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Background: Pandemic COVID-19 pneumonia due to SARS-2 is an important cause of morbidity and mortality. Emerging evidence links poor outcomes to an inflammatory cytokine storm.Methods: We treated 89 hospitalized patients with COVID-19 pneumonia and heightened systemic inflammation (elevated serum C reactive protein and interleukin-6 levels) with an infusion of tocilizumab (TCZ), a human monoclonal IgG1 antibody to the interleukin-6 receptor.Results: Clinical and laboratory evidence of improvement was evident when baseline and 1-2-day post-infusion indices were compared. Among the 72 patients receiving supplemental oxygen without mechanical ventilation, severity of condition on the NEWS2 scale scores fell from 5 to 2 (P<0.001), C reactive protein levels fell from 95 to 14 mg/L (P<0.001), and lymphocyte counts rose from 900 to 1000/uL (P=0.036). Sixty-three of 72 patients were discharged from the hospital, one patient died, and eight patients remained in the hospital at the time of this writing. Among the 17 patients receiving mechanical ventilation, despite a rapid decrease in CRP levels from 89 to 35 mg/L (P=0.014) and early improvements in NEWS2 scores in 10 of 17 patients, 10 patients ultimately died and the other seven remain in the hospital at the time of this writing. Overall, mortality was only seen in patients who had markedly elevated CRP levels (>30 mg/L) and low lymphocyte counts (<1000/uL) before TCZ administration.Conclusions: Inflammation and lymphocytopenia are linked to mortality in COVID-19. Inhibition of IL-6 activity by administration of tocilizumab, an anti-IL-6 receptor antibody, is associated with rapid improvement in both CRP and lymphocyte counts and in clinical indices. Controlled clinical trials are needed to confirm the utility of IL-6 blockade in this setting. Additional interventions will be needed for patients requiring mechanical ventilation.

Background:. Emerging evidence links morbidity and mortality of pandemic COVID-19 pneumonia to an inflammatory cytokine storm. Methods: Eighty nine patients with COVID-19 pneumonia and heightened systemic inflammation (elevated serum C reactive protein and interleukin-6 levels) were treated with Tocilizumab (TCZ), a human monoclonal IgG1 antibody to the interleukin-6 receptor. Results: Clinical and laboratory improvement was seen comparing baseline and 1-2 day post-infusion indices. Among 72 patients not receiving mechanical ventilation, NEWS2 scores fell from 5 to 2 (p <0.001) C reactive protein levels fell from 95 to 14 mg/L (p <0.001) and lymphocyte counts rose from 900 to 1000/uL (p=0.036). Sixty three of 72 patients were discharged from hospital, one patient died, and 8 remained in hospital at time of writing. Among 17 patients receiving mechanical ventilation, despite a rapid decrease in CRP levels from 89 to 35 mg/L (p = 0.014) and early improvements in NEWS2 scores in 10 of 17, ten patients died and seven remain in hospital at time of writing. Overall, mortality was only seen in patients who had markedly elevated CRP levels (>30 mg/L) and low lymphocyte counts (<1000/uL) before TCZ administration. Conclusions: Inflammation and lymphocytopenia are linked to mortality in COVID-19. Inhibition of IL-6 activity by administration of Tocilizumab, an anti IL-6 receptor antibody is associated with rapid improvement in both CRP and lymphocyte counts and in clinical indices. Controlled clinical trials are needed to confirm the utility of IL-6 blockade in this setting. Additional interventions will be needed for patients requiring mechanical ventilation.

