NONLINEAR MAIN COMPONENTS OF THE CYTOKINE PROFILE IN CHILDREN WITH COMMUNITY-ACQUIRED PNEUMONIA

Cytokines are the most important mediators that control and regulate immune and inflammatory responses through complex networks and serve as biomarkers of many diseases. Quantitative determination of cytokines helps in determining the patient's immune status and adjusting therapy for various inflammatory diseases, such as sepsis, pneumonia. Since community-acquired pneumonia remains a common cause of childhood morbidity and mortality, the prognosis of the severity of the disease in children is an urgent problem at the present stage. In addition, the immune system and reaction change their properties with the growth and development of children, therefore, differences in the age of patients with pathological conditions should be taken into account. The aim of the study was to identify associations between cytokines in healthy children and in children with VP, depending on the age of patients and the severity of the pathological process. The work was carried out at the Department of Microbiology, Virology and Immunology, the Department of Propaedeutics of Childhood Diseases and Pediatrics and at the Research Institute of Immunology of the South Ural State Medical University of the Ministry of Health of the Russian Federation. The study included 117 children aged 1 to 18 years with a radiologically confirmed diagnosis of community-acquired pneumonia, severe and mild, hospitalized in the departments of respiratory infections of MBUZ DGKB No. 7 and MAUZ DGKB No. 8 in Chelyabinsk. To assess the severity of the condition of patients with VP, the criteria of severity in children with community-acquired pneumonia, presented in the clinical recommendations of 2022, were used. The comparison group was formed from 28 healthy children who did not have community-acquired pneumonia at the time of examination, as well as other signs of acute respiratory viral infection and were not under dispensary observation for any chronic pathology. All the children were comparable in gender and age. The levels of IL-1β, IFN-γ, IL-6, IL-4, IL-10, IL-2, TNF-α, IFN-λ2 (IL-28A), IFN-λ3 (IL-28B), IL-8, MCP-1, IL-17AF were determined, GM-CSF in blood serum using test systems based on the "sandwich" method of solid-phase ELISA using peroxidase as an indicator enzyme. For statistical analysis, a multidimensional method was used – nonlinear analysis of the principal components using the CATPCA algorithm. The study revealed a consistent increase in blood serum in children with IL-1ß, IL-4, IL-10, IL-2, TNF-α, IFN-λ2 (IL-28A), IFN-λ3 (IL-28B), IL-8, MCP-1, IL-17AF, GM-CSF, and the greatest correlation with severity was shown by IFN-λ2 (IL-28A), IFN-λ3 (IL-28B) and MCP-1, which can be considered additional biomarkers of the severity of community-acquired pneumonia. There was also a significant variability of the cytokine profile in healthy children and its significant narrowing in pneumonia, especially severe

ИССЛЕДОВАНИЕ МАРКЕРОВ ФИБРОЗА ПЕЧЕНИ У БОЛЬНЫХ С ЖИРОВЫМ ГЕПАТОЗОМ В СОЧЕТАНИИ С АТЕРОСКЛЕРОЗОМ В БАССЕЙНЕ ВИСЦЕРАЛЬНЫХ ВЕТВЕЙ БРЮШНОЙ АОРТЫ

 Background. Investigation of synergistic action of atherosclerosis and fatty liver disease is one of the most topical problems of gastroenterology. Aim. Study the characteristics of clinical and laboratory parameters in patients with hepatic steatosis in combination with atherosclerosis of unpaired visceral branches of the abdominal aorta. Materials and methods. The research included 39 patients aged over 50 years with a diagnosis of hepatic steatosis. All patients underwent clinical, laboratory and instrumental studies include certain C-reactive protein, the calculation of indices FIB-4 and Forns, and Doppler ultrasound of the abdominal aorta and its unpaired branches. Results. Patients with atherosclerosis in the pool of the abdominal aorta were significantly older and more likely to suffer coronary heart disease. C-reactive protein in patients with a combination of hepatic steatosis and atherosclerosis visceral branches of the abdominal aorta was significantly higher in comparison with a group of isolated hepatic steatosis (2,66±1,87 and 0,85±0,74 and mg/dl, respectively, p=0.006). Surrogate marker of liver fibrosis FIB-4 index is positively correlated with resistance in the the common hepatic artery (rs=0,717, p=0,03), stage of hypertension (rs=0,624, p=0,017) and the presence of comorbidities among coronary heart disease (rs=0,609, p=0,02). Forns-index is positively correlated with systolic velocity in the superior mesenteric artery (rs=0,574, p=0,032). Conclusion. In patients with hepatic steatosis and atherosclerosis visceral branches of the abdominal aorta detected higher levels of C-reactive protein than in patients without atherosclerosis visceral branches of the abdominal aorta. The positive correlation between the surrogate markers of liver fibrosis (FIB-4, Forns index) and hemodynamics in the upper-mesenteric and common hepatic artery.Актуальность. Исследование взаимопотенциирующей роли атеросклероза и жировой болезни печени является одной из наиболее актуальных проблем гастроэнтерологии. Цель исследования. Изучить особенности клинико-лабораторных показателей у больных со стеатозом печени в сочетании с атеросклерозом непарных висцеральных ветвей брюшной аорты. Материалы и методы. В исследование было включено 39 пациентов в возрасте старше 50 лет, с установленным диагнозом стеатоза печени. Всем пациентам выполнялось клинико-лабораторное и инструментальной исследование, включавшее определение С-реактивного белка, расчет индексов FIB-4 и Forns, а также ультразвуковую допплерографию брюшной аорты и ее непарных ветвей. Результаты. Пациенты с атеросклерозом в бассейне брюшной аорты были старше и значимо чаще страдали ишемической болезнью сердца. Уровень С-реактивного белка в группе пациентов с сочетанием стеатоза печени и атеросклероза висцеральных ветвей брюшной аорты значимо выше в сравнении с группой изолированного стеатоза печени (2,66±1,87 и 0,85±0,74 мг/дл соответственно, p=0,006). Суррогатный маркер фиброза печени FIB-4 положительно коррелирует с индексом резистентности в общей печеночной артерии (rs=0,717, p=0,03), стадией гипертонической болезни (rs=0,624, p=0,017) и наличием среди сопутствующих заболеваний ишемической болезни сердца (rs=0,609, p=0,02). Forns-индекс положительно коррелирует с систолической скоростью в верхней брыжеечной артерии (rs=0,574, p=0,032). Заключение. У больных со стеатозом печени и атеросклерозом висцеральных ветвей брюшной аорты выявлены более высокие показатели С-реактивного белка, чем у пациентов без атеросклероза висцеральных ветвей брюшной аорты. Установлены положительные корреляции между суррогатными маркерами фиброза печени (FIB-4, Forns index) и показателями гемодинамики в верхнебрыжеечной и общепеченочной артериях

