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Objectives: To assess and compare the long-term drug survival (time to drug discontinuation) of biological agents (BA) in patients with rheumatoid arthritis (RA) in clinical practice. Factors associated with discontinuation of BAs were also investigated.Method: We conducted an observational longitudinal study of RA patients taking BAs from 1999 to 2013. The primary endpoint was BA discontinuation due to: adverse drug reactions (ADRs), inefficacy, and other causes. Incidence rates of discontinuation (IRs) per 100 patient-years were estimated using survival techniques. Comparisons between BA discontinuation rates and other associated factors were made using Cox regression models.Results: We included 851 courses of BA therapy (1869 patient-years). Adalimumab (33%) was the BA most frequently used, followed by etanercept (24.4%), infliximab, and rituximab. Treatment was suspended in 558 cases [IR 29.8, 95% confidence interval (CI) 27-32]. In the first year of therapy 68% continued on BAs, and after 10 years the retention rate did not exceed 10%. The IR due to inefficacy was 12.1 (95% CI 10.6-13.8) and the IR of ADRs was 13.6 (95% CI 12-15). The unadjusted IR was higher for rituximab than for tumour necrosis factor (TNF) antagonists. In multivariate analysis, infliximab was the BA with the highest risk of discontinuation, compared to adalimumab. Calendar period, taking subsequent courses of BAs, concomitant therapy, and specific comorbidities were also independent factors associated with discontinuation.Conclusions: After several years of BA treatment in clinical practice, the survival rate was low, mainly as a result of ADRs and inefficacy. We also found differences between the discontinuation rates of BAs and other clinical factors that modify their survival. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the variability in the characteristics and management of rheumatoid arthritis (RA) patients between rheumatology attending physicians and training residents in Spain. Methods: A retrospective medical record (MR) review was performed in a probabilistic sample of 1379 RA patients from 46 centres distributed in 16 of the 19 autonomous communities (AC) of Spain. RA patients' sociodemographic and clinical characteristics, healthcare resources use, and their single responsible physician's (defined as an identifiable single physician who attended the patient in more than 75% of visits) characteristics were recorded following a standardized protocol. Multivariate analyses were performed to assess differences in the characteristics and management of RA patients between attending physicians and training residents. Results: A total of 1205 RA patients had a single responsible physician and were analysed (nearly 75% women with rheumatoid factor positive and more than 25% with persistent active disease), 49 of whom were followed by training residents and 1156 by attending physicians. In the multivariate analyses, irrespective of patient and disease characteristics, training residents' patients reported more hospital admissions, laboratory tests, and imaging techniques compared to attending physicians. Training residents also less frequently used combined therapy with disease-modifying antirheumatic drugs (DMARDs). Conclusion: Training residents and attending physicians differ in RA patients' care. More efforts in training programmes are necessary to guarantee proper RA management and to improve the profile of the future rheumatologists. [ABSTRACT FROM AUTHOR]

Objetive: To evaluate the frequency and timing of sustained drug-free remission (SDFR) in patients with giant cell arteritis (GCA) and to identify potential predictive factors of this outcome., Methods: Retrospective review of all patients included in the large Spanish multicentre registry for GCA (ARTESER) with at least two years of follow-up. SDFR was defined as the absence of typical signs, symptoms, or other features of active GCA for ≥12 months after discontinuation of treatment., Results: We included 872 patients. Forty-seven percent had received concomitant treatment with tocilizumab and/or immunosuppressants, mainly methotrexate.SDFR was achieved in 21.2% (185/872) of the patients. The cumulative rates of patients achieving SDFR at 2, 3, and 4 years were 6.3%, 20.5%, and 25.3%, respectively.Patients who achieved SDFR could reduce their prednisone dosage to 10 mg/day (p = 0.090) and 5 mg/day (p = 0.002) more quickly than those who did not. Relapses were less frequent in patients with SDFR (p = 0.006).The presence of relapses (incident rate ratio: 0.492, p < 0.001) and the need for intravenous methylprednisolone boluses at diagnosis (IRR: 0.575, p = 0.003) were significantly associated with a decreased likelihood of achieving SDFR.Only 5 patients (2.7%) experienced a recurrence, with a median onset of 19 months after achieving SDFR (IQR 25th-75th: 14-35 months)., Conclusion: Within 3-4 years of diagnosis, only one-quarter of patients with GCA successfully reached the SDFR. Once the SDFR was achieved, the likelihood of experiencing recurrence was low. Relapses and the need for glucocorticoid boluses appear to be predictors of long-term GC need., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: Despite the growing interest in psychological variables and mental health in young people with rheumatic diseases (RMDs), the impact of these conditions on self-concept, self-esteem, or body image is unclear. The purpose of this study was to synthesize existing research related to these domains in young people with RMDs., Methods: Review registered on PROSPERO as CRD42023444009. The search strategy includes all articles up to September 2023, to collect qualitative and quantitate studies assessing self-concept, self-esteem, or body image in young people with RMDs. All identified articles were described, rated and Risk of bias was assessed., Results: We identified 350 studies, of which 11 were analysed in this study. Our results indicated that self-concept, body image and self-esteem were a common challenge in young people with RMDs and might negatively impact physical and psychosocial health-related quality of life (QoL). The social domain of self-concept was impaired, mainly in female patients. Although studies that evaluated self-esteem show varied results, it seems that self-esteem was worse in females and was associated mainly with depression, but also with poorer QoL. Glucocorticoids consistently were associate with poor body image in all conditions due to visible side-effects of medication. Visible signs of the disease also might lead to poor body image., Conclusion: This review identifies important gaps and areas of improvement for future research in these issues in young patients with RMDs. This review highlights the need to actively engage patients and ensure that their psychological concerns are addressed to improve their healthcare and long-term quality of life outcomes., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: DC declare payment or honoraria for lectures, presentations, speakers bureaus (Pfizer and GSK),support for attending meetings and/or travel (Pfizer and Rubio) and participation on a Data Safety Monitoring Board or Advisory Board (Sanofi and Lilly). LL declare payment or honoraria for lectures, presentations, speakers bureaus (Pfizer). Other authors declare that they have no competing interests., (Copyright © 2024. Published by Elsevier Inc.)

