Showing papers by "Eduardo Collantes-Estevez published in 2017"

Ubiquinol Effects on Antiphospholipid Syndrome Prothrombotic Profile: A Randomized, Placebo-Controlled Trial.

Abstract: Objective—Antiphospholipid syndrome (APS) leukocytes exhibit an oxidative perturbation, directly linked to alterations in mitochondrial dynamics and metabolism. This disturbance is related to the p...

Identification and management of comorbidity in psoriatic arthritis: evidence- and expert-based recommendations from a multidisciplinary panel from Spain.

Abstract: The objective is to establish recommendations, based on evidence and expert opinion, for the identification and management of comorbidities in patients with psoriatic arthritis (PsA). The following techniques were applied: discussion group, systematic review, and Delphi survey for agreement. A panel of professionals from four specialties defined the users, the sections of the document, possible recommendations, and what systematic reviews should be performed. A second discussion was held with the results of the systematic reviews. Recommendations were formulated in the second meeting and voted online from 1 (total disagreement) to 10 (total agreement). Agreement was considered if at least 70% voted ≥7. The level of evidence and grade of recommendation were assigned using the Oxford Centre for Evidence-Based Medicine guidance. The full document was critically appraised by the experts, and the project was supervised at all times by a methodologist. In a final step, the document was reviewed and commented by a patient and a health management specialist. Fourteen recommendations were produced, together with a checklist to facilitate the implementation. The items with the largest support from evidence were those related to cardiovascular disease and risk factors. The panel recommends paying special attention to obesity, smoking, and alcohol consumption, as they are all modifiable factors with an impact on treatment response or complications of PsA. Psychological and organizational aspects were also deemed important. We herein suggest practical recommendations for the management of comorbidities in PsA based on evidence and expert opinion.

Disease Activity As a Major Determinant of Quality of Life and Physical Function in Patients With Early Axial Spondyloarthritis.

Abstract: Objective: To describe health-related quality of life (HRQOL) and physical function in patients with early axial spondyloarthritis (SpA) and to assess their associations with disease activity and radiographic damage. Methods: This was a cross-sectional study drawing upon baseline data of axial SpA patients (Assessment of SpondyloArthritis international Society criteria) from the ESPERANZA cohort. Linear regression analyses were used to evaluate the associations between disease activity and radiographic damage (spine and sacroiliac joints) with HRQOL, physical function, and spinal mobility. Results: In total, 259 patients were included. The mean ± SD age was 32.2 ± 6.9 years, disease duration was 13.3 ± 6.8 months, Ankylosing Spondylitis Quality of Life score was 5.9 ± 4.8, Bath Ankylosing Spondylitis Functional Index score was 2.4 ± 2.3, Bath Ankylosing Spondylitis Metrology Index score was 1.4 ± 1.3, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score was 3.8 ± 2.3, C-reactive protein (CRP) level was 9.7 ± 13.2 mg/liter, and Bath Ankylosing Spondylitis Radiology Index for the spine (BASRI-s) score was 1.7 ± 1.6. HRQOL was mainly associated with disease activity on univariate analysis (β values for BASDAI 0.646, patient global visual analog scale [VAS] 0.641, night back pain VAS 0.598, physician VAS 0.560, and CRP level 0.275; P < 0.01 for all), whereas the association with radiographic damage was weaker (standardized β for BASRI-s 0.142; P < 0.05). On multivariate models, HRQOL only remained significantly associated with disease activity (standardized β for BASDAI 0.330; P < 0.01, and physician VAS 0.205 and night back pain VAS 0.210; P = 0.01). Similarly, physical function was associated with disease activity and radiographic damage on univariate analysis, but only with disease activity (BASDAI β 0.466; P < 0.01) on multivariate analysis. However, spinal mobility was associated with radiographic damage in both univariate and multivariate analyses. Conclusion: Patients with axial SpA already have impaired quality of life and physical function, albeit mildly, at the beginning of their disease course. Both outcomes are mainly associated with disease activity in these patients.

Optimization of biological therapy in rheumatoid arthritis patients: outcomes from the CREATE registry after 2 years of follow-up.

