МУЛЬТИПЛЕКСНОЕ ОПРЕДЕЛЕНИЕ ОНКОМАРКЕРОВ НА РАЗНЫХ СТАДИЯХ КОЛОРЕКТАЛЬНОГО РАКА

 Introduction. Colorectal cancer is one of the most common cancers worldwide. In the Republic of Kazakhstan, over the past decade, the incidence rates of colon and rectal cancers have increased by 23 % and 17 %, respectively. Although colorectal cancer screening rates have increased over time, it is necessary to identify new serum markers for early detection and prognosis of this cancer. The aim of the study was to evaluate the  diagnostic value of serum biomarkers for colorectal cancer. Material and Methods. Biomarkers were studied by immunofluorescence method using xMap technology, which included simultaneous immunofluorescence determination on magnetic spheres CA125, CA15–3, CA19–9, CEA, CYFRA21–1, sFAS, sFasL, HE4, Osteopontin, VEGF-A, pd-L1. Results. The study showed no significant differences in the levels of markersbetween healthy subjects (control group) and patients with bowel diseases. In cancer patients, СEA and OpN markers increased with increasing tumor stage, and were significantly higher than those observed in patients with bowel diseases and controls. The CA125 marker was significantly higher in patients with stage IV cancer then in patients with I–III stages. Conclusion. Our study revealed that the new pd-L1 marker can serve as a significant biomarker for colorectal cancer.  Введение. Колоректальный рак (КРР) занимает одно из ведущих мест в структуре онкологической заболеваемости, в том числе в азиатских странах. В Республике Казахстан прирост заболеваемости раком ободочной кишки за последнее десятилетие составил 23 %, раком прямой кишки  – 17 %. Несмотря на действующие программы скрининга  колоректального рака, продолжается поиск новых, в том числе сывороточных, маркеров для ранней диагностики, а у  пациентов с выявленным КРР – панелей маркеров для прогноза течения заболевания. Целью исследования является изучение диагностической ценности и динамики сывороточных биомаркеров у больных КРР разных стадий. Материал и методы. Биомаркеры изучены  иммунофлуоресцентным методом с использованием технологии xMap, который включал в себя одновременное иммунофлуоресцентное определение на магнитных сферах CA125, CA15–3, CA19–9, CEA, CYFRA21–1, sFAS, sFasL, HE4,  Остеопонтин, VEGF-A, pd-L1. Результаты. Показано, что уровень исследованных  маркеров не имел значимых различий у здоровых лиц и у больных с неонкологической патологией толстой кишки. При КРР выявлена статистически значимая зависимость уровня только 2 биомаркеров – CEA и ОПН – от стадии заболевания. У больных КРР IV стадии наблюдается значимое повышение CA125 по сравнению с новообразованиями I–III стадий. Такие маркеры, как CA19–9, HE-4, CA15–3, CYFRA 21–1, наряду с CEA, могут быть предложены для применения в комплексной  диагностической панели. Полученные результаты  позволяют сделать вывод о диагностических перспективах  маркера pd-L1 при колоректальном раке.

The Presence of PDL-1 on CD8+ Lymphocytes Is Linked to Survival in Neonatal Sepsis

Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection. Neonatal sepsis is the main cause of death in newborns, especially preterm infants. The pathogenesis of sepsis is based on a hyper-inflammatory syndrome combined with an immunosuppressive mechanism in sepsis. This study aimed to find critical parameters that are associated with the outcome of newborns with suspected sepsis. Understanding the association might have clinical relevance for immuno-monitoring, outcome prediction, and targeted therapy. Methods: A total of 210 newborn infants no older than 4 days with suspected sepsis at admission in Karaganda (Kazakhstan) were prospectively enrolled. Blood cultures were incubated, and pathogens in positive cultures were determined by MALDI-TOF. An immunological assay for blood cell components was conducted by flow cytometry with antibody cocktails. The diagnostic criteria for neonatal sepsis were identified by qualified neonatologists and included both clinical sepsis and/or positive blood culture. The analyzed infants were grouped into non-septic infants, surviving septic infants, and deceased septic infants. The results showed that deceased septic newborns had a lower level of CD8+ lymphocytes and higher PDL-1 expression in comparison with surviving septic newborns. PDL-1 expression on CD8+ T cells might play an immunosuppressive role during neonatal sepsis and might be used as a laboratory biomarker in the future

Association of Biomarker Level with Cardiovascular Events: Results of a 4-Year Follow-Up Study

Background. Given the high rates of morbidity and mortality from cardiovascular disease (CVD), the primary and secondary CVD prevention is one of the public health priority. Inflammation and endothelial dysfunction are the major drivers of atherosclerosis development and progression. In this regard, the study of the biomarker application as a tool to better identify high-risk individuals is an up-to-date sector of modern cardiology. The simultaneous measurement of multiple biomarkers can increase the risk stratification for people who are not known to have cardiovascular events in their history. The study aimed to investigate the predictive value of chemokine (C-X-C motif) ligand 16 (CXCL16), endocan, and heart-type fatty acid binding protein (H-FABP) in the cardiovascular event development in people who are not known to have cardiovascular events in their history. Method. We examined 363 people aged 30 to 65 who have been living permanently in the city of Saran, Karaganda region. The selected participants were people registered at a clinic at the city of Saran, who were screened between August and September 2014. Results. The follow-up period was 48 months (from August-September 2014 to November 2018). The results showed that CXCL16 (p<0.001), endocan (p<0.001), and H-FABP (p=0.002) biomarker levels are significantly higher in outcome groups compared with those of the no-outcome group. Univariate regression analysis proved the prognostic significance of all biomarkers in cardiovascular events development. The multivariate regression analysis after the adjustment confirmed that the CXCL16 increase was associated with the “composite endpoint” (CE) development (p<0.001) while the endocan increased due to the development of major cardiovascular events (MACE) (p=0.008); we did not find the association of the risks of event development with the H-FABP level increase (p=0.83)

