, we analyzed patients who received allografts and present 4 different clinical situations that illustrate the informativity level of this method.

Modeling systems with piecewise constant parameters imposes special requirements on the computational algorithms used. In places where the parameters are discontinuous, the model variables may experience discontinuities or smoothness disturbances. In this case, the conditions for matching the values of the variables on both sides of the discontinuity boundary, reflecting the physical conditions at this boundary, must be satisfied. The paper proposes computational algorithms for modeling these systems, based on the formulation of the initial initial-boundary value problem in the form of a system of partial differential equations for generalized functions. In this case, the initial conditions, conditions on the external and internal boundaries are included in these equations in a weak form. The latter circumstance makes it possible to avoid the need to subordinate the basis functions, according to which the desired solution is expanded, to the conditions on the outer and inner boundaries, which is an important circumstance, especially for problems with many spatial variables. The paper presents a solution to the generalized Riemann problem with conditions on the outer or inner boundary for a differential equation with second-order derivatives with respect to spatial variables. The solution to the Riemann problem is based on the formulation of the problem in the form of a partial differential equation for generalized functions and the construction of a fundamental solution to the problem operator. When constructing a computational algorithm, the solution of the generalized Riemann problem is used on the inner and outer boundaries. The proposed technique allows, by using high-degree polynomials as basis functions, to build computational algorithms of a high order of approximation.

The review is dedicated to the analysis of ecological aspects of pollen allergy (pollinosis). The characteristic of pollen as a natural aerosol component is given. The information related to aeropalinological monitoring and its importance in public health service is presented. The peculiarity of this pathology is its regional variety associated with differences in plant species compositions and pollen periods. The problem of immune response formation to pollen has been studied most profoundly. At that it is known that sensibilization is not always associated with clinical signs. Russian and foreign data about correlation studies between the pollen quantity and the disorder symptom load are discussed. It is shown that there is no decisive answer to the question about threshold pollen counts of certain plants and its impact on different stages of respiratory diseases. The detailed analysis of the correlation between the symptoms and quantitative variables of pollen allergens may provide useful information for risks evaluation of disease exacerbation as well as for tactics elaboration of hypoallergic measures. This is a cross-disciplinary issue involving allergology, aerobiology and ecology. The perspective of further development of this subject in order to obtain more accurate vision of the reasons, mechanisms and patterns of all parts of multifactorial process of pollinosis formation is discussed.

The article considers a clinical case of the grave course of the flu А(Н1N1)pdm09 with development of the viral and bacterial pneumonia and acute respiratory distress-syndrome (ARDS) in the baby. A description of the respiratory support is provided, the data on catamnesis in a year are given.

The correlation of gene polymorphisms rs4025935 (large deletion), rs1695 (313A>G), rs71748309 (large deletion), and rs1800566 (609C>T) of GSTM1, GSTT1, and NQO1 genes encoding glutathione-S-transferases (GST) M1, P1, and T1 and NADPH-quinone oxidoreductase with the risk of development of classical Ph-negative myeloproliferative neoplasms (polycythemia vera, essential thrombocythemia, and primary myelofibrosis) was studied in the Caucasian ethnicity population of Vyatka region of the Russian Federation. It was found that NQO1*609T allele, NQO1*609T genotypes, and homozygous carriage of a deletion (null) allele of GSTT1 gene are associated with the risk of development of myeloproliferative neoplasms (OR=1.29, 95%CI=1.02-1.64, p=0.04; OR=1.39, 95%CI=1.04-1.85, p=0.03; and OR=1.48, 95%CI=1.03-2.12, p=0.03, respectively). However, no influence of GSTM1 and GSTP1 gene polymorphisms on the risk of development of myeloproliferative disorders was registered.

