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Low molecular weight heparins, in particular enoxaparin, have a wide range of applications, including prevention and treatment of deep vein thrombosis. The most common adverse effects of these drugs are bleeding and thrombocytopenia, but a clinician should be aware of another less common but not less important adverse effect such as an elevated transaminase level. In 2019, we observed two cases of enoxaparin-induced hepatotoxicity. In the first one, enoxaparin 0.4 ml subcutaneously twice a day was prescribed to a 40-year-old woman as a bridge therapy to discontinue warfarin before elective surgery. In the second case, a 27-year-old man received enoxaparin 0.4 ml subcutaneously twice a day for the prevention of deep vein thrombosis. The elevation of transaminase level for more than 3 times above the norm was noted in both patients which required discontinuation of the drug.

Background. Gastric cancer is the second leading cause of cancer-related death due to advanced disease. A special role in the pathogenesis and metastasis of the tumor is assigned to tumor stem cells (TSC ), responsible for resistance to chemotherapy and radiotherapy and causing tumor progression.Objective: to determine the CD 44 and CD 133 markers of TSC in tumor tissues of non-metastatic and metastatic gastric cancer using the immunohistochemical method.Material and Methods. A prospective study of tumors in patients with gastric cancer was conducted: Group 1 – 20 people with T3–4aN0–3M0G2 tumor, average age 58.9 ± 9.7; Group 2 – 20 people with T3–4aN0–3M1G2 tumor, with metastases in the peritoneum, average age 53.4 ± 11.9. The expression of CD 44 and CD 133 in the tumor tissue was determined by immunohistochemistry.Results. Differences were found in the number of tumor cells expressing the CD 44 marker in the presence and absence of metastases in patients with gastric cancer – their number was 10.0 ± 3.08 and 6.0 ± 2.3, respectively. The CD 133 molecule was detected in 100 % of cases having metastases, while in cases having no metastases, the marker was detected only in 80 % of cases. The average percentage of CD 133 + cells was 21.3 ± 11.6 % in patients with metastatic gastric cancer and 10.0 ± 2.4 % in patients having no metastases.Conclusion. The degree of expression of the CD 44 and CD 133 markers had characteristic differences in patients with gastric cancer, which can be used further to explain the results of the treatment and the prognosis of the disease.

The purpose was to study antitumor effects of the group K rotaviruses strains No. 228 and No. 100 in the experiment on a model of transplantable murine melanoma. Material and methods. The study included 65 С57Black/6 mice with transplantable B16/F10 melanoma and two strains of the Reoviridae family members characterized as rotaviruses, not belonging to the known groups, with the working title “group K rotaviruses (RVK)”. Animals received RVK in “vaccination” (before tumor transplantation) and “treatment” (after tumor formation) modes. Live and inactivated strains were used. RVK were administered intramuscularly as 0.3 ml of virus-containing culture fluid with at least 5x109 viral particles per 1 ml, with a total of 4 injections. Life span of mice and morphological characteristics of tumors were evaluated. Results. Injections of both strains increased the survival of tumor-bearing mice by 1.7-1.9 times in 4 of 8 experimental groups, compared to controls. The modes of RVK administration showed some differences: the survival was longer in mice with the “vaccination” mode compared to the “treatment” mode. Morphological changes in tumors were similar after application of both modes and inclued dystrophic changes of tumor cells, formation of extensive necrosis areas, and leukocyte infiltration. Discussion. Live and inactivated RVK had unidirectional effects implying its association with immunomodulatory action rather than with a direct lytic effect on the tumor. Conclusions. Both studied strains of rotaviruses in the group K had antitumor effect in the model of transplantable В16/F10 murine melanoma in the «vaccination» mode.

The objective of the paper is to study the clinical and functional characteristics of chronic H. pylori-associated gastritis in the elderly patients. Materials and Methods. A group of elderly patients (n=116) (aged 69.5±3.2) with chronic H. pylori-associated gastritis was formed during a prospective clinical study. All patients underwent esophagogastroduodenoscopy with biopsy. OLGA staging system was used for histological assessment. The dyspeptic index (DI) was used to measure dyspepsia. The patients were followed up for 48 weeks. Results. Dyspepsia was found only in 41.3 % of patients, while 58.7 % of patients had asymptomatic disease progression. Atrophic changes in the gastric mucosa were found in 30.1 % of the trial subjects. The efficacy of the eradication therapy was 88.7 %. During the study, the endoscopic picture of the gastroduodenal zone improved. There was no progression of atrophic and metaplastic changes in the gastric mucosa. Conclusion. Thus, in elderly patients, chronic H. pylori-associated gastritis is often asymptomatic. Eradication of H. pylori infection promotes disease remission and prevents morphological changes in the gastric mucosa. Keywords: chronic gastritis, Helicobacter pylori, atrophic gastritis, dyspepsia, old age, eradication therapy. Цель – изучить клинико-функциональные особенности течения хронического H. pylori-ассоциированного гастрита у лиц пожилого возраста. Материалы и методы. В процессе проспективного клинического исследования была сформирована группа больных (n=116) пожилого возраста (69,5±3,2 года) с хроническим H. pylori-ассоциированным гастритом. Всем больным была выполнена эзофагогастродуоденоскопия с биопсией. Для гистологической оценки применяли классификацию OLGA. Для оценки диспепсического синдрома использовали диспепсический индекс (ДИ). Длительность наблюдения больных составила 48 нед. Результаты. Наличие диспепсического синдрома было установлено у 41,3 % больных, 58,7 % пациентов имели бессимптомное течение заболевания. У 30,1 % обследуемых выявлены атрофические изменения слизистой оболочки желудка. Эффективность проведенной эрадикационной терапии составила 88,7 %. В процессе исследования установлено улучшение эндоскопической картины гастродуоденальной зоны. Отмечено отсутствие прогрессирования атрофических и метапластических изменений слизистой оболочки желудка. Выводы. У больных пожилого возраста течение хронического H. pylori-ассоциированного гастрита чаще имеет бессимптомный характер. Эрадикация инфекции H. pylori способствует ремиссии заболевания и предотвращает морфологические преобразования слизистой оболочки желудка. Ключевые слова: хронический гастрит, Helicobacter pylori, атрофический гастрит, синдром диспепсии, пожилой возраст, эрадикационная терапия.

Aim. To analyze the expression of the p53 and Ki67 markers in patients with stage IIIC-IV ovarian cancer by immunohistochemical (IHC) method as a criterion for the treatment effectiveness. Materials and Methods. The study included 93 patients with ovarian cancer stage IIIC-IV aged 34-77 years. The patients were divided into 4 groups: group 1 – with neoadjuvant chemotherapy and intramuscular injections of recombinant interferon-gamma; group 2 – with neoadjuvant chemotherapy and intraperitoneal injections of recombinant interferon-gamma; group 3 (controls) – standard chemotherapy without interferon-gamma; group 4 (comparison group) – with surgery as the first stage of treatment. All tumor samples were studied by IHC method for the expression of p53 protein and Кi-67 marker of proliferative activity. Results. Neoadjuvant chemotherapy did not affect the levels of p53, compared to the group without chemotherapy. Inclusion of interferon-gamma to neoadjuvant chemotherapy resulted in statistically significant decrease in p53 expression, mainly with intraperitoneal administration. Study of proliferative potential of tumors in patients with intraperitoneal injections of interferon-gamma showed 1.3 times higher predomination of tumors with low proliferative activity com-pared to patients with intramuscular administration, 3.5 times higher compared to the group re-ceiving chemotherapy without interferon-gamma, and 7 times higher than in patients with sur-gery. High proliferative activity was noted only in tumor cells of patients without neoadjuvant chemotherapy. Conclusions. The IHC study demonstrated that inclusion of interferon-gamma to chemotherapy decreases proliferative potential of tumors and expression of р53 by tumor cells in ovarian cancer patients, especially with intraperitoneal introduction in the course of neoadjuvant chemotherapy.

Purpose of the study. Evaluation of the expression of E- and N-cadherins in tumor tissues in postmenopausal patients with primary operable luminal breast cancer (BC) without Her2/neu overexpression for inclusion in the panel of a comprehensive assessment of tumor biological parameters for the disease prognosis. Patients and methods. The study included 120 patients divided into two groups: patients with luminal A and luminal B subtypes. To evaluate the prognostic significance of E- and N- cadherins in both groups of patients, we analyzed expression levels and correlation using the Mann- Whitney U-test and Spearman correlation criterion; overall survival, progression-free and tumor- specific one, at various values of the studied biomarkers — by the Kaplan- Meier method. Results. The differences in the mean expression levels were not statistically significant (p>0,05). E-cadherin was twice higher in luminal A BC (55.4±5.2) compared to luminal B BC (28.1±4.9), N-cadherin in luminal A BC (12.8±5.3) was 1.3 times lower than in luminal B BC (17.06±5.4). Patients with luminal B BC demonstrated a tendency to the loss of E-cadherin and increased expression of N-cadherin, which is often associated with poor prognosis. However, the correlation between these markers was not statistically significant (p>0,05). Conclusions. Thus, despite the differences in levels of E- and N-cadherin expression, these markers did not show their prognostic significance, and therefore, they were not included in the panel for a comprehensive assessment of tumor biological parameters when determining the prognosis of luminal breast cancer without Her2/neu overexpression in postmenopausal women.

The development of the tumor process involves the involvement of various functional elements of innate and adaptive immunity. A special role in the reorganization of tissues, changes and evolution of the properties of cancer cells is given to cytokines, the study of the role of which in these processes with various types of neoplasms and, in particular, with nonmetastatic gastric cancer is an urgent task. The aim of the work was to determine the characteristics of the cytokine status in the tissues of patients with non-metastatic gastric cancer. Materials and methods. In the extracts of tumor tissue, perifocal zone, omentum, peritoneum of patients with gastric cancer without metatstases (T3-4aN0-3M0, n = 20, 58.9 ± 9.7 years), the concentration of IL-1P, IL-2, IL -6, IL-8, IL-18, TNF-a, IL-10 and IL-1RA in tumor tissue, the perifocal zone, as well as in the omentum and peritoneum. Results and discussion. In the tumor tissue, an increase in the content of IL-1P, IL-8 and a decrease in IL-2, TNF-a and IL-10 were noted. In the perifocal zone, a decrease in the concentration of IL-1P, IL-6, IL-8 was revealed with an increased content of IL-2, IL-1RA, IL-10, TNF-a and IL-18. Against this background, the omentum and peritoneum compared with the tumor, the concentration of IL-1P, IL-18 and IL-1RA is reduced, against the background of an increase in the concentration of IL-2, IL-6, TNF-a and IL-10. Findings. It was shown that tumor tissue has some features in the cytokine profile compared with unaffected tissues, which can be used to further evaluate the development of the pathological process.

