Higher Levels Of IL-6 Research Articles

Effectiveness and safety profile of mesenchymal stem cell secretome as a treatment for severe cases of COVID-19: a randomized controlled trial

Background: Mesenchymal stem cells (MSCs) are known to have immunomodulatory, anti-inflammatory, anti-apoptotic, and angiogenesis effects that are useful for relieving inflammation, recovery, and protection of lung tissues in COVID-19 patients. Secretome, a secretory product of MSCs, has several advantages over MSCs. We conducted a study to investigate secretomes’ effectiveness and safety profile as a treatment for severe COVID-19. Methods: A double-blind, multicenter, randomized, placebo-controlled trial was conducted between February 2021 and July 2021 in three top COVID-19 referral hospitals in the Greater Jakarta area, Indonesia. Eligible subjects (n=40) were randomized in a 1:1 ratio to an intervention group (n=20) and a control group (n=20). The primary outcome of this study was the changes in inflammatory markers and the ratio of inflammatory to anti-inflammatory markers. The secondary outcomes of this study included clinical outcome, laboratory outcome, radiological outcome, RT-PCR result conversion, and safety profile of MSC secretome. Results: Our analysis showed that on the 14th day after placebo administration, IL-6 level in the control group was significantly increased [4.110 (2.403–12.820) at baseline to 13.320 (2.958–33.285) on the 14th day after intervention, p=0.017]. The IL-6/IL-10 ratio in the control group was significantly increased (p=0.036) on the 14th day after placebo administration. We also found that most of the subjects who received placebo had high levels of IL-6 and ferritin (p=0.043) on the seventh day after the intervention. However, we found no significant differences in inflammatory marker levels on the seventh day and 14th day after intervention between both groups. There was no adverse event reported. There were no significant differences in the laboratory outcome, radiology outcome, RT-PCR result conversion, and safety profiles between both groups. Conclusions: MSC secretome can control inflammation in patients with severe COVID-19 and has a good safety profile. MSC secretome is a promising treatment modality for severe COVID-19.

Serum Interleukin 6 Level and Nutrition Status as Potential Predictors of Clinical Leprosy Development Among Household Contacts in Endemic Areas.

BackgroundLeprosy is a chronic infectious disease that can lead to severe lifelong disabilities. Close contacts of patients with leprosy have a higher risk of acquiring the disease. Nevertheless, there is a lack of reliable markers to predict Mycobacterium leprae infection. We aimed to identify new potential markers for developing clinical leprosy among contacts.MethodsSerum levels of interleukin (IL) 6, IL-8, IL-10, hemoglobin, ferritin, and transferrin saturation were measured in 67 patients with multibacillary leprosy (MB), 65 household contacts (HHCs) of MB patients, and 127 endemic controls (ECs). By means of multivariate logistic regression and receiver operating characteristic (ROC) analyses, we analyzed baseline variables and laboratory parameters that showed significant differences between MB in the HHC and EC groups and obtained the respective areas under the curve (AUC). Optimal cutoff values of the associated cytokines were also determined.ResultsElevated IL-6 level was observed in MB patients compared to HHCs and ECs (P = .022 and .0041, respectively). Anemia and iron deficiency were also higher in the MB group compared to HHCs or ECs (P < .001). Likewise, we observed an increased risk of having MB leprosy in underweight HHCs (odds ratio [OR], 2.599 [95% confidence interval {CI}, .991–6.820]) and underweight ECs (OR, 2.176 [95% CI, 1.010–4.692]). Further ROC analysis showed that high serum IL-6 level, underweight, anemia, and iron deficiency can discriminate leprosy from their HHCs (AUC, 0.843 [95% CI, .771–.914]; P = .000; optimal cutoff value of IL-6 = 9.14 pg/mL).ConclusionsOur results suggest that serum IL-6 and nutrition status could serve as potential prognostic markers for the development of clinical leprosy in infected individuals.

Differentiation of circulating monocytes into macrophages with metabolically activated phenotype regulates inflammation in dyslipidemia patients.