An approximation of matrix Green’s function for a hyperbolic system of linear differential equations of the first order has been created. An algorithm for an approximate solution of the generalized Riemann problem of discontinuity decay in the presence of additional conditions at the boundaries has been proposed. A computational algorithm for the approximate solution of boundary value problems for hyperbolic systems of equations has been set up on the basis of these solutions. The algorithm is implemented for a system of equations describing the propagation of elastic waves in a block-fractured medium. The results of the numerical experiments aimed at studying the possible mechanisms of propagation of elastic waves to a considerable depth without scattering have been presented.

The article considers behavior of elastic strip in the framework of plane strain under compression. Conditions are formulated in integral form on the boundaries where the forces are imposed. All the boundary conditions are imposed on the boundary of the body in the strained state, which is necessary for investigating the continuous dependence of the solution to the corresponding task on the functions describing the difference between the shape of cross-section of the strip and a rectangle. The study of the analyticity of the problem solution with respect to small near zero parameters is carried out. The solution is found by perturbation method up to the first order of terms.

The present open randomized comparative study had the objective to compare the effectiveness of two strategies for the treatment of early spring pollinosis in 23 children at the age varying from 2 to 17 years in the phase of exacerbation. The patients of the study group underwent 10 sessions of sylvinite speleoclimatotherapy 60 min in duration each in addition to conventional pharmacotherapy. The children included in the control group were treated by traditional medicamental therapy alone. The estimation of clinical symptoms on day 10 after the onset of the treatment with the use of a scoring system has demonstrated a marked decrease in the severity of allergic rhinitis (p = 0.003), conjunctivitis (p = 0.01), and the total number of signs and symptoms of the disease (p = 0.002) in the children managed with the use of sylvinite speleoclimatotherapy. Positive dynamics in the patients of the control group was less pronounced (p0.05). The aeropollinological data are presented giving evidence of the absence of a high pollen concentration in the air of the speleoclimatic chamber and its high content in the atmospheric air at the height of thepollen season of early spring allergens. The clinical manifestations of the allergic conditions were shown to depend on the concentration in the atmospheric air of the causative allergens from their principle plant sources (r = 0.66, p = 0.039 in the control patients in comparison with r = 0.42, p = 0.22 in the children treated by sylvinite speleoclimatotherapy. It is concluded that the results of the present study confirm the clinical effectiveness of sylvinite speleoclimatotherapy used in the acute phase of pollinosis. The combination of this modality with traditional medicamental therapy accelerates elimination of clinical symptoms of allergic rhinitis and conjunctivitis; moreover, it reduces the frequency of recurrent respiratory disorders.