Author(s): Rutz, JJ; Shields, CA; Lora, JM; Payne, AE; Guan, B; Ullrich, P; O’Brien, T; Leung, LR; Ralph, FM; Wehner, M; Brands, S; Collow, A; Goldenson, N; Gorodetskaya, I; Griffith, H; Kashinath, K; Kawzenuk, B; Krishnan, H; Kurlin, V; Lavers, D; Magnusdottir, G; Mahoney, K; McClenny, E; Muszynski, G; Nguyen, PD; Prabhat, M; Qian, Y; Ramos, AM; Sarangi, C; Sellars, S; Shulgina, T; Tome, R; Waliser, D; Walton, D; Wick, G; Wilson, AM; Viale, M | Abstract: Atmospheric rivers (ARs) are now widely known for their association with high-impact weather events and long-term water supply in many regions. Researchers within the scientific community have developed numerous methods to identify and track of ARs—a necessary step for analyses on gridded data sets, and objective attribution of impacts to ARs. These different methods have been developed to answer specific research questions and hence use different criteria (e.g., geometry, threshold values of key variables, and time dependence). Furthermore, these methods are often employed using different reanalysis data sets, time periods, and regions of interest. The goal of the Atmospheric River Tracking Method Intercomparison Project (ARTMIP) is to understand and quantify uncertainties in AR science that arise due to differences in these methods. This paper presents results for key AR-related metrics based on 20+ different AR identification and tracking methods applied to Modern-Era Retrospective Analysis for Research and Applications Version 2 reanalysis data from January 1980 through June 2017. We show that AR frequency, duration, and seasonality exhibit a wide range of results, while the meridional distribution of these metrics along selected coastal (but not interior) transects are quite similar across methods. Furthermore, methods are grouped into criteria-based clusters, within which the range of results is reduced. AR case studies and an evaluation of individual method deviation from an all-method mean highlight advantages/disadvantages of certain approaches. For example, methods with less (more) restrictive criteria identify more (less) ARs and AR-related impacts. Finally, this paper concludes with a discussion and recommendations for those conducting AR-related research to consider.

The problem of drug abuse in various territories of the Russian Federation continues to be critically important. The availability of large administrative territory uniting numerous regions with diverse characteristics results in polarization of drug abuse indicators. The purpose of study is to analyze regional characteristics of drug abuse in the Russian Federation to develop general scope of drug abuse spreading to propose effective anti-drug policy meeting challenges of current drug abuse situation. The regions of the Russian Federation that suffer, according to official statistics data, maximum and minimum indices of drug abuse are considered. The results of analysis of current medical statistics (indices of number of people with first-time established drug dependence syndrome, as well as number of people with first-time established diagnosis of "harmful drug abuse", number of cases of acute drug intoxication, etc.), law enforcement statistics (indices of number of established crimes related to illicit drug trafficking, structure of the most common drugs, etc.). The analysis of related publications, as well as research data from sociological studies of deviant behavior implemented by the Federal Center of Theoretical and Applied Sociology of the Russian Academy of Sciences was also implemented. The conclusions are presented concerning most risky regional characteristics in drug abuse sphere, as well as regional particularities that function as a kind of protective factors against the drug abuse prevalence.

Aspergillus fumigatus colonization in the patients with cystic fibrosis (CF) may cause sensitization against A. fumigatus and/or allergic bronchopulmonary aspergillosis (ABPA), which significantly worsens the course of underlying disease. At the present time, new diagnostic tests are searched for detection of fungal sensitization in these patients. The aim of this work was to evaluate an opportunity of application of basophile activation test with A. fumigatus allergen in vitro using flow cytometry, aiming for identification of fungal sensitization in the CF patients. The study included 190 patients with CF aged 1 to 37 years. All the patients underwent common allergy screening (skin tests with fungal allergens, determination of serum levels of total IgE and specific IgE for the fungal allergens), and mycological examination (microscopy and culture of respiratory substrates). Computed tomography of the chest was performed upon clinical indications. The basophil activation test with the A. fumigatus allergen was performed in 10 CF patients with ABPA, and 10 CF patients without ABPA, in addition to the standard allergological examination. Frequency of sensitization to A. fumigatus in the patients with cystic fibrosis was 27%, the incidence of allergic bronchopulmonary aspergillosis was 5.7%. The number of eosinophils, total IgE and specific IgE levels in CF patients with ABPA were significantly higher than in CF patients without ABPA. In blood of the ABPA patients we have identified 68.5 (52.5-81.5%) of basophilic leukocytes activated by A. fumigatus allergen, with a stimulation index of 17.07 (10.30-27.70). In appropriate comparison group, the stimulation index did not exceed 1.5 (p = 0.000). Direct positive correlation between the levels of specific IgE to A. fumigatus and the number of basophils activated by A. fumigatus allergens was revealed (r = 0.77; р < 0.05). FVC values and the body mass index in CF patients with ABPA were significantly lower when compared with the patients without fungal sensitization. Introduction of the basophil activation test, along with standard techniques, may enable a more differentiated assessment of ABPA development in CF patients. Timely detection of associations between A. fumigatus sensitization and clinical status of CF patients will facilitate early and effective administration of specific therapy.

An adult patient with progressive chronic cerebral ischemia associated with moyamoya disease who underwent combined revascularization of both cerebral hemispheres in step-by-step fashion is reported in the article. The feature of this case is a large volume of revascularization procedures with double-barrel extra-intracranial anastomoses combined with indirect synangioses. This surgical approach ensured early postoperative development of extensive collateral network and complete compensation of impaired cerebral circulation. Particular attention is paid to description and discussion of preoperative diagnosis, the choice of surgical treatment, as well as the features of surgical technique. The advantages and disadvantages of this approach are discussed in comparison with literature data.В работе представлено редкое клиническое наблюдение: взрослый пациент с прогрессирующей хронической ишемией головного мозга, обусловленной болезнью моямоя, которому проведена этапная комбинированная реваскуляризация обоих полушарий мозга. Особенностью этого случая является большой объем выполненных реваскуляризирующих вмешательств в виде «двуствольных» экстраинтракраниальных анастомозов в сочетании c комбинацией непрямых синангиозов. Подобная тактика хирургического лечения позволила уже в короткие сроки после операции добиться развития обширной сети коллатералей и полностью компенсировать имевшийся дефицит мозгового кровообращения. Особое внимание уделено описанию и обсуждению предоперационной диагностики, выбору тактики хирургического лечения, а также особенностям техники оперативного вмешательства. Обсуждаются преимущества и недостатки использованного подхода по сравнению с данными, представленными в литературе.

Context: Physiological insights into blood flow alterations in cortical vessels after superficial temporal artery-middle cerebral artery (STA-MCA) bypass surgery are important for the prognosis of bypass sustainability and hemodynamic patency. Aims: This study aims to assess the impact of STA-MCA bypass on local hemodynamics for patients with symptomatic carotid occlusions and Moyamoya disease. Settings and Design: This article presents a prospective nonrandomized study of intraoperative blood flow measurements in cortical branches of MCA and donor vessel before and after cerebral revascularization. Materials and Methods: Evaluation of local hemodynamic parameters was established for 112 patients with symptomatic carotid occlusive disease and cerebrovascular insufficiency during STA-MCA bypass surgery. We used intraoperative Doppler ultrasonography (89 patients – 72%), flowmetry (56 cases – 50%), and in 33 cases both methods. For physical justification of observed facts, we performed computational simulation with OpenFOAM CFD framework using Navier-Stokes nonstationary hemodynamic model. Statistical Analysis Used: All calculations were performed with IBM SPSS Statistics version 10.0 software. We used parametric (Z-test and Student's t-test) and nonparametric models (Wilcoxon, Mann–Whitney). For categorical values, we used Fisher's exact test. Results: Local cerebral hemodynamics after revascularization surgery significantly depended on initial perfusion deficit and the ability of bypass to reverse the blood flow in proximal parts of cortical artery (86 cases, 77%). Mechanism of cortical blood flow alteration was related to donor vessel cut flow value and potential consumption threshold of acceptor artery. Conclusions: Knowledge of hemodynamic principles of flow redistribution after STA-MCA bypass is important to improve bypass stainability and leads to better revascularization results.

Background. The intracranial changes in children with mild traumatic brain injury in acute period are identified by a combination of clinical-neurological and ultrasonographic evaluations of the condition severity. Aim. The aim of the study was to assess the possibility of performing comprehensive clinical and ultrasonographic evaluations in for determining the severity of the neurological condition of children with mild traumatic brain injury in an acute phase. Materials and Methods. Clinical and ultrasonographic assessment of the severity of the neurological condition was performed on 256 patients with clinical criteria suggesting mild traumatic brain injury. Ultrasonography was used as the main neuroimaging. Results. We found that the diagnostic sensitivity of clinical and ultrasonographic examination for detecting traumatic structural intracranial changes in children with mild traumatic brain injury was 90% (95% confidence interval [CI] 0.71–0.98), diagnostic specificity was 97% (95% CI 0.96–0.98), and diagnostic efficiency was 94.9% (95% CI 0.918–0.971). Conclusions. A comprehensive clinical ultrasonographic approach can be effectively used to assess the severity of the neurological condition of children with mild traumatic brain injury in the acute phase.

