Background:Patients diagnosed with Rheumatoid Arthritis (RA) have an increased risk of comorbidities and secondary mortality, in a large extent due to cardiovascular events.Objectives:To identify the frequency of comorbidity, mortality and variables related to its increase in a cohort of patients with rheumatoid arthritis established (RAE).Methods:Controlled cross-sectional observational study of a cohort of 188 patients with RAE a 10 year follow-up (5 years if not complete this period).Results:62.8% were women, mean age of patients at the time of inclusion was high 73.3 (+/-13.8) years and mean duration of disease was 12,8 (+/-6,99) years. Regarding CV risk factors, 26.6% smoked, 60.6% hypertension and 52.1 % diabetic. Regarding comorbidities, the most frequent were serious infections (45.2%), CVD (35.1%), Osteoporosis (31.9%), Depression (31.9%) and Kidney disease (26.6%). During follow-up, an improvement was observed inflammatory parameters and activity levels (p <0.001) Table 1. Mortality was associated to CVD and severe infection, and depression to lower mortality (p 0.05). Overall mortality was 32.4%. A logistic regression was performed in the group of patients with time greater evolution 10 years of our cohort, to be able to better represent the influence of disease carrying with her for longer, whose results are shown in Table 2. Analysand survival, men, CVD, severe infections, and Positive Rheumatoid Factor were associated with higher mortality, while treatment with Methotrexate was associated with increased survival. Among the causes of death, the most frequent were infections, CVD and solid cancer.Conclusion:-The incidence of comorbidities in our cohort is similar to that described in the literature.-Relationship between mortality and CVD and severe infection is demonstrated.-The mortality rate observed is higher than that described in the literature, which be influenced by the advanced age of the patients in the cohort and high time evolution of RA.References:[1]Lee YK, Ahn GY, Lee J, Shin JM, Lee TH, Park DJ, Song YJ, Kim MK, Bae SC. Excess mortality persists in patients with rheumatoid arthritis. Int J Rheum Dis. 2021 Jan 19. doi: 10.1111/1756-185X.14058. Epub ahead of print. PMID: 33463890.[2]Mikuls, T. R. (2003). Co-morbidity in rheumatoid arthritis. Best Practice & Research Clinical Rheumatology, 17(5), 729-752.[3]Naz, S. M., & Symmons, D. P. M. (2007). Mortality in established rheumatoid arthritis. Best Practice & Research Clinical Rheumatology, 21(5), 871-883.Table 1.Student’s t test for paired data.VariablesBasal10 yearPDAS285,25 (15,08)2,89 (1,06)0,036VAS38,61 (36,45)26,93 (24,97)<0,001HAQ1,04 (0,79)0,88 (0,87)NSTJC4,96 (5,38)1,40 (2,57)<0,001SJC3,55 (3,69)0,72 (2,11)<0,001ESR (mm/h)31,47 (21,19)25,86 (18,47)<0,001CRP (mg/L)15,24 (16,13)9,41 (21,02)0,001Hemoglobin (mg/dL)13,44 (7,92)13,52 (7,64)NSGlucose (mg/dL)102,26(35,97)103,83 (37, 98)NSCholesterol (mg/dL)203,56 (46,11)195,65 (38,12)0,042LDL (mg/dL)123,91 (40,69)119,58 (33,89)NSHDL (mg/dL)56,73 (19,07)54,84 (20,38)NSTriglycerides (mg/dL)110,85 (60,77)113,44 (55,61)NSTable 2.Logistic regression model. Hosmer-Lemeshow Chi square 9.035 Gl 7 p 0.25. Likelihood ratio test Chi square 64.658 Gl 5 p <0.001. NS, Not significant.VariableUnivariate analysisOR (IC 95%)pMultiivariate analysisFINAL MODELOOR (IC 95%)PDyslipidemia1,02 (0,47-2,23)0,965HT4,73 (1,79-12,48)0,002DM1,42 (0,59-3,44)0,438CV disease11,25 (4,45-28,44)< 0,00112,33 (3.89-39,04)< 0,001Hyperuricemia3,27 (1,39-7,65)0,006Thyroid disease0,56 (0,15-2,11)0,393Interstitial lung disease2,48 (0,77-7,99)0,1277,37 (1,48-36,84)0,015Osteoporosis2,38 (1,07-5,29)0,033Renal disease8,25 (3,41-19,97)< 0,0014,14 (1,34-12,80)0,014Depressión0,32 (0,12-0,84)0,0210,20 (0,06-0,74)0,015Solyd CA1,12 (0,44-2,87)0,809Hematologic CA<0,001 (NS)0,999Amyloidosis2,65 (0,16-43,52)0,496Severe infecction6,22 (2,53-15,29)< 0,0015,59 (1,66-18,79)0,005COVID-19 infection1,31 (0,12-14,91)0,828Disclosure of Interests:None declared

Objectives:To analyze survival, causes of death, and risk factors associated with mortality in a cohort of patients with Systemic Sclerosis (SSc) at a single centerMethods:We performed a retrospective observational study of a cohort of patients with SSc undergoing follow-up during 2012 and until August 2020. We used the Kaplan-Meier method to estimate survival from onset of symptoms and multivariate Cox regression analysis to obtain independent risk factors associated with mortalityResults:The study population included 85 patients (women, 85.8%; mean age at diagnosis, 64.4 ± 12.7 years). A total of 19 patients (22.6%) died (table 1). Of these 11 (57.9%) died of a cause related to the disease itself (interstitial lung disease [ILD], 5 (26.3%); pulmonary hypertension, 2 (10.5%); or a combination of both, 3 (15.8%). The main cause of non–SSc-related death was cancer (21.1%). Survival rates at 5, 10, and 20 years were 98%, 92%, and 75%, respectively. Survival was statistically significantly poorer for the absence of ACA, the presence of antitopoisomerase I antibodies, proximal skin thickening, pulmonary hypertension, ILD, cancer and