NETosis is assumed to be involved in the pathogenesis of common rheumatic diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS). However, the levels of circulating NETosis biomarkers and the extent of changes in these markers in specific rheumatic diseases are not fully understood. In this study, cell-free DNA (cfDNA) concentration as a non-specific marker, as well as myeloperoxidase (MPO) and citrullinated histone H3 (H3cit) as specific markers of NETosis, were investigated in SLE, RA, PsA, and AS. Analysis of covariance, accounting for sex, age and disease duration, showed that total cfDNA was elevated in SLE and AS compared with healthy subjects. Nuclear and mitochondrial cfDNA were elevated in four diseases. However, nuclear cfDNA was increased to a greater extent in SLE but mitochondrial cfDNA was higher in RA. MPO and H3cit were significantly elevated in SLE compared with other diseases, although MPO was also higher in RA. Elevated concentrations of MPO and H3cit in SLE were associated with the presence of concomitant cardiovascular diseases. The effect of biological therapy on mitochondrial cfDNA, MPO, and H3cit was also shown. The proinflammatory cytokine IL-18, implicated in the induction of NETosis, was similarly elevated in the four rheumatic diseases. Thus, the most striking signs of NETosis are found in SLE, although they are also present in RA. PsA and AS were mainly characterized by an increase in cfDNA. These data highlight characteristic changes in NETosis markers in four rheumatic diseases.

Гипокалиемия у госпитализированных пациентов с пневмонией на фоне COVID-19

Цель. Наличие легочной артериальной гипертензии (ЛАГ) у больных с системной склеродермией (ССД) ассоциировано с неблагоприятным прогнозом. Целью настоящей работы — оценить распространенность ЛАГ, ассоциированной с ССД, среди пациентов с впервые выявленной легочной гипертензией (ЛГ), включенных в регистр ФГБУ “СЗФМИЦ им. В. А. Алмазова”, и провести анализ применимости алгоритмов ранней диагностики ЛГ у пациентов с ССД. Материал и методы. В сравнительный анализ включены пациенты с идиопатической ЛАГ (ИЛАГ) и ЛАГ, ассоциированной с ССД (ЛАГ-ССД). Всем пациентам выполнялся развернутый протокол эхокардиографического исследования сердца (ЭхоКГ), тест с шестиминутной ходьбой (ТШХ), комплексная оценка функции внешнего дыхания. Для верификации диагноза ЛАГ использовалась катетеризация правых камер сердца (КПК). Результаты. Обследовано 33 пациента с ССД, предъявляющих жалобы на одышку, у 14 пациентов была верифицирована ЛАГ и назначена специфическая терапия. С помощью алгоритма PHAROS удалось дополнительно выделить группу риска из 6 пациентов для дальнейшего наблюдения. Среди обследованных пациентов больные с ИЛАГ составили 44%, больные с ЛАГ-ССД — 11%. Большинство пациентов в обеих группах имели III-IV ФК (ВОЗ) ЛГ: 55% среди ИЛАГ и 74% в группе ЛАГ-ССД. У пациентов с ССД были ниже показатели систолической функции ПЖ по данным ЭхоКГ [FAC=26±7% (р=0,028); TAPSE=15±3 мм (р=0,027); TAS’V=9±2 см/сек (р=0,023)]; значения диффузионной способности легких (DLco): 46±14% против 62±16% в группе ИЛАГ (р=0,001) и дистанция прохождения в ТШХ: 326±105 метров против 383±106 метров (р=0,041). Эти данные согласуются с данными зарубежных регистров и свидетельствуют о серьезном прогнозе у пациентов с ЛАГ-ССД. Заключение. Настоящее исследование продемонстрировало актуальность выработки новых алгоритмов для ранней диагностики ЛАГ и начала специфической терапии с учетом тяжести прогноза больных с ЛАГ-ССД. В современных рекомендациях по диагностике ЛАГ алгоритм DETECT рекомендован к исполнению у больных с ССД длительностью более 3 лет и DLco менее 60%. Продемонстрирована целесообразность включения в алгоритм обследования больных с ССД дополнительных эхокардиографических критериев диагностики ЛГ для повышения специфичности алгоритма.