Macrophages are mediators of inflammation having an important role in the pathogenesis of cardiovascular diseases. Recently, a pro-inflammatory subpopulation, known as metabolically activated macrophages (MMe), has been described in conditions of obesity and metabolic syndrome where they are known to release cytokines that can promote insulin resistance. Dyslipidemia represents an important feature in metabolic syndrome and corresponds to one of the main modifiable risk factors for the development of cardiovascular diseases. Circulating monocytes can differentiate into macrophages under certain conditions. They correspond to a heterogeneous population, which include inflammatory and anti-inflammatory subsets; however, there is a wide spectrum of phenotypes. Therefore, we decided to investigate whether the metabolic activated monocyte (MoMe) subpopulation is already present under dyslipidemia conditions. Secondly, we assessed whether different levels of cholesterol and triglycerides play a role in the polarization towards the metabolic phenotype (MMe) of macrophages. Our results indicate that MoMe cells are found in both healthy and dyslipidemia patients, with cells displaying the following metabolic phenotype: CD14varCD36+ABCA1+PLIN2+. Furthermore, the percentages of CD14++CD68+CD80+ pro-inflammatory monocytes are higher in dyslipidemia than in healthy subjects. When analysing macrophage differentiation, we observed that MMe percentages were higher in the dyslipidemia group than in healthy subjects. These MMe have the ability to produce high levels of IL-6 and the anti-inflammatory cytokine IL-10. Furthermore, ABCA1 expression in MMe correlates with LDL serum levels. Our study highlights the dynamic contributions of metabolically activated macrophages in dyslipidemia, which may have a complex participation in low-grade inflammation due to their pro- and anti-inflammatory function.

High plasma IL-6 levels following haploidentical allogeneic hematopoietic stem cell transplantation post-transplant cyclophosphamide as predictor of early death and worse outcome

IntroductionHaploidentical hematopoietic stem cell transplantation (haplo-HSCT) can be used as an alternative procedure in the absence of HLA-compatible donors. The use of high doses of cyclophosphamide after infusion improves the prognosis and eliminates the need for T cell depletion in vivo. Among the main complications of haplo-HSCT are acute graft-versus-host disease (a-GVHD) and cytokine release syndrome (CRS). This is a systemic inflammatory response that leads to the release of inflammatory proteins, including IL-6. This syndrome has several clinical features, with mild to severe symptoms. This study aimed to compare plasma IL-6 levels in patients submitted to different HSCT types and to associate them with the presence of acute graft versus host disease (a-GVHD), CRS and survival. MethodsA total of 84 patients (22 haploidentical and 62 non-haploidentical) were evaluated at different times. The IL-6 levels in haplo and non-haplo-HSCT recipients were measured before transplantation and on days D7, D14, D28, D60, and D100. ResultsIL-6 levels were higher in haplo-HSCT recipients than in non-haplo-HSCT recipients, remaining elevated from D14 until D100 (P = 0.006) and a cut-off ≥11 pg/mL on D7, which is related to worse overall survival. In our study, we found no association with a-GVHD (P = 0.239), a common complication of this type of transplant, but we found a relationship between the increase in IL-6 and CRS (P = 0.021). ConclusionIL6 can be used as a biomarker for patients submitted to haplo-HSCT, allowing clinical interference in patients having levels of IL-6 times larger than normality values, avoiding early death in this group of patients.

Corticosteroids as risk factor for COVID-19-associated pulmonary aspergillosis in intensive care patients

PurposeCorticosteroids, in particular dexamethasone, are one of the primary treatment options for critically ill COVID-19 patients. However, there are a growing number of cases that involve COVID-19-associated pulmonary aspergillosis (CAPA), and it is unclear whether dexamethasone represents a risk factor for CAPA. Our aim was to investigate a possible association of the recommended dexamethasone therapy with a risk of CAPA.MethodsWe performed a study based on a cohort of COVID-19 patients treated in 2020 in our 13 intensive care units at Charité Universitätsmedizin Berlin. We used ECMM/ISHM criteria for the CAPA diagnosis and performed univariate and multivariable analyses of clinical parameters to identify risk factors that could result in a diagnosis of CAPA.ResultsAltogether, among the n = 522 intensive care patients analyzed, n = 47 (9%) patients developed CAPA. CAPA patients had a higher simplified acute physiology score (SAPS) (64 vs. 53, p < 0.001) and higher levels of IL-6 (1,005 vs. 461, p < 0.008). They more often had severe acute respiratory distress syndrome (ARDS) (60% vs. 41%, p = 0.024), renal replacement therapy (60% vs. 41%, p = 0.024), and they were more likely to die (64% vs. 48%, p = 0.049). The multivariable analysis showed dexamethasone (OR 3.110, CI95 1.112–8.697) and SAPS (OR 1.063, CI95 1.028–1.098) to be independent risk factors for CAPA.ConclusionIn our study, dexamethasone therapy as recommended for COVID-19 was associated with a significant three times increase in the risk of CAPA.Trial registrationRegistration number DRKS00024578, Date of registration March 3rd, 2021.