the diffuse subtype. The multivariate analysis performed to determine which factors were independently associated with mortality confirmed that older age at diagnosis of the disease, lower FVC in spirometry at diagnosis of ILD, and proximal skin thickening were associated with greater mortalityTable 1.Clinical and immunological characteristics of patients who died and patients who livedDead(n=19)Alive(n=66)p-valueFemale sex, n (%)17 (89.5)55 (83.3)0.594Age at diagnosis (years), mean (SD)56.9 (13.7)50.4 (13.6)0.076Time since diagnosis (years), mean (SD)11.6 (7.3)14.2 (9.2)0.215lcSSc, n (%)6 (33.3)50 (75.7)< 0.001dcSSc, n (%)12 (66.7)10 (15.1)< 0.001Digital ulcers, n (%)9 (47.4)33 (50)0.748Calcinosis, n (%)1 (5.3)16 (24.2)0.061Telangiectasias, n (%)15 (78.9)56 (84.8)0.184ILD, n (%)15 (78.9)32 (48.5)0.021 FEV1 at diagnosis of ILD, mean (SD)78.3 (19.3)78.7 (17.7)0.955 FVC at diagnosis of ILD, mean (SD)65.2 (13.1)78.1 (20.7)0.043 DLCO at diagnosis of ILD, mean (SD)56.9 (17.5)63.9 (16.7)0.301Pulmonary hypertension, n (%)11 (57.9)14 (21.9)0.002 sPAP (mmHg), mean (SD)49.2 (24.7)30.2 (8.2)0.009Gastrointestinal involvement, n (%)13 (68.4)30 (45.4)0.125Cardiac involvement, n (%)3 (15.8)11 (16.7)0.907Muscle involvement, n (%)1 (5.3)2 (3.03)0.851Arthritis or arthralgia, n (%)5 (26.3)23 (34.8)0.436Renal crisis, n (%)02 (3.03)<0.001Cancer, n (%)5 (26.3)2 (3.03)0.001Positive ACA, n (%)5 (26.3)35 (53.03)0.034Positive ATA, n (%)10 (52.6)9 (13.6)< 0.001Abbreviations: ILD: diffuse interstitial lung disease, SSc: systemic sclerosis, FEV1: forced expiratory volume in the first second, FVC: forced vital capacity, DLCO: diffusing capacity for carbon monoxide, sPAP: systolic pulmonary artery pressure, ACA: anticentromere antibody, ATA: antitopoisomerase I antibody.Conclusion:Survival at 10 years was greater than 90% in the study cohort. The main causes of death were ILD, pulmonary hypertension and cancer. The main factors associated with mortality were proximal skin thickening, older age at diagnosis, and lower forced vital capacityDisclosure of Interests:None declared

Background:Liver damage in rheumatoid arthritis (RA) is most common in the form of asymptomatic abnormal liver biopsies. It is difficult to differentiate between hepatic manifestations of the primary disease and potential hepatotoxicity of the therapies. Inflammation, oxidative stress, apoptosis and loss of lipid droplets are involved in the hepatic fibrogenesisObjectives:1)To analyze the impact of RA in the liver function and 2)To evaluate the direct effect of anti-citrullinated protein antibodies (ACPAs) in the liver fibrosis.Methods:150 RA patients and 100 healthy donors (HD) were included. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), phosphatase alkaline (ALP), albumin and levels of autoantibodies and inflammatory markers were evaluated in serum. In vitro studies: Hep G2 cells were treated with IgG-ACPAs isolated from RA patients. Molecules involved in lipid metabolism, insulin resistance, oxidative stress and inflammation were analyzed by RT-PCR and Western blot. Activation of intracellular pathways involved in fibrogenesis were analyzed. Lipid accumulation was evaluated by fluorescence microscopy. Mouse model: 20 CB57J/BL mice were used; 5 mice were used as non-diseased group, and 15 were used in CIA modelling. Liver samples were collected. Genes involved in insulin signal, lipid accumulation, macrophage infiltration and polarization and inflammation were evaluated. Activation of intracellular pathways related to fibrogenesis were analyzed. Immunohistochemistry was used to evaluate the percentage of fibrotic cells.Results:Within the normal range of hepatic enzymes, the percentage of RA patients with levels of AST, ALT and ALP above the mean was significantly higher compared to HD. In contrast, percentage of RA patients displaying levels of albumin bellow the mean was significantly elevated compared to HD. Differences remained significant after adjusting for potential confounders (treatment). Moreover, high levels of AST and ALT were associated with ACPAs and inflammatory markers. IgG-ACPAs induced the expression of inflammatory and oxidative stress markers and decreased genes involved in insulin signal and lipid accumulation in Hep G2 cells. In addition, lipid content decreased after IgG-ACPAs treatment. The phosphorylation of intracellular pathways involved in fibrogenesis was modulated by Ig-ACPAs.The induction of arthritis in mice elevated inflammatory cytokines and markers of macrophages presence and polarization state M1 and reduced genes related to lipid droplets in the liver. Phosphorylation of ERK and mTOR was increased in the liver of CIA mice. Additionally, the percentage of cells positive for α-smoth muscle antibody was increased in the liver of CIA mice.Conclusion:(1) RA patients displayed a subclinical alteration of the hepatic enzymes levels associated with levels of autoantibodies ACPAs, which may suggest that RA is associated with an abnormal liver function induced by autoantibodies. (2) ACPAs may induce alterations in hepatic cells, increasing inflammation and oxidative ...