Objectives: A subset of patients with rheumatoid arthritis (RA) who remains symptomatic after failing to multiple drugs are deemed to have "difficult-to-treat RA" (D2T RA). Fatigue is a burdensome symptom for RA patients, hindering their improvement. Our purpose was to evaluate the role of fatigue in D2T RA., Methods: This cross-sectional study included rheumatoid arthritis (RA) patients between 2018 and 2022, treated with biological agents or targeted synthetic disease-modifying antirheumatic drugs. D2T RA was defined attending EULAR criteria. Independent variable was fatigue (dimensions and impact) assessed by the Bristol Rheumatoid Arthritis Fatigue Multidimensional Questionnaire and Numerical Rating Scales. Covariables: sociodemographic, clinical and treatment. To identify factors independently associated to D2T RA, multivariable logistic regression was run., Results: The study included 145 patients and 38 (26.21%) developed D2T RA. D2T RA group were older, with more comorbidity and disability. D2T RA patients scored higher for global fatigue (p = 0.003), and almost for all their dimensions except for cognitive fatigue (p = 0.06) and fatigue coping (p = 0.07). Females with D2T RA showed more fatigue than those with non-D2T RA. In the adjusted models, all fatigue dimensions were associated with D2T RA: global fatigue RA (OR: 1.03; p = 0.007), physical (OR: 1.09; p = 0.008), living (OR: 1.09; p = 0.016), cognitive (OR: 1.1; p = 0.046) and emotional (OR: 1.18; p = 0.012)., Conclusions: Despite the absence of an explicit mention of fatigue in the definition of D2T RA, it appears to be associated to this outcome. Fatigue should be evaluated in a multidimensional perspective, and gender-specific differences should be considered., (© 2024. The Author(s).)

Background: Switching between therapies is a recommended strategy for psoriatic arthritis (PsA) patients who experience treatment failure; however, studies including real-life data are scarce., Objectives: To assess the incidence rate (IR) of switching between biologics and targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs) due to inefficacy in PsA, and to compare the risk of switching due to inefficacy across different b/tsDMARDs groups., Design: A longitudinal retrospective study, spanning from 2007 to 2022, was conducted on patients with PsA treated with b/tsDMARDs at an outpatient rheumatology clinic., Methods: The primary outcome was switching between b/tsDMARDs due to inefficacy. The independent variable was the exposure to b/tsDMARDs during follow-up. As covariates, clinical, treatment-related, and sociodemographic variables were considered. Survival techniques were run to estimate the IR of switching due to inefficacy per 100 patients*year and confidence interval at 95% (95% CI). Cox multivariate regression analyses were run to assess the risk of b/tsDMARDs switching due to inefficacy, expressed as hazard ratio (HR) and 95% CI., Results: In all, 141 patients were included, with 893.09 patients*year follow-ups. 52.48% of them were females in their fifties. In total, 262 courses of treatment were recorded. During the study period, 56 patients presented 121 switches and 103 related to inefficacy (IR: 11.53 (9.51-13.98)). Tumor necrosis factor-alpha inhibitors (TNFi) showed the lowest IR. In the bivariate analysis, all b/tsDMARDs had more risk of switching compared to TNFi (HR: anti-lL-17 vs TNFi: 2.26 (1.17-4.36); others vs TNFi: 3.21 (1.59-6.45)); however, this statistical significance was no longer present in the multivariate analysis once adjustments were made for the covariates. Still, the final model achieved statistical significance in the following variables: gender, clinical symptoms, prescription year, therapy courses, glucocorticoids, and sulfasalazine., Conclusion: In this study, we did not find differences in the rate of switching due to inefficacy among different groups of b/tsDMARDs. Other concomitant treatments, sociodemographic, and clinical variables were identified as risk factors for switching due to inefficacy., Competing Interests: The authors declare that there is no conflict of interest., (© The Author(s), 2024.)