e17530 Background: Despite the progress made in diagnosis and treatment, ovarian cancer (OC) is still the third most common genital cancer. Poor results of therapy for various forms of OC stimulate the search for fundamentally new approaches to the treatment. One of the main reasons for resistance to chemotherapeutic agents includes multidrug resistance (MDR) of tumor cells. The most characterized of its various mechanisms is the elevated activity of the ABC family protein - ABCB1 (Pgp or MDR1). The purpose of the study was evaluation of the expression of this ABC transporter as a predictive factor in platinum-containing chemotherapy in OC patients. Methods: 100 patients aged 29-79 years with advanced stage IIIC - IV OC with/without ascites were recruited between 2016 and 2020. Depending on the treatment results, patients were divided into 2 groups: group 1 (n = 59) - patients with platinum sensitivity; group 2 (n = 41) - patients with platinum resistance during the treatment or within 6 months after its completion. IHC analysis was performed using rabbit polyclonal anti-MDR1 antibodies (Affinity Biosciences) diluted 1:600 and the Reveal Polyvalent HRP-DAB Detection System. The percentage and the intensity of staining were assessed: 0, 1+ weak, 2+ moderate, 3+ strong. MDR1 expression was considered positive when staining was detected in more than 10% (cut-off) tumor cells with intensities of 2+ and 3+. Statistical analysis of results was performed in the Statistica 13.0 program (StatSoftInc., USA). Results: Patients with MDR1+ prevailed in group 2 (98%), and patients with MDR1- in group 1 (32%). The average expression of MDR1 in tumor cells in group 2 (64.0±7.0) was statistically significantly higher by 1.7 times (p = 0.003) than in group 1 (37.2±6.8) by the Mann-Whitney U-test. When distributed according to Pearson's χ2 criterion, positive MDR1 as a risk factor in the platinum-resistant group increased the risks of refractory to platinum therapy by 19 times (95% CI 2.4-148.8). Conclusions: The study demonstrated predictive significance of the MDR1 biomarker in platinum treatment in patients with ovarian cancer.

e21069 Background: Metabolites of the intestinal microbiota, including adipokines, batokins, and myokines, are involved in carcinogenesis, antitumor immune defense and ensuring the effectiveness of antitumor treatment, including chemotherapy and immunotherapy. Methods: The study included 100 patients with lung cancer (LC), 70% males and 30% females: stage I – 10%, II - 14%, III – 50%, IV – 26%. 21 patients (12 males and 9 females) received treatment with PD-1/PD-L1 inhibitors: stage I - 2 (9%), II - 1 (5%), III - 5 (24%), IV - 12 (62%). Therapy included atezolizumab and pembrolizumab – 9 patients each (43%), nivolumab – 3 (14%). Complete response was registered in 2 (9%), partial response in 5 (24%), stabilization - 4 (19%), progression - 8 (38%). One patient developed an immune-mediated adverse event (Guillain-Barré syndrome), so checkpoint inhibitors (CPI) were canceled. Serum levels of adipokines, myokines, batokines, and growth factors were determined by ELISA before and during treatment. The control group included 100 healthy donors. Results: Levels of VEGF and NGF were statistically significantly higher in patients with lung cancer than in donors, without differences in other parameters. Differences were revealed depending on the LC stage: leptin was higher in stages I and IV (Me 52.8 and 46.3 ng/ml, respectively) compared with stages II and III (Me 27.4 and 16.4 ng/ml, respectively) and with donors (Me 12.5 ng/ml). In stages III and IV, levels of VEGF increased (Me 504 and 473 pg/ml, respectively; in donors Me 239 pg/ml), while BDNF decreased (Me 2.7 and 0.4, respectively, in donors Me 12.6 μg/ml); NGF in stages I and II was not detected, unlike stages III and IV. Immunotherapy with CPI elevated levels of adiponectin (Me 12.5 and 16 μg/ml, respectively), and reduced levels of myostatin (Me 26.4 and 2.8 μg/ml, respectively) and NGF (Me 130 and 53 pg/ml, respectively). Only NGF could be regarded as a predictive factor of the response to CPI, since it was detected in high amounts only in patients with subsequent LC progression, while in patients with a positive response to treatment or stabilization, it was absent both before and after immunotherapy. Conclusions: Serum levels of some adipokines, myokines, batokins, and growth factors in LC patients differ depending on the cancer stage and the result of CPI immunotherapy; thus, NGF can be used as a predictor of the immunotherapy effectiveness. The study was performed with financial support from the Federal Medical and Biological Agency of Russia under contract No. 0373100122120000017 dated 20.05.2020.

e16508 Background: Bladder cancer (BC), which accounts for 4.5% of the total cancer incidence, is the cause of frequent severe disability and a significant deterioration in the quality of life of patients. BC development is determined by a number of factors, involving the immune system; however, its role is poorly understood. The purpose of the study was to determine characteristics of parameters of the cellular immunity in patients with non-muscle invasive BC. Methods: The study included 14 patients with newly diagnosed stage I BC. Patients were divided into two groups: with low-grade tumors (LG), n = 7, mean age 57 years; with high-grade tumors (HG), n = 6, mean age 60 years. All patients underwent transurethral resection of the bladder, and tumor tissues (TT, size up to 1.5 cm) and perifocal tissues (PT, at least 0.5 cm from the tumor) were obtained. The specimens were disintegrated to obtain the cell suspension. The relative numbers of the main populations of leukocytes and T- and B-lymphocytes, as well as some subpopulations of T-lymphocytes, were determined using the BD FACSCanto II flow cytometer and a panel of antibodies according to the manufacturer's instructions (Becton Dickinson, USA). Results: Reduction of lymphoid tissue infiltration by 78% was observed in TT in HG patients, compared to the LG group; levels of CD8+ lymphocytes, CD3+CD4-CD8- and CD3+CD4+CD8+ cells, NK- and B-lymphocytes were lower by 27%, 33%, 51%, 45% and 62%, respectively. Levels of Treg in HG TT were 32% lower than in LG. The numbers of activated CD4+, CD8+ cells were unchanged, but TT infiltration by naive lymphocytes of both populations was increased by 28% and 31%, respectively. In HG PT, a decrease in the total number of lymphocytes by 27% was observed, together with higher levels of CD3+CD4+CD8+ cells and NK- and B-lymphocytes by 200%, 213% and 31%, respectively. Conclusions: BC patients with various tumor grades demonstrate different distributions of lymphocyte populations in tumor and perifocal tissues; the functional activity of these cells can both contribute to the disease development and determine the risk of recurrence.

e15509 Background: Intravasation and circulation of tumor cells involves active invasion of cells with an enhanced migration potential as a result of the epithelial-mesenchymal transition (EMT). The ZEB1 protein is one of the key regulators of this process. Our purpose was to evaluate the association between the amount of circulating tumor cells (CTCs) in the peripheral blood of patients with different stages of colorectal cancer and the expression of ZEB1 by tumor cells. Methods: The study included 299 patients (aged 42-86 years, mean age 64.2±1.7) with stage II-IV CRC T1-4N0-2M0-1; histologically verified G1-G3 adenocarcinoma in all patients. The numbers of CTCs were measured in the peripheral blood before surgery using the Veridex CellSearch system (Janssen). CTCs were registered taking into account morphological characteristics and expression of epithelial cell adhesion markers EpCAM, CD45, cytokeratins 8,18,19. The blood sample was evaluated according to the following criteria: 0 CTCs, 1-3 CTCs, and more than 3 CTCs. Tissues of surgically removed tumors were studied with IHC analysis using rabbit polyclonal anti-ZEB1 antibodies (Biorbyt Ltd.) diluted 1:200 and the Reveal Polyvalent HRP-DAB Detection System. The percentage and the intensity of staining were assessed: 0, 1+ weak, 2+ moderate, 3+ strong. ZEB1 expression was considered positive when staining was detected in more than 10% (cut-off) tumor cells with intensities of 2+ and 3+. Statistical analysis of results was performed in the Statistica 13.0 program (StatSoftInc., USA). Results: From 1 to 402 CTCs were determined in 62.9% cases (in 188 of 299 patients); CTCs were not registered in 37.1% cases (111 of 299). Positive ZEB1 expression was observed in 80.6% (241 of 299 patients), while the negative one was much more rare – 19.4% (58 of 299 patients). The rates of CTC detection significantly increased with the positive ZEB1+ expression, compared to the negative expression (75.1% vs. 12.1%). CTCs >3 were detected in the blood in 39.0% in ZEB1+ tumors, but not in ZEB1- tumors. 1-3 CTCs were observed 3 times more often in ZEB1+ tumors (36.1% vs. 12.1; p≤0.05). Conclusions: Statistically significant association was revealed between the epithelial-mesenchymal transition marker ZEB1 expression by tumor cells and the amount of CTCs in the peripheral blood (p < 0.001).

e21573 Background: The purpose of the study was to assess the possible synergism of strains of a new rotavirus group (Reoviridae family) and PD-1 inhibitor pembrolizumab (P) on the growth of murine transplantable melanoma В16/F10. Methods: The study was performed using a strains 228 and 100 of a new group of rotaviruses (working title «group K», RVK) ( http://jbks.ru/archive/issue-10/article-6 ). RVK is a live attenuated and apathogenic strain growing on the PEKC culture (pig embryo kidney cells) with 5·109 viral particles/mL. Melanoma B16/F10 was transplanted subcutaneously (2x106 living tumor cells/mL) to 40 female mice C57/Bl6. RVK strains (0.3 ml of a virus-containing fluid) were injected intramuscularly once a week during 5 weeks before tumor transplantation and P was administrated intramuscularly (0,04 µg once a week during the life span of the mice) after formation of the visible tumor. The 1 experimental group received RVK 228+P, the 2 – RVK 100+P, the 3 – only P, the 4 group was tumor-bearing control; n was 10 in each group. Results: 1 week after melanoma transplantation tumor was visible and palpable in all the mice except those of the 1 group; 10 days after transplantation tumor size was 0.028±0.0046 cm3 in the 1 group, 0.14±0.055 in the 2 group, 0.24±0.05 in the 3 group, 0.21±0.042 in the control group. A week later these parameters were 0.6±0.24, 0.99±0.3, 1.3±0.25, и 2.1±0.3 сm3 respectively, i.e. in all the experimental groups they were decreased vs control (р < 0.05). 3 weeks after transplantation the melanoma size became equal in the 3 and 4 groups (2.0±0.38 и 2.43±0.38 сm3 respectively) while in mice of the 1 group it remained decreased (1.17±0.26 сm3; р < 0.05). 1 month after transplantation the minimal tumor size was observed in mice of the 2 group (1.9±0.6 cm3), in the 1 group it was 2.6±0.17 сm3. By this time only 1 mouse survived in control group while 5 mice survived in the 3 and 1 groups, 6 mice in the 2 group. So in both of the groups vaccinated with RVK before P tumor burden was less than in controls and in mice with only P. The life span of all the experimental groups was similar and significantly higher than in controls. Conclusions: Application of RVK strains №228 and №100 in vaccination mode enhanced the antitumor effect of PD-1 inhibitor pembrolizumab on B16/F10 growth; this defines a solid rationale for their joint use. Strain 228 demonstrates the result in early and strain 100 – in later term of tumor growth.

