Antirheumatic drugs and COVID-19: frustrations and hopes

In accordance with current views on the pathogenesis of the new coronavirus infection, some antirheumatic drugs are considered as therapeutic agents for suppressing the hyperinflammatory response in severe COVID-19. The review presents literature data on the efficacy and safety of certain basic anti-inflammatory and genetically engineered drugs in patients with COVID-19. Hydroxychloroquine is not indicated for the treatment of SARS-CoV-2 infection of any severity due to the lack of therapeutic benefits, the likelihood of a worse prognosis in more severe patients and the development of adverse reactions, especially when used concomitantly with azithromycin. The use of systemic glucocorticoids (GC) in patients with COVID-19 who require oxygen support leads to a decrease in mortality and an improvement in the prognosis of the disease. However, the optimal time of administration, dose and duration of HA administration remain the subject of further research. Despite the encouraging data, it is too early to draw final conclusions about the feasibility of using tocilizumab in COVID-19, since no randomized clinical trials have demonstrated a clear advantage of the drug in terms of reducing mortality. The use of anakinra does not reduce the need for noninvasive / invasive lung ventilation or the mortality of patients with COVID-19. Two drugs from the group of tumor necrosis factor inhibitors - infliximab and adalimumabare currently being considered as possible treatment options for COVID-19. The use of a combination of baricitinib and remdesivir for the treatment of COVID-19 patients requiring oxygen support has been approved. New RCTs are needed to study the effectiveness of other anti-rheumatic drugs in COVID-19

Post covid syndrome and rheumatic diseases: focus on rheumatoid arthritis (own data)

Introduction. In modern reality postcovid syndrome (PCS) is characterized by clinical heterogeneity and multi-organ involvement, often presenting a differential diagnostic and therapeutic problem. However, in most studies of PCS, stratification of patients taking into account individual comorbid conditions was not performed. Thus, only an extremely small number of studies have been devoted to assessing the course of PCS in rheumatic diseasesPurpose. To characterize the features of the course of COVID-19 in patients with rheumatoid arthritis, as well as to conduct a comparative assessment of clinical and demographic parameters in groups of patients with rheumatoid arthritis, differentiated by the presence of PCS.Materials and methods. The material of the questionnaire which contained questions regarding socio-demographic data of respondents, information on rheumatological history, comorbid diseases, data on past COVID-19, including cases of re-infection, and PCS.Results.The study included 32 adult patients (29 women, 90%) with a reliable diagnosis of rheumatoid arthritis. Of the 32 patients who underwent COVID-19, in 23 cases it was possible to form a judgment about the presence or absence of PCS. To study PCS, 23 patients were stratified into two groups: 11 (47.8%) patients developed PCS (Group 1) and 12 patients had COVID-19 without consequences (Group 2). Both groups were represented predominantly by women (90.9% and 91.7%, respectively). In the general group 37.5% of patients with COVID-19 required inpatient treatment. The number of symptoms associated with COVID-19 did not correlate with RA activity, however, patients with higher RA activity were more likely to report increased arthralgia as a symptom of COVID-19. 47.8% of COVID-19 survivors experienced PCS. The average age, the number of comorbid diseases and the severity of RA symptoms at the time of COVID-19 were relatively higher in the group of patients with RA and PKS. Patients with PKS also noted a higher frequency of hospitalizations and a more severe course of COVID-19.Conclusions. A quantitative assessment of the risk of developing PKS is needed, which will serve as a basis for developing a strategy aimed at prevention, timely diagnosis and treatment of this syndrome in patients with RS. To this end, further studies on larger cohorts of patients are required

Multimode Quantitative Scanning Microwave Microscopy of In Situ Grown Epitaxial Ba\u3csub\u3e1-x\u3c/sub\u3eSr\u3csub\u3ex\u3c/sub\u3eTiO\u3csub\u3e3\u3c/sub\u3e Composition Spreads

We have performed variable-temperature multimode quantitative microwavemicroscopy of in situepitaxial Ba1−xSrxTiO3 thin-film composition spreads fabricated on (100) LaA1O3 substrates. Dielectric properties were mapped as a function of continuously varying composition from BaTiO3 to SrTiO3. We have demonstrated nondestructive temperature-dependent dielectric characterization of local thin-film regions. Measurements are simultaneously taken at multiple resonant frequencies of the microscope cavity. The multimode measurements allow frequency dispersion studies. We observe strong composition-dependent dielectric relaxation in Ba1−xSrxTiO3 at microwave frequencies

Полиартрит, ассоциированный с COVID-19 (клинический случай)

The article describes the clinical observation of the onset of polyarthritis after COVID-19. Clinical data, laboratory tests' and instrumental methods results in dynamics, as well as approaches to therapy are presented. The discussion reflects modern views on the causes of the development of articular syndrome after SARS-CoV-2, with special attention to the need for a careful study of the history, clinical and laboratory data of patients with COVID-19.В статье приводится описание клинического наблюдения дебюта полиартрита после перенесенного COVID-19. Представлены клинические данные и результаты лабораторных и инструментальных методов обследования в динамике, а также подходы к терапии. В обсуждении отражены современные взгляды на причины развития суставного синдрома после SARS-CoV-2, указано на необходимость внимательного изучения анамнеза, клинических и лабораторных данных пациентов с COVID-19