In this study of the alterations of Glypicans 1 to 6 (GPCs) and Notum in plasma, bone marrow mesenchymal stromal cells (BM-MSCs) and osteoblasts in Osteoarthritis (OA), the levels of GPCs and Notum in the plasma of 25 patients and 24 healthy subjects were measured. In addition, BM-MSCs from eight OA patients and eight healthy donors were cultured over a period of 21 days using both a culture medium and an osteogenic medium. Protein and gene expression levels of GPCs and Notum were determined using ELISA and qPCR at 0, 7, 14 and 21 days. GPC5 and Notum levels decreased in the plasma of OA patients, while the BM-MSCs of OA patients showed downexpression of GPC6 and upregulation of Notum. A decrease in GPC5 and Notum proteins and an increase in GPC3 were found. During osteogenic differentiation, elevated GPCs 2, 4, 5, 6 and Notum mRNA levels and decreased GPC3 were observed in patients with OA. Furthermore, the protein levels of GPC2, GPC5 and Notum decreased, while the levels of GPC3 increased. Glypicans and Notum were altered in BM-MSCs and during osteogenic differentiation from patients with OA. The alterations found point to GPC5 and Notum as new candidate biomarkers of OA pathology.

Objective: This study aimed to estimate the incidence of giant cell arteritis (GCA) in Spain and to analyse its clinical manifestations, and distribution by age group, sex, geographical area and season., Methods: We included all patients diagnosed with GCA between 1 June 2013 and 29 March 2019 at 26 hospitals of the National Health System. They had to be aged ≥50 years and have at least one positive results in an objective diagnostic test (biopsy or imaging techniques), meet 3/5 of the 1990 American College of Rheumatology classification criteria or have a clinical diagnosis based on the expert opinion of the physician in charge. We calculated incidence rate using Poisson regression and assessed the influence of age, sex, geographical area and season., Results: We identified 1675 cases of GCA with a mean age at diagnosis of 76.9±8.3 years. The annual incidence was estimated at 7.42 (95% CI 6.57 to 8.27) cases of GCA per 100 000 people ≥50 years with a peak for patients aged 80-84 years (23.06 (95% CI 20.89 to 25.4)). The incidence was greater in women (10.06 (95% CI 8.7 to 11.5)) than in men (4.83 (95% CI 3.8 to 5.9)). No significant differences were found between geographical distribution and incidence throughout the year (p=0.125). The phenotypes at diagnosis were cranial in 1091 patients, extracranial in 337 patients and mixed in 170 patients., Conclusions: This is the first study to estimate the incidence of GCA in Spain at a national level. We found a predominance among women and during the ninth decade of life with no clear variability according to geographical area or seasons of the year., Competing Interests: Competing interests: Disclosures that might be interpreted as constituting possible conflict(s) of interest for the study: Ed Research funding/consulting and conferences fees from: Abbvie, Novartis, Roche, Pfizer, Janssen, Lilly, MSD, BMS, UC Pharma, Grünenthal and Sanofi. JL had consultation fees/participation in company-sponsored speaker’s bureau from Roche, Galápagos, Novartis, UCB Pharma, MSD, Celgene, Astra Zeneca and Grünenthal and received support for attending meetings and/or travel from Janssen, Abbvie, Roche, Novartis, MSD, UCB Pharma, Celgene, Lilly, Pfizer, Galápagos. Patricia Moya Alvarado had consultation fees/participation in company-sponsored speaker’s bureau from Roche, Novartis, Abbvie, MSD, Lilly, Pfizer and Celgene and received support for attending meetings and/or travel from Novartis, Lilly and, Pfizer. SC has received research support from MSD and Pfizer and had consultation fees/participation in company-sponsored speaker’s bureau from Amgen, BMS, Eli-Lilly, MSD, Roche, Gedeon-Richter, Grünenthal Pharma and UCB. SC is also assistant professor of the cátedra EPID-Future, funded by UAM-Roche, Universidad Autónoma de Madrid (UAM), Spain. RB received grants/research support from AbbVie, MSD and Roche, and had consultation fees/participation in a company-sponsored speaker’s bureau from AbbVie, Pfizer, Roche, Lilly, UCB, Bristol-Myers, Janssen, and MSD. The following authors did not declare financial disclosure: DF-L, IH-R, JN, MD-Á, MS-D, JMB, CMM, JS, EG-A, VA, LA, NG-P, CL, VAN, JC, IC-S, FO-S and TCSM., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: The aim of this study is to evaluate risk factors for severe coronavirus disease 2019 (COVID-19) in patients with immune-mediated rheumatic diseases, stratified by systemic autoimmune conditions and chronic inflammatory arthritis., Methods: An observational, cross-sectional multicentre study was performed. Patients from 10 rheumatology departments in Madrid who presented with severe acute respiratory syndrome coronavirus-2 infection between February 2020 and May 2021 were included. The main outcome was COVID-19 severity (hospital admission or mortality). Risk factors for severity were estimated, adjusting for covariates (socio-demographic, clinical, and treatments), using logistic regression analyses., Results: In total, 523 patients with COVID-19 were included, among whom 192 (35.6%) patients required hospital admission and 38 (7.3%) died. Male gender, older age, and comorbidities such as diabetes mellitus, hypertension, and obesity were associated with severe COVID-19. Corticosteroid doses >10 mg/day, rituximab, sulfasalazine, and mycophenolate use, were independently associated with worse outcomes. COVID-19 severity decreased over the different pandemic waves. Mortality was higher in the systemic autoimmune conditions (univariate analysis, P < .001), although there were no differences in the overall severity in the multivariate analysis., Conclusions: This study confirms and provides new insights regarding the harmful effects of corticosteroids, rituximab, and other therapies (mycophenolate and sulfasalazine) in COVID-19. Methotrexate and anti-tumour necrosis factor therapy were not associated with worse outcomes., (© Japan College of Rheumatology 2022. Published by Oxford University Press.)

