POSSIBILITIES OF USING LOW-MOLECULAR-WEIGHT HEPARIN IN THE COMPLEX TREATMENT OF WOMEN WITH TUMORS OF THE REPRODUCTIVE SYSTEM

Benign and malignant tumors of the organs of the female reproductive system are the most common diseases requiring medical and surgical treatment. They are rarely the cause of acute complications. However, the thromboembolic disease is a serious illness, sometimes causing death due to acute the pulmonary embolism. Venous thromboembolism secondary to Benign and malignant tumors of the organs of the female reproductive system should be considered in a female presenting with abdominal mass and pelvic pressure. Thromboembolic disease secondary to large tumors should be treated with anticoagulation then hysterectomy. The article presents an analysis of modern literature on optimal prevention of the pulmonary thromboembolism in patients with tumors of the female reproductive system. There are analysis data of 17 (0.7 %) cases of the pulmonary thromboembolism that occurred of 2358 gynecological and oncogynecologic patients

Efficiency of Transarterial Chemoembolization with Drug-Eluting Microspheres in the Treatment of Metastatic and Primary Liver Tumors

Background: Transarterial chemoembolization (TACE) is coming into use in the treatment of liver tumors, with drug-eluting microspheres as one of the technique variations. However, at the moment there are no systematic studies that would answer the questions: what is the role of the method in the treatment regimen for patients with primary and metastatic liver tumor and at what stage should it be used? Aim: to evaluate the effectiveness of transarterial chemoembolization with drug-eluting microspheres for the treatment of metastatic and primary malignant liver tumors at different stages of the disease. Methods: We performed а retrospective observational uncontrolled study of 65 patients with liver metastases (Group 1), and 10 patients with primary malignant liver tumors (Group 2), who underwent 102 operations of transarterial chemoembolization with drug-eluting microspheres. To plan transarterial chemoembolization and evaluate its effectiveness, computed tomography and magnetic resonance imaging were used every 89 weeks during the treatment. Results: After two transarterial chemoembolization controls, Group 1 included 51 responders (79%) and 14 non-responders (21%). Among the responders by the 16th week there was a decrease in the volume of the tumor mass in the liver from 12.4 [4.7; 24.6] to 5.2 cm3 [2; 15.5] for colorectal cancer, from 26 [18; 35] to 19 cm3 [13; 25] for neuroendocrine cancer, from 12 [4; 20] to 4 cm3 [0.6; 9] for adenocarcinomas of different localizations. There was no progression in Group 2, while, by week 16, there was a decrease in the tumor volume from 142 [51; 206] to 68 cm3 [23; 185] for hepatocellular carcinoma, from 465 [330; 600] to 187 cm3 [137;237] for intrahepatic cholangiocarcinoma. With repeated transarterial chemoembolization, a decrease in the volume of the tumor mass was also noted, while the time without progression decreased from 303 [170; 369] to 180 [105; 225] days in Group 1, from 266 [200; 367] to 120 [62; 215] days in Group 2. Conclusions: Transarterial chemoembolization with drug-eluting microspheres is an effective treatment for primary and metastatic liver tumors. It should be considered as a palliative therapy, which allows achieving a good antitumor response at different stages of cancer

Evaluation of External and Internal Threats to Sanitary-Epidemiological Welfare of the Population in the Context of Mass Sporting Events

Mass gatherings (MGs) always incur some kind of potential hazard associated with incipiency of emergency situations with sanitary-epidemiological bias (ES). Upcoming Universiade (World Student Games) in Kazan (July, 2013) raises an issue of implementation of a unified system of approaches to the effective provision of sanitary-epidemiological welfare of the population, taking due account of peculiarities and specific conditions under which the MG will be conducted. Therewith key objective of this study has been formulated as elaboration of the system based on epidemiological assessment of real and potential threats at the MG. Analyzed have been the data on 37 MGs carried out over the period of 25 years since 1987 up to 2012; investigated is epidemiological situation in 170 participating states. Worked out is a scheme of qualitative determination of potential epidemiological threat on the basis of comprehensive assessment of epidemiological risks in the endemic territories of the troubled regions. Distinguished is a complex of measures for the provision of sanitary-epidemiological welfare when managing the Universiade in Kazan heedful of high potential epidemiological hazard of this event