Cytokine profile in hospitalized patients with COVID-19 of different severity

Analysis of cytokine profile markers in conjunction with the clinical manifestations of coronavirus disease 2019 (COVID-19) can provide valuable information about the pathogenetic manifestations of the disease, and therefore, in the future, determine drugs that affect the cytokine storm and have an anti-inflammatory effect.Aim. To identify correlations between the parameters of the developed cytokine profile and the clinical course in hospitalized patients with COVID-19 of different severity.Material and methods. The study included 70 hospitalized patients with a confirmed diagnosis of COVID-19, with a mean age of 58 [50;69] years, including 40 men (57%) and 30 women (43%). The average lung involvement according to computed tomography (CT) at admission was CT-2 [1;3]. Peripheral venous blood was taken at admission, which averaged 7 [6; 8] days from the symptom onset. Standard biochemical parameters were studied, as well as 47 cytokines and chemokines using the Multiplex system (Merck KGaA, Darmstadt, Germany).Results. Correlations was found between the lung involvement degree and the level of IL-8 (r=0,31, p&lt;0,05), IL-15 (r=0,35, p&lt;0,05), IL-18 (r=0,31, p&lt;0,05), MCP-1 (r=0,36, p&lt;0,05), MIG (r=0,50, p&lt;0,05), TNF-α (r=0,41, p&lt;0,05). An inverse correlation was also found in the level of blood oxygen saturation with the same indicators as follows: IL-8 (r=-0,27, p&lt;0,05), IL-15 (r=-0,34, p&lt;0,05), IL-18 (r=-0,31, p&lt;0,05), MCP-1 (r=-0,40, p&lt;0,05), MIG (r=-0,56, p&lt;0,05), TNF-α (r=-0,45, p&lt;0,05). IL-6 levels were significantly elevated in patients with severe COVID-19 (CT3, CT4), while no increase in IL-6 was observed in patients with moderate disease (CT1, CT2). It is noteworthy that in patients with diabetes, the highest values of IL-12, IL-9 were recorded.Conclusion. Hyperinflammatory syndrome in severe COVID-19 is manifested by high levels of IL-6, MIG, MDC, MCP-1, M-CSF, TNF-α, β, IL-8, IL-18, IL-15. With the CT-1 and CT-2, an increase in only the level of IL-18, IL-8 is noted. The identified patterns prove and make it possible to explain a number of systemic inflammatory changes that occur with COVID-19.

From Active to Non-active Giant Cell Arteritis: Longitudinal Monitoring of Patients on Glucocorticoid Therapy in Combination With Leflunomide.

In the present study, we longitudinally monitored leukocyte subsets, expression of neutrophil surface adhesion molecules (CD62L and CD11b) and serum analytes in therapy-naïve patients with active giant cell arteritis (GCA). We collected blood samples at the baseline, and at weeks 1, 4, 12, 24, and 48 of follow-up, and evaluated short- and long-term effects of glucocorticoids (GC) vs. GC and leflunomide. Our aim was to identify candidate biomarkers that could be used to monitor disease activity and predict an increased risk of a relapse. Following high doses of GC, the numbers of CD4+ T-lymphocytes and B-lymphocytes transiently increased and then subsided when GC dose tapering started at week 4. In contrast, the numbers of neutrophils significantly increased during the follow-up time of 12 weeks compared to pre-treatment time. Neutrophil CD62L rapidly diminished after initiation of GC therapy, however its expression remained low at week 48, only in patients under combinatorial therapy with leflunomide. Levels of acute phase reactant SAA and IL-6 decreased significantly after treatment with GC and leflunomide, while levels of IL-8, IL-18, and CHI3L1 did not change significantly during the follow-up period. CHI3L1 was associated with signs of transmural inflammation and vessel occlusion and might therefore serve as a marker of fully developed active GCA, and a promising therapeutic target. Patients with relapses had higher levels of IL-23 at presentation than patients without relapses (p = 0.021). Additionally, the levels of IL-23 were higher at the time of relapse compared to the last follow-up point before relapse. IL-23 might present a promising biomarker of uncontrolled and active disease and could give early indication of upcoming relapses.

Circulating Cytokines in Metastatic Breast Cancer Patients Select Different Prognostic Groups and Patients Who Might Benefit from Treatment beyond Progression.

