ПОВЫШЕНИЕ УРОВНЯ ПРОВОСПАЛИТЕЛЬНЫХ ЦИТОКИНОВ В ПЛАЗМЕ КРОВИ У ПАЦИЕНТОВ С ХРОНИЧЕСКОЙ ТРОМБОЭМБОЛИЧЕСКОЙ ЛЕГОЧНОЙ ГИПЕРТЕНЗИЕЙ

HighlightsIL-8 and MCP-1 have a significant role in the CTEPH pathogenesis, which indicates the importance of nonspecific immunity in the formation and progression of CTEPH. The coupling between cytokines and hemodynamic parameters, cardiac structural changes and plasma biochemical parameters were determined. AbstractBackground. Chronic thromboembolic pulmonary hypertension (CTEPH) pathogenesis is complex and not fully understood. Particular attention to the microvascular damage genesis in CTEPH is given to aseptic inflammation, which in turn could be mediated through various molecular mechanisms. According to the conflicting and incomplete data on changes in the profile of factors controlling inflammation in CTEPH, research in this field would identify new therapeutic targets for the prevention and treatment of CTEPH.Aim. To study the profile of plasma proinflammatory cytokines in patients with chronic thromboembolic pulmonary hypertension (CTEPH) and evaluate the coupling of these cytokines with the main morphofunctional and laboratory values of the disease severity.Methods. 34 patients with CTEPH were included in this study. To characterize the group, the following methods were used: echocardiographic examination, catheterization of the right cardiac chambers. Biomarkers of heart failure, systemic inflammation, as well as erythropoiesis and iron metabolism were assessed in all patients. The control group included 10 donors. To study the proinflammatory cytokine profile in plasma, interleukins (IL) 6, 8, 18, monocyte chemoattractant protein-1 (MCP-1) and matrix metalloproteinase 9 were determined using standard enzyme-linked immunosorbent assay (ELISA) kits.Results. Hemodynamic and morphofunctional changes in the pulmonary circulation specific to pulmonary hypertension were determined with catheterization of the right cardiac chambers and echocardiography. During plasma proinflammatory cytokines analysis, a significant increase in the level of IL-8 (p = 0.030) and MCP-1 (p = 0.031) in CTEPH group compared to the control group was observed. No significant differences for other analyzed markers were found. In the elaboration of the correlation analysis, moderate inverse coupling between proinflammatory markers and hemodynamic parameters characterizing the CTEPH severity were revealed, as well as positive correlations with parameters of remodeling of the right cardiac chambers and iron metabolism.Conclusion. The increased levels of IL-8 and MCP-1 in patients with CTEPH identified in the present study indicate a significant role of nonspecific immunity in the formation and progression of CTEPH. The coupling between cytokines and hemodynamic parameters, structural cardiac changes and plasma biochemical parameters were determined. Based on the obtained data, it is possible to develop new medicinal substances, targeting towards proinflammatory cytokines, their receptors and signaling pathways.Основные положенияИЛ-8 и MCP-1 играют существенную роль в патогенезе хронической тромбоэмболической легочной гипертензии, что указывает на важное значение неспецифического иммунитета в формировании и прогрессировании данного заболевания. Определена связь цитокинов с показателями гемодинамики, структурными изменениями сердца и биохимическими показателями плазмы крови. РезюмеАктуальность. Патогенез хронической тромбоэмболической легочной гипертензии (ХТЭЛГ) сложен и до конца не изучен. Особое внимание в генезе микрососудистого поражения при ХТЭЛГ уделяют асептическому воспалению, которое в свою очередь может быть опосредовано различными молекулярными механизмами. Учитывая противоречивые и неполные данные об изменении профиля факторов, контролирующих воспаление при ХТЭЛГ, исследования в этой области позволят определить новые терапевтические мишени для профилактики и лечения ХТЭЛГ.Цель. Изучить профиль провоспалительных цитокинов в плазме крови у пациентов с ХТЭЛГ и оценить связь этих цитокинов с основными морфофункциональными и лабораторными показателями тяжести течения заболевания.Материалы и методы. В исследование включены 34 пациента с верифицированным диагнозом ХТЭЛГ. Для характеризации группы использованы эхокардиографическое исследование и катетеризация правых камер сердца. У всех больных оценены биомаркеры сердечной недостаточности, системного воспаления, а также эритропоэза и обмена железа. В группу контроля вошли 10 человек-доноров. Для изучения профиля провоспалительных цитокинов в плазме крови определены интерлейкины (ИЛ) 6, 8, 18, моноцитарный хемоаттрактантный белкок 1 (MCP-1) и матриксная металлопротеиназа 9 с помощью стандартных наборов для иммуноферментного анализа.Результаты. По данным катетеризации правых камер сердца и эхокардиографии определены гемодинамические и морфофункциональные изменения малого круга кровообращения, характерные для легочной гипертензии. При анализе уровня провоспалительных цитокинов в плазме крови в группе ХТЭЛГ по сравнению с группой контроля отмечено значимое повышение ИЛ-8 (p = 0,030) и MCP-1 (p = 0,031). По другим проанализированным маркерам значимых различий не получено. В результате корреляционного анализа выявлены умеренные обратные взаимосвязи провоспалительных маркеров с гемодинамическими параметрами, характеризующими тяжесть ХТЭЛГ, а также положительные корреляционные связи с показателями ремоделирования правых камер сердца и обмена железа.Заключение. Установленное в настоящем исследовании повышение уровней ИЛ-8 и MCP-1 у пациентов с ХТЭЛГ указывает на значительную роль неспецифического иммунитета в формировании и прогрессировании ХТЭЛГ. Определены взаимосвязи цитокинов с показателями гемодинамики, структурными изменениями сердца и биохимическими показателями плазмы крови. На основе полученных данных возможна разработка новых лекарственных субстанций, мишенями для которых будут провоспалительные цитокины, их рецепторы и сигнальные пути