Complex of Measures Aimed at Prevention of Ebola Virus Disease Importation and Transmission, Performed within the Frames of Sanitary Protection of the Territories of the Russian Federation

An estimated scope of measures, aimed at the prevention of Ebola virus disease importation and transmission in the territory of the Russian Federation, targets the maximum level of hazard to the population. It has a complex interagency character, whereby the Federal service for surveillance in the sphere of consumers rights protection and human welfare functions as coordinator and principal executing agency. The measures affect the following areas: regulatory compliance and methodological support, sanitary-quarantine control reinforcement at the entry points on the state border of the Russian Federation, strengthening of anti-epidemic preparedness of the Rospotrebnadzor and public healthcare institutions and authorities, including operational preparedness of the laboratory facilities, information support within the framework of epidemiological surveillance, and involvement in the activities under the international collaboration for epidemic response and control. Practices have been completed as regards series of actions conducted from the time of the case identification and further on; evacuation of the infected and suspected individuals, procedures for sanitary disinfection, interventions in the relation to contact persons, and readiness for anti-epidemic measures performance

Tumor inflating lymphocytes. Purification, expanding and cytotoxicity analisys on primary tumor cultures

Background. Tumor Infiltrating Lymphocytes (TILs) is one of the most promising sources of autologous cytotoxic T-cells for adoptive immunotherapy, which has already shown high efficiency in the treatment of metastatic melanoma. However, the isolation of TILs from solid tumors is technically difficult. A suppressive tumor microenvironment, in particular, a high level of expression of check-point inhibitors PD-1 CTLA4, tissue hypoxia and other factors cause that T cells isolated from the tumor do not proliferate well and do not exhibit cytotoxic properties. Aims. In this study, we isolated TILs from surgical material obtained by resection of solid tumors (primary and metastatic adenocarcinomas of various localization, melanoma, glioblastoma), studied their population composition and developed protocols for the purification expanding, and activation of CD4+, CD8+ cytotoxic antitumor lymphocytes. Methods. An urgent task is the activation of TILs, turning off immunosuppressive mechanisms and increasing their antitumor cytotoxic activity. Various approaches are used for this: activation by a cocktail of cytokines and antibodies, editing the lymphocyte genome by knocking out suppressor genes or, conversely, transduction of activating genes, coincubation with feeder cells, etc. Cells were obtained from samples of resected tumors in 16 patients; in each case we obtain an autologous pair: the primary tumor culture and the TILs culture. Results. We could isolate viable lymphocytes in 100% of cases. Isolated TILs were successfully expanded in our specialized medium using various combinations of IL-2, IL-15, IL-21, IL-7, anti-CD3 and anti-CD28. Immunophenotyping showed that the obtained TILs are a heterogeneous mixture of CD4+, CD8+ cells containing populations of CD3+CD8+CD45+(CTL) CD3+CD4+CD45+ (T-helpers), CD4+CD25+CD127- (Т-regulatory cells), CD3-CD56+CD45+ (NK-cells), CD3+CD56+CD45+ (Т-NK-cells). The initial cultures of TILs were also characterized by a high level of PD1 expression, indicating their low antitumor cytotoxicity. Using different protocols of isolation, expansion, and activation, we obtained a cell preparation containing 80% of CD8+ PD-1- activated TILs in an amount sufficient for adoptive therapy (500106 or more). An in vitro study of the cytotoxicity of obtained TILs in primary cultures of homologous tumors using RTCA Icelligence showed high cytotoxicity, providing almost 100% tumor cell death. Conclusion. Our developed protocol for the production and activation of TILs can be recommended for the phase III clinical trials of adoptive immunotherapy of recurrent, highly metastatic solid tumors

Assessment of the Potential Epidemic Hazard as Regards International Public Events in Terms of the Currently Important Infectious Diseases