Introduction: In patients with rheumatoid arthritis (RA), nurses are considered as essential, not only to ensure pharmacological safety, but also in the promotion in self-care and decision-making, favouring the empowerment of patients. This systematic review aimed to summarize the available literature on the health education by the nurse in patients with RA., Material and Methods: Following Cochrane Collaboration procedures, the PRISMA statement and PRISMA checklist, relevant quantitative studies published were retrieved from the CINAHL, Scopus, PubMed and Medic databases and then systematically reviewed. The search ended in August 2021. Nineteen studies were retained for inclusion and evaluated with the Scottish Intercollegiate Guidelines Network for Systematic Reviews., Results: We found statistically significant improvement in self-care (five studies), disease activity (three studies), quality of life (two studies), satisfaction (five studies) and adherence (one study) with the nursing-led management of patients with established rheumatoid arthritis., Discussion: Although there is solid evidence of improvement in satisfaction and self-care, there seems to be a trend also to improve other outcomes, such as DAS28, from the EULAR recommendations, the expansion of the therapeutic arsenal for rheumatoid arthritis and shared decision-making. In addition, recently and due to the implementation of new technologies, the role of the nurse has been evaluated through virtual consultations. The results of recent studies have shown that this an effective and well-accepted novel approach for the management of patients with stable rheumatoid arthritis., Conclusion: Our study suggests that nurse-led health education, in addition of improvement in satisfaction and self-care, improve activity disease scores in RA patients., (Copyright © 2023 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.)

Objectives: Most studies on difficult-to-treat rheumatoid arthritis (D2T RA) have focused on established RA. Here, we analyse whether disease activity in the early stages of RA could influence progression to a D2T RA under real-life conditions. Other clinical and treatment-related factors were also analysed., Methods: A longitudinal multicentre study of patients with RA was conducted from 2009 to 2018. Patients were followed up until January 2021. D2T RA was defined based on EULAR criteria (treatment failure, signs suggestive of currently active/progressive disease and management being perceived as problematic by the rheumatologist and/or patient). The main variable was disease activity in the early stages. The covariates were sociodemographic, clinical and treatment-related factors. We ran a multivariable logistic regression analysis to investigate risk factors associated with progression to D2T RA., Results: The study population comprised 631 patients and 35 (5.87%) developed D2T RA. At the time of diagnosis, the D2T RA group were younger, with a higher disability, 28-joint Disease Activity Score (DAS28) score, tender joint count and pain scores. In our final model, DAS28 was not statistically significantly associated with D2T RA. No differences were found between groups for therapy. Disability was independently associated with D2T RA (OR: 1.89; p=0.01)., Conclusions: In this cohort of patients newly diagnosed with RA, our results do not allow us to prove the influence of active disease according to DAS28. However, we did find that younger patients and those with elevated initial disability scores are more likely to develop D2T RA regardless of other factors., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: Competing interests: None declared.

Competing Interests: Competing interests: None declared.

Background and Objective: A thorough understanding of the pathogenic mechanisms elicited by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) still requires further research. Until recently, only a restricted number of autopsies have been performed, therefore limiting the accurate knowledge of the lung injury associated with SARS-CoV-2. A multidisciplinary European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group of Forensic and Post-mortem Microbiology-ESGFOR team conducted a non-systematic narrative literature review among coronavirus 2019 disease (COVID-19) pneumonia cases assessing the histopathological (HP) effects of positive airways pressure. HP lung features were recorded and compared between mechanically ventilated (>24 hours) and control (ventilation <24 hours) patients. A logistic regression analysis was performed to identify associations between mechanical ventilation (MV) and HP findings., Methods: A PubMed and MEDLINE search was conducted in order to identify studies published between March 1st 2020 and June 30th 2021., Key Content and Findings: Seventy patients (median age: 69 years) from 24 studies were analysed, among whom 38 (54.2%) underwent MV longer than 24 hours. Overall, main HP features were: diffuse alveolar damage (DAD) in 53 (75.7%), fibrosis (interstitial/intra-alveolar) in 43 (61.4%), vascular damage-including thrombosis/emboli- in 41 (58.5%), and endotheliitis in only 8 (11.4%) patients. Association of DAD, fibrosis and vascular damage was detected in 30 (42.8%) patients. Multivariate analysis, adjusted by age and gender, identified MV >24 hours as an independent variable associated with DAD (OR =5.40, 95% CI: 1.48-19.62), fibrosis (OR =3.88, 95% CI: 1.25-12.08), vascular damage (OR =5.49, 95% CI: 1.78-16.95) and association of DAD plus fibrosis plus vascular damage (OR =6.99, 95% CI: 2.04-23.97)., Conclusions: We identified that patients mechanically ventilated >24 hours had a significantly higher rate of pulmonary injury on histopathology independently of age and gender. Our findings emphasize the importance of maintaining a protective ventilator strategy when subjects with COVID-19 pneumonia undergo intubation., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-605/coif). J Rello serves as an unpaid editorial board member of Annals of Translational Medicine from April 2016 to March 2022. The other authors have no conflicts of interest to declare., (2022 Annals of Translational Medicine. All rights reserved.)