Acute urticaria: differential diagnosis and treatment

Acute urticaria remains one of the most topical pediatric problems. Acute urticaria lasts for up to 6 weeks, during which blisters appear with varying frequency and intensity. In about 40% of cases, urticaria is accompanied by angioedema. The prevalence of acute urticaria is 1 to 5% in the population, and in the child population the frequency of acute urticaria reaches 6.7%. According to recent estimates, 10 to 20% of the population has had an episode of acute urticaria during their lifetime. About 50% of children with acute urticaria have concomitant allergic diseases. The management of children with acute urticaria presents significant diagnostic and therapeutic challenges. Treatment of acute urticaria in children begins with elimination of the significant trigger – appropriate measures are taken (withdrawal of the drug, administration of an elimination diet, therapy of infectious and inflammatory processes). First-line drugs for acute urticaria are H1-antihistamines, and it is recommended to use H1-antihistamines of the II generation. However, if clinical manifestations develop rapidly, if the patient has generalized urticarial rashes, angioedema, gastrointestinal symptoms, parenteral forms of first-generation antihistamines may be used to relieve the acute allergic reaction. Patients who do not respond to treatment with antihistamines may respond to short-term therapy with systemic glucocorticoids, although the efficacy of this treatment has yet to be tested in controlled clinical trials. The prognosis for acute urticaria is favorable – in most cases, acute spontaneous urticaria remains the only episode in the patient’s life. The disease develops into a chronic form in 5% of patients, and other estimates suggest that the symptoms of urticaria persist in 9.5% of children for up to 6 months

SARS-CoV-2 escape from cytotoxic T cells during long-term COVID-19

Here, the authors report accelerated intrahost evolution of SARS-CoV-2 in an immunocompromised patient with non-Hodgkin’s lymphoma with 318 days long COVID-19, and show that changes in the viral genome resulted in escape from T cellular immune response

Diagnosis and Treatment Patterns of Chronic Thromboembolic Pulmonary Hypertension in Russia, Kazakhstan, Turkey, Lebanon, and Saudi Arabia: A Registry Study

Background: Patients with chronic thromboembolic pulmonary hypertension (CTEPH) in countries with limited resources have, to date, been poorly represented in registries. Objective: This work assesses the epidemiology, diagnosis, hemodynamic and functional parameters, and treatment of CTEPH in Russia, Kazakhstan, Turkey, Lebanon, and Saudi Arabia. Methods: A prospective, cohort, phase IV, observational registry with 3-year follow-up (n = 212) in patients aged ≥ 18 years diagnosed with CTEPH was created. Clinical, hemodynamic, and functional parameters were obtained at an initial visit, follow-up visits, and a final visit at the end of 3 years’ observation or end of follow-up. Data were recorded on electronic case report forms. Parameters evaluated included 6-minute walking distance (6MWD), use of pulmonary endarterectomy (PEA), balloon pulmonary angioplasty (BPA), pulmonary hypertension (PH)-targeted therapy, and survival. All statistical analyses were exploratory and descriptive, and were performed in the overall population. Results: The most common symptoms were typical of those expected for CTEPH. Almost 90% of patients underwent right heart catheterization at diagnosis or initial study visit. In total, 66 patients (31%) underwent PEA before the initial visit; 95 patients (45%) were considered operable, 115 (54%) were inoperable, and two (1%) had no operability data. Only 26 patients (12%) had been assessed for BPA at their initial visit. PH-targeted therapy was documented at diagnosis for 77 patients (36%), most commonly a phosphodiesterase type 5 inhibitor (23%). Use of PH-targeted therapy increased to 142 patients (67%) at the initial visit, remaining similar after 3 years. Use of riociguat increased from 6% of patients at diagnosis to 38% at 3 years. Between baseline and end of observation, results for patients with paired data showed an increase in 6MWD. Survival at the end of observation was 88%. Conclusions: These data highlight the current diagnosis and management of CTEPH in the participating countries. They show that early CTEPH diagnosis remains challenging, and use of off-label PH-targeted therapy is common. ClinicalTrials.gov: NCT02637050; registered December 2015. Graphical Abstract: (Figure presented.)