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Introduction Psoriatic arthritis (PsA) is considered a multifaceted disease, with patients reporting low health-related quality of life (HRQoL). Data on disease burden are substantial and there exists a need for properly designed studies to learn more about the evolution of HRQoL in this condition. This study aims to identify factors associated to HRQoL evolution in PsA patients followed-up in a real-world setting in Spain. Methods We conducted a retrospective longitudinal observational study including incident patients from the rheumatology outpatient clinic of Hospital Clínico San Carlos (Madrid, Spain), diagnosed for the first time of PsA, defined as having received any ICD9/ICD10 diagnosis code of PsA, from 2007 to 2016, and followed-up until loss of follow-up, death, or November 2017. The influence of demographic and clinical variables in baseline HRQoL [assessed with the Rosser Classification Index (RCI)] was analyzed using bivariable and multivariable generalized linear models. The influence of those variables and of treatment-related factors in repeated measures of HRQoL was analyzed using bivariable and multivariable generalized estimating equations (GEE) models nested by patient. Results Two hundred and thirty patients were included in the analysis, with 3384 registered visits. At baseline, older age, a previous diagnosis of obesity, and the presence of enthesitis were significantly associated with worse HRQoL. During follow-up, using an exchangeable working correlation structure, the presence of enthesitis was also associated with worse HRQoL, coefficient (95% CI) − 0.006 (− 0.01 to − 0.002), p = 1.00E−03; conversely, treatment with methotrexate or antimalarials was associated with better HRQoL with 0.007 (0.001–0.014), p = 0.020 and 0.003 (0.001–0.005), p = 3.00E−03, respectively. Conclusions Musculoskeletal manifestations and comorbidities exert a deleterious effect in HRQoL of PsA patients. Therefore, the optimal management of this condition needs to also address these manifestations in order to try to restore the QoL of these patients. Supplementary Information The online version contains supplementary material available at 10.1007/s40744-021-00349-1.

Background: Non-infectious non-anterior uveitis (NINA) is a sight-threatening condition that often requires immunomodulatory drugs (IMDs) for its management. Objectives: To evaluate the published evidence regarding the use of IMDs in adult patients with NINA uveitis including intermediate (IU) and posterior uveitis (PU), panuveitis (PanU) and macular edema (ME). Methods: We performed a systematic literature review. Search strategies were designed for Medline, Embase, and Cochrane Libraries for articles up to 2019 to evaluate the efficacy and safety of the IMDs. A quality assessment was performed using the Jadad Scale. Results: Nineteen randomized clinical trials were selected from the 1,103 articles retrieved. Characteristics of patients, treatment dosages and outcome measures were heterogeneous. The outcomes most frequently analyzed were visual acuity (VA), macular thickness and vitreous haze (VH). Different IMDs were used at their usual dosages. Methotrexate (MTX), micophenolate mofetil, cyclosporine A (CsA), tacrolimus, adalimumab and sarilumab were effective in NINA uveitis. Rituximab combined with MTX was effective in PU. Interferon-β was superior to MTX, albeit with more adverse events in IU with ME. CsA was similar to cyclophosphamide (Cyc) in Behçet uveitis. Tacrolimus was safer and similar to CsA. Cyc was effective in serpiginoid choroiditis, but when combined with azathioprine in PU, but did not improve VA. Secukinumab did not prevent NINA uveitis recurrences, although intravenously it showed a higher response rate than when used subcutaneously. Daclizumab did not show any benefits in Behçet NINA uveitis. Conclusion: Several IMDs and their combinations can be useful in treating NINA uveitis. The available studies were heterogeneous regarding patient characteristics and outcomes. Sin financiación 5.532 JCR (2020) Q2, 7/34 Rheumatology 1.955 SJR (2020) Q1, 6/122 Anesthesiology and Pain Medicine No data IDR 2020 UEM

ObjectivesTo describe patients with autoimmune inflammatory rheumatic diseases (AIRD) who had COVID-19 disease; to compare patients who required hospital admission with those who did not and assess risk factors for hospital admission related to COVID-19.MethodsAn observational longitudinal study was conducted during the pandemic peak of severe acute respiratory syndrome coronavirus 2 (1 March 2020 to 24 April). All patients attended at the rheumatology outpatient clinic of a tertiary hospital in Madrid, Spain with a medical diagnosis of AIRD and with symptomatic COVID-19 were included. The main outcome was hospital admission related to COVID-19. The covariates were sociodemographic, clinical and treatments. We ran a multivariable logistic regression model to assess risk factors for the hospital admission.ResultsThe study population included 123 patients with AIRD and COVID-19. Of these, 54 patients required hospital admission related to COVID-19. The mean age on admission was 69.7 (15.7) years, and the median time from onset of symptoms to hospital admission was 5 (3–10) days. The median length of stay was 9 (6–14) days. A total of 12 patients died (22%) during admission. Compared with outpatients, the factors independently associated with hospital admission were older age (OR: 1.08; p=0.00) and autoimmune systemic condition (vs chronic inflammatory arthritis) (OR: 3.55; p=0.01). No statistically significant findings for exposure to disease-modifying antirheumatic drugs were found in the final model.ConclusionOur results suggest that age and having a systemic autoimmune condition increased the risk of hospital admission, whereas disease-modifying antirheumatic drugs were not associated with hospital admission.

[Abstract] Introduction: Non-infectious uveitis include a heterogeneous group of sight-threatening and incapacitating conditions. Their correct management sometimes requires the use of immunosuppressive drugs (ISDs), prescribed in monotherapy or in combination. Several observational studies showed that the use of ISDs in combination could be more effective than and as safe as their use in monotherapy. However, a direct comparison between these two treatment strategies has not been carried out yet. Methods and analysis: The Combination THerapy with mEthotrexate and adalImumAb for uveitis (CoTHEIA) study is a phase III, multicentre, prospective, randomised, single-blinded with masked outcome assessment, parallel three arms with 1:1:1 allocation, active-controlled, superiority study design, comparing the efficacy, safety and cost-effectiveness of methotrexate, adalimumab or their combination in non-infectious non-anterior uveitis. We aim to recruit 192 subjects. The duration of the treatment and follow-up will last up to 52 weeks, plus 70 days follow-up with no treatment. The complete and maintained resolution of the ocular inflammation will be assessed by masked evaluators (primary outcome). In addition to other secondary measurements of efficacy (quality of life, visual acuity and costs) and safety, we will identify subjects’ subgroups with different treatment responses by developing prediction models based on machine learning techniques using genetic and proteomic biomarkers. Ethics and dissemination: The protocol, annexes and informed consent forms were approved by the Reference Clinical Research Ethic Committee at the Hospital Clínico San Carlos (Madrid, Spain) and the Spanish Agency for Medicines and Health Products. We will elaborate a dissemination plan including production of materials adapted to several formats to communicate the clinical trial progress and findings to a broad group of stakeholders. The promoter will be the only access to the participant-level data, although it can be shared within the legal situation. Trial registration number: 2020-000130-18; NCT04798755. This work was supported by the Instituto de Salud Carlos III, grant number [ICI19/00020]. Sponsor: Fundación para la Investigacion Biomédica del Hospital Clínico San Carlos. Executive Committee: Administrative and executive arm of the clinical trial, providing overall oversight for the study and making decisions on day-to-day operational issues (Study Coordinator (Luis Rodriguez-Rodriguez), a representative from the Spanish Clinical Trial Network (Amanda López Picado), and 5 Site Directors (these seats will be rotatory, with changes every 6 months months)); Data Coordinating and Analysis Committee: Supervising data collection,management and quality control, designing the statistical analysis plan, performing unmasked data analysis and preparing interim and final reports for the Data Security Monitoring Board and the Executy Committee (Study Coordinator (Luis Rodriguez-Rodriguez), a representative from the Spanish Clinical Trial Network (Amanda López Picado) and Ester Carreño); Biobank and Biomarker Identification Committee (Maintaining an up-to-date manual of operations for blood extraction, processing and storage, and monitoring procedures adherence, supervising biological sample collection, sample shipment coordination, coordinating the phamacogenetic and proteomic analysis (Study Coordinator (Luis Rodriguez-Rodriguez), a representative from the Instituto de Salud Carlos III Biobank Platform (Elena Molino), a representative the Instituto de Investigación Biomédica de A Coruña, a representative from, the Data Coordinating and Analysis Committee); Data Security Monitoring Committee (PierGiogio Neri, Andrew Dick, Loreto Carmona)