Введение. Антикоагулянты (АК) являются лекарственными средствами (ЛС) высокого риска причинения вреда пациенту. Безопасность применения АК во многом зависит от соблюдения врачами клинических руководств и инструкций по медицинскому применению ЛС. Цель. Проанализировать выполнение врачами стационара клинических рекомендаций и инструкций по медицинскому применению АК у пациентов с фибрилляцией предсердий (ФП) и тромбозом глубоких вен (ТГВ). Материал и методы. В ретроспективное когортное исследование включено 100 пациентов с ФП или ТГВ, пролеченных в 2016-2017 гг. в многопрофильном стационаре г. Москвы. С помощью системы поддержки принятия решения (СППР) лекарственные назначения в историях болезни сопоставлялись с клиническими руководствами и инструкциями по медицинскому применению АК для выявления отклонений от рекомендаций по назначению АК (соблюдение показаний/противопоказаний и режима дозирования АК). Результаты. Из 50 пациентов с ФП антикоагулянтная терапия в стационаре была назначена 43 (86%) пациентам, включая 20 (46,5%) назначений прямых оральных антикоагулянтов (ПОАК), 17 (39,5%) варфарина и 6 (14%)-низкомолекулярных гепаринов (НМГ). Для пациентов с ТГВ структура назначений АК в качестве основной терапии составила: 39,5% ПОАК, 33,5% НМГ и 27% варфарин. Уровень приверженности врачей рекомендациям по назначению АК пациентам с ФП и ТГВ (соблюдение показаний и противопоказаний) был равен 88%. При несоблюдении рекомендаций по назначению АК частота нежелательных лекарственных событий была статистически значимо выше, чем при соблюдении рекомендаций (34% против 11%, соответственно; отношение шансов (ОШ) 3,9; 95% доверительный интервал (ДИ) 0,9-15,3; p=0,045). Врачи соблюдали рекомендации по режиму дозирования АК в 63,5% случаях. При несоблюдении рекомендаций по дозированию АК прямые затраты в стационаре на терапию АК были статистически значимо выше, чем при соблюдении: 4,04 тыс руб (интерквартильный размах, interquartile range, IQR=7,501 тыс руб) против 1,13 тыс руб (IQR=5,911 тыс руб), соответственно; p=0,02. Заключение. Несоблюдение клинических рекомендаций и инструкций по медицинскому применению АК может повышать риск развития нежелательных лекарственных событий и увеличивать стоимость антикоагулянтной терапии. СППР является перспективным инструментом как для клинического аудита антикоагулянтной терапии, так и для повышения приверженности врачей клиническим рекомендациям при назначении АК пациентам с ФП и ТГВ. Ключевые слова: антикоагулянты, фибрилляция предсердий, тромбоз глубоких вен, нежелательные лекарственные события, приверженность клиническим рекомендациям.

Introduction. Guidelines on Biological Therapy for Bronchial Asthma of the European Academy of Allergy and Clinical Immunology (EAACI) identified a number of controversial issues for additional outcome analysis using randomized clinical trials and data from routine clinical practice. In particular, there is unmet need to clarify algorithms for prescribing biologicals using predictors of response and its timing, taking into account risk factors and multimorbidity. Omalizumab is a recombinant humanized monoclonal anti-IgE antibody of IgG1 class used for the treatment of severe refractory atopic bronchial asthma (BA) and a variety of IgE-mediated diseases. Among biological agents, this "pioneer molecule" has the greatest experience in the "allergology and immunology" profile. Detailed description of the "nonresponders" portraits will allow to perform the therapy response assessment on time and facilitate rational planning of individual therapy, which is a prerequisite for biologicals era. Using only routine methods, it is possible to perform initial and dynamic screening to phenotype a heterogeneous cohort of patients with severe asthma and chose the optimal strategy. Aim. To identify predictors of nonresponse to omalizumab anti-IgE therapy in patients with severe atopic BA and to establish optimal timing of efficacy assessment using retrospective analysis of data from the Biologic Therapy Registry of Allergology and Immunology in routine clinical practice. Materials and methods. A retrospective single-center registry study was conducted at the Allergy and Immunology Reference Center from June 2017 to August 2021. 135 patients with severe BA, with confirmed perennial sensitization, who received omalizumab according to the recommendations of the current version of GINA, were selected from the clinical and dynamic observational system (registry). Dosing regimen and administration frequency of omalizumab were determined in accordance with the instructions for the drug. Assessment of therapy efficacy was performed at the time point 4, 6 and 12 months. Patients were subgrouped into "responders" and "non-responders" according to the following criteria: ACT score less than 19 and/or difference between initial ACT score in dynamics less than 3 points; forced expiratory volume in the first second less than 80%; combination of these two criteria. Nonparametric methods of descriptive statistics were used in data processing: median, interquartile range. Differences were considered significant at p0.05. MannWhitney U-test, KruskalWallis one-way analysis of variance, and Fisher's 2 test were used to compare quantitative characteristics. Results. Heterogeneous subgroups of patients differing in reaching the criteria of "non-responders" to treatment were identified; the informativity of modifiable and unmodifiable factors differed at time-points of dynamic observation. In the differential analysis, two profiles of "nonresponders" were defined in combination with the most significant predictors of "nonrsponse" to omalizumab. According to the data obtained, one of the clinical phenotypes, namely the combination of severe asthma with the Samters triad, corresponded to the characteristics of the patient "nonresponders": age of onset is about 30 years, females, severe exacerbations of BA while taking non-steroidal anti-inflammatory drugs, accompanied with high levels of eosinophilia. Conclusion. The data obtained illustrates the hypothesis of pathogenetic heterogeneity of severe BA with the phenomenon of overlapping phenotypes and can serve as an additional orienteer for creating the individual plan of anti-IgE therapy in real clinical practice.