Objectives: The aim of this study was to assess the cause-specific mortality rate related to COVID-19 (CMR) in patients with rheumatic and musculoskeletal diseases (RMDs) and COVID-19 and to analyze the role of the different RMDs in their mortality risk., Methods: An observational longitudinal study was conducted during the first pandemic wave in our center. Patients with the diagnosis of RMDs and COVID-19 were included. Main outcome is the death related to COVID-19. Independent variable - type of RMDs: autoimmune rheumatic diseases (ARD), such as chronic inflammatory arthritis (CIA) and connective tissue diseases (CTD) and non-autoimmune Rheumatic Diseases (non-ARD). Survival techniques were used to estimate the CMR per 1000 patients-month with a 95% confidence interval (CI), and Cox multivariate regression analysis was run to examine the effect of ARD compared to non-ARD on mortality risk adjusted by confounders. Results were expressed by Hazard Ratio (HR) and CI., Results: Overall, 405 patients were included (642.5 patients-month). During the study period, 44 (10.86%) deaths were recorded. CMR was 68.48 (50.96-92.01). After adjusting for confounders, HR of mortality in ARD compared to non-ARD did not achieve statistical significance [HR: 1.15 (0.64-2.07)], neither CTD versus CIA nor CTD versus non-ARD. Age and certain comorbidities which are being diagnosed in March compared to April or May [HR: 2.43 (1.1-5.55)] increased the mortality risk. Glucocorticoids and disease-modifying antirheumatic drugs (DMARDs) dropped from the final model., Conclusion: In patients with RMDs and COVID-19, CMR was 6.8% patients-month. This study shows that mortality risk is higher in males, older patients, and similar between CTD, CIA, and non-ARD. COVID-19 management improved after the first month of pandemic., Plain Language Summaries: Mortality related to the outbreak of COVID-19 in patients with rheumatic and musculoskeletal diseases Why was this study done? - To report the COVID-19-specific mortality rate in patients with a variety of RMDs during the first pandemic peak in a tertiary hospital in Madrid and to analyze the role of specific types of ARD and other possible factors in the risk of death related to COVID-19. What did the researchers do? - We performed a retrospective observational study during the first wave of the COVID-19 pandemic in Madrid, Spain. What did the researchers find? - In this study, neither the different diagnoses of RMDs, including CIA, CTD, or non-ARD disease or its treatment were not implicated as a potential risk of death related to COVID-19- In consonance with other studies, RMDs patients and COVID-19, older age, male sex, and certain comorbidities implied more mortality risk- Our data reflect COVID-19 severity in a particular context, time, and population. In times of the absence of COVID-19 vaccine, healthcare, social, and political measures taken to contain the coronavirus outbreak have worked properly. What do the findings mean? - The presence of comorbidities in RMDs patients represents a greater risk than the different types of RMDs themselves, in the development of COVID-19 fatal outcome. It is important to integrate the control of comorbidities in the daily management., Competing Interests: Conflict of interest statement: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s), 2022.)

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., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Background: This study aimed to assess the baseline characteristics and clinical outcomes of coronavirus disease 2019 (COVID-19) in pediatric patients with rheumatic and musculoskeletal diseases (RMD) and identify the risk factors associated with symptomatic or severe disease defined as hospital admission, intensive care admission or death., Methods: An observational longitudinal study was conducted during the first year of the SARS-CoV-2 pandemic (March 2020-March 2021). All pediatric patients attended at the rheumatology outpatient clinics of six tertiary referral hospitals in Madrid, Spain, with a diagnosis of RMD and COVID-19 were included. Main outcomes were symptomatic disease and hospital admission. The covariates were sociodemographic and clinical characteristics and treatment regimens. We ran a multivariable logistic regression model to assess associated factors for outcomes., Results: The study population included 77 pediatric patients. Mean age was 11.88 (4.04) years Of these, 30 patients (38.96%) were asymptomatic, 41 (53.25%) had a mild-moderate COVID-19 and 6 patients (7.79%) required hospital admission. The median length of hospital admission was 5 (2-20) days, one patient required intensive care and there were no deaths. Previous comorbidities increased the risk for symptomatic disease and hospital admission. Compared with outpatients, the factor independently associated with hospital admission was previous use of glucocorticoids (OR 3.51; p = 0.00). No statistically significant risk factors for symptomatic COVID-19 were found in the final model., Conclusion: No differences in COVID-19 outcomes according to childhood-onset rheumatic disease types were found. Results suggest that associated comorbidities and treatment with glucocorticoids increase the risk of hospital admission., (© 2021. The Author(s).)