The major and upward trend in the number of published research related to rheumatic and musculoskeletal diseases, in which artificial intelligence plays a key role, has exhibited the interest of rheumatology researchers in using these techniques to answer their research questions. In this review, we analyse the original research articles that combine both worlds in a five-year period (2017-2021). In contrast to other published papers on the same topic, we first studied the review and recommendation articles that were published during that period, including up to October 2022, as well as the publication trends. Secondly, we review the published research articles and classify them into one of the following categories: disease classification, disease prediction, predictors identification, patient stratification and disease subtype identification, disease progression and activity, and treatment response. Thirdly, we provide a table with illustrative studies in which artificial intelligence techniques have played a central role in more than twenty rheumatic and musculoskeletal diseases. Finally, the findings of the research articles, in terms of disease and/or data science techniques employed, are highlighted in a discussion. Therefore, the present review aims to characterise how researchers are applying data science techniques in the rheumatology medical field. The most immediate conclusions that can be drawn from this work are: multiple and novel data science techniques have been used in a wide range of rheumatic and musculoskeletal diseases including rare diseases; the sample size and the data type used are heterogeneous, and new technical approaches are expected to arrive in the short-middle term.HighlightsThe rheumatology research community is increasingly adopting novel AI techniquesThere is an upward trend in the number of articles that combine AI and rheumatologyRheumatic and musculoskeletal rare diseases are gaining from AI techniquesIndependent validation of the models should be promoted

Objectives We aimed to describe persistent symptoms and sequelae in patients with rheumatic and musculoskeletal diseases (RMD) after admission owing to coronavirus disease 2019 (COVID-19), assessing the role of autoimmune rheumatic diseases (ARDs) compared with non-autoimmune rheumatic and musculoskeletal diseases (NARDs) on persistent symptoms and sequelae. Methods We performed an observational study including RMD patients who attended a rheumatology clinic in Madrid and required admission owing to COVID-19 (between March and May 2020) and survived. The study began at discharge and ran until October 2020. Main outcomes were persistence of symptoms and sequelae related to COVID-19. The independent variable was the RMD group (ARD and NARD). Covariates included sociodemographics, clinical and treatment data. We ran a multivariate logistic regression model to assess the risk of the main outcomes by RMD group. Results We included 105 patients, of whom 51.5% had ARD and 68.57% reported at least one persistent symptom. The most frequent symptoms were dyspnoea, fatigue and chest pain. Sequelae were recorded in 31 patients. These included lung damage in 10.4% of patients, lymphopenia in 10%, a central retinal vein occlusion and an optic neuritis. Two patients died. Eleven patients required re-admission owing to COVID-19 problems (16.7% ARD vs 3.9% NARD; P = 0.053). No statistically significant differences were found between RMD groups in the final models. Conclusion Many RMD patients have persistent symptoms, as in other populations. Lung damage is the most frequent sequela. Compared with NARD, ARD does not seem to differ in terms of persistent symptoms or consequences, although ARD might have more re-admissions owing to COVID-19.

Background: Mesenchymal stem cells (MSCs) are a promising treatment of different musculoskeletal diseases including osteoarthritis and rheumatoid arthritis (RA). Results from different approaches in this treatment have been not conclusive. Aim: To analyze factors related to interactions between peripheral blood mononuclear cells (PBMCs) and MSCs and the influence of cellular activation. Materials & methods: PBMCs from RA patients and healthy controls (HC) were obtained. MSCs from bone marrow (BM-MSCs) were obtained from six donors. CD4, CD25, CD69 and CD127 expression was measured by flow cytometry. Repeated measures analysis of variance (ANOVA) models were performed using activation, co-culture with BM-MSCs and time of culture (24 h, 72 h, 6 days) as within-subject variables. Results: PBMCs activated and co-cultured with BM-MSCs showed a lower proportion of CD25-positive and CD25high/CD127low-negative cells in both RA and HC. Additionally, a maintained expression of CD69 was also observed in RA and HC when PBMCs were activated and co-cultured with BM-MSCs. Conclusion: Both PBMC activation grade and RA disease activity influence the immunomodulatory effect of BM-MSCs on T-cell activation.

Resumen La descompresion subacromial artroscopica aislada (DSA) es un procedimiento quirurgico ampliamente utilizado que presenta un elevado porcentaje de exito. Sin embargo, hasta un 25% de los pacientes puede presentar dolor residual tras la intervencion. No esta claro si el procesamiento aberrante del dolor, como ocurre en la fibromialgia (FM), podria ejercer un efecto deletereo en los resultados obtenidos. Para testar esta hipotesis hemos realizado un estudio casos-controles retrospectivo de los pacientes en los que se ha realizado una descompresion subacromial artroscopica como procedimiento quirurgico unico. Material y metodos Se seleccionaron 26 pacientes con diagnostico preoperatorio de fibromialgia de una serie de 293 pacientes intervenidos mediante DSA entre 2008-2015. Seis pacientes se perdieron durante el seguimiento. Cada paciente con diagnostico de fibromialgia fue emparejado con un control (n = 20). Los resultados fueron evaluados mediante la escala DASH, Constant, Constant relativo a la edad y sexo (rCS) y la escala visual analogica (EVA). La satisfaccion del paciente fue evaluada con una pregunta dicotomica. Se considero fracaso del procedimiento la presencia de una puntuacion superior a 3 en la EVA en el ultimo seguimiento. Resultados La media de edad de los grupos FM/control fue de 51/48 anos, con un seguimiento medio de 36/42 meses respectivamente. Ambos grupos experimentaron una mejoria postoperatoria significativa en las escalas de EVA, DASH y rCS (p Conclusiones La fibromialgia puede ser considerada como factor pronostico que condiciona un peor resultado postoperatorio tras DSA. Sin embargo, debido a la mejoria clinica que experimentan estos pacientes frente a su estado preoperatorio, recomendamos realizar este tratamiento quirurgico cuando exista indicacion.

Isolated arthroscopic subacromial decompression (IASD) is a widely used surgical procedure with high success rates. However, up to 25% of patients experience residual pain. It is unclear whether aberrant central nervous system processing of pain as described in fibromyalgia (FM) could have a detrimental effect on outcomes. To test this hypothesis, the authors conducted a retrospective case–control study of patients undergoing IASD. Material and methods Between 2008 and 2015, 26 patients with preoperative diagnosis of fibromyalgia and an IASD procedure were identified. Six patients were lost to follow-up. Each fibromyalgia patient was matched with one control patient (n = 20) recruited from the remainder with IASD. Outcomes were assessed by DASH score (Disability Arm Shoulder and Hand), Constant (CS), relative Constant score (rCS) and Visual Analogue Scale (VAS). Patient satisfaction was determined with a single 2-level question. Failure of the IASD was defined as persistent pain (VAS > 3) at last follow-up. Results The average age of the sample was FM/Control group 51/48, with a mean follow-up of 36/42 months respectively. Both groups exhibited significant clinical improvement in the pain VAS, DASH and rCS at final follow-up (p Mean postoperative scores FM/Control group were: Constant 63.5/74 (p = .07), rCS 82/88 (p = 18), DASH 38.9/20.7 (p = 009), VAS 3.8/2.8 (p = 2). Eighty-five percent of patients in the control group were satisfied with the surgery compared with 55% in the FM group (p = 03). Failure of the procedure was 60% in the FM group, and 30% in the control group (p = .056). Conclusions Fibromyalgia can be considered a prognostic factor of a poor postoperative outcome after an IASD. However the clinical improvement experienced by these patients over their preoperative situation leads us to recommend their surgical treatment when indicated.