Association of sTREM&#x2010;1 and Neutrophil-to-Lymphocyte Ratio as Prognostic Markers in COVID-19 Short- and Long-Term Mortality

Lyudmila Turgunova,1 Irina Mekhantseva,1 Lyudmila Akhmaltdinova,1 Mikhail Kostinov,2,3 Zhibek Zhumadilova,1 Anar Turmukhambetova1 1Karaganda Medical University, Department of Internal Medicine, Karaganda, Kazakhstan; 2I.I. Mechnikov Research Institute of Vaccines and Sera, Moscow, Russia; 3Sechenov First Moscow State Medical University, Department of Epidemiology and Modern Vaccination Technologies, Moscow, RussiaCorrespondence: Irina Mekhantseva, Email [email protected]: Current problem related to COVID-19 is various complications after disease, especially long-term mortality after COVID-19. Routine blood tests presented their effectiveness in the diagnosis, prognosis and mortality of COVID-19. The neutrophil-to-lymphocyte ratio (NLR) is an important marker of systemic inflammation. Soluble Trigger receptor expressed on myeloid cells-1 (sTREM-1) is considered an intrinsic enhancer of inflammatory signals. This study examined the predictive value of these markers in COVID-19 mortality.Methods: A prospective study was conducted involving patients with COVID-19 in Karaganda, Kazakhstan. The neutrophil–to-lymphocyte ratio (NLR) was calculated as the absolute number of neutrophils divided by the absolute number of lymphocytes. The level of sTREM-1 in the blood serum was evaluated by ELISA.Results: Plasma sTREM-1 concentration greater than 59.08 pg/mL and an NLR greater than 2.29 had an increased risk of early mortality (hazard ratio = 8.07; 95% CI: 1.03– 62.17 and 9.24; 95% CI: 1.202– 71.08, respectively); for long-term mortality of sTREM-1 greater than 47.34 pg/mL (hazard ratio = 7.96; 95% CI: 1.072– 59.18) and NLR greater than 2.10 (hazard ratio = 11.52; 95% CI: 1.551– 85.52).Conclusion: This study suggests that early levels of sTREM-1 and NLR are associated with the risk of 6-month mortality after experiencing COVID-19.Keywords: COVID-19, mortality, neutrophil-to-lymphocyte ratio, sTREM‐1, prognostic marker

Bloodstream Infection Etiology among Children and Adults

Every year in the world, sepsis occurs in 31.5 million people, and the number of deaths reaches 5.3 million per year. There are not enough studies that describe etiological structure of sepsis pathogens in different groups of population of the Republic of Kazakhstan. In this study, we have investigated difference of local sepsis etiology and antibiotic susceptibility among children and adults. A total 200 blood samples were examined using the standard and express method of identification of bloodstream pathogens. The determination of antimicrobial sensitivity was carried out by the disc-diffusion method according to CLSI guidelines. Overall, 23/90 (25.5%) positive blood cultures were isolated from adult patients and 43/110 (39%) from pediatric patients. It was found that children are statistically more often affected with bacterial bloodstream infection than adults (p<0.05). The Gram-positive bacteria are the leading cause of sepsis in both groups: S. epidermidis (35.5%) in pediatric patients and S. aureus (21.7%) in adults. However, statistical significance was detected in pediatric patients (p<0.05). The number of resistant strains of S. epidermidis (MRSE) in the group of children was 66.7%, while in adults, all S. epidermidis was resistant to azithromycin and cefoxitin (MRSE). S. aureus strains from adult patients and children had a similar picture of antibiotic patterns. The proportion of MRSA in pediatric patients was 16, 6%, and in adult patients, 20%. Enterobacterales (39%) were the second cause of sepsis in adult patients. 62.5% of Enterobacterales strains isolated from adults were phenotypically identified as ESBL, while in pediatric patients, 25% of ESBL producers were isolated. We have noted the resistance to antibiotics that are prescribed according to protocols of treatment of the Republic of Kazakhstan in the strains isolated from the patient’s blood

Inflammatory Serum Biomarkers in Colorectal Cancer in Kazakhstan Population

Colorectal cancer is a type of oncopathology widespread in Kazakhstan. The genetic component, as well as the possible etiopathogenetic mechanisms, is widely studied. One of the most promising areas is the study of diagnostic and prognostic possibilities of inflammatory biomarkers in patients with different degrees of tumor differentiation. The following biomarkers were included in the study panel: stem cell factor (SCF), vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF2), interleukin 6 (IL6), interleukin 8 (IL8), macrophage migration inhibitory factor (MIF), soluble Fas (SFAS), soluble Fas ligand (sFASL), transforming growth factor β (TGF), tumor necrosis factor (TNF), TNF-related apoptosis-inducing ligand (TRAIL), and programmed death ligand 1 (PD-L1). The data of our study show that most of the basic proinflammatory cytokines are involved in the systemic process and their levels do not depend on the level of tissue differentiation. Serum PD-L1 has shown itself to be a promising marker for tumor growth, which depends on the degree of differentiation