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Osteoarthritis (OA) is closely linked to the increase in the number of senescent cells in joint tissues, and the senescence-associated secretory phenotype (SASP) is implicated in cartilage degradation. In the last decade, extracellular vesicles (EV) in combination with the use of miRNAs to modify post-transcriptional expressions of multiple genes have shown their utility in new therapies to treat inflammatory diseases. This work delves into the anti-inflammatory effect of extracellular vesicles derived from mesenchymal stem cells (MSC) previously modified to inhibit the expression of miR-21. We compare the efficacy of two treatments, MSC with their miR-21 inhibited through lentiviral transfection and their EV, against inflammation in a new OA animal model. The modified MSC and their EV were intraperitoneally injected in an OA animal model twice. One month after treatment, we checked which therapy was the most effective to reduce inflammation compared with animals untreated. Treated OA model sera were analyzed for cytokines and chemokines. Subsequently, different organs were analyzed to validate the results obtained. EV were the most effective treatment to reduce chemokines and cytokines in serum of OA animals as well as SASP, in their organs checked by proteomic and genomic techniques, compared with MSC alone in a statistically significant way. In conclusion, MSC-miR-21−-derived EV showed a higher therapeutic potential in comparison with MSCs-miR-21-. They ameliorate the systemic inflammation through inactivation of ERK1/2 pathway in OA in vivo model. Graphical abstract Workflow of the realization of the animal model of OA by injecting cells into the joint cavity of the left knee of the animals, which produces an increase in serum cytokines and chemokines in the animals in addition to the increase in SASP and markers of inflammation. Inhibition of miR-21 in MSCs, from the stroma of the human umbilical cord, by lentivirus and extraction of their EVs by ultracentrifugation. Finally, application of MSC therapy with its miR-21 inhibited or its EVs produces a decrease in serum cytokines and chemokines in the treated animals, in addition to an increase in SASP and markers of inflammation. The cell-free therapy being the one that produces a greater decrease in the parameters studied

Resumen Introduccion Los estudios de opinion sobre la percepcion del reumatologo de la practica asistencial en osteoporosis (OP) pueden ayudar a identificar areas de mejora en la gestion de esta patologia. Objetivo Conocer y analizar el enfoque organizativo que adoptan los reumatologos espanoles ante la OP para definir prioridades estrategicas y establecer unos estandares de calidad. Material y metodo Un grupo de expertos diseno una encuesta sobre creencias y conductas en OP en la practica del reumatologo. La encuesta se remitio a los socios de la Sociedad Espanola de Reumatologia (SER). Mediante ronda Delphi se consensuaron las prioridades estrategicas en OP. Resultados El grupo de expertos consensuo como prioridades estrategicas en OP: 1) La SER deberia impulsar la inclusion de la OP en el conjunto de prestaciones de todos los servicios de reumatologia, asi como ampliar la oferta formativa especifica para medicos y enfermeras; 2) Los servicios de reumatologia debieran fomentar el papel de la enfermera en OP, impulsar la implantacion y el seguimiento de indicadores de calidad e implantar protocolos de derivacion consensuados con atencion primaria ademas de impulsar su formacion en esta area; 3) La SER y los servicios de reumatologia deberian impulsar la implantacion de la consulta electronica y la consulta monografica o dedicada a OP asi como la participacion del reumatologo en unidades de fractura, Fracture Liaison Service. Conclusiones Las prioridades estrategicas en OP derivadas de la encuesta a los reumatologos espanoles ayudan a identificar las areas de mejora a nivel organizativo, estructural y de estandares de calidad en esta patologia.