3522 Background: Cancer stem cells (CSCs) capable of self-sustaining and multipotent differentiation are considered among the most important factors limiting treatment effectiveness. ALDH1 is a marker of colorectal cancer (CRC) CSCs; it is involved in cell differentiation and proliferation, determines resistance to alkylating chemotherapeutic agents, and also induces epithelial-mesenchymal transition (EMT), which increases the invasive and metastatic potential of tumors. The purpose of the study was to assess the association between the expression of the ALDH1 CSC marker in tissues of CRC of different stages and clinical and morphological factors of the disease prognosis. Methods: The study included 299 patients (aged 42-86 years, mean age 64.2±1.7) with stage II-IV CRC T1-4N0-2M0-1; histologically verified G1-G3 adenocarcinoma in all patients. Tissues of surgically removed tumors were studied with IHC analysis using mouse monoclonal anti-ALDH1 antibodies (clone B-5, Santa Cruz Biotechnology) diluted 1:1800 and the Reveal Polyvalent HRP-DAB Detection System. The percentage of cells positively stained for ALDH1 among all tumor cells was assessed. Statistical analysis was performed using the STATISTICA 13.0 program (StatSoftInc., USA). Results: Positive ALDH1+ expression was registered in 52.5% of all patients, negative expression – in 47.5%. Statistically significant association was observed between the ALDH1 expression and the CRC stage, since the ALDH1+ expression increased from stage II to stage IV (p = 0.003). The ALDH1 expression was statistically significantly associated with the depth of tumor invasion (p = 0.018) and the presence of distant metastases (p < 0.001). No significant relationship was observed between the ALDH1 expression and regional lymph node metastasis (p = 0.788). Statistically significant association was registered between the ALDH1 expression and the tumor grade (p < 0.001), perineural invasion (p = 0.010) and lymphocytic infiltration (p < 0.001). No significant relationship was observed between the tumor histological structure (p = 0.979), lymphovascular invasion (p = 0.772) and ALDH1 expression. Tumor site was not statistically significantly associated with ALDH1 expression (p = 0.349). Conclusions: The study demonstrated statistically significant association between the ALDH1 expression and clinical and morphological characteristics of CRC, determining invasive and metastatic potential of the tumor, and ALDH1 may be an independent prognostic factor and a new therapeutic target for the regulation of the progression process.

e17528 Background: Resistance to chemotherapy is a complex problem in the treatment of patients with ovarian cancer (OC). Various intercellular intermediates are involved in the phenomenon, and cytokines are the most important of them; however, the involvement of individual representatives in the processes is poorly understood. Our purpose was to analyze levels of some cytokines in tumors of OC patients with different responses to chemotherapy they receive. Methods: Samples of ovarian tumors were obtained from 100 patients (aged 29-79 years) with advanced ovarian cancer stage IIIC-IV with/without ascites. All patients recruited in 2016-2020 received standard combination treatment with surgery and platinum-containing polychemotherapy (Pt CT). Based on the results of neoadjuvant Pt CT, patients were divided into groups: patients with stabilization or progression–group 1 “without effect”; patients with complete/partial regression–group 2 with positive effect. All patients gave their informed consent for the study. Levels of IL-6, IL-8 and IL-10 were measured in cytosolic fractions of tissue samples using standard ELISA test systems (Vektor-Best, Russia). Results were presented as Me (LQ; UQ). The significance of differences between the samples was assessed using the Mann-Whitney test (the differences were considered significant at p

e15510 Background: Tumor is a structure where malignant cells interact, among others, with cells of the adaptive and innate immune systems largely determining the tumor microenvironment. The role of TILs in the disease prognosis has been shown. The amount of CTCs is one of the factors that significantly affect the risk and rate of metastasis. The purpose of the study was to assess an association between TILs and CTCs in the peripheral blood of patients with various stages of colorectal cancer (CRC). Methods: The study included 299 patients (aged 42-86 years, mean age 64.2±1.7) with stage II-IV CRC T1-4N0-2M0-1. TILs were identified in tumor material after standard histological processing. Lymphocytes were counted per 100 epithelial cells in 5 fields of view at a magnification of x400; the result was expressed as a percentage ( < 5% weak, 5-30% moderate, >30% strong). The numbers of CTCs were measured in the peripheral blood using the Veridex CellSearch system (Janssen), taking into account the expression of epithelial cell adhesion markers EpCAM, cytokeratins 8,18,19 and absence of the CD45 expression. The blood sample was evaluated according to the following criteria: 0 CTCs, 1-3 CTCs, and more than 3 CTCs. Statistical analysis of results was performed in the Statistica 13.0 program (StatSoftInc., USA). Results: Weak lymphocytic infiltration was detected in 32.8%, moderate - in 48.1%, strong - in 19.1% of cases. CTCs were detected in 62.9% cases (in 188 of 299 patients). The percentages of patients with 1-3 CTCs and with >3 CTCs were equal - 50% (94 of 188). CTCs were not registered in 37.1% cases (111 of 299). The absence of CTCs was noted equally often in moderate and strong lymphocytic infiltration – 43.7% and 43.8%. The presence of tumor cells in the peripheral blood was most often detected in weak lymphocytic infiltration, being 1.4 times more frequent than in moderate and strong infiltration (76.5% vs. 56.3% and 56.2%) (p = 0.019, c2= 11.890). Conclusions: The study demonstrated a significant relationship between the level of CTCs and the intensity of lymphocytic infiltration in the tumor (p≤0.05), which can be used as a new prognostic approach.

The aim of this work consists in the analysis of modern scientific conceptions about infectious salmon anemia (ISA) etiologically linked with ISAV (infectious salmon anemia virus) (Orthomyxoviridae, Isavirus). ISA is deadly disease of Salmonidae fishes. Discussion. ISA began to extend actively among salmon breeding farms since the extremity of the XX century and poses nowadays serious threat of fishing industry as there are no not only anti-ISAV chemopreparates and effective vaccines, but also scientifically based ideas of ISAV ecology. In the offered review data on the discovery history, taxonomical status, virion morphology and genome structure as well as ecology of ISAV, clinical features, pathogenesis and laboratory diagnostics, actions in the epizootic foci for the prevention of further distribution and prophylaxis of ISA, arrangement for protection against salmon louses and utilized approaches to anti-ISAV vaccines development are discussed. There is very important that ISAV is capable to be transferred by salmon louses – pelagic crustaceans (Copepoda: Caligidae) that allows to classify ISAV as arbovirus ecological group which are transferred due to biological transmission by arthropods (copepods) to vertebrate animals (salmons). It is the only example known so far when representatives of Crustacea act as a vector for arboviruses. Conclusion. Investigation of ISAV ecology turns into one of "touchstones" allowing to judge technological readiness of mankind to master resources of the World Ocean.

Sarcopenia is a progressive degenerative disorder affecting ≥40% of older adults over the age of 70 years. It is characterized by involuntary muscle loss leading to functional disability, weakness, and frailty in the elderly. Numerous mechanisms have been suggested as potential contributors to sarcopenia onset, including anorexia of aging, protein imbalances, and oxidative stress. While consensus preventive and management approaches for sarcopenia are not yet clearly defined, it is unquestionable that nutrition plays a critical role. This review focuses on the more widely studied, potent nutrients used to attenuate sarcopenia: protein/amino acids, vitamin D and calcium, antioxidants and omega-3 fatty acids. In efforts to achieve optimum delivery of these nutrients to target tissues in older adults it is important to also consider the issue of compromised digestive system that occurs with aging, which will contribute to suboptimal nutrients absorption and utilization. Therefore, this review aims to summarize key sarcopenia-attenuating nutrients and to distinguish for each identified nutrient whether a dietary or a supplemental form is the most effective therapy for nutrient delivery in sarcopenic older adults.

The article presents a case of using genetically engineered biopharmaceutical tocilizumab in a child with systemic juvenile idiopathic arthritis. On the initial stage, the treatment was characterized by resistance to high doses of glucocorticoids and cytostatic drugs. Successful termination of visceral and articular manifestations of systemic juvenile idiopathic arthritis and normalization of laboratory indicators of disease activity in the setting of use of interleukin 6 receptor blocker were described. We observed stable improvement of the child’s condition during a year-long follow-up in the setting of the selected anti-inflammatory therapy pattern.

