Assessment of Adipokines, CXCL16 Chemokine Levels in Patients With Rheumatoid Arthritis Combined With Metabolic Syndrome

Funding Information: The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The study received intra-institutional funding and Scientific and technical program of Ministry of Healthcare of the Republic of Kazakhstan (program and target financing) [Development of scientific bases of formation of preventive environment in order to preserve the public health]. Publisher Copyright: © The Author(s) 2021.Objective: Rheumatoid arthritis (RA), which is a chronic systemic inflammatory disease, is associated with accelerated atherosclerosis and an increased risk of cardiovascular disease (CVD), but the causal factors have yet to be completely elucidated. The studies show that the prevalence of metabolic syndrome (MtS) was significantly higher in RA patients compared to the population. In RA and MetS inflammation and atherosclerosis are closely linked. The level of chemokines and adipokines, which may play a role in the development of atherogenesis in RA with MetS patients is currently unknown. In this study, we investigated the level of chemokine C-X-C motif chemokine ligand 16 (CXCL16) and adipokine in RA with MetS patients and assessed the association of biomarkers with clinical and biochemical activity scores of RA and components of MetS. Methods: Blood serum of 298 people (48—patients with RA and MetS, 82—with RA without MetS, 105—with MetS, 63—control group without both RA and MetS) was tested for (CXCL16), Resistin, Leptin and Fibroblast Growth Factor 21 (FGF21) levels by fluorescent antibody technique. Statistical analysis was performed using SPSS version 18.0. Results: The biomarker study showed the highest level in the RA with MetS patient group; but as compared with the RA group the differences were insignificant. CXCL16 (Me = 426.2 pg/ml (Q25-75 250.5-527.6), resistin (Me = 8685.4 pg/ml (Q25-75 6480.8-13 629.1), and FGF21 (Me = 443.6 pg/ml (Q25-75 772.9-916.3) proved to be significantly augmented in RA with MetS patients group, and in RA without MetS patients group (Me = 312.7 (Q25-75 199.4-517.7) pg/ml; Me = 8265.3 (Q25-75 5779.7-13 340.5) pg/ml; Me = 412.4 (Q25-75 300.4-497.4) pg/ml, respectively) as compared with MetS patients group (Me = 189.4 (Q25-75 130.3-280.6) pg/ml; Me = 5364.8 (Q25-75 2368.9-10 160.9) pg/ml; Me = 133.2 (Q25-75 76.2-268.6) pg/ml, respectively; P = <.001). Leptin level in all groups was higher than in the control group, but there were no differences between groups. The correlation analysis found a positive relationship between the leptin level and the waist circumference (rs = 0.39; P =.007) in the RA with MetS patients, the association of biomarkers with DAS28 score and ESR did not have any statistical significance. Conclusions: The augmented chemokine, resistin and FGF21 in the RA with MetS patients proves the systemic inflammation which is the basis of RA; the augmented leptin is linked to the abdominal obesity. These data are somewhat of an explanation of the increased risk of the CVD development in RA with MetS people. A differentiated specification can be useful to assess the cardiovascular risk of patients and justify prompt personalized treatment.publishersversionPeer reviewe

The Correction Methods of the Intestinal Microflora in Chronic Colonic Stasis by Siphon Enema and Probiotics as a Means of the Hirschsprung-associated Enterocolitis Prevention