Background: Clinical studies with work participation (WP) as an outcome domain pose particular methodological challenges that hamper interpretation, comparison between studies and meta-analyses., Objectives: To develop Points to Consider (PtC) for design, analysis and reporting of studies of patients with inflammatory arthritis that include WP as a primary or secondary outcome domain., Methods: The EULAR Standardised Operating Procedures were followed. A multidisciplinary taskforce with 22 experts including patients with rheumatic diseases, from 10 EULAR countries and Canada, identified methodologic areas of concern. Two systematic literature reviews (SLR) appraised the methodology across these areas. In parallel, two surveys among professional societies and experts outside the taskforce sought for additional methodological areas or existing conducting/reporting recommendations. The taskforce formulated the PtC after presentation of the SLRs and survey results, and discussion. Consensus was obtained through informal voting, with levels of agreement obtained anonymously., Results: Two overarching principles and nine PtC were formulated. The taskforce recommends to align the work-related study objective to the design, duration, and outcome domains/measurement instruments of the study (PtC: 1-3); to identify contextual factors upfront and account for them in analyses (PtC: 4); to account for interdependence of different work outcome domains and for changes in work status over time (PtC: 5-7); to present results as means as well as proportions of patients reaching predefined meaningful categories (PtC: 8) and to explicitly report volumes of productivity loss when costs are an outcome (PtC:9)., Conclusion: Adherence to these EULAR PtC will improve the methodological quality of studies evaluating WP., Competing Interests: Competing interests: AB: research grants from Abbvie and Celgene and honoraria for consultancy or speakers honoraria from UCB, Biogen, Sandoz, Eli Lilly and Galapagos (all to her department); EN has received speaker honoraria/participated in advisory boards for Celltrion, Pfizer, Sanofi, Gilead, AbbVie and Lilly; FPS: research grant from AbbVie, Novartis; consultancy or speaking fees: AbbVie, Angelini, AstraZeneca, Biogen, Eli Lilly, Laboratórios Vitória, MSD, Novartis, Tecnimed, UCB; SR: research grant from MSD; consultancy or speaking fees: AbbVie, Eli Lilly, MSD, Novartis, Sanofi, UCB; JKW: consultancy fees from Celgene, Eli Lilly, Novartis; RW: consultancy and speakers bureau Celltrion and Galapagos/Gilead., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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., (© 2021. The Author(s).)

Psoriasis is a common skin disease. Up to 30% of patients with psoriasis develop psoriatic arthritis (PsA) resulting, by far, the most prevalent coexisting condition. Heterogeneity of clinical and radiological presentation is a major challenge to diagnosis of PsA. Initial reports about PsA emphasized a benign course in most patients, but it is now recognized that psoriatic arthritis often leads to impaired function and a reduced quality of life. PsA is a progressive disease characterized by diverse clinical features, often resulting in diagnostic delay and treatment that are associated with poor clinical and structural outcomes. New effective treatments may halt PsA progression, and consequently, treatment goals have evolved from simple reduction of pain to achieving full remission or minimal disease activity. This emerging treat-to-target strategy paradigm emphasize a need for early diagnosis; sensitive imaging techniques may be of value in this process. While radiography and CT depict structural damage, US and MRI have emerged as helpful tools to evaluate magnitude and severity of active inflammatory lesions. This review aims to describe the role of imaging modalities in diagnosis, follow-up and prognosis of PsA., (© 2021. The Author(s).)

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., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest., (© The Author(s), 2021.)

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., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest., (© The Author(s), 2021.)

Background: To assess mortality rate (MR) and standardized mortality rate (SMR) of rheumatoid arthritis-related interstitial lung disease (RA-ILD) patients and to evaluate the role of radiographic patterns in mortality., Methods: A longitudinal multicentric study was conducted in RA-ILD patients from 2005 to 2015 and followed-up until October 2018 in Madrid. Patients were included in the Neumologia-Reumatología y Enfermedades Autoinmunes Registry, from diagnosis of ILD. The main outcome was all-cause mortality. The radiographic pattern at baseline [usual interstitial pneumonia (UIP), nonspecific interstitial pneumonia (NSIP), or others] was the independent variable. Covariables included sociodemographic and clinical data. Survival techniques were used to estimate MR, expressed per 1000 persons-year with their 95% confidence intervals [CI]. Cox multiple regression model was run to examine the influence of radiographic patterns on survival. SMR [CI] was calculated comparing MR obtained with MR expected in the general population of Madrid by indirect age-gender standardization., Results: 47 patients were included with a follow-up 242 patients-year. There were 16 (34%) deaths, and most frequent causes were acute ILD exacerbation and pneumonia. MR was 64.3 [39.4-104.9], and 50% of the patients died at 8.3 years from ILD diagnosis. After adjusting for confounders, (UIP compared to NSIP was associated with higher mortality risk. The overall SMR was 2.57 [1.4-4.17]. Women of 60-75 years of age were the group with the highest SMR., Conclusions: RA-ILD is associated with an excess of mortality compared to general population. Our results support that UIP increases the risk of mortality in RA-ILD, regardless other factors.