espanolIntroduccion La arteritis de celulas gigantes (ACG) es una vasculitis que afecta a arterias de mediano y gran calibre. La biopsia de la arteria temporal es la tecnica diagnostica de eleccion. Atendiendo a la demanda asistencial que supone, pretendemos evaluar la utilidad de la ecografia Doppler en los pacientes con sospecha de ACG, su sensibilidad y especificidad como prueba diagnostica y si puede suplir a la biopsia. Materiales y metodos Se ha realizado un estudio prospectivo de 57 pacientes entre febrero de 2015 y julio de 2016, que han sido diagnosticados con exploracion mediante ecografia Doppler y biopsia de arteria temporal. Resultados Fueron incluidos 57 pacientes, de los cuales 3 fallecieron durante el seguimiento y una paciente fue excluida del estudio al negarse a la biopsia. Otros 21 pacientes fueron diagnosticados de ACG por un especialista reumatologo tras un minimo de 6 meses de seguimiento. Presentaron ecografia positiva 22 pacientes, de los cuales 8 fueron diagnosticados de ACG y 4 de polimialgia reumatica. En nuestro estudio, la sensibilidad de la ecografia es del 42,6% y la especificidad es del 65,7%. Otros 19 pacientes presentaron biopsia positiva: todos ellos fueron diagnosticados de ACG. La biopsia presento una sensibilidad de un 73,7% y una especificidad de un 100%. Conclusiones Segun nuestro estudio, la utilidad de la ecografia es limitada y son necesarias nuevas investigaciones para determinar su papel en esta entidad. EnglishBackground Giant cell arteritis (GCA) is a vasculitis that affects medium- and large-sized arteries. Temporal artery biopsy is the gold standard for diagnosis. In view of the high demand for temporal biopsies, the purpose of this study is to evaluate the usefulness of Doppler ultrasonography in patients with suspected giant cell arteritis, to determine its sensitivity and specificity as a diagnostic test and to determine whether it would be possible to substitute biopsy for ultrasonography. Materials and methods A prospective study was undertaken including 57 patients from February 2015 to July 2016, who have undergone both ultrasonography and temporal biopsy. Results A total of 57 patients were included, 3 of whom died during the follow-up, and a patient was excluded from the study when she refused to have the biopsy. Another 21 patients were diagnosed with GCA by a rheumatologist after a minimum of 6 months of follow-up and 22 patients had positive ultrasonography, 8 of whom were diagnosed with GCA and 4 with polymyalgia rheumatica. In our study, the sensitivity of ultrasonography was 42.6%, and the specificity was 65.7%. A total of 19 patients had a positive biopsy, all of them were diagnosed with GCA. In our study, the sensitivity of the biopsy was 73.7% and the specificity was 100%. Conclusions In view of the data from our study, the usefulness of ultrasonography is questionable, and research about the role of ultrasonography in this disease should be further studied.

Short report [Abstract] Objectives: The aim of this study was to explore the preferences of patients with rheumatic diseases and their perceived experience regarding participation in shared decision making (SDM) when they were prescribed a subcutaneous (SC) biological drug. Methods: A printed survey was handed to 1,000 patients with inflammatory rheumatic diseases treated with SC biological drug. The survey included closed questions about preferences regarding decision making and about patients' experience when they were prescribed an SC biological drug. Descriptive statistics were performed with stratification by patient profiles, using chi-square for comparisons between groups. Results: A total of 592 surveys were received (response rate 59.2%, mean age 51.7 years, 57.6% women). Some 28.2% of patients reported preferring to take part in treatment selection, a percentage that was higher in younger patients, in those with higher academic degree and in those who search information in sources different to that of health care professionals. Over half of patients (56.3%) perceived that the rheumatologist considered their opinion when prescribing an SC biological drug, a percentage higher in younger people. Only in 40.8% of cases did the patients' preference match their perception of their participation in the process. No differences were observed by sex, disease or number of biologics. Conclusions: Patients with inflammatory rheumatic diseases want information about their treatments but mostly leave the prescription decision to the rheumatologist. Younger people, or those with higher academic degree, more often want to participate in the SDM. There are discrepancies between patient preferences and perceptions of this process.

This article belongs to the Special Issue Extracellular Vesicles Research in Inflamm-Aging [Abstract] The accumulation process of proinflammatory components in the body due to aging influences intercellular communication and is known as inflammaging. This biological mechanism relates the development of inflammation to the aging process. Recently, it has been reported that small extracellular vesicles (sEVs) are mediators in the transmission of paracrine senescence involved in inflammatory aging. For this reason, their components, as well as mechanisms of action of sEVs, are relevant to develop a new therapy called senodrugs (senolytics and senomorphic) that regulates the intercellular communication of inflammaging. In this review, we include the most recent and relevant studies on the role of sEVs in the inflammatory aging process and in age-related diseases such as cancer and type 2 diabetes. J.F.L. was funded by Xunta de Galicia, Grant Number ED481D-2021-020. M.C.A. received a grant from the Spanish National Health Institute Carlos III (PI20/00497) Xunta de Galicia; ED481D-2021-020