Cancer induces immune suppression to overcome its recognition and eradication by the immune system. Cytokines are messengers able to modulate immune response or suppression. There is great interest in the evaluation of their changes during treatment in order to identify their relationship with clinical outcome. We evaluated 18 cytokines in breast cancer patients treated with eribulin before starting treatment (T0) and after four courses of therapy (T1). Longitudinal modifications were considered and cytokine clusters through PCA and HCPC correlated to patients’ outcomes were identified. Forty-one metastatic breast cancer patients and fifteen healthy volunteers were included. After clustering, we identified at T0 six patient clusters with different risk of relapse and death. At T1, only four clusters were identified, and three of them accounted for thirty-eight of forty-one patients, suggesting a possible role of treatment in reducing heterogeneity. The cluster with the best survival at T1 was characterized by low levels of IL-4, IL-6, IL-8, IL-10, CCL-2, CCL-4, and TGF-β. The cluster showing the worst survival encompassed high levels of IL-4, IL-6, IL-8, IL-10, CCL-2, and IFN-γ. A subgroup of patients with short progression-free survival (PFS) and long overall survival (OS) was comprised in the cluster characterized by low levels of CCL-2, IL-6, IL-8, IL-10, and IL-12 at T0. Our data support the prognostic significance of longitudinal serum cytokine analysis. This approach may help identify patients for whom early treatment stop avoids needless toxicity or might justify treatment beyond early progression. Further investigations are required to validate this hypothesis.

Assessment of serum level of interleukin-6 in aplastic anemia

Background Aplastic anemia (AA) is a severe bone marrow failure condition with a high mortality rate in its severe form if left untreated. Interleukin (IL)-6 is a pleiotropic cytokine with various biological activities, including B-cell terminal differentiation, T cell, and macrophage stimulation. Moreover, they are critical for tissue damage in acute inflammation and have also been shown to be potent inhibitors of myelopoiesis. Aim Our purpose was to assess IL-6 level in AA patients and to correlate it with AA severity. Patients and methods The study was conducted on 40 individuals divided into 20 patients with AA and in-patient clinic of Hematology Department, Faulty of Medicine, Tanta University Hospitals, and 20 apparently healthy participants used as a reference-control group. Results Pallor, weakness, and bleeding were present among 95% of the studied AA cases, while fever and infection were found among 90% of the studied AA cases. High levels of IL-6 were observed in AA. A correlation of increased levels with disease severity has been demonstrated. Conclusion High levels of IL-6 were observed in AA. Increased levels showed a correlation with disease severity, and therefore appear to play an essential role in AA.

Peripheral Blood Cytokines Levels in Senegalese Women with Cervical Cancer during Chemotherapy

Cervical cancer is the leading cause of cancer deaths of women in developing world. Several studies demonstrated evidences of inflammatory cytokines implication in cancer progression including in initiation, promotion and invasion by affecting the immune surveillance. Our aim was to measure blood circulating pro- and anti-inflammatory cytokines levels, their profiles according to treatment issue and relation with prognostic factors in cervical cancer during chemotherapy. Blood samples were collected from a cohort of 35 cervical cancer women and 42 women healthy controls (HC) with no history of malignancy. For each CP, three samples were taken at three-week intervals. The first one (S1) was taken before initiation of the chemotherapy protocol. S2 and S3 were samples collected respectively at day 21 and day 42. Cytokines levels were evaluated by ELISA. Mean age of patients was 54.1 year (35 - 77 yo). In groups, no relation was observed between age and cytokines levels. Before chemotherapy, high levels of IL-6, IL-4 and IFN-γ were observed in CP compared to HC (p 0.001) and at the same period, IL-10 and TNF-α levels were significantly low in CP (p 0.05) and negatively correlated (r = —0.79; p = 0.017). In this CP group, IL-4 levels were positively correlated between S1 and S2 (r = 0.72; p = 0.002) and between S1 and S3 (r = 0.74; p = 0.019). Similar correlations were observed for TNF-α levels: S1/S2 (r = 0.54; p = 0.027), S2/S3 (r = 0.82; p = 0.009) and S1/S3 (r = 0.66; p = 0.036) with a significant increase of TNF-α in blood during treatment. Depending on chemotherapy’s efficacy, CP patients were separated into 1) non responders (NR), 2) partial responders (PR) and 3) good responders (GR). Compared to PR and GR groups, NR patients showed: a) higher serum levels of IL-6, IL-10 and IFN-γ during the follow-up and b) lower serum levels of IL-4 and TNF-α. In addition, serum levels of IL-4 were significantly higher in GR patients however TNF-α was the predominant cytokines in PR group. Our results highlight the variation of circulating cytokines such as IL-6, IL-10 and IFN-γ during cervical cancer chemotherapy. In addition, this study suggested that IL-4 and TNF-α might represent potential biomarkers candidate in cervical cancer. Applications in cancer management need further investigations particularly about the relevant prognostic indicator following chemotherapy and validation studies must provide more assurance for translation into clinical practice.

Postoperative cytokine levels and their predictive value in critical patients after major abdominal surgery: a retrospective cohort study.