AIM: The purpose of the current article is to study the state of the intestinal microflora in the context of chronic colonic stasis and assesses the methods of its correction by means of siphon enema and probiotics’ implication (bifidumbacterin and lactobacterin) to prevent the development of HAEC. METHODS: This study was conducted in the Astana City Children’s Hospital No. 2 and involved 60 children who applied for medical help with symptoms of chronic constipation. They were admitted to the hospital in a planned or emergency manner with suspected Hirschsprung’s disease in the period from 2015 to 2017, after approval of the Ethics Committee. An X-ray contrast study of the large intestine (irrigography) was performed in all the children for a diagnostic purpose. The following parameters of the state of the large intestine were studied: The function of the ileocecal valve (Bauhin’s valve), the diameter and shape of the large intestine, the presence of pathological formations, and symptoms of intestinal obstruction. Statistical analysis was carried out using Student’s test for dependent and independent samples by means of the BioStat Software. RESULTS: After treatment, the bacteriological examination of stool samples demonstrated an increase in the number of beneficial microorganisms and a decrease in the number of opportunistic microorganisms. The growth in the number of patients with the normal intestinal microflora (14 patients – 70%) was observed along with the reduction in the number of patients with intestinal dysbiosis, with a statistically significant difference (p &lt; 0.001). CONCLUSION: The developed method of correcting the quantitative composition of the intestinal microflora is very effective and can be implemented in clinical practice

CELIAC DISEASE AND GALLBLADDER: PATHOPHYSIOLOGICAL ASPECTS AND CLINICAL ISSUES

Celiac Disease (CD) is an immune-mediated disorder which primarily affects the small intestine; however, extra-intestinal organs are often affected by the pathological process, too. As regards the digestive system, liver alterations in CD patients have been widely described, which can also extend to the biliary tract. Notably, gallbladder function can be altered in CD patients. In this review, we specifically analyze and summarize the main pathophysiological aspects and clinical evidence of gallbladder dysfunction in CD patients, in order to discuss the potential medical complications and clinical research gaps. In addition to some perturbations of bile composition, CD patients can develop gallbladder dysmotility, which mainly expresses with an impaired emptying during the digestive phase. The main pathophysiological determinant is a perturbation of cholecystokinin secretion by the specific duodenal enteroendocrine cells in response to the appropriate nutrient stimulation in CD patients. This situation appears to be reversible with a gluten-free diet in most cases. Despite this gallbladder impairment, CD patients do not seem to be more predisposed to gallbladder complications, such as calculous and acalculous cholecystitis. However, very few clinical studies have actively investigated these clinical aspects, which may not be completely evidenced so far; alternatively, the substantial improvements in the last two decades regarding CD diagnosis, which have reduced the diagnostic delay (and related dietary treatment), may have lessened the potential clinical consequences of CD-related gallbladder dysfunction. Specific clinical studies focused on these aspects are needed for a better understanding of the clinical implications of gallbladder alterations in CD patients

PSORIASIS IS ASSOCIATED WITH ELEVATED GUT IL-1Α AND INTESTINAL MICROBIOME ALTERATIONS

Psoriasis is a chronic inflammatory condition that predominantly affects the skin and is associated with extracutaneous disorders, such as inflammatory bowel disease and arthritis. Changes in gut immunology and microbiota are important drivers of proinflammatory disorders and could play a role in the pathogenesis of psoriasis. Therefore, we explored whether psoriasis in a Central Asian cohort is associated with alterations in select immunological markers and/or microbiota of the gut

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

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

Identifying Key Biomarkers in Pediatric Pulmonary Hypertension: An Investigative Approach

This study assesses the utility of early biomarkers—5-hydroxyindoleacetic acid (5-HIAA) and insulin-like growth factor 1 (IGF-1)—for diagnosing and monitoring pulmonary hypertension (PH) in children with congenital heart defects (CHD). Due to the risks associated with invasive diagnostics, such as right heart catheterization, non-invasive biomarkers provide a safer alternative for early PH detection. This cohort-based study utilized blood and urine samples to measure 5-HIAA and IGF-1 levels via enzyme immunoassays. Our findings revealed significant changes in 5-HIAA concentrations across various biological matrices, supporting its potential as a diagnostic tool. Specifically, altered levels in urine and plasma reflect its role in serotonin metabolism and vascular remodeling in PH. IGF-1 levels were notably reduced in plasma, suggesting its involvement in PH pathophysiology. ROC analysis confirmed the diagnostic efficacy of these biomarkers, particularly 5-HIAA’s high specificity and sensitivity. In conclusion, 5-HIAA and IGF-1 levels correlate well with PH, underscoring their diagnostic value for early PH detection in children with CHD