BACKGROUND: Immune checkpoint inhibitors are highly effective in treating malignant neoplasms, but they often cause immune-related adverse events. The mechanisms of their pathogenesis are not well understood, and there are no reliable markers in clinical practice for assessing the risk of their occurrence. This study addresses the lack of research by validating a panel of markers. This will allow for personalized preventive management of patients and reduce the frequency of premature treatment discontinuation. AIM: The study aimed to identify the most informative prognostic markers for immune-related adverse events by evaluating dynamic changes in plasma cytokine levels in patients with malignant neoplasms who were receiving checkpoint inhibitor therapy. METHODS: A prospective study of patients with malignant neoplasms receiving checkpoint inhibitor therapy was conducted between 2023 and 2024 at the St. Petersburg Hospital of the Russian Academy of Sciences. The risk of immune-related adverse events was assessed as part of the dynamic observation (105 days with 2.0–2.5-week intervals). The primary endpoint was changes in plasma cytokine concentrations, determined by multiplex analysis and analyzed using nonparametric statistical tests such as the Shapiro–Wilk test, Mann–Whitney U test, and Šidák correction. RESULTS: The study included 21 patients with malignant neoplasms who completed the entire observation program. Six patients (28.6%) developed immune-related adverse events, whereas 15 (71.4%) did not. The development of immune-related adverse events was found to be associated with a significant increase in cytokine concentrations, suggesting a predominance of type 1 and type 17 T-helper cells. Of the evaluated biomarkers, interleukin 12p70 (IL-12p70), IL-15, and transforming growth factor-beta (TGF-β) had the greatest prognostic value for predicting complications. These biomarkers exhibited high sensitivity and specificity in pairwise group comparisons (p 0.005). During the manifestation of immune-related adverse events, the plasma concentrations of the following markers were as follows: IL 12p70: 2.51 [2.09–2.93] pg/mL; TGF-β: 14.54 [13.52–17.12] ng/mL; IL-15: 20.86 [15.51–26.21] pg/mL. The analysis confirmed that these markers are the most reliable predictors of an excessive immune response. No complications unrelated to the primary mechanism of action of the study therapy were reported. CONCLUSION: This study demonstrated for the first time the possibility of a predictive risk assessment for immune-related adverse events prior to checkpoint inhibitor therapy initiation based on IL-12p70, IL-15, and TGF-β levels. These findings allow for personalized patient management strategies that balance treatment efficacy with the prevention of complications. The study had two main limitations: its small sample size (n = 21) and the fact that patients were recruited from a single site.

Introduction. The problem of early detection of pulmonary arterial hypertension (PAH) is closely related to the diagnosis of systemic sclerosis (SSc). It is especially important in patients with slight manifestations of the disease, making it diffcult to verify the diagnosis before the clinic of right ventricular heart failure, and low knowledge of the general practitioners of the available diagnostic opportunities.The aim of the work was to identify the earliest clinical signs of PAH associated with SSc for its early diagnosis.Material and methods. The study included 51 patients with limited SSc. The investigators evaluated the extent of skin lesion, levels of the level of N­terminal brain natriureticpropeptide (NT­proBNP) and uric acid, the fluorescent pattern and titer of antinuclear factor. All patients underwent an echocardiography, nailfold videocapillaroscopy, a comprehensive assessment of external respiratory functions. When there were symptoms of PAH, right heart catheterization was performed to confrm it.Results. PAH was detected in 19 of the 51 patients included in the study. Patients with PAH were signifcantly older than those without PAH: (60±8) and (54±7) years, respectively (p=0.02); there were also differences between these groups in the signs of right cardiac remodeling (p<0.05), in the indices estimated in the six­minute walk test (p<0.05), in the assessment of lung diffusing capacity (p<0.001), in levels of NT­proBNP and uric acid (p<0.001), in the density of the nailfold capillaries (p=0.009); in a semiquantitative assessment of nailfold capillary alterations (p=0.022). Among patients with PAH associated with SSc, seven patients were diagnosed with SSc for the frst time after referring to cardiologists and verifying the genesis of PAH, while other 12 patients were previously observed by rheumatologists. Differences in the duration of the period from the onset of symptoms to the diagnosis of SSc (p=0.043) were revealed between these groups.Conclusion. The study shows the probability of the presence of SSc in patients with suspected idiopathic PAH, that determines the necessity of additional immunological and instrumental examinations in such patients.