Resumen Objetivo Conocer las fuentes de las que los pacientes espanoles con enfermedades reumaticas tratados con farmacos biologicos subcutaneos obtienen informacion, cuales consideran mas relevantes y su satisfaccion con la informacion recibida en el hospital. Metodos Reumatologos de 50 hospitales entregaron una encuesta anonima, desarrollada ad hoc por 4 reumatologos y 3 pacientes, a 20 pacientes consecutivos con artritis reumatoide, espondiloartritis axial o artritis psoriasica tratados con biologicos subcutaneos. La encuesta incluyo preguntas con respuestas cerradas sobre los aspectos mencionados previamente. Resultados Recibieron la encuesta 1.000 pacientes, 592 la devolvieron cumplimentada (tasa de respuesta: 59,2%). El reumatologo fue mencionado como la fuente de informacion mas importante (75%), seguido del medico de atencion primaria, la enfermeria y los recursos electronicos. El 45,2% recibio informacion oral y por escrito sobre el biologico, el 46,1% solo oral, el 6% solo por escrito. Un 8,7% declaro no haber sido ensenado a inyectarse el biologico. El porcentaje de pacientes satisfechos con la informacion recibida fue elevado (87,2%), aunque la satisfaccion fue menor en temas relacionados con la seguridad. Si la informacion provenia del reumatologo, la satisfaccion era mayor (89,6%) que cuando provenia de otras vias (59,6%; p Conclusiones El reumatologo es clave a la hora de transmitir informacion satisfactoria al paciente en tratamiento biologico. Debe ademas actuar de guia, ya que un elevado porcentaje busca informacion en fuentes distintas.

[Abstract] Objective. To determine and analyse the organisational approach adopted by Spanish rheumatologists to osteoporosis (OP) to define strategic priorities. Material and method. A group of experts designed a questionnaire on OP in the rheumatologist practice. The survey was sent to the Spanish Society of Rheumatology (SER) members. Through the Delphi round, strategic priorities were agreed upon in OP. Results. The priorities are: 1) The SER should promote the inclusion of OP in 100% of the services and expand the training offer; 2) Rheumatology services should promote the role of the nurse in OP, promote quality indicators and referral protocols agreed with primary care in addition to promoting their training in this area; 3) The SER and Rheumatology services should promote electronic consultation, OP monographic clinics and participation in Fracture Liaison Service units. Conclusions. Strategic priorities in OP help identify areas of improvement at organisational, structural and quality standards level in this pathology. [Resumen] Introducción. Los estudios de opinión sobre la percepción del reumatólogo de la práctica asistencial en osteoporosis (OP) pueden ayudar a identificar áreas de mejora en la gestión de esta patología. Objetivo. Conocer y analizar el enfoque organizativo que adoptan los reumatólogos españoles ante la OP para definir prioridades estratégicas y establecer unos estándares de calidad. Material y método. Un grupo de expertos diseñó una encuesta sobre creencias y conductas en OP en la práctica del reumatólogo. La encuesta se remitió a los socios de la Sociedad Española de Reumatología (SER). Mediante ronda Delphi se consensuaron las prioridades estratégicas en OP. Resultados. El grupo de expertos consensuó como prioridades estratégicas en OP: 1) La SER debería impulsar la inclusión de la OP en el conjunto de prestaciones de todos los servicios de reumatología, así como ampliar la oferta formativa específica para médicos y enfermeras; 2) Los servicios de reumatología debieran fomentar el papel de la enfermera en OP, impulsar la implantación y el seguimiento de indicadores de calidad e implantar protocolos de derivación consensuados con atención primaria además de impulsar su formación en este área; 3) La SER y los servicios de reumatología deberían impulsar la implantación de la consulta electrónica y la consulta monográfica o dedicada a OP así como la participación del reumatólogo en unidades de fractura Fracture Liaison Service (FLS). Conclusiones. Las prioridades estratégicas en OP derivadas de la encuesta a los reumatólogos españoles ayudan a identificar las áreas de mejora a nivel organizativo, estructural y de estándares de calidad en esta patología.

Aim To assess the experience with health care among patients with type 2 diabetes (T2DM) and to evaluate patients’ demographic variables and healthcare‐related characteristics which may affect their experience. Methods A cross‐sectional survey was delivered to T2DM adults. Patient experiences were assessed with the ‘Instrument for Evaluation of the Experience of Chronic Patients’ (IEXPAC) questionnaire, a validated 12‐item survey, which describes patient experience within the last 6 months (items 1–11) and hospitalization in the last 3 years (item 12), with possible scores ranging from 0 (worst) to 10 (best experience). Results A total of 451 T2DM patients responded to the survey (response rate 72.3%; mean age 69.5 ± 10.1 years, 67.8% men). The mean overall IEXPAC score was 5.92 ± 1.80. Mean scores were higher for productive interactions (7.92 ± 2.15) and self‐management (7.08 ± 2.27) than for new relational model (1.72 ± 2.01). Only 32.8% of patients who had been hospitalized in the past 3 years reported having received a follow‐up call or visit after discharge. Multivariate analyses identified that regular follow‐up by the same physician and follow‐up by a nurse were associated with a better patient experience. Continuity of healthcare score was higher only in those patients requiring help from others. Conclusions The areas of T2DM care which may need to be addressed to ensure better patient experience are use of the Internet, new technologies and social resources for patient information and interaction with healthcare professionals, closer follow‐up after hospitalization, and a comprehensive multidisciplinary approach with regular follow‐up by the same physician and a nurse., Improving healthcare experience among patients with chronic conditions (eg type 2 diabetes [T2DM]) may be considered a therapeutic goal as it is associated with better clinical effectiveness and safety.Using the IEXPAC tool in 451 patients with T2DM, we identified positive aspects of patient experience, regarding productive interactions, and self‐management score, but not for the new relational model. Being followed regularly by the same physician and receiving additional follow‐up by a nurse were associated with a better experience.Improvement areas of T2DM care to ensure better patient experience may include the use of the internet, new technologies and social resources for patient information and interaction with healthcare professionals, closer follow‐up after hospitalization, and a comprehensive multidisciplinary approach with regular follow‐up by the same physician and a nurse.