Introduction: Rheumatic and musculoskeletal diseases (RMDs) have a significant impact on patients’ health-related quality of life (HRQoL) exacerbating disability, reducing independence and work capacity, among others. Predictors’ identification affecting HRQoL could help to place efforts that minimize the deleterious impact of these conditions on patients’ wellbeing. This study evaluates the influence of demographic and clinical predictors on the HRQoL of a cohort of RMD patients, measured using the Rosser classification index (RCI). Methods: We included patients attending the Hospital Clínico San Carlos (HCSC) rheumatology outpatient clinic from 1 April 2007 to 30 November 2017. The primary outcome was the HRQoL assessed in each of the patient’s visits using the RCI. Demographic and clinical variables extracted from a departmental electronic health record (EHR) were used as predictors: RMD diagnoses, treatments, comorbidities, and averaged HRQoL values from previous periods (for this last variable, values were imputed if no information was available). Association between predictors and HRQoL was analyzed using penalized generalized estimating equations (PGEEs). To account for imputation bias, the PGEE model was repeated excluding averaged HRQoL predictors, and common predictors were considered. Discussion: A total of 18,187 outpatients with 95,960 visits were included. From 410 initial predictors, 19 were independently associated with patients’ HRQoL in both PGEE models. Chronic kidney disease (CKD), an episode of prescription of third level analgesics, monoarthritis, and fibromyalgia diagnoses were associated with worse HRQoL. Conversely, the prescription in the previous visit of acid-lowering medication, colchicine, and third level analgesics was associated with better HRQoL. Conclusion: We have identified several diagnoses, treatments, and comorbidities independently associated with HRQoL in a cohort of outpatients attending a rheumatology clinic.

Using the Immunochip custom SNP array, which was designed for dense genotyping of 186 loci identified through genome-wide association studies (GWAS), we analyzed 11,475 individuals with rheumatoid arthritis (cases) of European ancestry and 15,870 controls for 129,464 markers. We combined these data in a meta-analysis with GWAS data from additional independent cases (n = 2,363) and controls (n = 17,872). We identified 14 new susceptibility loci, 9 of which were associated with rheumatoid arthritis overall and five of which were specifically associated with disease that was positive for anticitrullinated peptide antibodies, bringing the number of confirmed rheumatoid arthritis risk loci in individuals of European ancestry to 46. We refined the peak of association to a single gene for 19 loci, identified secondary independent effects at 6 loci and identified association to low-frequency variants at 4 loci. Bioinformatic analyses generated strong hypotheses for the causal SNP at seven loci. This study illustrates the advantages of dense SNP mapping analysis to inform subsequent functional investigations.

OBJECTIVESTo describe persistent symptoms and consequences in Rheumatic and Musculoskeletal diseases (RMD) discharged from the hospital after Covid-19; to assess the roll of autoimmune rheumatic diseases (ARD) compared to and non-autoimmune rheumatic and musculoskeletal diseases (NARD) on persistent symptoms and consequences.METHODSWe performed a cross-sectional observational study. RMD attended at a rheumatology outpatient clinic in Madrid with Covid-19 that required hospital admission were included. The main outcomes were persistence of symptoms and health consequences related to Covid19 after discharge. Independent variable was RMD group (ARD and NARD) and covariates were sociodemographic, clinical, and treatments. We ran a multivariable logistic regression model to assess the risk by RMD group on main outcomes.RESULTSWe included 105 patients and 51.5% had ARD. 68.57% reported at least one persistent symptom. The most frequent were dyspnea, fatigue, and chest pain. 31 patients had consequences. Lung damage was found in 11.4% of the patients, 18% had blood test abnormalities (10% lymphopenia), two died, one developed central retinal vein occlusion and one patient developed optic neuritis. 11 patients required readmission due to Covid-19 problems (16.7% ARD vs 3.9% NARD; p=0.053). No statistically significant differences by RMD groups were found in the final models.CONCLUSIONMany RMD patients have persistent symptoms, similar to other populations. This study also highlights that lung damage is the most frequent consequence. ARD compared to NARD does not seem to differ in terms of persistent symptoms or consequences, although ARD might have a greater number of readmissions due to Covid-19.

Aims: To analyze the association between colchicine prescription and COVID-19-related hospital admissions in patients with rheumatic and musculoskeletal diseases (RMDs). Methods: Patients attending a rheumatology outpatient clinic from a tertiary care center in Madrid, Spain, from 1 September 2019 to 29 February 2020 were included. Patients were assigned as exposed or unexposed based on whether they were prescribed with colchicine in their last visit to the clinic during the 6 months before the start of the observation period. Treatment changes during the observation period were also considered. The primary outcome was COVID-19-related hospital admissions between 1 March and 20 May 2020. Secondary outcome included COVID-19-related mortality. Several weighting techniques for data balancing, based and non-based on the propensity score, followed by Cox regressions were performed to estimate the association of colchicine prescription on both outcomes. Discussion: The number of patients entered in the study was 9379, with 406 and 9002 exposed and unexposed follow-up periods, respectively. Generalized Boosted Models (GBMs) and Empirical Balancing Calibration Weighting (EBCW) methods showed the best balance for COVID-19-related hospital admissions. Colchicine prescription did not show a statistically significant association after covariable balancing ( p-value = 0.195 and 0.059 for GBM and EBCW, respectively). Regarding mortality, the low number of events prevented a success variable balancing and analysis. Conclusion: Colchicine prescription does not play a significant protective or risk role in RMD patients regarding COVID-19-related hospital admissions. Our observations could support the maintenance of colchicine prescription in those patients already being treated, as it is not associated with a worse prognosis. Plain language title: Colchicine influence in COVID-19-related hospital admissions

Aims: In this pandemic, it is essential for rheumatologists and patients to know the relationship between COVID-19 and inflammatory rheumatic diseases (IRDs). We wanted to assess the role of targeted synthetic or biologic disease-modifying antirheumatic drugs (ts/bDMARDs) and other variables in the development of moderate-severe COVID-19 disease in IRD. Methods: An observational longitudinal study was conducted during the epidemic peak in Madrid (1 March to 15 April 2020). All patients attended at the rheumatology outpatient clinic of a tertiary hospital in Madrid with a medical diagnosis of IRD were included. Main outcome: hospital admission related to COVID-19. Independent variable: ts/bDMARDs. Covariates: sociodemographic, comorbidities, type of IRD diagnosis, glucocorticoids, non-steroidal anti-inflammatory drugs (NSAIDs), and conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). Incidence rate (IR) of hospital admission related to COVID-19 was expressed per 1000 patient-months. Cox multiple regression analysis was run to examine the influence of ts/bDMARDs and other covariates on IR of hospital admission related to COVID-19. Results: A total of 3951 IRD patients were included (5896 patient-months). Methotrexate was the csDMARD most used. Eight hundred and two patients were on ts/bDMARDs, mainly anti-TNF agents, and Rtx. Hospital admissions related to COVID-19 occurred in 54 patients (1.36%) with an IR of 9.15 (95% confidence interval: 7–11.9). In the multivariate analysis, older, male, comorbidities, and specific systemic autoimmune conditions (Sjögren, polychondritis, Raynaud, and mixed connective tissue disease) had more risk of hospital admissions. Exposition to ts/bDMARDs did not achieve statistical significance. Use of glucocorticoids, NSAIDs, and csDMARDs dropped from the final model. Conclusion: This study provides additional evidence in IRD patients regarding susceptibility to moderate–severe infection related to COVID-19.