HIGH SARS-COV-2 SEROPREVALENCE IN KARAGANDA, KAZAKHSTAN BEFORE THE LAUNCH OF COVID-19 VACCINATION

COVID-19 exposure in Central Asia appears underestimated and SARS-CoV-2 seroprevalence data are urgently needed to inform ongoing vaccination efforts and other strategies to mitigate the regional pandemic. Here, in a pilot serologic study we assessed the prevalence of SARS-CoV-2 antibody-mediated immunity in a multi-ethnic cohort of public university employees in Karaganda, Kazakhstan. Asymptomatic subjects (n = 100) were recruited prior to their first COVID-19 vaccination. Questionnaires were administered to capture a range of demographic and clinical characteristics. Nasopharyngeal swabs were collected for SARS-CoV-2 RT-qPCR testing. Serological assays were performed to detect spike (S)- reactive IgG and IgA and to assess virus neutralization. Pre-pandemic samples were used to validate the assay positivity thresholds. S-IgG and -IgA seropositivity rates among SARSCoV- 2 PCR-negative participants (n = 100) were 42% (95% CI [32.2–52.3]) and 59% (95% CI [48.8–69.0]), respectively, and 64% (95% CI [53.4–73.1]) of the cohort tested positive for at least one of the antibodies. S-IgG titres correlated with virus neutralization activity, detectable in 49% of the tested subset with prior COVID-19 history. Serologically confirmed history of COVID-19 was associated with Kazakh ethnicity, but not with other ethnic minorities present in the cohort, and self-reported history of respiratory illness since March 2020. Overall, SARS-CoV-2 exposure in this cohort was ~15-fold higher compared to the reported all-time national and regional COVID-19 prevalence, consistent with recent studies of excess infection and death in Kazakhstan. Continuous serological surveillance provides important insights into COVID-19 transmission dynamics and may be used to better inform the regional public health response

Genetic Predictors of the Development of Complications after Coronary Stenting

Due to the fact that there are scientific discussions about the significance of gene polymorphisms in the risk of developing cardiovascular complications after a percutaneous coronary intervention, it is of interest to evaluate the genetic predictors of the development of cardiovascular events. This study is a molecular genetic study. Association with the genes of biomarkers for inflammation and immune response increases the risk of cardiovascular events: rs1234313 (TNFSF4): (A/G, OR-4.57 (2.35–8.87), p ≤ 0.0001), (A/G-A/A, OR-3.14 (1.75–5.63), p ≤ 0.0001), and (A/G, OR = 4.01 (2.19–7.36), p ≤ 0.0001); rs3184504 (SH2D3); ATXN2: (C/T, OR-2.53 (1.28–5.01), T/T, OR-2.99 (1.13–7.92), p = 0.017)), (C/T-T/T, OR-2.61 (1.35–5.07), p = 0.000), and (OR-1.89 (1.15–3.09), p = 0.009)). According to the lipid metabolism biomarker genes, rs2943634: (A/C OR-2.57 (1.18–5.62), p = 0.013); according to the endothelial biomarker genes, rs2713604: (DNAJB8-AS1; GATA2): (C/T, OR-4.27 (2.35–7.76), p ≤ 0.0001), (C/T-C/C, OR-4.13 (2.31–7.40), p ≤ 0.0001), (OR-4.05 (2.24–7.30), p ≤ 0.0001), and (C/T, OR-3.46 (1.99–6.00), p ≤ 0.0001). The regression analysis found that in the presence of the rs2943634 gene polymorphism, the risk of late cardiovascular events increases by 4.007 times with 95% CI (1.502:10.692), p = 0.006. The genes of biomarkers for the risk of cardiovascular events are rs1234313(TNFSF4), rs3184504 (SH2D3; ATXN2), rs2943634, and rs2713604 (DNAJB8-AS1; GATA2). The only predictor of the development of new cardiovascular events was rs2943634, which belongs to the group of lipid metabolism biomarkers