It remains uncertain as to what impact cytokine expression level has on patient outcomes. The association of serum levels of interleukin-1β (IL-1β), IL-2, IL-6, IL-8, IL-10, tumor necrosis factor-α (TNF-α), and procalcitonin with critically ill patient outcomes after major abdominal surgery still need to be explored. From January 1, 2018 to June 30, 2019, a retrospective cohort study was conducted on patients admitted to the surgical intensive care unit (SICU). Levels of IL-1β, IL-2, IL-6, IL-8, IL-10, TNF-α, and procalcitonin were assessed in 1,228 patients undergoing major abdominal surgery with blood samples drawn within 24 h after surgery. Of the 1,228 patients admitted to the SICU for the first time, 1,152 survived and 76 patients died, with a mortality rate of 6.2% (76/1,228). The results of univariate and multivariate analyses revealed that non-survivors had higher levels of IL-1β (OR =2.438, P<0.001) and IL-2 (OR =1.561, P=0.006). Of 62 (5.0%) readmitted to the SICU, the data of 59 were collected, and showed 46 patients survived and 13 died, giving a mortality rate of 22.0% (13/59), which was 3.5 times higher than the mortality rate during the first SICU admission. Serum IL-6 level associated with SICU readmission (OR =1.37, P=0.029). Furthermore, non-survivors had a longer SICU stay and higher rates of mechanical ventilation and continuous renal replacement therapy (CRRT). High levels of IL-1β and IL-2 were associated with mortality, and a high level of IL-6 was a risk factor for SICU readmission in critically ill patients who underwent major abdominal surgery. The mortality rate was higher during the second SICU stay.

The Impact of Metabolic Syndrome on Quality of Life Among Individuals With Knee Osteoarthritis Living in Egypt.

Background:Several studies have linked metabolic syndrome (MetS) to osteoarthritis (OA), but they have not looked into how MetS can affect the health-related quality of life (HRQOL) of OA individuals.Objectives:We aimed to assess the association of MetS and its components, including obesity, hypertension, hyperglycemia, and dyslipidemia, with HRQOL among Egyptians with knee OA.Methods:This cross-sectional study comprised 116 adult Egyptian participants with knee OA. They were divided into 2 groups based on whether or not they had the MetS. All participants were subjected to a thorough medical history taking and a detailed medical examination. The Kellgren and Lawrence (K/L) scale evaluated OA in all individuals using anteroposterior knee radiographs. The Health Assessment Questionnaire-Disability Index (HAQ-DI) and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) were used to assess participants’ HRQOL; their higher scores indicate more disability. Spearman rank and Pearson’s correlation analyses were used to assess the association between variables.Results:Diabetes, hypertension, dyslipidemia, and obesity were significantly associated with the OA + MetS group with a prevalence of 77.6%, 82.8%, 77.6%, and 50.0%, respectively. According to the K/L scale, 70.7% of the OA + MetS group had grade IV knee affection. The HAQ-DI and WOMAC scores were significantly (P < .001) higher among the OA + MetS individuals compared with the OA individuals. Interleukin (IL)-6 serum levels were also significantly higher in the OA + MetS group (P = .036) and increased significantly with the more serious radiological damage and functional disability. We found significant positive correlations between HAQ-DI and WOMAC with waist circumference (P = .004, .001), as well as triglycerides (P = .006, .008), cholesterol (P = .041, .048), fasting blood sugar (P < .001, < .001) and significant negative correlations with high-density lipoprotein levels (P = .628, .002).Conclusions:Individuals with knee OA with MetS showed more significant radiological damage, severe functional disability, and poor HRQOL. They also had higher levels of IL-6, which correlated significantly with the degree of disability, promoting it as a significant therapeutic target.

Cross-sectional assessment of mild cognitive impairment in pre-dialysis chronic kidney disease and its association with inflammation and changes seen on MRI: what the eyes cannot see.

Introduction:Mild cognitive impairment (MCI) is a prevalent and underdiagnosed condition in chronic kidney disease (CKD), that shares common pathophysiological factors such as chronic inflammation.Objective:To evaluate the association of MCI in CKD stages 1-5 using inflammatory markers and changes by magnetic resonance imaging (MRI).Patients and Methods:Cross-sectional study in adult patients with pre-dialysis CKD. MCI was assessed by the Montreal Cognitive Assessment (MoCA) and the estimated glomerular filtration rate (eGFR) by the Chronic Kidney Disease Epidemiology Collaboration equation. Sociodemographic and clinical data were collected from medical records. The cytokines IL-4, IL-6, IL-17, TNF-α and hs-CRP were determined. Brain MRI was performed in a 1.5 Tesla device, without paramagnetic contrast. A descriptive analysis followed by a comparison of abnormal versus normal MoCA scores among all studied variables. A linear regression analysis was performed using MoCA as a dependent variable, adjusted for confounding factors.Results:Of 111 invited patients, eighty completed the neuropsychological assessment and 56 underwent MRI, and were included in the study. Mean age was 56.3 ± 8.3 years and 51.8% (n = 29) had altered MoCA. When compared to the group with normal MoCA, the group with altered MoCA had higher levels of IL-6 and IL-17. There was no correlation between altered MoCA with eGFR or with MRI abnormalities.Conclusão:MCI assessed by MoCA was prevalent in patients with pre-dialysis CKD, it was associated with inflammation and showed no correlation with MRI changes.