The Role of Outer Membrane Vesicles of Agents of Particularly Dangerous Infections in the Pathogenesis and Immunogenesis of Infectious Process

The literature review is devoted to the modern concepts of the vesiculation phenomenon and its biological role in pathogenic bacteria – causative agents of particularly dangerous human infections. Data on the production, structure, composition, and functions of the outer membrane vesicles (OMV) of bacteria have been summarized. In recent years, the interest of researchers in the formation of spherical structures (so called bubbles or vesicles) from outer membrane of gram-negative bacteria has significantly increased. Such structures are surrounded by the double layer of a phospholipid membrane, the outer layer of which is enriched with lipopolysaccharide molecules. The inner space of vesicles could include various antigens, receptors, adhesins, toxins, enzymes, porins, etc. The formation of vesicles by the outer membranes of bacteria is recognized as a normal physiological manifestation of bacterial activity aimed at adaptation to environmental conditions. The investigation of the biological role of OMV showed their connection with the pathogenesis and immunogenesis of bacterial diseases. The review provides information on the peculiarity of induction, OMV composition and their participation in the processes of patho- and immunogenesis of severe infections caused by groups I–II PBA – the gram-negative causative agents of plague, tularemia, brucellosis, glanders, melioidosis, cholera, and formation of extracellular vesicles in a gram-positive anthrax pathogen. The particular attention is paid to the issue of developing safe and effective next-generation vaccine preparations based on bacterial vesicles

Хронический гепатит В у пациентов ревматологического стационара: проблемы скрининга и реактивации инфекции

   Objective: to evaluate the completeness of screening for hepatitis B virus (HBV) infection in HBsAg-positive patients admitted to a rheumatology hospital and to follow the history of HBV reactivation/seroversion during antirheumatic therapy.   Material and methods. The results of initial and repeated (if applicable) hospitalizations were analyzed in 80 patients with rheumatic diseases (RD), including 55 (69%) women and 25 (31 %) men, with Australian surface antigen (HBsAg), admitted to the V.A. Nasonova Institute of Rheumatology from January 1, 2020 to July 20, 2022 (30 months).   Results and discussion. The total number of hospitalizations to the clinic during the observation period, including repeat admissions, was 13,681. The number of hospitalizations in 80 patients with HBV infection during the observation period, including repeat admissions, was 144, of which for systemic vasculitis – 6 (8 %), other systemic connective tissue diseases – 16 (20 %), osteoarthritis and post-traumatic changes of joints – 14 (15 %), inflammatory joint diseases – 42 (54 %). Cases of HBV reactivation/seroverion, both in anamnesis and during observation, were detected in 9 (11 %) patients, and most frequently (n = 5) they were registered during methotrexate therapy.   Conclusion. HBV infection in patients with RD leads to significant difficulties in the selection of drug therapy, due to the risk of reactivation of the infection. The results obtained indicate incomplete screening of patients with RD for HBV infection during the preclinical phase. Further investigation is needed to develop clear recommendations for the management of patients with RD infected with HBV.   Цель исследования – оценить полноту выполнения скрининга на наличие инфекции, вызванной вирусом гепатита В (HBV), у больных, позитивных по HBsAg, поступающих в стационар ревматологического профиля, и проследить историю реактивации/серореверсии HBV на фоне антиревматической терапии.   Материал и методы. Проанализированы результаты первичной и повторной (при наличии) госпитализации у 80 больных с ревматическими заболеваниями (РЗ), среди которых было 55 (69 %) женщин и 25 (31 %) мужчин, имеющих поверхностный «австралийский» антиген (HBsAg), госпитализированных в ФГБНУ «Научно-исследовательский институт ревматологии им. В. А. Насоновой» с 1. 01. 2020 по 20. 07. 2022 г. (30 мес).   Результаты и обсуждение. Общее число госпитализаций в клинику за время наблюдения, включая повторные, составило 13 681. Число госпитализаций у 80 больных с HBV-инфекцией за период наблюдения, включая повторные, составило 144, из них по поводу системных васкулитов – 6 (8 %), других системных заболеваний соединительной ткани – 16 (20 %), остеоартрита и посттравматических изменений суставов – 14 (15 %), воспалительных заболеваний суставов – 42 (54 %). Случаи реактивации/серореверсии HBV как в анамнезе, так и в процессе наблюдения выявлены у 9 (11 %) больных, причем наиболее часто (n = 5) они регистрировались на фоне терапии метотрексатом.   Заключение. Инфицированность HBV больных с РЗ создает значительные трудности при подборе лекарственной терапии, поскольку существует опасность реактивации инфекции. Полученные результаты свидетельствуют о неполном обследовании пациентов с РЗ на HBV-инфекцию на догоспитальном этапе. Необходимы дальнейшие исследования для выработки четких рекомендаций по ведению больных с РЗ, инфицированных HBV