Current gold-standard strategies for bone regeneration do not achieve the optimal recovery of bone biomechanical properties. To bypass these limitations, tissue engineering techniques based on hybrid materials made up of osteoprogenitor cells—such as mesenchymal stem cells (MSCs)—and bioactive ceramic scaffolds—such as calcium phosphate-based (CaPs) bioceramics—seem promising. The biological properties of MSCs are influenced by the tissue source. This study aims to define the optimal MSC source and construct (i.e., the MSC–CaP combination) for clinical application in bone regeneration. A previous iTRAQ analysis generated the hypothesis that anatomical proximity to bone has a direct effect on MSC phenotype. MSCs were isolated from adipose tissue, bone marrow, and dental pulp, then cultured both on a plastic surface and on CaPs (hydroxyapatite and β-tricalcium phosphate), to compare their biological features. On plastic, MSCs isolated from dental pulp (DPSCs) presented the highest proliferation capacity and the greatest osteogenic potential. On both CaPs, DPSCs demonstrated the greatest capacity to colonise the bioceramics. Furthermore, the results demonstrated a trend that DPSCs had the most robust increase in ALP activity. Regarding CaPs, β-tricalcium phosphate obtained the best viability results, while hydroxyapatite had the highest ALP activity values. Therefore, we propose DPSCs as suitable MSCs for cell-based bone regeneration strategies.

Background: Acceptance has become one of the most widely studied processes regarding chronic pain because of its ability to influence participants' adaptation and coping responses. Leading researchers have found relationships between variables such as anxiety, reinforcement sensitivity, and the responses of the participants' environment to their behavior and acceptance. In contrast, few studies have been found that investigate the variables that predict the acceptance of pain. This study has set out to explore the relationships between pain-related anxiety, sensitivity to contingencies, and the punishment responses of significant people toward pain behaviors regarding pain acceptance.Methods: With a view to fulfilling this purpose, a cohort of 62 participants with rheumatoid arthritis was chosen, and the subjects were assessed through the following self-report measures: Chronic Pain Acceptance Questionnaire, CPAQ; Pain Anxiety Symptoms Scale, PASS-20; The Sensitivity to Punishment and Sensitivity to Reward Questionnaire, SPSRQ, and The West Haven-Yale Multidimensional Pain Inventory, WHYMPI. The study's initial objectives were achieved by means of a stepwise multiple linear regression analysis.Results: The linear regression analyses revealed a negative and significant correlation between anxiety, reinforcement sensitivity, and the significant persons' responses to pain behaviors and pain acceptance.Conclusion: The results suggest that the identification of these variables might be important for addressing these participants' pain. Finally, the discussion focuses on our findings' implications as regards their use in clinical practice.

Background: Bone innate ability to repair without scaring is surpassed by major bone damage. Current gold-standard strategies do not achieve a full recovery of the bone biomechanical properties. To bypass these limitations, tissue engineering techniques based on hybrid materials made up of osteoprogenitor cells, like mesenchymal stem cells (MSCs), and bioactive ceramic scaffolds, like calcium phosphate-based (CaPs), are promising. Biological properties of the MSCs, including osteogenic potential, are influenced by the tissue source. The aim of this study is to define the MSC source and construct (MSC and scaffold combination) most interesting for its clinical application in the context of bone regeneration.Methods: MSCs of 9 healthy donors were isolated from adipose tissue, bone marrow and dental pulp. MSCs were cultured both on plastic surface and on CaPs (hydroxyapatite and β-tricalcium phosphate) to compare their biological features: proliferation rate, osteogenic potential, cell viability and activity, ability to colonize the CaPs and ALP activity. Results: iTRAQ results generated the hypothesis that anatomical proximity to bone has a direct effect on MSC phenotype. On plastic, MSCs isolated from dental pulp (DPSCs) were the MSCs with the highest proliferation capacity and the greatest osteogenic potential. On both CaPs, DPSCs are the MSCs with the greatest capacity to colonize bioceramics. Furthermore, results show a trend for DPSCs are the MSCs with the most robust increase in the ALP activity.Conclusion: Based in our results, we propose DPSCs as a suitable MSCs for bone/dental regeneration cell-based strategies.

Bone innate ability to repair without scaring is surpassed by major bone damage. Current gold-standard strategies do not achieve a full recovery of bone biomechanical properties. To bypass these limitations, tissue engineering techniques based on hybrid materials made up of osteoprogenitor cells, like mesenchymal stem cells (MSCs), and bioactive ceramic scaffolds, like calcium phosphate-based (CaPs), are promising. Biological properties of the MSCs, are influenced by the tissue source. The aim of this study is to define the MSC source and construct (MSC and scaffold combination) most interesting for its clinical application in bone regeneration. iTRAQ generated the hypothesis that anatomical proximity to bone has a direct effect on MSC phenotype. MSCs were isolated from adipose tissue, bone marrow and dental pulp. MSCs were cultured both on plastic surface and on CaPs (hydroxyapatite and β-tricalcium phosphate) to compare their biological features. On plastic, MSCs isolated from dental pulp (DPSCs) were the MSCs with the highest proliferation capacity and the greatest osteogenic potential. On both CaPs, DPSCs are the MSCs with the greatest capacity to colonize bioceramics. Furthermore, results show a trend for DPSCs are the MSCs with the most robust increase in the ALP activity. We propose DPSCs as a suitable MSCs for bone regeneration cell-based strategies.What do you want to do ?New mailCopy

Objective. Previously, only the HLA-DRB1 alleles have been assessed in rheumatoid arthritis (RA). The aim of the present study was to identify the key major histocompatibility complex (MHC) susceptibility factors showing a significant association with anti-carbamylated protein antibody-positive (anti-CarP+) RA. Methods. Analyses were restricted to RA patients who were anti-cyclic citrullinated peptide antibody negative (anti-CCP), because the anti-CCP status dominated the results otherwise. Therefore, we studied samples from 1,821 anti-CCP- RA patients and 6,821 population controls from Spain, Sweden, and the Netherlands. The genotypes for similar to 8,000 MHC biallelic variants were assessed by dense genotyping and imputation. Their association with the anti-CarP status in RA patients was tested with logistic regression and combined with inverse-variance meta-analysis. Significance of the associations was assessed according to a study-specific threshold of P < 2.0 x 10(-5). Results. The HLA-B*08 allele and its correlated amino acid variant Asp-9 showed a significant association with anti-CarP+/anti-CCP- RA (P < 3.78 x 10(-7); I-2 = 0). This association was specific when assessed relative to 3 comparator groups: population controls, anti-CarP-/anti-CCP- RA patients, and anti-CCP- RA patients who were positive for other anti-citrullinated protein antibodies. Based on these findings, anti-CarP+/anti-CCP- RA patients could be separated from other antibody-defined subsets of RA patients in whom an association with the HLA-B*08 allele has been previously demonstrated. No other MHC variant remained associated with anti-CarP+/anti-CCP- RA after accounting for the presence of the HLA-B*08 allele. Specifically, the reported association of HLA-DRB1*03 was observed at a level comparable to that reported previously, but it was attributable to linkage disequilibrium. Conclusion. These results identify HLA-B*08 carrying Asp-9 as the MHC locus showing the strongest association with anti-CarP+/anti-CCP- RA. This knowledge may help clarify the role of the HLA in susceptibility to specific subsets of RA, by shaping the spectrum of RA autoantibodies.