Intensity of CD36 expression by monocyte subpopulations and blood lipid spectrum parameters in patients without established atherosclerotic cardiovascular disease

Introduction. At the current stage of the study of atherosclerosis, it has been established that chronic activation of innate immunity, causing persistent low-intensity sterile inflammation, plays a crucial role at all stages of atherogenesis. Laboratory evaluation of signaling pathways associated with molecular patterns (DAMPs) in atherosclerosis and related to cardiovascular diseases (CVD) may contribute to the discovery of new diagnostic and prognostic markers. Objective: to study the relationship between lipid metabolism parameters and CD36 exposure to circulating monocytes in patients without established CVD. Material and methods. The study included 42 patients aged 4064 years without established atherosclerotic CVD, 19 (45.2 %) men and 23 (54.7 %) women. Dyslipidemia was detected in 95.2 % of patients. The blood serum concentrations of total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, glucose, glycated hemoglobin, high-sensitivity C-reactive protein (hs-CRP), creatinine were determined with subsequent calculation of glomerular filtration rate. Phenotyping of circulating monocyte subpopulations was performed by flow cytometry on a Navios 6/2 device (Beckman Coulter, USA). Results and discussion. According to the results of correlation analysis, non-HDL cholesterol levels were inversely correlated with absolute (r = 0.394; p = 0.013) and relative (r = 0.432; p = 0.006) content of CD14+CD16++CD36+TLR2+ monocytes. LDL cholesterol levels were also inversely correlated with the relative content of CD14+CD16+CD36+TLR2+ monocytes (r = 0.417; p = 0.018). According to correlation analysis, the level of non-HDL cholesterol inversely correlated with the intensity of CD36 expression on classical (r = -0.650; p < 0.0001), intermediate (r = 0.323; p = 0.045) and non-classical (r = 0.480; p = 0.002) monocytes. Also, CD36 expression intensity on classical (r = 0.449; p = 0.004) and non-classical (r = 0.382; p = 0.016) monocytes was inversely correlated with remnant cholesterol levels. In addition, increased non-HLA cholesterol levels were associated with decreased TLR2 expression on CD14+ CD16++ monocytes (r = 0.381; p = 0.018). It should be noted that a decrease in CD36 expression on intermediate monocytes was also associated with an increase in hs-CRP (r = 0.657; p = 0.003). Conclusion. In patients without established atherosclerotic CVD, an increase in cholesterol content of atherogenic lipoprotein fractions was associated with a decrease in the number of CD14+CD16++ and CD14+CD16+ monocytes co-expressing CD36 and TLR2 as well as with a decrease in CD36 expression on classical, intermediate and non-classical monocytes

Circulating Ageing Neutrophils as a Marker of Asymptomatic Polyvascular Atherosclerosis in Statin-Naïve Patients without Established Cardiovascular Disease

Background: Current data on the possible involvement of aging neutrophils in atherogenesis are limited. This study aimed to research the diagnostic value of aging neutrophils in their relation to subclinical atherosclerosis in statin-naïve patients without established atherosclerotic cardiovascular diseases (ASCVD). Methods: The study was carried out on 151 statin-naïve patients aged 40–64 years old without ASCVD. All patients underwent duplex scanning of the carotid arteries, lower limb arteries and abdominal aorta. Phenotyping and differentiation of neutrophil subpopulations were performed through flow cytometry (Navios 6/2, Beckman Coulter, USA). Results: The number of CD62LloCXCR4hi-neutrophils is known to be significantly higher in patients with subclinical atherosclerosis compared with patients without atherosclerosis (p = 0.006). An increase in the number of CD62LloCXCR4hi-neutrophils above cut-off values makes it possible to predict atherosclerosis in at least one vascular bed with sensitivity of 35.4–50.5% and specificity of 80.0–92.1%, in two vascular beds with sensitivity of 44.7–84.4% and specificity of 80.8–33.3%. Conclusion: In statin-naïve patients 40–64 years old without established ASCVD with subclinical atherosclerosis, there is an increase in circulating CD62LloCXCR4hi-neutrophils. It was also concluded that the increase in the number of circulating CD62LloCXCR4hi-neutrophils demonstrated moderate diagnostic efficiency (AUC 0.617–0.656) in relation to the detection of subclinical atherosclerosis, including polyvascular atherosclerosis