Abstract: The current strategy for managing rheumatoid arthritis (RA) focuses on achieving clinical remission. Once remission is achieved and sustained over time, the most efficient strategy is dose optimization. This work describes the results of dose optimization after 2 years of follow-up in patients with RA treated with biological therapy and identifies predictive variables of response. Cohort: patients from the CREATE registry who, as of 1 November 2013, had been in clinical remission (DAS28 ≤2.6) for at least 6 months. Intervention: Dose optimization was 20–50% of the standard dose. Outcome measurement were effectiveness (percentage of patients who continued to meet criteria for clinical remission) and efficiency (dose reduction and mean savings). Sixty-eight patients with RA were optimized, with initial mean DAS28 of 2.2 ± 0.7. After 2 years of follow-up, the mean DAS28 was 2.4 ± 0.7, a non-statistically significant difference. Twenty-eight patients (41.2%) continued in clinical remission with dose optimization after 2 years. Mean survival time was 14.2 months (95% CI 12.0–16.5). Of the 40 patients who needed to return to a standard dose, 57.5% managed to achieve remission again at 2 years. Mean dose reduction at 2 years was 21.17%, reaching a mean saving of €5576 ± 5099 per patient. In actual clinical practice, over 40% of patients with established RA who had been in sustained clinical remission managed to continue in remission 2 years after receiving optimized doses. The savings achieved was about 21% of the actual direct health costs for patients in the CREATE registry.

THU0624 Asessment of psychic experiences in patients with rheumatic diseases

Abstract: Background There are several studies that report psychiatric comorbidity in patients with rheumatic disease, mainly the presence of mood disorders. Some of them describe non-affective psychosis related with inflammatory processes. Population with chronic inflammatory disease could present subclinical psychotic experiences that can interfere in the patient9s functional status. The Community Assessment of Psychic Experiences (CAPE) scale is a validated and widely used tool for the evaluation of these experiences in the general population. Objectives To identify the presence of psychic experiences in different populations with a diagnosis of rheumatic disease, and to compare it with a sample of healthy subjects. Methods 124 subjects completed surveys including SF-12 and CAPE questionnaires, as well as other demographic and behavioral variables. Among them, 70 had Spondylarthritis (SpA) (age 44.3±13 years, 62% female), 23 rheumatoid arthritis (RA) (age 51.2±13 years, 82% female) and the rest were individuals without rheumatic diseases (47.6±12 years, 58% female). Results Results of the SF-12 test in their mental and physical domains, and the CAPE questionnaire in their dimensions (positive, negative, depressive and total symptoms) are shown in the table, expressed as mean value (SD) and in the graph expressed as density histograms with mean values. Significant statistical differences, according a t de Student test with control group is shown in both (* p There were no significant differences in the mental component of the SF-12. These differences appear at the physical component, since patients have impaired their mobility and function due to their disease. About the CAPE questionnaire, patients had a little bit higher score due mainly to the appearance of depressive symptoms. The values of positive symptoms of psychosis remained within the normal range for diseases analyzed. Conclusions In our study, we found significant differences in the dimensions, especially depressive, of the CAPE scale among patients with rheumatic diseases (especially in SpA) and healthy subjects. This gives us an idea of the importance of considering the psychological problems of patients (anxiety, depression, ...) to improve the treatment of rheumatic disease. Acknowledgements We would like to thank these patients9 organizations for their collaboration in our study: Coordinadora Espanola de Asociaciones De Espondiloartritis (CEADE), Asociaciόn Cordobesa de Enfermos de Espondilitis (ACEADE), Asociaciόn Cordobesa de Enfermos de Artritis Reumatoide (ACOARE). Disclosure of Interest None declared

AB0127 ANTI-DS-DNA antibodies regulate atherothrombosis in systemic lupus erythematosus through the induction of netosis, inflammation and endothelial activation