Luis Cea-Calvo,1 Ignacio Marín-Jiménez,2 Javier de Toro,3 María J Fuster-RuizdeApodaca,4,5 Gonzalo Fernández,1 Nuria Sánchez-Vega,1 Domingo Orozco-Beltrán6 1Medical Affairs Department, MSD Spain, Madrid, Spain; 2IBD Unit, Gastroenterology Department, Clinical Research Institute Gregorio Marañón (IiSGM), Gregorio Marañón University Hospital, Madrid, Spain; 3Rheumatology Department, A Coruña University Hospital, A Coruña, Spain; 4SEISIDA (Spanish AIDS Multidisciplinary Society), Madrid, Spain; 5Department of Social and Organizational Psychology, Universidad Nacional de Educación a Distancia (UNED), Madrid, Spain; 6Clinical Medicine Department, Miguel Hernandez University, San Juan de Alicante, SpainCorrespondence: Luis Cea-CalvoMedical Affairs Department, MSD Spain, Josefa Valcárcel 38, Madrid 28027, SpainTel +34 913210740Email luis.cea@merck.comPurpose: To investigate relationships between intentional and non-intentional non-adherence behaviors and patient experience with healthcare and beliefs in medications.Patients and Methods: This is a post hoc analysis of a cross-sectional anonymous survey distributed between May and September 2017 to patients with rheumatic disease, inflammatory bowel disease, HIV infection or diabetes mellitus from outpatient and primary care clinics in Spain. Patients answered five questions about non-adherence behaviors and completed questionnaires on their experience with healthcare (IEXPAC: Instrument to Evaluate the EXperience of PAtients with Chronic diseases) and beliefs about medicines (BMQ: Beliefs About Medicines Questionnaire).Results: Among 1530 respondents, 53% showed ≥ 1 non-adherence behavior; 35% had ≥ 1 non-intentional non-adherence behavior, and 33% had ≥ 1 intentional non-adherence behavior. Patients with HIV infection had the lowest frequency of intentional non-adherence behaviors. Non-intentional non-adherence was associated with patient beliefs (inversely with BMQ overall score) and patient experiences (inversely with IEXPAC Factor 3 sub-score, self-management). Intentional non-adherence was strongly associated with beliefs scores (directly with BMQ concerns and inversely with BMQ necessity sub-score) and inversely associated with HIV infection.Conclusion: The different associations of intentional and non-intentional non-adherence behaviors found in this study help to understand how patient experiences and beliefs influence medical non-adherence, and in the development of strategies for reducing non-adherence.Keywords: BMQ, chronic disease, IEXPAC, intentional behavior, medication adherence, patient beliefs

[Abstract] Background: Calcium gluconate extravasation is a process that can cause serious lesions, such as necrosis and calcification of the soft tissues. The aim of the present study was to analyze the beneficial effects of four possible local antidotes for calcium gluconate extravasation: hyaluronidase, sodium thiosulfate, triamcinolone acetonide, and physiologic saline solution. Methods: Seventy-four BALB/c mice were used in the study. The substances selected for use in this study were calcium gluconate (4.6 mEq/ml), hyaluronidase (1500 IU/ml), sodium thiosulfate (25%), triamcinolone acetonide (40 mg/ml 0.5 mg/kg), and saline solution 0.9%. Five minutes were allowed to lapse after the calcium gluconate infiltration, and then an antidote was infiltrated. After 3 weeks, a skin biopsy was performed and a radiographic and histologic study was carried out. Results: Only in the group infiltrated with sodium thiosulfate did all skin lesions disappear after the 3-week period after infiltration. In the radiographic study, calcium deposits larger than 0.5 mm were observed in 40 percent of cases without an antidote, in 33 percent with triamcinolone acetonide, in 13 percent with a saline solution, and in none with thiosulfate and hyaluronidase. In the histologic study, calcium deposits were found in 53 percent of cases without antidote, 100 percent of cases with triamcinolone acetonide, 33 percent of cases with saline solution, and 13 percent of cases with sodium thiosulfate or hyaluronidase. Conclusion: Sodium thiosulfate and hyaluronidase prevent the development of calcium deposits after calcium gluconate extravasation.