Background: In this pandemia, it is essential for rheumatologist and patients to know the relationship between COVID-19 and inflammatory rheumatic diseases (IRD). We want to assess the role of targeted synthetic or biologic disease modifying antirheumatic drugs (ts/bDMARDs) and other variables in the development of moderate-severe COVID-19 disease in IRD. Methods: An observational longitudinal study was conducted (1stMar to 15thApr 2020). All patients from the rheumatology outpatient clinic from a hospital in Madrid with a medical diagnosis of IRD were included. Main outcome: hospital admission related to COVID-19. Independent variable: ts/bDMARDs. Covariates: sociodemographic, comorbidities, type of IRD diagnosis, glucocorticoids, NSAIDs and conventional synthetic DMARDs (csDMARDs). Incidence rate (IR) of hospital admission related to COVID-19, was expressed per 1,000 patients-month. Cox multivariate regression analysis was run to examine the influence of ts/bDMARDs and other covariates on IR. Results: 3,591 IRD patients were included (5,896 patients-month). Concerning csDMARDs, methotrexate was the most used followed by antimalarials. 802 patients were on ts/bDMARDs, mainly anti-TNF agents, and rituximab. Hospital admissions related to COVID-19 occurred in 54 patients (1.36%) with an IR of 9.15 [95%CI: 7-11.9]. In the multivariate analysis, older, male gender, presence of comorbidities and specific systemic autoimmune conditions (Sjoegren, polychondritis, Raynaud and mixed connective tissue disease) had more risk of hospital admissions regardless other factors. Exposition to ts/bDMARDs did not achieve statistical signification. Use of glucocorticoids, NSAIDs, and csDMARDs dropped from the final model. Conclusion: This study provides additional evidence in IRD patients regarding susceptibility to moderate-severe infection related to COVID-19.

OBJECTIVES: To describe patients with inflammatory rheumatic diseases (IRD) who had COVID-19; to compare patients who need hospital admission versus those that did not and assess risk factors of hospital admission related to COVID-19. METHODS: We performed a prospective observational study, from 1st March 2020 until the 24th of April. All patients being attended at the rheumatology outpatient clinic of a tertiary hospital of Madrid, with medical diagnosis of inflammatory rheumatic disease, and with symptomatic COVID-19 disease were included. Main variable was the hospital admission related to COVID-19. Covariates: sociodemographic, clinical and treatments. We performed a multivariate logistic regression model to assess risk factors of hospital admission. RESULTS: 123 patients with IRD and COVID-19 disease were identified and included. We found 54 patients that need hospital admission, 59.2% were women, with a mean age at hospital admission of 69.7 (15.7) years, and a median lag time from symptoms onset to hospital admission of 5 (3-10) days. The median length of stay was 9 (6-14) days. A total of 12 patients died (22%) during their hospital admission. Factors independently associated with hospital admission were being older (OR 1.08; p=0.00), and type of diagnosis (OR 3.55; p=0.01), compared to those who were ambulatory. DMARDs dropped from the model. Male sex, associated comorbidities and glucocorticoids use showed a tendency risk (p

We developed and independently validated a rheumatoid arthritis (RA) mortality prediction model using the machine learning method Random Survival Forests (RSF). Two independent cohorts from Madrid (Spain) were used: the Hospital Clínico San Carlos RA Cohort (HCSC-RAC; training; 1,461 patients), and the Hospital Universitario de La Princesa Early Arthritis Register Longitudinal study (PEARL; validation; 280 patients). Demographic and clinical-related variables collected during the first two years after disease diagnosis were used. 148 and 21 patients from HCSC-RAC and PEARL died during a median follow-up time of 4.3 and 5.0 years, respectively. Age at diagnosis, median erythrocyte sedimentation rate, and number of hospital admissions showed the higher predictive capacity. Prediction errors in the training and validation cohorts were 0.187 and 0.233, respectively. A survival tree identified five mortality risk groups using the predicted ensemble mortality. After 1 and 7 years of follow-up, time-dependent specificity and sensitivity in the validation cohort were 0.79–0.80 and 0.43–0.48, respectively, using the cut-off value dividing the two lower risk categories. Calibration curves showed overestimation of the mortality risk in the validation cohort. In conclusion, we were able to develop a clinical prediction model for RA mortality using RSF, providing evidence for further work on external validation.

Background: Rheumatoid arthritis (RA) is one of the leading chronic inflammatory rheumatism. First-line therapy with synthetic disease modifying anti-rheumatic drugs (sDMARD) is insufficiently effective in 40% of cases and these patients are treated with biotherapies. The increases use of these drugs each year is becoming a public health issue with considerable economic burden. This cost is 20 times higher than that of sDMARD. However, among patients treated with biotherapies, clinical practice shows that about one-third will not respond to the selected drug. In non-response cases, practitioners currently have no choice but to perform an empirical switching between different treatments, because no tool capable of predicting the response or non-response to these molecules is currently available.Methods : The study is a prospective, phase III, controlled, multicenter, and randomized, single-blind (patient) clinical trial, including RA patients with a previous failure to anti-TNF therapies. The main objective is the analysis of the clinical and pharmacoeconomic impact after 6 months of treatment. Intervention arm: Prescription of biotherapy (rituximab, adalimumab, abatacept) using SinnoTest® software, a prediction software based on proteomic biomarkers. Control arm: Prescription of biotherapy based on current practice, without the SinnoTest® software (any biotherapy). In addition, a sub study will be carried out within this trial to generate a biobank and further analyze the proteomic profile of the patients and their modification throughout the study.Discussion : This clinical trial study will be the first validation study of a biotherapy response prediction software, bringing personalized medicine into the management of RA. We expect that the findings from this study will bring several benefits for the patient and the Health Care System. Trial registration : The study was registered at clincaltrials.gov (NCT04147026). Registered on 31 October, 2019.

Chronic pain is a complex experience that has now become a major public health issue. This has prompted many researchers to study attention, understanding it to be a crucial factor that allows altering the experience of pain, while attributing considerable importance to sustained attention. Accordingly, the main studies in this field stress the importance of emotion regulation processes and emotions on the perception of painful stimuli and attentional processes themselves. Nevertheless, only a handful of studies have been found that directly study the relationship between these variables. Within this context, this article sets out to analyse emotional regulation processes, emotional variables (depression and anxiety), the experience of pain, and age on the ability to maintain the vigilance response in a sample of patients with chronic pain. This involved selecting a sample of 49 patients with rheumatoid arthritis and examining their performance in an ad-hoc sustained attention test. With a view to complying with the study’s main purpose, the participants were also assessed through the use of the following self-report measures: the Beck Depression Inventory (BDI-I); the Hospital Anxiety and Depression Scale (HADS); the McGill Pain Questionnaire, and the Difficulties in Emotion Regulation Scale (DERS). Linear regression analyses revealed a significant impact of the aging process on the performance times in the attention task. Likewise, age and depression recorded a significant correlation with the mistakes made during the task. These results suggest that higher depression levels and an older age might be related to a worse adaptation to pain management techniques based on attention processes, such as mindfulness.