Association of inflammatory markers with the disease & mutation status in pancreatic cancer.

Background & objectives:Inflammation has been studied to be an important contributory factor to carcinogenesis through pro-inflammatory markers such as interleukin (IL)-6 and C-reactive protein (CRP). Furthermore, K-ras mutation is an important genetic alteration in the pathogenesis of pancreatic cancer. This study aimed to compare these inflammatory markers in pancreatic ductal adenocarcinoma (PDAC) with the diseased and healthy controls (HCs) and to check for any association between IL-6 and CRP serum levels with the disease status, survival and K-ras mutation status of PDAC patients.Methods:The study included 135 PDAC, 25 chronic pancreatitis (CP) patients and 25 HCs. The serum levels of IL-6 and CRP were detected by enzyme-linked immunosorbent assay and K-ras mutations were detected by polymerase chain reaction-restriction fragment length polymorphism technique.Results:The serum levels of both these markers were elevated in PDAC cases than that in HCs. High IL-6 levels and higher CRP levels were found to be associated with locally advanced disease, lymphatic invasion, metastasis and advanced stage of the PDAC. In patients with unresectable PDAC, higher IL-6 levels were found to be associated with the presence of K-ras mutations.Interpretation & conclusions:Higher IL-6 and CRP levels in patients with advanced PDAC suggest an important role of these inflammatory markers in tumour progression. Furthermore, the association of mutations in the K-ras gene with serum IL-6 indicates cross-talks that may contribute to the progression of the PDAC.

Опыт применения биологической терапии (тоцилизумаб) у детей с тяжелыми формами COVID-19

Objective. To analyze the accumulated clinical experience in the management of patients with severe and extremely severe forms of COVID-19 coronavirus infection using biological therapy with an assessment of its efficacy and safety. Patients and methods. Forty-seven patients with severe and extremely severe COVID-19 infection were under observation, who were prescribed biological therapy with tocilizumab according to indications. All patients underwent a complete comprehensive clinical, laboratory and instrumental examination based on the current clinical protocol for the treatment of children with COVID-19 coronavirus infection. Results. Before and after biological therapy, no significant differences in the parameters of complete blood count and urinalysis were obtained. The study of biochemical blood parameters and coagulogram in dynamics showed a significant decrease in the levels of LDH and CPK, as well as inflammatory markers CRP and PCT, fibrinogen. Most patients had extremely high levels of proinflammatory cytokine IL-6 in the acute period of the disease, which decreased by 3.5 times after biological therapy, on average, 3–5 days after the start of treatment with tocilizumab, which coincided with a clinical improvement in the condition of patients. Prolonged SARS-CoV-2 isolation was noted according to nasopharyngeal smear PCR in 37 (88%) children up to 3–5 days after tocilizumab administration and in 10 (21%) patients over 10–14 days. On days 3–5 after the application of biological therapy, there was a decrease in the volume of lung damage to 50.7 ± 26.9% on average [0; 90], however, by 10–14 days, most patients still had signs of viral pneumonia up to 50.2 ± 27.2% of lung damage [0; 80] without clinical manifestations. Conclusion. After tocilizumab administration, most children with severe COVID-19 showed clinical and laboratory improvement in the form of normalized body temperature and reduced severity of intoxication syndrome, a 3.5-fold decrease in the level of IL-6, a decrease in the values of markers of systemic inflammation (CRP, PCT, fibrinogen) with a significant increase in antibody titer to SARS-CoV-2 IgM/IgG, in connection with which further observation was carried out by specialists at the outpatient stage. Key words: children, SARS-CoV-2, COVID-19, tocilizumab

Bisacurone attenuates diabetic nephropathy by ameliorating oxidative stress, inflammation and apoptosis in rats.