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.

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., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest., (© The Author(s), 2021.)

Objectives: To 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., Methods: An 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., Results: The 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., Conclusion: Our 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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The susceptibility of patients with rheumatic diseases and the risks or benefits of immunosuppressive therapies for COVID-19 are unknown., Methods: We performed a retrospective study with patients under follow-up in rheumatology departments from seven hospitals in Spain. We matched updated databases of rheumatology patients with severe acute respiratory syndrome coronavirus 2-positive PCR tests performed in the hospital to the same reference populations. Rates of PCR+ confirmed COVID-19 were compared among groups., Results: Patients with chronic inflammatory diseases had 1.32-fold higher prevalence of hospital PCR+ COVID-19 than the reference population (0.76% vs 0.58%). Patients with systemic autoimmune or immune-mediated disease (AI/IMID) showed a significant increase, whereas patients with inflammatory arthritis (IA) or systemic lupus erythematosus did not. COVID-19 cases in some but not all diagnostic groups had older ages than cases in the reference population. Patients with IA on targeted-synthetic or biological disease-modifying antirheumatic drugs (DMARDs), but not those on conventional-synthetic DMARDs, had a greater prevalence despite a similar age distribution., Conclusion: Patients with AI/IMID show a variable risk of hospital-diagnosed COVID-19. Interplay of ageing, therapies and disease-specific factors seem to contribute. These data provide a basis to improve preventive recommendations to rheumatic patients and to analyse the specific factors involved in COVID-19 susceptibility., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To asses the clinical course in RA-related interstitial lung disease (RA-ILD) patients with and without rituximab (RTX). The influence of other variables was also evaluated., Methods: A longitudinal multicentre study was conducted in RA diagnosed with ILD from 2007 until 2018 in Madrid. Patients were included in a registry [pNEumology RhEumatology Autoinmune diseases (NEREA)] from the time of ILD diagnosis. The main endpoint was functional respiratory impairment (FI), when there was a decline ≥5% in the predicted forced vital capacity compared with the previous one. Pulmonary function was measured at baseline and in follow-up visits every 6-12 months. The independent variable was therapy with RTX. Covariables included sociodemographic, clinical, radiological and other therapies. Survival techniques were used to estimate the incidence rate (IR) and 95% CI of functional impairment, expressed per 100 patient-semesters. Cox multivariate regression models were run to examine the influence of RTX and other covariates on FI. Results were expressed as the hazard ratio (HR) and CI., Results: A total of 68 patients were included. FI occurred in 42 patients [IR 23.5 (95% CI 19, 29.1)] and 50% of them had FI within 1.75 years of an ILD diagnosis. A multivariate analysis showed that RTX exposure resulted in a lower risk of FI compared with non-exposure [HR 0.51 (95% CI 0.31, 0.85)]. Interstitial pneumonia, glucocorticoids, disease activity and duration also influenced FI., Conclusion: RA-ILD patients deteriorate over time, with the median time free of impairment being <2 years. Patients exposed to RTX had a higher probability of remaining free of FI compared with other therapies. Other factors have also been identified., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

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+2 vs. 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: 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., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest., (© The Author(s), 2019.)

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.

The study aims to analyze the association between the bone and cartilage/periarticular components of the radiographic joint damage and disability over the course of disease, in a cohort of rheumatoid arthritis (RA) patients from a day-to-day clinical practice. The secondary aim is to study the role of demographic and disease-related variables in this association. We performed a retrospective longitudinal study including 736 RA patients. Disability was assessed with the health assessment questionnaire (HAQ), and radiographic joint damage of hands and wrists with the Sharp van-der-Heijde score (total (SHS), erosion (ES), and narrowing/(sub)luxation (NSLS) components]. Generalized estimating equations models, adjusted by disease activity, demographic and disease-related variables, were used to test the relationship between SHS and medium-term (median value of the HAQs performed in the following year after each radiograph) and long-term (set of HAQ measures performed during follow-up, at least 1 year apart from the first x-ray) disability. Interaction terms between the SHS and demographic and disease-related variables were introduced in the models. To account for multiple testing, Bonferroni correction was applied. NSLS was independently associated with medium-term disability, even after Bonferroni correction. We observed significant and positive interactions between NSLS and age at x-ray, and with the ES. SHS showed no association with long-term disability. The cartilage/soft tissue component of the radiographic joint damage seems to exert a much more important role in medium-term disability than the erosive component. This association could be modulated by the age at the x-ray and by the magnitude of the erosive damage.