Chronic pain is a serious public health problem that has grown exponentially in recent years, which is why it has received the attention of numerous researchers. Most of the studies in the field of chronic pain have focused on care as a mediating variable on the perception of painful stimuli and emotions. Nevertheless, there are very few studies that have gone in the opposite direction. This study’s aim is therefore to analyse the impact of emotional variables (anxiety and depression), the rating of pain, and age on vigilance processes in a sample of patients with chronic pain. To do so, the attentional performance of a cohort of 52 patients with chronic pain was measured through the use of a modified dot-probe task. Furthermore, all the participants were evaluated using the following self-report measures: Beck’s Depression Inventory-II (BDI-II), the McGill Pain Questionnaire, and the Pain Anxiety Symptoms Scale-20 (PASS-20). Stepwise multiple linear regression analysis revealed a significant negative correlation between the pain rating index and the number of mistakes the participants made during the attention test. There was also a positive and significant correlation with age and another negative and significant correlation with cognitive anxiety regarding the overall performance times during the undertaking of the experimental task. These results point to the importance of a more in-depth understanding of the impact that the emotional variables and other variables such as age have on attentional processes and the rating of pain. Finally, the discussion focuses on the implications these results could have for clinical practice or for future research studies in this field.

Purpose: To estimate the incidence rate (IR) and identify risk factors associated to inflammatory relapse after immunosuppressive drug (ISD) discontinuation in noninfectious uveitis patients. Methods: Multicenter longitudinal retrospective study, including patients from four uveitis clinics followed-up until December 2018. Hazard ratios for different variables were estimated using multivariable Cox models. Results: 32 patients (34 episodes of ISD discontinuation) were analyzed (median and maximum follow-up time: 2.4 and 19.2 years, respectively). Fourteen patients presented at least one relapse: anterior (8 patients), intermediate (5) and posterior (8). IR (95% confidence interval) of the first relapse was 14.3 (8.6–23.8) episodes per 100 patient-years (median survival time: 4.8 years). Early use of ISDs, panuveitis, and higher oral corticosteroid dosage at discontinuation were associated with higher hazards of relapse in multivariable analysis. Conclusions: Relapse is a frequent and early event after ISD discontinuation. Identifying relapse risk factors could support the physician’s decision regarding ISD discontinuation. Instituto de Salud Carlos III (ISCIII), Ministerio de Sanidad, Consumo y Bienestar Social (Contrato de investigación Miguel Servet: CPII17 / 00014 a LRR). 3.728 JCR (2021) Q2, 23/62 Ophthalmology 1,232 SJR (2021) Q1, 21/128 Ophthalmology No data IDR 2021 UEM

Background: This research describes the incidence and factors associated with opportunistic infections in rheumatoid arthritis (RA) patients treated with biological disease-modifying antirheumatic drugs (bDMARDs). Methods: A retrospective longitudinal study was carried out from 2007 to 2018. We included RA patients treated with a tumor necrosis factor (TNF)-targeted bDMARD or non-TNF-targeted bDMARD from the start of bDMARDs. An independent variable was the development of an indicator of opportunistic infection after biological (IOIb) treatment. Secondary variables included sociodemographic, clinical, and treatments. We used survival techniques to estimate the incidence of IOIb, per 1000 patient-years (95% CI). We performed a Cox multivariate regression analysis model to compare the risk of IOIb. Results were expressed as a hazard ratio (HR). Results: A total of 441 RA patients were included, that started 761 different courses of bDMARDs. A total of 81% were women with a mean age at first bDMARD of 57.3 ± 14 years. A total of 71.3% of the courses were TNF-targeted bDMARDs and 28.7% were non-TNF-targeted bDMARDs. There were 37 IOIb (25 viral, 6 fungal, 5 bacterial, 1 parasitic). Nine of these required hospitalization and one died. The global incidence of IOIb was 23.2 (16.8–32). TNF-targeted bDMARDs had 25 IOIb, incidence 20.5 (13.9–30.4), and non-TNF-targeted bDMARDs had 12 IOIb, incidence 31.7 (18–55.9). In the multivariate analysis, glucocorticosteroids (HR 2.17, p = 0.004) and lower lymphocyte count increased the risk for IOIb (HR 0.99, p = 0.005). Conclusions: The incidence of IOIb due to bDMARDs was 23 cases per 1000 patient-years. Close monitoring should be taken in the RA patients treated with bDMARDs and glucocorticosteroids, mainly in elderly patients and those with a low total lymphocyte count at the beginning of bDMARD treatment.

Our objective is to develop and validate a predictive model based on the random forest algorithm to estimate the readmission risk to an outpatient rheumatology clinic after discharge. We included patients from the Hospital Cl&iacute, nico San Carlos rheumatology outpatient clinic, from 1 April 2007 to 30 November 2016, and followed-up until 30 November 2017. Only readmissions between 2 and 12 months after the discharge were analyzed. Discharge episodes were chronologically split into training, validation, and test datasets. Clinical and demographic variables (diagnoses, treatments, quality of life (QoL), and comorbidities) were used as predictors. Models were developed in the training dataset, using a grid search approach, and performance was compared using the area under the receiver operating characteristic curve (AUC-ROC). A total of 18,662 discharge episodes were analyzed, out of which 2528 (13.5%) were followed by outpatient readmissions. Overall, 38,059 models were developed. AUC-ROC, sensitivity, and specificity of the reduced final model were 0.653, 0.385, and 0.794, respectively. The most important variables were related to follow-up duration, being prescribed with disease-modifying anti-rheumatic drugs and corticosteroids, being diagnosed with chronic polyarthritis, occupation, and QoL. We have developed a predictive model for outpatient readmission in a rheumatology setting. Identification of patients with higher risk can optimize the allocation of healthcare resources.

The major environmental risk factor for rheumatoid arthritis (RA) is smoking, which according to a widely accepted model induces protein citrullination in the lungs, triggering the production of anti-citrullinated protein antibodies (ACPA) and RA development. Nevertheless, some research findings do not fit this model. Therefore, we obtained six independent cohorts with 2253 RA patients for a detailed analysis of the association between smoking and RA autoantibodies. Our results showed a predominant association of smoking with the concurrent presence of the three antibodies: rheumatoid factor (RF), ACPA and anti-carbamylated protein antibodies (ACarPA) (3 Ab vs. 0 Ab: OR = 1.99, p = 2.5 × 10–8). Meta-analysis with previous data (4491 patients) confirmed the predominant association with the concurrent presence of the three antibodies (3 Ab vs. 0 Ab: OR = 2.00, p = 4.4 ×10–16) and revealed that smoking was exclusively associated with the presence of RF in patients with one or two antibodies (RF+1+2vs. RF−0+1+2: OR = 1.32, p = 0.0002). In contrast, no specific association with ACPA or ACarPA was found. Therefore, these results showed the need to understand how smoking favors the concordance of RA specific antibodies and RF triggering, perhaps involving smoking-induced epitope spreading and other hypothesized mechanisms.