Diabetes nephropathy (DN) is a serious diabetic problem that may progress to renal failure. The root of Curcuma longa L., often known as turmeric, provides various health benefits. Bisacurone is a bioactive terpenoid found in small amounts in turmeric that possesses anti-inflammatory and antioxidant properties. The present study focuses on the potential protective effects of bisacurone against DN via reducing renal inflammation, oxidative stress, and apoptosis. Type 2 diabetes was created in rats by feeding them a high-fat/high-sugar diet for 8weeks, followed by a low dose of streptozotocin and Bisacurone (50 and 100μg/kg bisacurone) given for 4weeks. In diabetic rats, bisacurone reduced hyperglycemia, protected against body weight (BW) loss, lowered renal markers, reduced lipid profile alterations and avoided histological abnormalities. Bisacurone treatment reduced oxidative stress by decreasing malondialdehyde (MDA) levels while enhancing antioxidant defenses through superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) levels. Furthermore, bisacurone treatment activated the renal Nrf2/Keap1 signaling pathway but attenuated the high levels of NFκB p65, TNF-α, IL-1β, IL-6, Cox2, and iNOS. Bisacurone also reduced Bax, caspase-3, caspase-9 and cytochrome c but increased Bcl-2 in the kidneys of diabetic rats. In the present study, bisacurone reduces DN by reducing hyperglycemia, oxidative stress, inflammation, and apoptosis, while also increasing Nrf2/HO-1 signaling.

Purpura fulminans, presenting feature of multisystem inflammatory syndrome in children (MIS-C)

Introduction. Coronavirus disease 2019 (COVID-19) has been a worldwide health issue since early 2020, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Even though children do not usually present with se­vere COVID-19 unless the patient has an underlying di­sease, post­in­fectious complications, such as the multisystem in­flam­ma­to­ry syndrome in children (MIS-C), have been a sig­ni­fi­cant cause of child morbidity and mortality during the pan­de­mic. Even more challenging is that MIS-C has a very broad differential diagnosis due to its clinical heterogeneity. Case report. We report the case of a 6-month-old infant with­out another medical history who was brought to the ge­ne­ral practitioner’s office for persistent fever and cough. The symp­toms did not ameliorate under antipyretic and mucolytic treat­ment, so the patient later presented in the emergency room with associated dyspnea, diarrhea, vomiting and rapidly ge­ne­ra­li­zing purpuric skin lesions suggestive of purpura ful­mi­nans. He was admitted into our hospital and received em­pi­ri­cal antibiotic treatment. He also developed neck stif­fness. Meningococcemia was thus suspected; however, all cultures came out negative. Laboratory studies showed an important inflammatory syndrome, thrombocytopenia, se­vere anemia, coagulopathy, low protein C, protein S and an­ti­throm­bin levels, low fibrinogen, high D-dimer levels and hypo­al­bu­mi­ne­mia. Cerebral magnetic resonance imaging (MRI) showed no evidence of brain lesions. SARS-CoV-2 IgG-type antibodies were positive, therefore MIS-C was sus­pec­ted. The laboratory studies were extended and revealed high NT-proBNP, IL-6 and IL-2 soluble antigen levels. Other pos­si­ble diagnoses were excluded, which permitted our team to establish the diagnosis of MIS-C. The specific treatment was initiated with intravenous immunoglobulins (IVIG) and high-dose methylprednisolone associated with enoxaparin, broad-spectrum antibiotics and with symptomatic treatment. The patient rapidly evolved well, with the remission of fe­ver, inflammatory syndrome, coagulopathy and all other clinical and laboratory alterations. The skin lesions ame­lio­ra­ted as well, however, at a slower pace. Conclusions. MIS-C is a potentially life-threatening complication of COVID-19 in children. Therefore, clinicians must maintain a high degree of suspicion in the setting of the ongoing SARS-CoV-2 pandemic. However, the diagnostic criteria should be strictly followed due to the clinical similarities this pathology might have with other known diseases.

Modification of Immune Markers in Patients With Novel Coronavirus Infection Covid-19 Sars-cov-2

Patients with moderate Covid-19 severity were divided into three groups - with a complete absence of IL-6 in the circulation, with a low and rather high (17.75 - 99.5 pg / ml) content of IL6. It was revealed that at the lowest concentration of IL-6, patients had a mild variant of the moderate course of Covid-19 and recorded minimal levels of leukocytes, neutrophils, lymphocytes, monocytes, total T-lymphocytes and T-helpers, B- lymphocytes, immune indices “neutrophils/ lymphocytes”, CD4+/CD8+. However, with greater severity of the course of Covid-19 of moderate severity and a high content of IL-6, all these indicators significantly increased except for natural killer-effectors, the changes of which were of an opposite nature. It is suggested that a sufficiently high level of IL-6 in the case of moderately severe Covid-19 may be necessary to implement a balanced immune response, in contrast to a milder course, which in this sense may be insufficient. It can be assumed that the level of IL-6 can to a certain extent predict the severity of Covid-19.