Combined cerebral revascularization with direct and indirect components is recognized as the most appropriate method for treating patients with Moyamoya disease all over the world, however, large studies on its effectiveness in Russia have not yet been conducted.Was to evaluate the results of combined cerebral revascularization in patients with Moyamoya disease with an analysis of the clinical state and perfusion and angiographic features of neoangiogenesis.For the period from 2013 to 2020 in N.N. Burdenko National Medical Research Center of Neurosurgery 79 combined revascularizations were performed in 55 patients with Moyamoya disease. The average age was 13.9±10.11 years. All patients were examined according to a single protocol, including a comprehensive assessment of the clinical symptoms, the state of the brain tissue, the cerebral vascular system, and cerebral blood flow. The results of surgical treatment were evaluated in the early postoperative and long-term periods. The average follow-up period was 14.66±13.17 months. In the postoperative period, the dynamics of neurological status and cerebral blood flow were assessed and the features of neoangiogenesis from various components of revascularization were studied.In the early postoperative period, in 77.2% of cases, a good treatment result was observed, with no negative dynamics of the neurological status. Ischemic stroke in the operated hemisphere developed in 4 cases (5.1%). In the follow-up period, an improvement in neurological symptoms was observed in 76.6%. Improvement of cerebral blood flow was noted in 92.4% of cases, direct anastomoses functioned in 94.3%, and signs of neovascularization in the area of indirect synangiosis were observed in 80.0%. At the same time, a complementary influence of direct and indirect components of revascularization was revealed in ensuring good general angiographic and perfusion results.Combined revascularization is a highly effective method of surgical treatment of all patients with Moyamoya disease.Комбинированная реваскуляризация головного мозга с использованием прямых и непрямых компонентов признана наиболее целесообразным методом лечения пациентов с болезнью мойя-мойя во всем мире, однако крупных исследований по изучению ее эффективности в России до настоящего времени не было.Провести оценку результатов комбинированной реваскуляризации головного мозга у пациентов с болезнью мойя-мойя с анализом клинической картины, перфузионных и ангиографических особенностей неоангиогенеза.За период с 2013 по 2020 г. во ФГАУ «НМИЦ нейрохирургии им. акад. Н.Н. Бурденко» Минздрава России выполнено 79 комбинированных реваскуляризаций у 55 пациентов с болезнью мойя-мойя. Средний возраст больных составил 13,9±10,11 года. Все пациенты обследованы по единому диагностическому протоколу, включающему анализ клинического течения, комплексную оценку состояния мозговой ткани, сосудистой системы головного мозга и мозгового кровотока. Результаты хирургического лечения оценивали в раннем послеоперационном и отдаленном периодах. Средний срок катамнеза составил 14,66±13,17 мес. В послеоперационном периоде проведена оценка динамики неврологического статуса, мозгового кровотока, исследованы особенности неоангиогенеза при различных типах реваскуляризации.В раннем послеоперационном периоде в 77,2% случаев наблюдался хороший результат лечения с отсутствием отрицательной динамики неврологического статуса. Ишемический инсульт в прооперированном полушарии развился в 4 (5,1%) случаях. В отдаленном послеоперационном периоде улучшение очаговой и общемозговой неврологической симптоматики наблюдалось у 76,6% пациентов. Прямые анастомозы функционировали в 94,3% случаев, а признаки неоваскуляризации в области непрямых синангиозов наблюдались в 80,0%. Улучшение мозгового кровотока отмечалось в 92,4% случаев, при этом выявлено взаимодополняющее влияние прямых и непрямых компонентов реваскуляризации в обеспечении хорошего общего ангиографического и перфузионного результатов оперативного лечения.Комбинированная реваскуляризация является высокоэффективным методом хирургического лечения всех пациентов с болезнью мойя-мойя.

e22511 Background: Ewing's sarcoma is the second most common malignant tumor of bones and soft tissues in children and adolescents; it is characterized by an aggressive clinical course and extremely high metastatic potential. The process of its onset is well studied, but the processes of metastasis are of great interest both from a scientific point of view and in clinical practice. Epithelial-mesenchymal transition plays an essential role in tumor progression, and the ZEB1 protein is one of its key regulators. Our purpose was to evaluate the expression of ZEB1 as a prognostic factor in patients with localized and advanced Ewing's Sarcoma (ES) in children and adolescents. Methods: The study included 50 samples of primary ES of various locations. The patients (0-18 years) were divided into groups 1 (localized ES, n = 27) and 2 (advanced ES, n = 23). Rabbit polyclonal antibodies to ZEB1 (Biorbyt Ltd.) at a dilution of 1:200 and the Reveal Polyvalent HRP-DAB Detection System were used for IHC. The percentage and intensity of staining were evaluated: 0, 1+ weak, 2+ moderate, 3+ strong. ZEB1 expression was considered positive when staining was detected in more than 10% (cut-off) tumor cells with intensities of 2+ and 3+. Statistical analysis of results was performed in the Statistica 13.0 program (StatSoftInc., USA). Results: The average ZEB1 expression was in group 1 - 30.0±3.5%, in group 2 - 41.7±11.1%. The maximal accumulation of ZEB1 in the nuclei of tumor cells was observed in patients with advanced ES - 1.4 times (p = 0.248) higher than in patients with localized ES. However, the difference was not statistically significant (the Mann-Whitney U-test, p > 0.05). Conclusions: An IHC analysis revealed a tendency toward increased expression of ZEB1 in patients with advanced ES. However, a more extensive study is needed to evaluate the possible prognostic value of this marker.

e16557 Background: Gastric cancer (GC) is one of the most common malignant tumors and the second most common cause of cancer deaths in Russia. Many researchers note the ambiguous role of cytokines in the pathogenesis of tumor processes. The purpose of the study was to determine characteristics of the cytokine status in the omentum and peritoneum of patients with metastatic GC. Methods: The main group (Mgr) included 23 patients with T2-4N0-3M1 GC with metastases to the peritoneum and greater omentum, the mean age 58.9±9.7 years. The comparison group (Cgr) included 20 non-cancer patients, the mean age 55.9±9.7 years. Tissues of the omentum (OT) and peritoneum (PT) were obtained from all patients during cytoreductive and diagnostic surgeries. Ex tempore tissues were disintegrated using BD Medimachine (USA) with 0.9% NaCl; the cell suspension was centrifuged, and the supernatant was collected and aliquoted. Levels of cytokines IL-1β, IL-2, IL-6, IL-8, IL-18, TNF-α, IL-10 (Vektor-Best, Russia) and IL-1RA (eBioscience, Austria) were determined by ELISA. The results were expressed as the specific content per 1 g of protein evaluated by the biuret method (pg/mL/g of protein). Statisical analysis of the results was performed with the Statistica 10 program (StatSoft Inc., USA). Significance of differences was evaluated using the Mann-Whitney and Wilkinson tests; differences were considered significant at p < 0.05. Results: In Cgr, levels of IL-6, IL-8, IL-18 and IL-1β in OT were 4.1±1.1, 3.4±0.7, 21.2±5.5 and 10.8±2.1, while in Mgr – 55.3±24.4, 32.5±13.8, 144.9±48.4 and 21.01±5.4 pg/mL/g of protein, i.e. 13.7, 9.5, 6.9 and 1.9 times (p≤0.05) higher than in Cgr, respectively. The specific content of IL-1RA in OT was 12.6 times higher, p≤0.05 (215.7±69.8 vs. 2723.1±730.1), and the IL-10 concentration did not differ significantly. In PT of Cgr, levels of IL-8, IL-18 and IL-6 were 9.8±7.3, 35.2±21.7, 7.5±3.7, and in Mgr – 250.7±21.4, 322.9±16.9, 61.1±27.6 pg/mL/g, i.e. 25.7, 9.2 and 8.2 times (p≤0.05) higher than in Cgr. IL-1RA in PT of Mgr was 24.4 times higher than in Cgr, p≤0.05 (7656.2±3160.3 vs. 357.69±180.86). Conclusions: A certain microenvironment is formed in OT and PT affected by metastases, with specific features in the ratio and concentrations of various cytokines, which undoubtedly contribute to the formation of a secondary tumor.

e13087 Background: High incidence and mortality of breast cancer (BC) require a constant search for the most informative and effective methods of diagnosis and treatment evaluation. The purpose of the study was to analyze phenotypic characteristics of cancer stem cells in tumor tissues and regional metastases of breast cancer (BC). Methods: The study included 20 BC patients with regional metastases (lymph nodes) aged 32-74 years, mean age 56.1±3.3 years. IHC analysis was performed on sections from paraffin blocks of tumors using monoclonal mouse antibodies to CD44 (156-3C11 Thermo Scientific) at a dilution of 1:2500 and polyclonal rabbit antibodies to CD133 (Cloud-Clone Corp.) at a dilution of 1:700 using the Thermo Scientific automated stainer. Membrane staining and staining intensity were evaluated: 0, 1+ weak, 2+ moderate, 3+ strong staining. CD44 expression was considered positive when staining was detected in more than 10% (cut-off) tumor cells. CD133 expression was considered positive when staining was detected in more than 5% (cut-off) of the tumor. Results: CD44 + expression was detected in 80% of breast tumor tissues (16 samples), while in 20% this marker was not determined. The average CD44 expression was 27.2±13.9%. The expression of CD44 in regional metastases (RM) from BC was 35% (from 0 to 30%), on average 17.0±6.8%. When distributed according to the χ2 criterion in the tumor and RM, an association between factorial and resultant signs was statistically significant (8.286, at p < 0.004). CD133+ expression in tumor tissues was detected in 80%, with an average expression level of 56.0±14.6%, with a predominance of positive cytoplasmic staining in 60%. Determination of this marker in BC RM gave a positive result in 15% (3 samples), with expression fluctuations from 0 to 60%, the average level was 33.0±15.4%. When distributed according to the χ2 criterion in the tumor and RM, an association between factorial and resultant signs was statistically significant (16.942, at p < 0.001). Conclusions: Determination of tumor cells with the stem phenotype directly in the tissue of primary BC tumors and in tissues of regional metastases demonstrated that the percentage of CD44+ and CD133+ cells in the primary BC tumor was higher.

e16073 Background: The purpose of the study was a correlation analysis of parameters of local immunity and markers of the epithelial-mesenchymal transition (EMT) with the number of circulating tumor cells (CTCs) in patients with stage II-IV colorectal cancer (CRC). Methods: The study included 60 patients newly diagnosed with stage II-IV CRC. CTCs were detected with the Cell Search System (Janssen Diagnostics, LLC) prior to surgery. CTC≤3 were considered negative, CTC > 3 – positive. After surgery, IHC analysis of tumor infiltration with immune system cells was performed with monoclonal antibodies for human CD3, CD4, CD8, CD20 and CD56; expression of EMT-associated proteins (E-cadherin, N-cadherin) was measured. All patients were informed of the goal of the study and provided informed consent. Results: CTC-negative patients with later cancer stages showed the loss of connection between the local levels of CD4+ and CD8+, and in stage IV - between CD3+ and CD4+. Starting from stage III, a negative correlation was observed between the expressions of E- and N-cadherin, not associated with the studied indices of local cellular immunity. The presence of CTCs in all 3 investigated stages of CRC, apparently, causes the loss of many connections between the indicators of the 3 units of local cellular immunity. While negative correlations were revealed between T-, B- and NK-cells in CTC-negative status, in CTC+ their number decreased to 1. An important positive correlation was between local levels of CD3+ and CD8+, indicating the predominance of cytotoxic T cells in the tumor and detected at all stages in CTC-negative patients, losing significance in the presence of CTCs regardless of the stage. In stage II, the only correlation (inverse one) was observed between the parameters of local (CD4+) immunity and the expression of cadherins (E-cadherin), which probably reflected the presence of immunosuppressive and growth-stimulating Tregs fraction among these cells. Conclusions: In general, the presence of CTCs was more significant for the number and nature of interconnections of cellular parameters of the local immunity than the tumor stage.