To analyze the efficiency of the ALL-2009 protocol (ClinicalTrials.gov NCT01 193933) in patients with T-cell leukemias, particularly the role of autologous hematopoietic stem cell transplantation (auto-HSCT) after non-myeloablative BEAM conditioning, followed by maintenance therapy.Since 2009, the ALL-2009 study has enrolled 90 patients with T-cell acute lymphoblastic leukemia (T-ALL), the treatment results were assessed in 86 patients: 6 and 28 patients underwent allogeneic HSCT and auto-HSCT, respectively. A landmark analysis was used to compare survival rates in patients who had undergone auto-HSCT and in those who had not. For this, the median time from complete remission to the date of auto-HSCT was determined (the median was 6 months). Then to compare with the auto-HSCT group, only 27 patients who had been in complete remission for 6 months or more were included in a chemotherapy group.The achievement of complete remission in patients with thymic T-ALL (100%) was significantly higher than in those with early (85.7%) or mature (70%) variants. The patients with early and mature T-ALL as compared to those with thymic T-ALL showed high death rates in the remission induction (7.4 and 10% versus 0) and the patients with mature T-ALL had a.higher proportion of refractory forms (20% versus 0). The 5-year overall and relapse-free survival rates in all the T-ALL patients were 66 and 76%, respectively. After auto-HSCT, the risk of recurrence was 0% versus 21% after chemotherapy (p=0.03). The relapse-free survival rates significantly differed in the auto-HSCT and non-auto-HSCT groups: 100 and 66%, respectively (p=0.047).The long-term survival rates obtained during this multicenter study in the T-ALL patients treated according to the ALL-2009 protocol, the basis for which is the principle of continuity of cytostatic effects, are exclusively optimistic. Late consolidation with auto-HSCT following non-myeloablative BEAM conditioning, followed by maintenance therapy, considerably reduces the risk of recurrence.Цель исследования. Анализ эффективности протокола ОЛЛ-2009 (ClinicalTrials.gov NCT01193933) у больных Т-клеточными лейкозами, особенно роли трансплантации аутологичных гемопоэтических стволовых клеток (ауто-ТГСК) после немиелоаблативного режима кондиционирования ВЕАМ с последующей поддерживающей терапией. Материалы и методы. В исследование ОЛЛ-2009 с 2009 г. включили 90 больных острым Т-лимфобластным лейкозом (Т-ОЛЛ), результаты лечения оценены у 86 больных: 6 выполнена аллогенная ТГСК, 28 - ауто-ТГСК. Для сравнения выживаемости больных, которым выполнили или не выполнили ауто-ТГСК, использовали landmark-анализ. Для этого определяли медиану времени от достижения ПР до даты ауто-ТГСК (медиана составила 6 мес). Затем для сравнения с группой ауто-ТГСК в группу химиотерапии включили 27 больных, которые пережили в полной ремиссии 6 мес и более. Результаты. Достижение полной ремиссии у больных с тимическим Т-ОЛЛ (100%) существенно выше, чем у больных с ранним (85,7%) или зрелым (70%) вариантами. Для раннего и зрелого по сравнению с тимическим Т-ОЛЛ характерна высокая частота летальных исходов в период индукции ремиссии (7,4 и 10% по сравнению с 0), а для зрелого Т-ОЛЛ - и большая доля рефрактерных форм (20% по сравнению с 0). Общая и безрецидивная 5-летняя выживаемость всех больных Т-ОЛЛ составили 66 и 76% соответственно. При выполнении ауто-ТГСК вероятность развития рецидива составила 0 по сравнению с 21% при применении химиотерапии (р=0,03). Достоверно (р=0,047) различалась безрецидивная выживаемость больных, которым выполняли ауто-ТГСК или нет: 100 и 66% соответственно. Заключение. Полученная в рамках многоцентрового исследования долгосрочная выживаемость больных Т-ОЛЛ, лечившихся по протоколу ОЛЛ-2009, в основе которого лежит принцип непрерывности цитостатического воздействия, является исключительно оптимистичной. Поздняя консолидация с помощью ауто-ТГСК после немиелоаблативного кондиционирования ВЕАМ и последующая поддерживающая терапия значительно снижают вероятность развития рецидивов.

An optimized therapeutic rehabilitation program involved 393 patients with fractured long bones (humeral, radial/ulnar, femoral, crural) admitted to the Orthopedic Department of the Stavropol Regional Children's Clinical Hospital and the Rehabilitation Centre for Handicapped Children and Adolescents. Rehabilitation was performed in three consecutive stages, viz. immobilization, functional recovery and training. The proposed approach ensured rather fast functional recovery of the affected extremity even in cases with compound fractures. The rehabilitation program included polyenzyme therapy with wobenzym during 3-4 weeks after injury or surgical repositioning of bone fragments. Pain and oedema syndromes resolved twice as fast as after traditional treatment. The use of this program permitted to avoid development of contracture and disturbances of locomotary activity; moreover, it improved the quality of life in children with fractures of long tubular bones.

Conditions of activity of medical service of the Armed Forces of RF predetermines the necessity of utilizing new methods of organization of the process of access of medical-technical models and medical equipment, including complex equipment. The article presents several definitions, connected with aterm "medical technics and equipment". Medicine chest, wallets, complexes of medical equipment and medical tool kits could be accessed to the purchasing of medical service of the Armed Forces and cold be added to the normative documents after their state registration according to the right legal way.