International public events (IPE) present some actual epidemiological problems requiring proper methodological elaboration. In this respect for the first time developed has been the scheme of assessment of their potential epidemic hazard (PEH), based on integrated evaluation of epidemiological risk as regards infectious diseases listed in the IHR (2005). On the cholera model demonstrated is the fact that high priority hazard of public events emerges when those are combined with such elements of epidemiological risk as territory and time of a threat, as well as risk factors and risk contingents. Thus the integral effect of all elements realization is manifested through high probability of infectious disease importation, which is associated with emergency situation, into the public event location and the disturbance of mass gathering progress. Reliability and functionality of the developed scheme is verified on other infections too. PEH assessment procedure allows for timely identification of priority goals, for rating means and capacities, organizational resources, methodological and technological arrays for the provision of sanitary-epidemiological welfare and biological safety when managing public event

Improvement of the Scientifically-Substantiated Model of Sanitary-Epidemiological Welfare Provision During Mass Events by the Example of FIFA World Cup-2018 in Russia

In 2018, between June14 and July 15, final matches of the FIFA World Cup-2018 were held in 11 cities of the Russian Federation. That event was the biggest mass event with international participation in the history of Russia. During the period, in the process of sanitary-epidemiological welfare provision, developed earlier scintific-and-practical achievementds for prevention of emergency situations of sanitary-epidemiologoical character were implemented to the fullest extent. Objective of the study – analysis of evolution of the developed in Russia scientifically-substantiated approaches in the sphere of sanitary-epidemiological welfare provision of mass events and aggregation of the results of their implementation during preparation and holding of FIFA World-Cup-2018. Utilized were information-analytical materials from the Rospotrebnadzor Administrations by the constituent entities of the Russian Federatuion, Centers of Hygiene and Epidemiology in the entities of the Russian Federation, RusRAPI “Microbe” of the Rospotrebnadzor, data from Organizing Committee “Russia-2018”, Federal Turism Agency, information published in periodical press. Scientifically substantiated model of sanitary-epidemiological welfare provision during mass events was developed in the Russian Federation. It includes expert evaluation and quantification of potential epidemic hazard of mass event which allows for targeted prophylactic and anti-epidemic measures with rationalized loads and adequate frequency of repeat. The paper discusses the complex of measures carried out during preparation and holding of FIFA World Cup-2018 by the functional areas: sanitary protection of the territory; epidemiological surveillnace over relevant  anthropozoonotic, natural-focal zoonotic, sapronotic infectious diseaseas; sanitary surveillance over communal facilities, catering facilities, sites of accomodation of the participants and guests; sanitary-hygienic monitoring of ambient environment objects; provision of anti-epidemic preparadeness and readiness of the Rospotrebnadzor authorities and institutions and medical organizations; provision of readiness of laboratory facilities; involvement of additional forces and capacities and interagency cooperation in response to emergency situations of sanitary-epidemiological character

Experience in International Cooperation on Organization of Anti-Epidemic Measures by Health Care Institutions under COVID-19 Pandemic in the Republic of Uzbekistan

The results of the joint work of a panel of experts from Rospotrebnadzor and healthcare professionals of the Republic of Uzbekistan on organizing activities to counter the spread of the SARS-CoV-2 virus are described in the paper.The goal of the study was to determine the main driving forces of COVID-19 spread in the Republic of Uzbekistan and develop an action plan to reduce the incidence of coronavirus infection caused by the SARS-CoV-2 virus.Materials and methods. The organization of work in 14 health care institutions in Tashkent and Samarkand, as well as in Tashkent and Samarkand Regions, was analyzed: in 7 laboratories, 6 hospitals and 1 polyclinic. The routes for the movement of personnel, the demarcation of green and red zones, the features of disinfection and the use of personal protective equipment were studied. Attention is drawn to the diagnosis of COVID-19, the use of therapy aimed at reducing the period of virus shedding, the criteria for lifting quarantine restrictions for patients.Results and discussion. The main factors in the organization of work of institutions that contribute to the spread of COVID-19 among medical personnel and the population have been identifed: the lack of equipped gateways between the red and green zones with the accessibility of adequate disinfection, the wrong choice of personal protective equipment, monitoring of contact persons for 10 days, discharge from hospitals based on clinical improvement. The incorrect use of antiviral therapy, the lack of differentiated approaches to the selection of optimal regimens have been noted. Proposals are formulated for organizing the work of healthcare institutions, taking into account the requirements of biological safety. The introduction of targeted measures in addition to those previously adopted has led to a signifcant improvement in the epidemic situation: the total number of active cases in the Republic of Uzbekistan, despite the increase in testing volumes, decreased from 3,686 people on August 23 to 2335 on October 27. Towards December 20, 2020, 97 % of patients recovered completely. All diagnostic triage centers in the Republic of Uzbekistan are closed due to the absence of patients with COVID-19, most of the country’s medical institutions previously re-profled for patients with coronavirus infection have returned to the routine operations