e18031 Background: Cervical cancer is the fourth leading cause of cancer deaths among women worldwide. Since the uterus has receptors through which hormonal effects are realized, studies on the tissue receptor apparatus for estrogen and progesterone are relevant. The purpose of the study was to evaluate the correlation of PR and ER expression as a prognostic factor in cervical cancer. Methods: The study included 60 patients aged 28-65 years diagnosed with cervical cancer. Patients were divided into two groups: group 1 – endophytic pattern of tumor growth (n = 30), group 2 – exophytic pattern (n = 30). Eligibility criteria included morphologically confirmed squamous cell carcinoma of the cervix T1b-2aN0M0, stage I-II. Rabbit monoclonal antibodies for ER (Thermo scientific) and PR (Cell Marque) with the Reveal Polyvalent HRP-DAB Detection System were used for the IHC analysis. Statisical analysis of the results was performed with the Statistica 10 program (StatSoft Inc., USA). Results: The average expression of the ER marker was 5.4±3.03% for group 1 (endophytic tumors) and 13.9±8.2% for group 2 (exophytic tumors). The average PR expression was 0.5±0.3% and 1.6±1.1%, respectively. The maximal accumulation of both PR and ER in the nuclei of tumor cells was registered in patients of group 2, being 3.2 times (p = 0.931) and 2.6 times (p = 0.815) higher than in group 1, respectively. However, the difference was not statistically significant (the Mann-Whitney test, p > 0.05). The Spearman rank correlation test did not show statistically significant correlation between the groups and the markers (r = -0.218, p = 0.338). Statistically significant correlation was observed only in the group with exophytic pattern of tumor growth (r = 0.786, p < 0.01). Conclusions: The IHC analysis revealed a tendency to an increase in the expression of PR and ER in patients with exophytic tumors. However, the correlation between the expression of these indicators cannot be considered as a predictive factor in cervical cancer.

The main aim of the study was to investigate the effect of carotid endarterectomy on the prognosis of chronic cerebral ischemia in patients with symptomatic occlusions of the contralateral internal carotid artery, assess risks of surgical complications, and substantiate the staged surgical approach for treatment of patients with this pathology. The article analyzes the experience in surgical treatment of 83 patients with symptomatic ICA occlusions who underwent surgery for contralateral carotid artery stenosis. In 40 patients, only carotid endarterectomy (CEA) was performed on the side of hemodynamically significant stenosis (group 1). In 43 (52%) cases, apart from CEA, extracranial-intracranial (EC-IC) bypass was performed at the second stage (23 cases, group 2) or the first stage (19 cases, group 3). A surgical treatment approach was chosen based on clinical symptoms, severity of contralateral carotid artery stenosis, and the magnitude of perfusion deficiency in the territory of carotid occlusion. The conducted analysis revealed that patients with symptomatic occlusions and contralateral carotid artery stenoses represented a heterogeneous group with a different efficacy of carotid endarterectomy and with risks of perioperative complications. As cerebrovascular insufficiency in the territory of carotid occlusion and a related neurological deficit worsen, the risks of complications of contralateral carotid endarterectomy increase, and its clinical efficacy decreases. In these cases, cerebral revascularization on the ICA occlusion side should be performed at the first stage.Цель исследования - изучение влияния каротидной эндартерэктомии на прогноз клинического течения хронической церебральной ишемии у больных с симптоматическими окклюзиями противоположной внутренней сонной артерии, оценка рисков осложнений хирургических вмешательств и обоснование тактики этапного хирургического лечения больных с данной патологией. Материал и методы. Анализируется опыт хирургического лечения 83 больных с симптоматическими окклюзиями ВСА, оперированных по поводу стеноза сонной артерии с противоположной стороны. У 40 пациентов выполнялась только каротидная эндартерэктомия (КЭА) на стороне гемодинамически значимого стеноза (1-я группа). В 43 (52%) случаях, помимо КЭА, выполнялась операция по созданию экстра-интракраниального анастомоза, вторым этапом - в 23 случаях (2-я группа) и первым этапом - в 19 случаях (3-я группа). Выбор тактики хирургического лечения определялся клинической симптоматикой, степенью стеноза сонных артерий с противоположной стороны и величиной перфузионного дефицита в бассейне каротидной окклюзии. Результаты и заключение. Установлено, что пациенты с симптоматическими окклюзиями и контралатеральными стенозами сонных артерий представляют собой неоднородную группу, с разной эффективностью каротидной эндартерэктомии и рисками развития периоперационных осложнений. По мере нарастания цереброваскулярной недостаточности в бассейне каротидной окклюзии и связанного с ним неврологического дефицита повышаются риски осложнений контралатеральной КЭА и снижается ее клиническая эффективность. В подобных случаях первым этапом целесообразно выполнение реваскуляризации головного мозга на стороне окклюзии ВСА.

This review is devoted to moyamoya disease. It is a rare chronic steno-occlusive cerebrovascular disease. However, moyamoya disease is increasingly diagnosed by neurosurgeons in our country. Unlike atherosclerotic lesions of cerebral arteries, pathogenesis and course of this disease are much more complex and variable. Therefore, specialists often have certain difficulties in diagnosis, management and treatment of these patients. To date, a large number of surgical interventions have been proposed for the treatment of moyamoya disease. Revascularization approaches include direct procedures (extra-intracranial microanastomoses), indirect methods (synangioses) and combined revascularization. The purpose of the review is to systematize current literature data on the pathogenesis, diagnosis, clinical patterns and surgical treatment of patients with moyamoya disease. results Outcomes of surgical revascularization and the role of its various components in combined approach are under particular attention.Представленный обзор литературы посвящен болезни мойямойя — редкому хроническому стено-окклюзирующему цереброваскулярному заболеванию, которое все чаще выявляется нейрохирургами в России. В отличие от атеросклеротического поражения магистральных артерий головного мозга патогенез и клиническое течение этого заболевания гораздо сложнее и разнообразнее, поэтому у специалистов нередко возникают трудности в диагностике, ведении и лечении таких больных. К настоящему времени для лечения заболевания предложено много разнообразных оперативных вмешательств, направленных на реваскуляризацию мозга и включающих методы прямой (создание экстраинтракраниального микроанастомоза), непрямой (создание синангиозов) и комбинированной реваскуляризации. Целью обзора является освещение и систематизация накопленных данных мировой литературы, касающихся патогенеза, диагностики, клинической картины и тактики хирургического лечения пациентов с болезнью мойямойя. Особое внимание уделено результатам хирургической реваскуляризации и роли ее различных компонентов при комбинированных вмешательствах.

Surgical treatment of cerebral ischemia at the Burdenko Neurosurgical Center for the period from 1999 to 2019 is analyzed in the paper. The details of the treatment strategy in patients with steno-occlusive lesion of craniocervical arteries followed by cerebral ischemia developed over 20 years are discussed in the article. We have analyzed the features of surgical interventions on the major craniocervical arteries in a neurosurgical clinic and the results of this treatment.To demonstrate management of various lesions of major cerebral arteries in modern neurosurgical vascular hospital.In total, there were 3098 interventions on the major cerebral arteries in 2527 patients for this period. Mean age of patients ranged from 1.5 to 91 years (58±14 years). Interventions included open reconstructions of the carotid arteries (2031 surgeries), reconstructions of the vertebrobasilar arteries (135 surgeries), brain revascularization (658 surgeries), excision of the tumors of neurovascular bundle on the neck compressing carotid arteries (51 interventions). Endovascular interventions were performed in 223 cases and consisted of angioplasty and stenting of the extracranial segments of craniocervical arteries (185 surgeries), stenting of the intracranial arteries (30 surgeries) and endovascular thrombextraction (8 cases). Staged surgeries were performed in 541 patients (22.3%).Favorable outcomes were obtained in 87.6% of cases, satisfactory results - in 9% of patients. Clinical deterioration due to long-term postoperative complications and recurrent strokes occurred in 2.9% of cases. Postoperative morbidity rate was 4.6%, persistent neurological deficit developed in 2.6% of cases. Mortality rate was 0.5%.Surgical treatment of stenotic and occlusive lesion of the major cerebral arteries is an interdisciplinary problem. Solution of this issue is closely associated with technological progress, new discoveries in normal and pathological physiology, as well as clinical researches. Individualized choice of surgical approach is one the main modern trends of neurosurgical approach to this problem. At the same time, own surgical experience is the most important factor determining the results of arterial reconstructions.Представлен опыт хирургического лечения сосудистой патологии, приводящей к церебральной ишемии, в ФГАУ «Национальный медицинский исследовательский центр нейрохирургии им. акад. Н.Н. Бурденко» в период 1999—2019 гг. Обсуждаются разработанные за 20 лет алгоритмы выбора тактики лечения пациентов с клиническими проявлениями церебральной ишемии, обусловленной стенозирующей и окклюзирующей патологией брахиоцефальных артерий, особенности хирургических вмешательств на магистральных артериях в условиях нейрохирургической клиники и результаты этого лечения.Продемонстрировать возможности лечения разнообразной патологии магистральных артерий головного мозга в условиях современной нейрохирургической сосудистой клиники.За исследуемый период 2527 пациентам выполнено 3098 оперативных вмешательств на магистральных артериях головного мозга. Возраст больных варьировал от 1,5 лет до 91 года, составив в среднем 58±14 лет. Спектр оперативных вмешательств включал открытые реконструктивные операции на сонных артериях (2031 операция) и артериях вертебробазилярного бассейна (135 операций), реваскуляризацию головного мозга (658 операций), иссечение опухолей сосудисто-нервного пучка шеи, компримирующих сонные артерии (51 операция). Эндоваскулярные вмешательства выполнены в 223 случаях и представлены ангиопластикой и стентированием экстракраниальных сегментов брахиоцефальных артерий (185 операций), стентированием интракраниальных артерий (30 операций) и эндоваскулярной тромбэкстракцией (8 случаев). Этапные хирургические вмешательства выполнены у 541 (22,3%) пациента.В 87,6% случаев получены хорошие результаты, в 9% — удовлетворительные. В 2,9% случаев отмечено ухудшение клинической симптоматики вследствие развившихся осложнений и повторных нарушений мозгового кровообращения в отдаленном послеоперационном периоде. Осложнения хирургического лечения регистрировались в 4,6% случаев, при этом стойкие неврологические дефекты развились в 2,6% случаев, а летальный исход — в 0,5% случаев.Хирургическое лечение стенозирующей и окклюзирующей патологии магистральных артерий головного мозга представляет собой многогранную междисциплинарную проблему, решение которой тесно связано с технологическим прогрессом, новыми открытиями в области нормальной и патологической физиологии, а также с результатами клинических исследований. К основным современным тенденциям нейрохирургического подхода к решению этой проблемы можно отнести индивидуальный выбор тактики хирургического лечения. При этом личный хирургический опыт является важнейшим фактором, определяющим результаты артериальных реконструкций.