According to accumulated clinical data, one of the causes of severe damage to lung epithelial cells associated with SARS-CoV-2 (2019-nCoV) is an acute, timely underestimated "cytokine storm" (cytokine cascade, hypercytokinaemia) with characteristic signs of an expressed hyper-inflammatory syndrome with subsequent polyorganic failure. The study presents the results of the analysis of the effectiveness of tocilizumab therapy (TCZ) in patients (n = 181) of different age groups with developed pneumonia caused by SARS-CoV-2. The aim of the study was to evaluate the effectiveness of TCZ therapy in patients of different age groups with developed pneumonia in the frame of COVID-19. Methods. Patients (n = 181) with community-acquired pneumonia caused by coronavirus SARS-CoV-2 are included in a one-center, non-randomized, prospective study to evaluate the effectiveness of TCZ therapy conducted at the State Public Health Institution "City Clinical Hospital No.52" of the Moscow City Health Department. Patients were divided into 3 age subgroups – up to 50 years, 50–70 years and over 70 years. Patients with community-acquired SARS-CoV-2-induced pneumonia receiving non-invasive oxygen support and patients who had artificial lung ventilation (ALV) were given a single dose of 400 mg of TCZ in addition to basic therapy. Results. There are no significant differences between age groups in the severity of pneumonia according to the data of the computed tomography (CT), however, a more severe condition and a higher mortality rate (p < 0.001) were reliably observed in patients over 70 age compared to the other age groups. After TCZ treatment in patients of each age group, the severity of the condition assessed on the National Early Warning Score (NEWS2) has been significantly reduced compared to the baseline. Conclusion. According to the data of the pilot study the efficacy and safety of TCZ in patients of all presented age groups with COVID-associated pulmonary tissue lesion and signs of "cytokine storm" was demonstrated. At the same time, patients up to 50 years after the therapy of TCZ managed to achieve greater clinical efficiency compared to patients in other groups. According to the severity of the state and laboratory criteria, the lowest clinical efficacy of TCZ therapy was observed in patients over 70 years of age; as a consequence, the highest mortality rate was observed in the same group. At the same time, the TCZ therapy has not had a positive impact on the change of laboratory values and the severity of the disease in case of unfavorable outcome.

на втором визите и до 0,9 балла к моменту окончания наблюдения. Статистически значимая (р < 0,05) положительная динамика прослеживалась в отношении всех оцениваемых симптомов (боль в животе, запор, диарея, метеоризм, тенезмы). К окончанию наблюдения 59,6 % пациентов и 68,8 % врачей оценили результаты лечения как «отличные», 25,2 % пациентов и 20,4 % врачей-как «хорошие». Выводы. За время наблюдения отмечалось значительное уменьшение выраженности симптомов заболевания: боли в животе, запора, диареи, метеоризма, тенезмов. Не было зарегистрировано НЯ, связанных с приемом рифаксимина-α. Полученные данные подтверждают ранее опубликованные результаты рандомизированных контролируемых исследований по эффективности и безопасности рифаксимина-α при неосложненной дивертикулярной болезни. Ключевые слова: дивертикулярная болезнь, рифаксимин-α, неинтервенционное исследование Конфликт интересов: Исследование спонсировано компанией ООО «Альфасигма Рус». Благодарности: Авторы выражают благодарность контрактно-исследовательской организации «Лиганд ресерч» (Москва) за организацию исследования, представителям компании ООО «Альфасигма Рус» за спонсорскую и методологическую поддержку исследования.

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