Background In recent years, research has consistently proven the occurrence of genetic overlap across autoimmune diseases, which supports the existence of common pathogenic mechanisms in autoimmunity. Objectives The objective of this study was to further investigate this shared genetic component. Methods We performed a cross-disease meta-analysis of Immunochip data from 37,159 patients diagnosed with a seropositive autoimmune disease (11,489 celiac disease (CeD), 15,523 rheumatoid arthritis (RA), 3,477 systemic sclerosis (SSc), and 6,670 type 1 diabetes (T1D)) and 22,308 healthy controls of European origin using the R package ASSET. Results We identified 38 risk variants shared by at least two of the conditions analyzed, five of which represent new pleiotropic loci in autoimmunity. We also identified six novel genome-wide associations for the diseases studied. Cell-specific functional annotations and biological pathway enrichment analyses suggested that pleiotropic variants may deregulate gene expression in different subsets of T cells, especially Th17 and regulatory T cells. Finally, drug repositioning analysis evidenced several drugs that could represent promising candidates for CeD, RA, SSc and T1D treatment. Conclusion We have been able to advance in the knowledge of the genetic overlap existing in autoimmunity, thus shedding light on common molecular mechanisms of disease and suggesting novel drug targets that could be explored for the treatment of the autoimmune diseases studied. References [1] Richard-Miceli C, Criswell LA. Emerging patterns of genetic overlap across autoimmune disorders. Genome Med. 2012;4(1):6. [2] Bhattacharjee S, Rajaraman P, Jacobs KB, et al. A subset-based approach improves power and interpretation for the combined analysis of genetic association studies of heterogeneous traits. Am J Hum Genet. 2012;90(5):821-35 Disclosure of Interests Ana Marquez: None declared, Martin Kerick: None declared, Alexandra Zhernakova: None declared, Javier Gutierrez-Achury: None declared, Wei-Min Chen: None declared, Suna Onengut-Gumuscu: None declared, Isidoro Gonzalez-Alvaro: None declared, Luis Rodriguez-Rodriguez: None declared, Miguel A Gonzalez-Gay Grant/research support from: Prof. MA Gonzalez-Gay received grants/research supports from Abbvie, MSD, Jansen and Roche., Speakers bureau: Consultation fees/participation in company sponsored speaker’s bureau from Pfizer, Lilly, Sobi, Celgene, Novartis, Roche and Sanofi., Maureen Mayes Grant/research support from: Maureen Mayes is a clinical trial investigator for Boehringer-Ingelheim; Galapagos, Reata, Sanofi, Merck-Serono, Consultant for: Maureen Mayes is a member of scientific advisory boards for Galapagos NV (Pharma), Boehringer-Ingelheim, Mitsubishi-Tanabe, Astellas: Grant Review Board for Actelion., Speakers bureau: Maureen Mayes received personal fees for being a conference speaker on the use of autoantibodies in connective tissue diseases for Medtelligence, Soumya Raychaudhuri: None declared, Stephen S. Rich: None declared, Cisca Wijmenga: None declared, Javier Martin Ibanez: None declared

Background: The contribution of cigarette smoking to the risk of rheumatoid arthritis (RA) is larger for seropositive than for seronegative patients. Current pathogenic models explain this difference via the production of anti-citrullinated protein antibodies (ACPA) induced by protein citrullination in the lungs as a consequence of smoking. However, there are inconsistent results with this model including the van Wesemael et al. report, which found an association of smoking with the concurrent presence of ACPA, rheumatoid factor (RF) and anti-carbamylated protein antibodies (ACarPA), rather than with ACPA. Objectives: We aimed to explore the relationship between smoking and the presence of FR, ACPA and ACarPA and their combinations in patients with RA. Methods: Six cohorts with 2253 RA patients were obtained to replicate the van Wesemael et al. results. After replication, they were combined with the three cohorts from that study comprising 2238 patients to a total of 4491 patients. The results from the different cohorts were combined by fixed-effects meta-analysis. Most analyses involved comparisons between two levels of smoking exposure, never and ever smokers, considering the RF-/ACPA-/ACarP-patients as the reference. Results: Analysis of the replication set confirmed the predominant association of smoking with the concurrent presence of the three RA autoantibodies (OR = 1.99, P = 2.5 x 10-8), whereas the patients with one or two antibodies were not different from the patients without antibodies (OR = 1.22, p = 0.4 and OR = 1.22, p = 0.3, respectively). The combined meta-analysis with all the cohorts clarified the dominant association of smoking with the triple concordant seropositivity (OR = 2.00, p = 4.4 x 10-16). In contrast, there was no association with the patient bearing one autoantibody (OR = 1.12, p = 0.4), and an in-between association with the concurrent presence of two antibodies (OR = 1.26, p = 0.009). Moreover, the association with the presence of three antibodies was significantly larger than with two antibodies (OR = 1.54, p = 1.4 x 10-6), whereas the association with the presence of two antibodies was not larger than with one autoantibody (OR = 1.11, p = 0.3). In the patients remaining after exclusion of the triple seropositive, the smokers were exclusively associated with the RF+ (OR = 1.28, p = 0.03 and OR = 1.30, p = 0.004 in the double and single positive patients, respectively). This association was independent of the reference, either the triple seronegative (OR = 1.29, p = 0.001) or all the RF-patients (OR = 1.32, p = 0.0002). Conclusion: Smoking increases RA susceptibility by promoting pathways leading to the concurrent presence of the three RA autoantibodies and, in its defect, to the production of RF. These actions are not covered by current pathogenic models and suggest that smoking accelerates epitope spreading. Reference [1] van Wesemael, et al. Arthritis Res Ther. 2016;18:285. Acknowledgement: Supported by grants PI17/01606 and RD16/0012/0014 of the Instituto de Salud Carlos III (Spain) that are partially financed by FEDER. Disclosure of Interests: Cristina Regueiro : None declared, Luis Rodriguez Rodriguez: None declared, Raquel Lopez-Mejias: None declared, Laura Nuno: None declared, Ana Triguero-Martinez: None declared, Eva Perez-Pampin: None declared, Alfonso Corrales: None declared, Alejandro Villalva: None declared, Yolanda Lopez-Golan: None declared, Lydia Abasolo: None declared, Sara Remuzgo Martinez: None declared, Ana Ortiz: None declared, Eva Herranz: None declared, ANA MARTiNEZ-FEITO: None declared, Carmen Conde : None declared, ANTONIO MERA VARELA: None declared, Alejandro Balsa Grant/research support from: Abbvie, Pfizer, Novartis, BMS, Nordic, Sanofi, Consultant for: Abbvie, Pfizer, Novartis, BMS, Nordic, Sanofi, Sandoz, Lilly, Paid instructor for: Pfizer, Speakers bureau: Pfizer, Novartis, UCB, Nordic, Sanofi, Sandoz, Lilly, Isidoro Gonzalez-Alvaro: None declared, Miguel A Gonzalez-Gay Grant/research support from: Prof. MA Gonzalez-Gay received grants/research supports from Abbvie, MSD, Jansen and Roche., Speakers bureau: Consultation fees/participation in company sponsored speaker’s bureau from Pfizer, Lilly, Sobi, Celgene, Novartis, Roche and Sanofi., Benjamin Fernandez: None declared, Antonio Gonzalez: None declared