Abstract: Background The role of anti-dsDNA in the pathogenesis of the systemic lupus erythematosus (SLE) has been clearly established. However, the influence of these autoantibodies in the atherothrombotic status of SLE patients has not yet been evaluated Objectives 1. To analyse in vivo the involvement of anti-dsDNA antibodies in the development of CVD in SLE patients. 2. To evaluate in vitro the mechanisms underlying the effects of anti-dsDNA antibodies in these processes Methods The study was conducted in 50 SLE patients and 38 healthy donors. Endothelial function was assessed by measuring the post-occlusive hyperaemia using Laser-Doppler. Various markers of oxidative stress, inflammatory cytokines, prothrombotic mediators and NETosis, were quantified in purified leukocytes and plasma from SLE patients and controls. Activation of intracellular pathways was analyzed in monocytes using pathscan intracellular signaling array. In vitro, purified neutrophils, monocytes and lymphocytes from healthy donors and endothelial cells (ECs) were treated separately and in a trans-well co-culture system with anti-dsDNA antibodies isolated from the serum of SLE patients. Then, markers of inflammation, thrombosis, oxidative stress and NETosis were evaluated by flow cytometry (protein), RT-PCR (mRNA) and electron microscopy Results SLE patients showed impaired micro-vascular endothelial function (reduction of hyperaemia post occlusion area) and altered expression levels of pro-inflammatory proteins (IL6, IL8, MCP-1 and PCR), prothrombotic molecules (TF), oxidative stress markers (peroxides and mitochondrial membrane potential) and netosis-related molecules (NE, MPO and cell free-DNA). Monocytes from anti-dsDNA-positive SLE patients showed activation of various pathways related to inflammation, thrombosis and apoptosis (ErK, STAT-3, p38, JNK, GSK, Bad and Caspase-3). Association studies demonstrated that molecules related to inflammation and thrombosis, endothelial dysfunction, oxidative status and netosis were linked to the occurrence of thrombotic events, as well as to the presence of anti-dsDNA antibodies. In vitro treatment of purified leukocytes with anti-dsDNA antibodies promoted an increase in the production of NETosis, levels of peroxides and percentage of cells with altered mitochondrial membrane potential, as well as enlarged expression of a number of proinflammatory and prothrombotic molecules. In vitro treatment of HUVEC with anti-dsDNA antibodies promoted an increase in endothelial activation molecules (ICAM-1, VCAM-1 and E-selectin). Conclusions 1. Positivity for anti-dsDNA antibodies is linked to an increased pro-atherothrombotic status in SLE patients. 2. Anti-dsDNA antibodies, in vitro, promote NETosis on neutrophils, apoptosis on monocytes, modulate the expression of molecules related to inflammation and thrombosis, and induce endothelial activation. Together, that data suggest the involvement of such autoantibodies on atherothrombosis development in SLE Acknowledgements CTS-794 and ISCIII (FIS15/1333;RIER RD16/0012/0015) Disclosure of Interest None declared

THU0218 Circulating micrornas as biomarkers for diagnosis and typifying the atherothrombotic status in antiphospholipid syndrome

Abstract: Background The course of antiphospholipid syndrome (APS) may rapidly progress from asymptomatic to severe manifestations. Thus, timely diagnosis is essential to improve accuracy of therapy. The role of circulating microRNAs (miRNAs) as potential biomarkers of disease has not yet been analysed in APS. Objectives To investigate the contribution of circulating miRNAs to the pathogenesis of APS and their potential role as non-invasive biomarkers of the disease. Methods Ninety APS patients and 42 healthy donors (HD) were included in the study. Clinical and inflammatory parameters were analysed. As a complement to standard clinical follow-up, the ankle-brachial index (ABI) and carotid intima-media thickness (CIMT) were determined. miRNA expression profiling was performed in plasma by PCR-Array, and the Ingenuity Pathways analysis software (IPA) was used to identify specific miRNAs and target proteins associated to the pathogenesis of APS. RT-PCR and ELISA/Bioplex of selected genes and proteins were used to validate microarray data. The diagnostic value of specific miRNAs signatures (ratios) as disease biomarkers was evaluated by ROC curves analysis. To assess the specificity of these signatures in APS, the expression of the selected miRNAs was analysed in plasma from 23 thrombotic patients without associated autoimmune disease. Monocytes isolated from HD and endothelial cells (ECs) were treated in vitro with antiphospholipid antibodies (aPL-IgGs) purified from the serum of APS patients, and the changes promoted on the levels of selected miRNAs and their potential targets were analysed. Results The PCR-Array identified 39 circulating miRNAs differentially expressed, including 19 up-regulated and 20 down-regulated in APS. IPA analysis recognized 11 miRNAs as potential modulators of target genes involved in the physiopathology of APS. Logistic Regression and ROC curve analyses identified a signature of 10 miRNA ratios as biomarkers for diagnosis of APS with great accuracy (AUC:0.81), along with 2 miRNA ratios as biomarkers for typifying the atherothrombotic status (pathologic CIMT) of APS (AUC:0.76). Patients with thrombosis but without associated autoimmune disease displayed a specific miRNA profile, distinct from that of APS patients. The miRNA signature was related to clinical features of APS such as the occurrence of foetal loss and the type of thrombosis suffered, and correlated with parameters linked to autoimmunity (aPL-IgG titers), inflammation, and thrombosis (ABI, ESR, TF, PAI-1, MCP-1, VEGF-A and VEGF-R1). In vitro treatment of monocytes and endothelial cells with aPL-IgG antibodies promoted a significant deregulation in the secreted levels of the selected miRNAs and atherothrombotic target proteins. Conclusions miRNA levels in the serum of APS patients -modulated by aPL-IgG antibodies- are potential novel biomarkers for diagnosis and typifying of their atherothrombotic status, thus constituting a useful tool in the prevention and management of the disease. Acknowledgements Supported by CTS794 and ISCIII (FIS15/1333 and RIER RD16/0012/0015). Disclosure of Interest None declared