Safety and efficacy of convalescent plasma for COVID-19: the preliminary results of a clinical trial

Background. The lack of effective etiotropic therapy for COVID-19 has prompted researchers around the globe to seekr various methods of SARS-CoV-2 elimination, including the use of convalescent plasma. Aim. The aim of this work was to study the safety and efficacy of the convalescence plasma treatment of severe COVID-19 using the plasma containing specific antibodies to the receptor binding domain (RBD) of SARS-CoV-2 S protein in a titer of at least 1:1000. Methods. A single-center, randomized, prospective clinical study was performed at the FRCC FMBA of Russia with the participation of 86 patients who were stratified in two groups. The first group included 20 critically ill patients who were on mechanical ventilation the second group included 66 patients with moderate to severe COVID-19 and with spontaneous respiration. The patients in the second group were randomized into two cohorts in a ratio of 2:1. In the first cohort (46 patients), pathogen-reduced convalescent plasma was transfused (twice, 320 ml each), in the second cohort (20 patients) a similar amount of non-immune freshly frozen plasma was transfused to the patients. Results. The use of plasma of convalescents in patients with severe COVID-19 being on mechanical ventilation does not affect the disease outcome in these patients. The mortality rate in this group was 60%, which corresponds to the average mortality of COVID patients on mechanical ventilation in our hospital. In the second group, clinical improvement was detected in 75% and 51%, for convalescent and non-immune plasma, respectively. Of the 46 people who received convalescent plasma, three patients (6.5%) were transferred to mechanical ventilation, two of them died. In the group receiving non-immune plasma, the need for mechanical ventilation also arose in three patients (15%), of which two died. The hospital mortality in the group of convalescent plasma was 4.3%, which is significantly lower than the average COVID-19 hospital mortality at our Center (6.73%) and more than two times lower than the hospital mortality in the control group (n=150), matched by age and by the disease severity. Conclusions. Thus, we demonstrated a relative safety of convalescent plasma transfusion and the effectiveness of such therapy for COVID-19 at least in terms of the survival of hospitalized patients with severe respiratory failure without mechanical ventilation. In the absence of bioengineered neutralizing antibodies and effective etiotropic therapy, the use of hyperimmune convalescent plasma is the simplest and most effective method of specific etiopathogenetic therapy of severe forms of COVID-19

Immunotherapy in patients with cervical cancer

Immunotherapy, also known as therapy with immune checkpoint inhibitors, has shown good results in the treatment of both solid tumors and hematological malignancies. Patients with diseases that were considered incurable earlier now have an opportunity for long-term disease stabilization and high frequency of clinical remissions. This review focuses on clinical benefits and toxicity profiles of immune checkpoint inhibitors used for cervical cancer, as well as on the ways to improve prognosis and indications for immunotherapy. Correct choice of biomarkers for predicting the response to immunotherapy will ensure more precise selection of patients. This review of immunotherapy methods aims to help clinicians with the indications for this relatively new treatment which has revolutionized treatment standards. Immunotherapy has many forms, including oncolytic virus therapy, chimeric antigen receptor T-cell therapy (CAR), cancer vaccines, and adoptive T-cell therapy, in particular, immune checkpoint inhibitors, first generation of which includes monoclonal antibodies against PD-1 (pembrolizumab, nivolumab, and cemiplimab), against PD-L1 (atezolizumab, avelumab, and durvalumab), and against CTLA-4 protein (ipilimumab)