Background: Psoriatic arthritis (PsA) is a chronic, progressive and inflammatory arthritis. It is consider a multifaceted disease, with a high impact on patient’s psychological and physical well-being, with patients reporting lower health-related quality of life (HRQoL). Data of burden of disease is substantial and even though there are some studies that identify risk factors with longstanding PsA, there exists a need for properly designed studies to learn more about the evolution of HRQoL throughout the follow-up in this condition. Objectives: To analyze the evolution on HRQoL in patients with PsA and to to evaluate factors that may influence this evolution. Methods: Retrospective longitudinal observational study including incident patients diagnosed with PsA from 2007 to 2016, and followed-up until loss of follow-up or December 2017; with at least two registered visits; having received any ICD9/ICD10 diagnosis code of PsA; and with symptoms onset after 16 years of age. Patients were collected from the rheumatology outpatient clinic of a tertiary hospital (Hospital Clinico San Carlos, Madrid, Spain). Clinical information was collected from a departmental electronic health record, including demographic, clinical, comorbidities, treatment, and HRQoL related variables (measured with the Rosser Classification index). The influence of these variables in repeated measures of HRQoL was analysed using bivariate and multivariate generalized estimating equations (GEE) models nested by patient. Those variables with a p-value Results: We included 187 patients, with a median follow-up of 3.6 years (interquarltile range: 0.8 to 6.3). 48% were women, with a median age at the onset of symptoms and diagnosis of 45 and 49 years, respectively. 86% of patients had a personal history of Psoriasis. Regarding clinical manifestations during the follow-up, 83%, 30%, 26%, and 22% of the patients presented with peripheral arthritis, inflammatory low back pain, enthesitis and dactylitis, respectively. In addition, they received treatment with nonsteroidal antiinflammatory medications (NSAIDs), oral glucocorticoids and disease-modifying antirheumatic drugs (DMARDs) 71%, 52% and 82%, respectively. 20% received biological agents. The Rosser median value at the first visit was 0.986, with an slight increase alter the first 2 years and a decline after 5 years of follow-up (Figure 1). With respect to the variables independently associated with HRQoL during follow-up, the history of osteoporotic fractures (p = 8.1x10-18) and chronic obstructive pulmonary disease (p = 5.0x10-8) were associated with a poorer quality of life. Conversely, treatment with methotrexate (p=6.4x10-5), and the use of bone-forming agents (p = 7.8x10-4) were associated with better HRQoL. History of osteoporosis and use of biphosphonates and denosumab were also associated with HRQoL, although not significantly after p-value adjustment. Conclusion: We have identified different factors associated with HRQoL during the evolution of patients with PsA. We observed that the presence of certain comorbidities were independently associated with a worse HRQoL. In addition, regarding different treatments, the use of methotrexate and bone-forming agents were independently associated with a better HRQoL. Disclosure of interests: None declared

Introduction Mesenchymal stem cells (MSCs) have the ability to differentiate into different types of cells of the mesenchymal lineage, such as osteocytes, chondrocytes, and adipocytes. It is also known that under inflammatory stimuli or in the appropriate experimental conditions, they can also act as regulators of inflammation. Thus, in addition to their regenerating potential, their interest has been extended to their possible use in cell therapy strategies for treatment of immune disorders. Objective To analyze, by RNA-seq analysis, the transcriptome profiling of allogenic MSCs under RA lymphocyte activation. Methods We identified the differentially expressed genes in bone marrow mesenchymal stem cells after exposure to an inflammatory environment. The transcriptome profiling was evaluated by means of the precise measurement of transcripts provided by the RNA-Seq technology. Results Our results evidenced the existence of blocking of both regenerative (differentiation) and immunomodulatory phenotypes under inflammatory conditions characterized by an upregulation of genes involved in immune processes and a simultaneous downregulation of genes mainly involved in regenerative or cell differentiation functions. Conclusions We conclude that the two main functions of MSCs (immunomodulation and differentiation) are blocked, at least while the inflammation is being resolved. Inflammation, at least partially mediated by gamma-interferon, drives MSCs to a cellular distress adopting a defensive state. This knowledge could be of particular interest in cases where the damage to be repaired has an important immune-mediated component. Electronic supplementary material The online version of this article (10.1186/s13075-019-1894-y) contains supplementary material, which is available to authorized users.

Cardiovascular disease (CV) is the most common cause of premature mortality in patients with rheumatoid arthritis (RA). This is the result of an accelerated atherosclerotic process. Adequate CV risk stratification has special relevance in RA to identify patients at risk of CV disease. However, current CV risk screening and management strategies underestimate the actual CV risk in RA. Consequently, the search for additional tools that may help to identify those patients at high CV risk has become a key objective in the last years. In this regard, non-invasive surrogates, such as carotid ultrasonography, have been found to be excellent predictors of future CV events. In addition, several studies have revealed the relevance of a genetic component in the development of CV disease in RA patients. Besides an association with HLA-DRB1* shared epitope alleles other gene polymor-phisms located inside and outside the HLA seem to influence the risk of cardiovascular disease in RA. Moreover, serum levels of some metabolic syndrome-related biomarkers, adipokines such as adiponectin and biomarkers of endothelial cell activation and inflammation such as Osteoprotegerin and Asymmetric dimethylarginine have recently been found useful for the prediction of CV disease in these patients. An update of the current knowledge on these potential markers, especially focused on new genetic and serological biomarkers is shown in this review. (C) 2016 The Authors. Published by Elsevier B.V., This work was supported by European Union FEDER funds and "Fondo de Investigation Sanitaria" (grants PI06/0024, PS09/00748, PI12/00060 and PI15/00525) from 'Institut de Salud Carlos III' (ISCIII, Health Ministry, Spain). It was also partially supported by RETICS Programs RD12/0009 (RIER) from 'Instituto de Salud Carlos III' (ISCIII, Health Ministry, Spain), and in part by grants from the European IMI BTCure Program. We wish to specially thank Mercedes Garcia-Bermudez, Begona Ubilla, Veronica Mijares, Patricia Fuentevilla Rodriguez, Virginia Portilla Gonzalez and all the clinicians from Spanish National Health Care system that have been involved in our studies.

OBJECTIVE RA patients with serum ACPA have a strong and specific genetic background. The objective of the study was to identify new susceptibility genes for ACPA-positive RA using a genome-wide association approach. METHODS A total of 924 ACPA-positive RA patients with joint damage in hands and/or feet, and 1524 healthy controls were genotyped in 582 591 single-nucleotide polymorphisms (SNPs) in the discovery phase. In the validation phase, the most significant SNPs in the genome-wide association study representing new candidate loci for RA were tested in an independent cohort of 863 ACPA-positive patients with joint damage and 1152 healthy controls. All individuals from the discovery and validation cohorts were Caucasian and of Southern European ancestry. RESULTS In the discovery phase, 60 loci not previously associated with RA risk showed evidence for association at P < 5×10(-4) and were tested for replication in the validation cohort. A total of 12 loci were replicated at the nominal level (P < 0.05, same direction of effect as in the discovery phase). When combining the discovery and validation cohorts, an intronic SNP in the Solute Carrier family 8 gene (SLC8A3) was found to be associated with ACPA-positive RA at a genome-wide level of significance RA [odds ratio (95% CI): 1.42 (1.25, 1.6), Pcombined = 3.19×10(-8)]. CONCLUSIONS SLC8A3 was identified as a new risk locus for ACPA-positive RA. This study demonstrates the advantage of analysing relevant subsets of RA patients to identify new genetic risk variants.

Aims: The aim of this study was to assess the effect of “outpatient readmissions” on the health-related quality of life (HR-QoL) of outpatients from a rheumatology clinic, meaning the effect of the patient’s return to the outpatient clinic after having received care and been discharged. Methods: We conducted an observational longitudinal retrospective study, with patients selected from the Hospital Clínico San Carlos Musculoskeletal cohort, based on having received at least one discharge from the outpatient clinic and having returned (readmission) at least once after the discharge. The main outcomes were the patients’ baseline HR-QoL (measured on the first visit of each episode) and the ΔHR-QoL (difference between the HR-QoL in the last and the first visit of each episode). Successive episodes of admission and readmission were chronologically ordered, paired and analyzed using nested linear mixed models, nested by patients and by admission–readmission tandem. We carried out bivariable and multivariable analyses to assess the effect of demographic, clinical, treatment and comorbidity-related variables in both main outcomes. Results: For the first main outcome, 5887 patients (13,772 episodes) were analyzed. Based on the multivariable level, readmission showed no significant marginal effect on the baseline HR-QoL ( p-value = 0.17). Conversely, when analyzing the ΔHR-QoL, we did observe a negative and significant marginal effect ( p-value = 0.028), meaning that readmission was associated with a lower gain in the HR-QoL during the follow-up, compared with the previous episode. Conclusion: In the outpatient setting, readmission exerts a deleterious effect in patients undergoing this process. Identification of outpatients more likely to be readmitted could increase the value of the care provided.