Objective: The aim of this study was to assess the reliability and validity of the Spanish version of the Rosser classification system for disease states in patients with musculoskeletal disorders., Methods: Our study was based on a questionnaire validation design. Patients were attended at an outpatient rheumatology clinic at Hospital Clínico San Carlos, Madrid, Spain. The Rosser classification system was completed by the physician from the research team (PMQ) and by the patient (HMQ). Criterion standards: The EuroQol-5D for the HMQ and the physician global estimate (DOCGL) for the PMQ. Internal consistency reliability was assessed using Cronbach α. Test-retest reliability and interobserver reliability were analyzed using the intraclass correlation coefficient. The criterion validity between HMQ and EuroQol-5D and between PMQ and DOCGL was assessed using the Spearman correlation coefficient., Results: The full analysis was based on 4 samples of patients (104 to 266 patients), most of whom were middle-aged women. For HMQ, Cronbach α was 0.70. Test-retest reproducibility was 0.7. With respect to criterion validity, significant correlations in the expected direction were observed. For PMQ, Cronbach α was 0.70, indicating excellent intraobserver and interobserver reliability. With respect to criterion validity, strong correlations were observed between the PMQ and the DOCGL., Conclusions: The Rosser classification system showed satisfactory reliability and suitable criterion validity for patients with musculoskeletal disorders. The instrument seems to be suitable for clinical decision making and research.

Objective: Recognition of a new type of rheumatoid arthritis (RA)-specific autoantibody, the anti-carbamylated protein antibodies (anti-CarP), has provided an opportunity to improve the management and understanding of RA. The current study was undertaken to assess the relationship between anti-CarP antibodies and HLA-DRB1 alleles in RA., Methods: Serum samples were obtained from 3 different collections, comprising a total of 1,126 RA patients. Serum reactivity against in vitro carbamylated fetal calf serum proteins was determined by enzyme-linked immunosorbent assay. HLA-DRB1 alleles were determined using either hybridization techniques or imputation from HLA-dense genotypes. Results of these analyses were combined in a meta-analysis with data from 3 previously reported cohorts. The carrier frequencies of the common HLA-DRB1 alleles were compared between the antibody-positive RA subgroups and the double-negative subgroup of RA patients stratified by anti-citrullinated protein antibody (ACPA)/anti-CarP antibody status, and also between the 4 RA patient strata and healthy controls., Results: Meta-analysis was conducted with 3,709 RA patients and 2,305 healthy control subjects. Results revealed a significant increase in frequency of HLA-DRB1*03 carriers in the ACPA-/anti-CarP+ subgroup as compared to ACPA-/anti-CarP- RA patients and healthy controls; this was consistently found across the 6 sample collections. This association of HLA-DRB1*03 with ACPA-/anti-CarP+ RA was independent of the presence of the shared allele (SE) and any other confounders analyzed. No other allele was specifically associated with the ACPA-/anti-CarP+ RA patient subgroup. In contrast, frequency of the SE was significantly increased in the ACPA+/anti-CarP- and ACPA+/anti-CarP+ RA patient subgroups, without a significant distinction between them. Furthermore, some alleles (including HLA-DRB1*03) were associated with protection from ACPA+ RA., Conclusion: These findings indicate a specific association of HLA-DRB1*03 with ACPA-/anti-CarP+ RA, suggesting that preferential presentation of carbamylated peptides could be a new mechanism underlying the contribution of HLA alleles to RA susceptibility., (© 2018, American College of Rheumatology.)

Objectives: To assess the incidence and the risk of relapses in giant cell arteritis (GCA) patients treated with and without methotrexate (MTX) in clinical practice. Other associated factors were also investigated., Methods: An inception cohort of GCA was assembled in the out-patient clinic at Hospital Clínico San Carlos, including patients from the date of diagnosis (Jan-1991 until Sept-2013), and followed-up until lost of follow up or Sept-2014., Main Outcome: relapse defined as recurrence of symptoms or signs of GCA with high ESR and the need to increase glucocorticoids at least 10mg over the previous dose. The independent variable was exposure to MTX over time. Covariables: Sociodemographic, clinical, and treatment. Incidence rates of relapses (IR) per 100 patient-year with their 95% confidence intervals [CI] were estimated using survival techniques. MTX influence on relapses was analysed by Cox models., Results: 168 patients were included (675 patient-year). 31% of patients had relapses (IR of 12 [9.6-14.9]), and the median number of relapses was 1[1-2]. 65% of the patients were on MTX, (mean dose: 10mg). In the bivariate analysis, the risk of relapses in patients with and without MTX did not achieve statistical signification (p=0.1). After adjusting in the multivariate analysis, exposure to MTX had 72% less risk of relapse compared to those without MTX (p<0.05). Other variables included in the final model were: visual alterations and malaise at clinical presentation of GCA., Conclusions: The use of MTX seems to decrease the risk of recurrences. We also found other factors influencing on relapses.