ABSTRACT
Background: Rheumatoid arthritis (RA) is the most common systemic autoimmune disease that primarily affects joints but is also often characterized by extra-articular involvement1. Cardiovascular diseases are the most important causes of sudden death in these patients, which present a risk of developing cardiovascular events increased by 48%2. The causes of increased cardiovascular risk are several and not completely understood, but recent evidence supports the key role of endothelial dysfunction in pathogenesis. In this complex scenario, it is known that IL-6 receptors are present at the endothelial level and can be activated leading to endothelial dysfunction. SARS-Cov-2 is a coronavirus responsible for the disease called 'coronavirus disease 2019' (CoViD-19) characterized by clinical manifestations ranging from a flu-like syndrome up to severe lung damage associated with systemic hyper cytokine syndrome that can lead to multiple organ failure and death. Therefore, both RA and Covid-19 are associated with an increased pro-thrombotic and cardiovascular risk and IL-6 might be crucial in the patho-physiological mechanisms of both diseases. Objectives: The main hypothesis of this study was to evaluate the possible role of IL-6 as a promoter of endothelial dysfunction in RA and CoViD-19. Methods: In vitro experiments were conducted on the endothelial cell line EA. hy926. Cells were treated for 24 h with fetal bovine serum (FBS), a pool of RA patients' sera or a pool of CoViD-19 patients' sera. The expression levels of adhesion molecules (V-CAM1/CD-106, I-CAM/CD-54, p-selectine/CD-62, tissue factor/CD-142) and apoptosis were analyzed using cytofuorimetric technique. In addition, the autophagy level, using the autophagy markers p62 and LC3II, were evaluated through a western-blot analysis. The same experiments were conducted co-treating cells with the same pool of sera in addition to tocilizumab (TCZ), an anti-IL-6 drug, to verify the reversibility of the process and test the role of the aforementioned cytokine. Data are reported as interquartile median values. The Kruskal Wallis test was used for unpaired samples and the Mann-Whitney test for paired samples. P<0.05 values were considered statistically signifcant. Results: EA. hy926 cells, when treated with both RA and CoViD-19 patients' sera, showed increased levels of activation molecules and apoptosis compared to FBS treated cells. In addition, we observed increased levels of both p62 and LC3 proteins after both rheumatoid arthritis and CoViD-19 patients' sera treatment. All these fndings were reversible in the presence of TCZ. The results are presented in Figure 1. Conclusion: Our data showed that treatment with RA and CoViD-19 patients' sera increase the activation and death of endothelial cells in vitro. The increased level of cells death is possibly due to a block of autophagy. The reversibility of the process after blocking IL-6 with TCZ co-treatment confrms the hypothesis that IL-6 can play a key role in the pathogenesis of endothelial damage in patients with RA and CoViD-19.
ABSTRACT
Background and aims: Epilepsy burden in sub-Saharan Africa (SSA) has increased dramatically in the last 20 years. People with epilepsy (PWE) are estimated to be over 20 millions, with about 1 neurologist every 3-5 millions inhabitants, meaning more than 90% of epileptic patients are managed by health workers (HW) with insufficient education in Epilepsy, and 75% of them have no access to treatments. Moreover COVID-19 pandemic is affecting epilepsy management in SSA through care disruption. Teleneurology has the potential to improve this situation, although poor education of HW is associated with its underutilization. We measured the changes of teleneurology requests from primary cares in SSA after an education program on epilepsy. Methods: Global Health Telemedicine (GHT) offers remote advices and education to HW of the Disease Relief through Excellent and Advanced Means (DREAM) program active in 10 SSA countries. GHT-DREAM recently started an epilepsy program in Malawi and Central African Republic (CAR) with education and training courses delivered both locally and remotely. Results: In Malawi and CAR DREAM follows 18,770 patients, 569 (3,0%) suffering from epilepsy. The total number of teleneurology requests increased from 91 in 2019 to 141 in 2020 to 802 in 2021;>90% were for PWE. Conclusion: Education and training in epilepsy increased the number of tele-requests by improving knowledge and communication between SSA HW and European neurologists. Partnerships can bring neurologists where there are none, contributing to limit COVID-19 care disruption thus reducing the treatment gap in SSA. Our results move towards the Intersectoral Global Action Plan 2022-2031 in SSA. (Figure Presented).