Tunable Multiferroic Properties in Nanocomposite PbTiO\u3csub\u3e3\u3c/sub\u3e-CoFe\u3csub\u3e2\u3c/sub\u3eO\u3csub\u3e4\u3c/sub\u3e Epitaxial Thin Films

We report on the synthesis of PbTiO3–CoFe2O4 multiferroic nanocomposites and continuous tuning of their ferroelectric and magnetic properties as a function of the average composition on thin-film composition spreads. The highest dielectric constant and nonlinear dielectric signal was observed at (PbTiO3)85–(CoFe2O4)15, where robust magnetism was also observed. Transmission electron microscopy revealed a pancake-shaped epitaxial nanostructure of PbTiO3 on the order of 30 nm embedded in the matrix of CoFe2O4 at this composition. Composition dependent ferroics properties observed here indicate that there is considerable interdiffusion of cations into each other

Удержание на терапии тофацитинибом пациентов с ревматоидным артритом (данные реальной клинической практики)

Evaluation of the reasons for discontinuation of therapy with Janus kinase inhibitors (JAKi) may provide a clue to their more effective use.Objective : to analyze the survival of tofacitinib (TOFA) therapy and the reasons for its discontinuation in rheumatoid arthritis (RA) in real clinical practice.Patients and methods. The study included 30 adult patients with RA hospitalized to the V.A. Nasonova Research Institute of Rheumatology from 2018 to 2020 for the biologic disease modifying antirheumatic drugs (bDMARDs) or JAKi treatment. Patients were followed up for 3 years or until treatment with TOFA was discontinued, whichever occurred first.Results and discussion. TOFA was prescribed as the first line therapy in 3 patients. In all these patients, the drug was discontinued for the following reasons: insufficient efficacy (IE) after 2 full years of treatment; adverse reaction (AR); administrative reasons (AdR), i.e. the inability to continue therapy due to the lack of drug supply at the place of residence. 11 patients received TOFA as the second line therapy, in 8 of them the treatment was interrupted: in 4 due to IE, in 3 due to AR (skin allergy) and in 1 due to AdR one year after its initiation. TOFA was prescribed as a third line therapy in 9 patients, in 2 of them the drug was discontinued due to IE and in 3 due to AR (allergic dermatitis in 2, dyspepsia in 1). Another 1 patient refused treatment due to a planned pregnancy. 6 patients received TOFA as the fourth line therapy, 5 of them (83.3%) continued to receive it for more than 3 years. In 1 patient, TOFA was discontinued after 1 month due to the dry cough and shortness of breath onset. In another 1 patient who was prescribed TOFA as the fifth line therapy, treatment was discontinued due to AR (recurrent Herpes zoster).Conclusion. As the results of the study show, no relationship was found between the incidence of AR or IE and clinical and demographic indicators, as well as the frequency of TOFA withdrawal and the line of therapy. At the same time, the shortest duration of retention on TOFA therapy was noted when it was prescribed as a first-line drug.Оценка причин отмены терапии ингибиторами Янус-киназ (uJAK) может дать ключ к более эффективному их применению.Цель исследования — анализ выживаемости терапии тофацитинибом (ТОФА) и причин его отмены при ревматоидном артрите (РА) в реальной клинической практике.Пациенты и методы. В исследование включено 30 взрослых пациентов с РА, госпитализированных в ФГБНУ «Научно-исследовательский институт ревматологии им. В.А. Насоновой» с 2018 по 2020 г. для назначения генно-инженерных биологических препаратов (ГИБП), а также и./AK. Пациенты оставались под наблюдением в течение 3 лет или до момента прекращения лечения ТОФА, в зависимости от того, какое событие наступало раньше.Результаты и обсуждение. В качестве первой линии терапии ТОФА был назначен 3 пациентам. У всех этих пациентов препарат был отменен по следующим причинам: недостаточная эффективность (НЭ) после 2 полных лет лечения; нежелательная реакция (НР); административные причины (АП), т. е. невозможность продолжать терапию в связи с отсутствием обеспечения препаратом по месту жительства. В качестве второй линии терапии ТОФА получали 11 больных, у 8 из них лечение было прервано: у 4 — из-за НЭ, у 3 — из-за НР (кожная аллергия) и у 1 — по АП через год после его начала. В качестве третьей линии терапии ТОФА был назначен 9 больным, у 2 из них препарат был отменен в связи с НЭ и у 3 — в связи с НР (аллергический дерматит — у 2, диспепсия — у 1). Еще 1 пациентка отказалась от лечения из-за запланированной беременности. В качестве четвертой линии терапии ТОФА получали 6 больных, 5 из них (83,3%) продолжали его прием более 3 лет. У 1 пациентки ТОФА был отменен через 1 мес в связи с впервые появившимися сухим кашлем и одышкой. Еще у 1 больного, которому ТОФА был назначен в пятой линии терапии, лечение было прекращено из-за НР (рецидивирующий Herpes zoster).Заключение. Как показали результаты исследования, связи между частотой возникновения НР или НЭ и клинико-демографическими показателями, а также частотой отмены ТОФА и линией терапии не выявлено. В то же время наименьшая длительность удержания на терапии ТОФА отмечена в случае его назначения в качестве препарата первой линии