Longitudinal Effects of Cultural and Psychosocial Factors on Biomarkers of Cardiovascular Risk in Caregivers

Dysfunctional thoughts about caregiving (DTAC) and familism (i.e. familistic obligation) were associated with worse caregiver emotional and cardiovascular health in cross-sectional studies. The aim of this study was to longitudinally examine the effects of familism and DTAC on cardiovascular health, considering caregiver kinship adjusting for well-established predictors of cardiovascular health. Study participants were 80 family dementia caregivers. Individual interviews and collection of blood samples were conducted in three yearly assessments. Linear mixed (random effects) regression analysis was performed to examine longitudinal associations of familism, DTAC, and circulating levels of cytokine interleukin (IL)-6, a cytokine and biomarker of cardiovascular disease risk (CVD). Caregiver age, gender, alcohol consumption, body mass index (BMI), hours caring, frequency and reaction of behavioral problems and caregivers’ transitions were used as covariates. Results showed that increases in DTAC, in familism and higher caregiver age were independently and significantly associated with higher levels of IL-6 over time in the group of spousal caregivers. No significant effects were found for any of the other covariates in spousal caregivers. In contrast, increases in BMI and in frequency of behavioral problems were significantly associated with increases in IL-6 over time in adult child caregivers. No significant effects were found for any of the rest of predictors in adult child caregivers. Findings suggest that high level of obligation familism and DTAC may a profile of increased vulnerability for CVD in spousal caregivers. In contrast, problem behaviors of the care recipient may characterize adult child caregivers in terms of an increased CVD risk.

466 The role of pulmonary act in the patient with SARS-CoV-2 infection

Already from the first data in China in early 2020 it emerged that patients with cardiovascular comorbidities had an increased risk of contracting SARS-CoV-2 infection and a more unfavourable clinical course. From March to May 2020, 85 patients affected by COVID-19 were enrolled, hospitalized at the Great Metropolitan Hospital of Reggio Calabria. The mean age was 63.6 ± 16.5 years. All patients underwent anamnesis, clinical evaluation, chest CT, ECG and measurement of markers of cardiovascular damage (Troponin I, CK-MB, LDH, D-dimer, BNP) and of inflammation (PCR, IL-6, and PCT). Thirty-one patients underwent echocardiography to look for signs of left ventricular dysfunction and/or repercussions of lung disease on the right sections. In particular, we evaluated parietal dimensions and thicknesses, biventricular function and transvalvular tricuspid and pulmonary flows and correlated the data obtained with ECG, radiological, clinical, and biohumoral parameters. The aim of our study was to evaluate the prognostic impact of cardiovascular involvement in COVID-19, investigating the effect of cardiovascular risk factors, levels of cardiovascular damage markers and newly emerging ECG and echocardiographic changes on a composite primary endpoint, consisting of the combination of exitus and the need for intensive care (ICU). For this purpose, the enrolled patients were divided into two subpopulations: those with better prognosis and those with poorer prognosis (ICU/exitus). We then analysed the reciprocal correlation of each of the investigated parameters and searched for the presence of echocardiographic signs of repercussion on the right sections of the pulmonary pathology. Among the patients with the poorest prognosis, 81.2% were hypertensive, 12.5% diabetic, 25% dyslipidaemic. Comparing the two subpopulations analysed, it emerged that patients with the worst prognosis were known hypertensive (P 0.02). Longer QTc intervals were associated with higher levels of CRP (P < 0.0001) and PCT (P 0.005). All markers of cardiovascular damage had significantly higher values in the most critically ill patients (P 0.001 for d-dimer, P < 0.001 for baseline and peak Troponin, P 0.001 for CK-MB, P 0.007 for BNP) and similar behaviour had indices of inflammation (P < 0.001 for PCR and IL-6). Patients with poorer prognosis had significantly lower lung AcT values ( P 0.002), which correlated with higher d-dimer levels (P 0.01) and more complicated hospital stays (P 0.02). There were no statistically significant differences between PAPs, right ventricular size, TAPSE, and pulmonary trunk diameter in the two subpopulations. Larger right ventricular diameters were associated with more dilated lung trunks (P 0.009) and higher IL-6 levels (P 0.004). The most interesting data of our study is the behaviour of pulmonary AcT: lower values of AcT were associated with higher levels of d-dimer, as an expression of a greater pulmonary microthrombotic burden, and a poorer prognosis, in the presence of PAPs basically normal. The dynamic analysis of this parameter, which is easy to calculate in the patient's bed, can play a crucial role in the instrumental follow-up of patients hospitalized for SARS-CoV-2 infection.