First of all, I would like to thank my colleagues for their interest in this article [1] and note the relevance of the problem of surgical treatment of moyamoya disease, which provoked this discussion. Moyamoya disease is a rare, atypical pathology for our country, the diagnosis and treatment of which is controversial among specialists, and the lack of agreed protocols is the cause of differences in the interpretation of the results of surgical treatment of such patients.

Background: PF-114 is a 4th-generation oral tyrosine kinase-inhibitor (TKI) active against wild-type and mutated BCR-ABL1 isoforms including BCR-ABL1T315I. We present data from a phase-1 study in patients with chronic or accelerated phase chronic myeloid leukaemia (CML) failing ≥2 TKIs or with BCR-ABL1T315I (NCT02885766) with ≥6 months therapy. Methods: 3+3 dose-escalation study to determine maximum tolerated dose (MTD) and dose-limiting toxicity (DLT). Secondary objectives included safety and efficacy based on haematological, cytogenetic, and molecular criteria. Adverse events (AEs) were graded using NCI-CTCAE v4.03. Results: 51 patients were enrolled. Daily doses were 50 mg (n=3), 100 mg (n=3), 200 mg (n=9), 300 mg (n=11), 400 mg (n=12), 500 mg (n=3), 600 mg (n=6), 750 mg (n=4) given continuously. Median age was 50 years (range, 29-82 years). Median CML duration pre-study was 10 years (range, 0.3-23 years). All patients had baseline ECOG performance scores 0-1. Twelve patients had BCR-ABL1T315I. Patients were heavily pre-treated: 25 received ≥3 prior TKIs; 5 patients with BCR-ABL1T315I received 1 prior TKI. Interim analysis was conducted at follow-up of ≥6 months (cut-off date January 16th 2019). Therapy was ongoing in 17 patients at doses 200 mg (n=4), 300 mg (n=9), 400 mg (n=3) and 600 mg (n=1) with median duration of exposure of 7,4 (range, 4,6-26), 9,2 (range, 7,4-26), 9,2 (range, 8,3-9,2) and 9,2 months. Other patients discontinued because of progression (n=18), adverse events (n=6), consent withdrawal (n=4), participation in another study (n=3) or other reasons (n=3). The MTD was 600 mg with the grade-3 psoriasis-like skin lesions the DLT, which occurred during the first 28 days of treatment. Reversible grade-3 skin toxicity occurred in 11 patients at doses ≥400 mg. There were no other drug-related non-hematologic grade-3 toxicities except 1 grade-3 toxic hepatitis at 400 mg and there were no detectable effects on ankle-brachial index or vascular occlusive events. The best safety/efficacy dose was 300 mg/d with 6 of 11 patients achieving a major cytogenetic response (MCyR) and 4 of them - a major molecular response (MMR). Higher doses were less effective probably because of toxicity-related therapy interruptions and discontinuations. Five of 12 patients with BCR-ABL1T315I responded, 3 of which achieved a complete hematologic response and 4 achieved MCyR. Conclusion: PF-114 was safe and effective in patients with CML failing ≥2 TKIs or with BCR-ABL1T315I. The most effective dose was 300 mg/d. Five of 12 patients with BCR-ABL1T315I responded. A pivotal study is beginning. Disclosures Turkina: Novartis: Consultancy, Speakers Bureau; Pfizer: Consultancy; Bristol Myers Squibb: Consultancy; fusion pharma: Consultancy; Novartis: Consultancy, Speakers Bureau. Vinogradova:Novartis: Consultancy; Fusion Pharma: Consultancy. Lomaia:Novartis: Other: Travel Grant;Lecture fee; Pfizer: Other: Travel Grant. Shukhov:Pfizer: Consultancy; Novartis: Consultancy. Chelysheva:Novartis: Consultancy, Honoraria; Fusion Pharma: Consultancy. Shikhbabaeva:Novartis: Consultancy; Fusion Pharma: Consultancy. Shuvaev:Fusion Pharma: Consultancy; Novartis: Consultancy; Pfize: Honoraria; BMS: Consultancy. Cortes:Pfizer: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Daiichi Sankyo: Consultancy, Honoraria, Research Funding; Biopath Holdings: Consultancy, Honoraria; Immunogen: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Astellas Pharma: Consultancy, Honoraria, Research Funding; Jazz Pharmaceuticals: Consultancy, Research Funding; BiolineRx: Consultancy; Sun Pharma: Research Funding; Merus: Consultancy, Honoraria, Research Funding; Forma Therapeutics: Consultancy, Honoraria, Research Funding. Baccarani:Novartis: Consultancy, Speakers Bureau; Incyte: Consultancy, Speakers Bureau; Takeda: Consultancy. Ottmann:Roche: Honoraria; Pfizer: Honoraria; Fusion Pharma: Honoraria; Takeda: Honoraria; Novartis: Honoraria; Celgene: Honoraria, Research Funding; Incyte: Honoraria, Research Funding; Amgen: Honoraria, Research Funding. Mikhailov:Fusion Pharma: Employment. Novikov:Fusion Pharma: Employment. Shulgina:Fusion Pharma: Employment. Chilov:Fusion Pharma: Consultancy.

e14210 Background: The purpose of the study was to determine the effect of a strain No. 228 of a new rotavirus group of the Reoviridae family on the growth of transplantable В16/F10 melanoma in mice and survival of animals. Methods: The study was performed using a strain No.228 of a new group of rotaviruses (working title «group K», RVK) ( http://jbks.ru/archive/issue-10/article-6 ). RVK is a live attenuated and apathogenic strain growing on the PEKC culture (pig embryo kidney cells) with 5·109 viral particles/mL. The dynamics of melanoma growth and survival of animals receiving RVK were studied on 25 male mice divided equally into 5 groups. RVK was administered intramuscularly and Per os once a week, respectively 0.3 mL and 25 µL to groups 1-2 21 days prior to the tumor inoculation, a total of 4 injections (“vaccination” regimen); to groups 3-4 – 7 days after tumor inoculation with the appearance of tumor nodes, a total of 3 injections (“treatment” regimen); group 5 – controls receiving saline. Groups 1 and 3 received live RVK, groups 2 and 4 - RVK inactivated by UV radiation. Results: Survival in both groups of animals with “vaccination” regimen was improved significantly, compared to controls (group 1 – 25.8±2.2 days after melanoma transplantation; group 2 – 25.4±1.1 days; controls – 14.6±3.08 days, p < 0.05). In groups with “treatment” regimen, survival was 19.2±3.08 days in group 3 and 21.6±3.52 days in group 4, the latter significantly higher than in controls (p < 0.05). Introduction of a live virus in the “vaccination” regimen resulted in significantly better survival compared to the “treatment” regimen (group 1 vs. group 3), while inactivated virus did not caused such a difference (groups 2 and 4). Conclusions: Improved survival of mice with B16/F10 melanoma after administration of RVK demonstrated its ability to inhibit tumor growth and confirmed our previously published data obtained on Guerin's carcinoma in rats. Administration of a live virus prior to the tumor inoculation cause stronger effect than after inoculation. Since inactivation of the virus does not eliminate its effect, apparently, it is associated with immunostimulating action, rather than with oncolytic one.

e12065 Background: Assessment of proliferative activity is important in terms of tumor prognosis. Topoisomerase IIα (TopIIα) and ki-67 are common markers of breast cancer (BC) cell proliferation. The purpose of the study was to assess the correlation between TopIIα and ki-67 expression as a prognostic factor in luminal, primary operable breast cancer without Her 2 neu overexpression in postmenopausal women. Methods: 60 postmenopausal patients with BC (invasive ductal carcinoma) were equally divided into 3 groups: I –luminal A BC, surgical treatment with subsequent radiotherapy and hormonal therapy; II – luminal B BC, surgical treatment with subsequent radiotherapy and hormonal therapy; III – luminal B BC, surgical treatment with subsequent radiotherapy, polychemotherapy and hormonal therapy. Mean age of patients: I – 76.16±3.14 years, II – 65.0±3.91, III – 74.0±2.54 years. Immunohistochemical study was performed with mouse monoclonal ki-67 (Thermo scientific) and TopIIα (Santa Cruz Biotechnology) antibodies using the Reveal Polyvalent HRP-DAB Detection System. Results were analyzed using the STATISTICA 10.0 program (StatSoftInc., USA). Results: The average expression levels of the ki-67 marker in the groups were: I - 12.3±1.4%, II - 15.1±3.1%, III - 37.0±7.1%; TopIIα expression – 3.5±1.6%, 16.0±5.9%, 21.7±6.4%, respectively. The statistically significant Spearman correlation between TopIIα and ki-67 was observed both as general in groups (r = 0.787 at p < 0.001) and in groups with luminal B subtype (groups II and III). Strong positive correlation between TopIIα and ki-67 was registered in groups II (r = 0.941 at p < 0.01) and III (r = 0.864 at p < 0.001) with luminal B subtype. Weak correlation was observed in group I with luminal A subtype (r = 0.477 at p≥0.05). Conclusions: The study revealed a correlative increase in the level of TopIIα with simultaneous overexpression of the ki-67 protein in the studied groups. This indicator can be considered predictive for breast cancer.

e12064 Background: Circulating tumor cells (CTC) are of great importance in modern cancer research. Biological characteristics of CTC allow using them as tumor markers of high prognostic value. Their quantitative evaluation during treatment can be used to monitor the response to treatment in patients receiving systemic chemotherapy (CT). The purpose of the study was to assess the role of CTC in the prognosis of treatment efficacy in patients with locally advanced Her-2 negative breast cancer. Methods: The study included 42 patients aged 30-65 years with stage IIIA, IIIB, IIIC locally advanced Her-2 negative breast cancer, ECOG-WHO Performance Status from 0 to 2, Karnofsky Performance Status from 100% to 80%. CTC were determined using the CellSearch Veridex System (Johnson & Johnson, USA), taking into account morphological characteristics and expression of epithelial cell adhesion markers EpCAM, CD45 and cytokeratins 8, 18 and 19. Results: CTC were found in 86% (36 of 42 patients) before treatment. CTC were not registered in 6 (14%) patients. 1 CTC was detected in 14% (6 patients); 2-3 CTC – 33% (14 patients); more than 3 CTC – 38% (16 patients). 12% (5) patients showed more than 10 CTC, with the maximum of 64 CTC in 1 patient. After 2 cycles of polychemotherapy, CTC were detected in 50% (21 patients). Other 21 patients did not show presence of CTC. Among CTC-positive patients, 1 CTC was detected in 4 patients (19%); from 2 to 3 CTC – in 9 patients (43%); more than 3 CTC – 8 patients (38%). 2 patients (10%) still showed more than 10 CTC – 28 and 33 CTC in the peripheral blood. After 2 cycles of polychemotherapy, the number of patients with more than 1 CTC decreased from 86% to 50%. Polychemotherapy regimen was changed for patients with increasing amounts of CTC. Conclusions: Determination of the CTC number allows evaluation of the treatment efficacy and is a specific marker for the change of applied polychemotherapy for such cancer type.

e15531 Background: High incidence and mortality rates of gastric cancer cause a constant search for the most informative and effective methods of diagnosis and treatment assessment. In this regard, studying the expression of markers with the stem phenotype in primary tumor tissues in patients with gastric cancer with and without metastases is of undoubted interest. Methods: The study included 20 gastric cancer patients aged 30-80 years: group 1 – gastric cancer T3-4аN0-3M0 (G2) without metastasis (58.9±9.7 years); group 2 – gastric cancer T3-4аN0-3M1 (G2) with peritoneal metastasis (53.4±11.9 years). Immunohistochemical study was performed on paraffin-embedded tumor tissue sections using mouse monoclonal antibodies to CD44 (156-3С11 Thermo Scientific) at a 1:2500 dilution and rabbit polyclonal antibodies to CD133 (Cloud-Clone Corp.) at a 1:700 dilution; the Thermo Scientific autostainer was used for staining. Membrane staining and staining intensity were assessed: 0, 1+ weak, 2+ moderate, 3+ strong staining. Positive expression was defined as ≥10% cut-off for CD44 and ˃5% for CD133. Results: Positive expression of CD44+ was detected in 67% (13) in group 2 vs. 20% (4) in group 1. In the metastatic group, the number of cells that stained positive for CD44 expression ranged from 9 to 15%, on average 10.0±3.08%, without metastases – from single cells to 13%, on average 6.0±2.3%. A chi-square test showed statistically significant association in the groups (8.256 at p = 0.004). Positive CD133+ expression in tumor tissues was registered in 100% (20) in group 2 and 80% (16) in group 1. The range of positively stained cells in group 2 was from 10 to 40%, on average 21.3±11.6%, in group 1 - from single cells to 14%, on average 10.0±2.4%. A chi-square test showed statistically significant association in the groups (4.444 at p = 0.036). Conclusions: Immunohistochemical study of the selected tumor cell markers in gastric cancer revealed some characteristics of their expression depending on the presence of metastases. The results can be the basis for further research for the most complete characterization of a heterogeneous tumor population in gastric cancer and the role of individual cells in the tumor growth, progression and metastasis.

Background Idiopathic pulmonary fibrosis (IPF) is a fatal condition with limited treatment options. However, in a previous small study, co-trimoxazole was found to be beneficial. Methods In a double-blind multicentre study, 181 patients with fibrotic idiopathic interstitial pneumonia (89% diagnosed as definite/probable IPF) were randomised to receive co-trimoxazole 960 mg twice daily or placebo for 12 months in addition to usual care. Measurements were made of forced vital capacity (FVC) (primary endpoint), diffusing capacity of carbon monoxide (Dlco) and EuroQol (EQ5D)-based utility, 6-minute walk test (6MWT) and Medical Research Council (MRC) dyspnoea score (secondary endpoints). All-cause mortality and adverse events were recorded (tertiary endpoints). Results Co-trimoxazole had no effect on FVC (mean difference 15.5 ml (95% CI −93.6 to 124.6)), Dlco (mean difference −0.12 mmol/min/kPa (95% CI 0.41 to 0.17)), 6MWT or MRC dyspnoea score (intention-to-treat analysis). The findings of the per-protocol analysis were the same except that co-trimoxazole treatment resulted in a significant improvement in EQ5D-based utility (mean difference 0.12 (95% CI 0.01 to 0.22)), a reduction in the percentage of patients requiring an increase in oxygen therapy (OR 0.05 (95% CI 0.00 to 0.61)) and a significant reduction in all-cause mortality (co-trimoxazole 3/53, placebo 14/65, HR 0.21 (95% CI 0.06 to 0.78), p=0.02)) compared with placebo. The use of co-trimoxazole reduced respiratory tract infections but increased the incidence of nausea and rash. Conclusions The addition of co-trimoxazole therapy to standard treatment for fibrotic idiopathic interstitial pneumonia had no effect on lung function but resulted in improved quality of life and a reduction in mortality in those adhering to treatment. ISRCTN22201583

To assess changes in local hemodynamic parameters in patients with symptomatic ICA occlusions and moyamoya disease after placement of extracranial-intracranial bypass (EC-IC bypass).The study included 112 patients who underwent surgical treatment at the National Scientific and Practical Center for Neurosurgery in the period between 1999 and 2015. Of these, 105 patients had ICA occlusions, and 7 patients had moyamoya disease. During the main stage of EC-IC bypass placement, all patients were monitored for local hemodynamic parameters using intraoperative contact Doppler ultrasonography - 89 (72%) patients (72%) and flowmetry - 56 (50%)). In 33 (29%) cases, both techniques were used. Forty two patients underwent preoperative SCT perfusion to assess the degree of perfusion deficit. Grade 1 cerebrovascular insufficiency (acute oligemia) was detected in 6 patients; grade 2 perfusion deficit (persistent oligemia) was found in 25 patients; grade 3 perfusion deficit (chronic oligemia) was present in 11 patients. Measurements were performed before bypass placement: the blood flow direction and hemodynamic parameters in the cortical arteries were evaluated; and after bypass placement: blood flow values and directions in the cortical artery, proximal and distal to the bypass area, were assessed.A total of 112 EC-IC bypasses were placed without perioperative complications and deaths. Bypass functioning was confirmed in 108 (96.3%) cases; bypass thrombosis occurred in 4 (3.7%) cases. The distal blood flow direction was observed in patients with ICA occlusions (105 patients) in all cases before EC-IC bypass placement. Patients with moyamoya disease had more often the proximal blood flow direction - 5 (71%) out of 7 cases. The cerebral blood flow parameters obtained in this study differed significantly, depending on the baseline degree of perfusion deficit. The blood flow rate was minimal in patients with grade 1 cerebrovascular insufficiency. After revascularization, local hemodynamics in the cortical arteries was significantly dependent on the ability of EC-IC bypass to reverse blood flow in the proximal acceptor artery. A change in the blood flow direction was observed in 86 (77%) cases. The mean volumetric blood flow in EC-IC bypass was 34.2±5.7 mL/min.The knowledge of baseline hemodynamic parameters and their changes after revascularization plays an important role in choosing the correct surgical technique, further bypass functioning, and, as a result, improvement of the clinical outcome after surgery.Цель исследования - оценка изменений параметров локальной гемодинамики у пациентов с симптоматическими окклюзиями внутренней сонной артерии (ВСА) и болезнью моя-моя после создания экстра-интракраниального микроанастомоза (ЭИКМА). Материал и методы. В исследование вошли 112 пациентов, которым проведено хирургическое лечение в НМИЦ нейрохирургии им. Н.Н. Бурденко с 1999 по 2015 г. Среди них были 105 пациентов с окклюзией ВСА и 7 - с болезнью моя-моя. У всех пациентов во время основного этапа создания ЭИКМА были изучены локальные показатели гемодинамики с использованием методов интраоперационной контактной допплерографии (89, 72%) и флоуметрии (56, 50%). В 33 (29%) случаях использовались оба метода. У 42 пациентов имелись данные о степени перфузионного дефицита на основании предоперационного СКТ-перфузионного исследования. У 6 пациентов выявлен I тип цереброваскулярной недостаточности (острая олигемия), у 25 - II тип перфузионного дефицита (сохраняющаяся олигемия), у 11 - перфузионный дефицит III типа (хроническая олигемия). До создания анастомоза оценивались направление кровотока и значения гемодинамических параметров в корковых артериях, после создания анастомоза оценивались значения и направление кровотока в корковой артерии проксимальнее и дистальнее области анастомоза. Результаты. Всего выполнено 112 операций по созданию ЭИКМА без периоперационных осложнений и летальности. Функционирование анастомоза было подтверждено в 108 (96,3%) случаях, тромбоз анастомоза наблюдался в 4 (3,7%). У пациентов с окклюзиями ВСА во всех случаях до ЭИКМА наблюдалось дистальное направление кровотока. У 5 (71%) из 7 пациентов с болезнью моя-моя чаще отмечалось проксимальное направление кровотока. Полученные в ходе исследования параметры мозгового кровотока достоверно отличались в зависимости от исходной степени перфузионного дефицита. У больных с цереброваскулярной недостаточностью I типа скорость кровотока имела наименьшие значения. Локальная гемодинамика в корковых артериях после реваскуляризации существенно зависела от способности ЭИКМА развернуть кровоток в проксимальных отделах акцепторной артерии. Изменение направления кровотока наблюдалось в 86 (77%) случаях. Средний объемный кровоток по ЭИКМА составил 34,2±5,7 мл/мин. Выводы. Знание исходных параметров гемодинамики и их изменений после реваскуляризации играет важную роль в обосновании правильной техники операции, контроле дальнейшего функционирования анастомоза и, как следствие, клинического состояния после операции.

e21597Background: The purpose of the study was to determine the expressions of matrix metalloproteinase (MMP-2) in tissues of melanocytic tumors and to evaluate it as a prognostic marker. Methods: ...

e14534Background: The purpose of the study was to assess a cancer preventive and oncolytic effect of a strain of a new group of rotaviruses (family Reoviridae) using a model of transplantable Gueri...

e15659Background: The purpose of the study was to assess an association between the tumor invasion and levels of cancer stem cells (CD44+ and CD133+) in colorectal cancer. Methods: The study includ...