Este trabajo ha sido parcialmente presentado como póster con defensa en el 34.o Congreso de la Sociedad Española de Medicina Familiar y Comunitaria (semFYC). [Resumen] Objetivo. Estudiar la prevalencia de osteoporosis y probabilidad de fractura en pacientes diagnosticados de cáncer de próstata. Diseño. Estudio observacional, descriptivo y transversal. Emplazamiento. Estudio realizado desde atención primaria del área sanitaria de Lugo en colaboración con los servicios de Reumatología y Urología de nuestro hospital de referencia. Participantes. Pacientes diagnosticados de cáncer de próstata sin enfermedad metastásica ósea, desde enero a diciembre del año 2012. Mediciones principales. Se recogieron variables epidemiológicas, clínicas, analíticas y densitométricas implicadas en la osteoporosis. Se estimó la probabilidad de fractura mediante la herramienta FRAX®. Resultados. Ochenta y tres pacientes cumplieron los criterios de inclusión. Ninguno fue excluido. La edad media fue de 67 años. El índice de masa corporal fue de 28,28. Veinticinco pacientes (30,1%) presentaban fracturas osteoporóticas previas. Otros factores de riesgo prevalentes fueron el alcohol (26,5%) y el tabaco (22,9%). Ochenta y dos sujetos presentaban valores de vitamina D por debajo de lo normal (98,80%). La densitometría de cuello femoral mostró que el 8,9% presentaron osteoporosis y el 54% osteopenia. La media del riesgo de fractura en esta población, estimado con la herramienta FRAX®, fue del 2,63% para fractura de cuello femoral y del 5,28% para fractura principal. Utilizando los puntos de corte para el riesgo de fractura propuestos por Azagra et al., 24 pacientes (28,92%) tuvieron un valor de FRAX® para fractura principal sin DXA de más del 5%, y 8 sujetos (9,64%), ≥ 7,5%. Conclusiones. La prevalencia de osteoporosis en esta población fue muy elevada. Los factores de riesgo asociados a osteoporosis más frecuentes fueron: fractura osteoporótica previa, consumo de alcohol, hábito tabáquico y antecedente familiar de fractura previa. La probabilidad de fractura mediante la herramienta FRAX® de cuello femoral fue baja. La hipovitaminosis D fue muy frecuente (98,8%). [Abstract] Objective. To study the prevalence of osteoporosis and fracture probability in patients diagnosed with prostate cancer. Design. Observational descriptive transversal study. Site. Study performed from Primary Care of Lugo in collaboration with Rheumatology and Urology Services of our referral hospital. Participants. Patients diagnosed with prostate cancer without bone metastatic disease from January to December 2012. Main measurements. Epidemiologic, clinical, laboratory and densitometric variables involved in osteoporosis were collected. The likelihood of fracture was estimated by FRAX® Tool. Results. Eighty-three patients met the inclusion criteria. None was excluded. The average age was 67 years. The Body Mass Index was 28.28. Twenty-five patients (30.1%) had previous osteoporotic fractures. Other prevalent risk factors were alcohol (26.5%) and smoking (22.9%). Eighty-two subjects had vitamin D below normal level (98.80%). Femoral Neck densitometry showed that 8.9% had osteoporosis and 54% osteopenia. The average fracture risk in this population, estimated by FRAX®, was 2.63% for hip fracture and 5.28% for major fracture. Cut level for FRAX® major fracture value without DXA > 5% and ≥ 7.5% proposed by Azagra et al. showed 24 patients (28.92%) and 8 patients (9.64%) respectively. Conclusions. The prevalence of osteoporosis in this population was very high. The more frequent risk factors associated with osteoporosis were: previous osteoporotic fracture, alcohol consumption, smoking and family history of previous fracture. The probability of fracture using femoral neck FRAX® tool was low. Vitamin D deficiency was very common (98.8%).

Introduction This study assessed whether mesenchymal stem cell (MSC)-derived extracellular vesicles influenced ageing and pluripotency markers in cell cultures where they are added. Methods MSC-derived extracellular vesicles from old and young rat bone marrows were isolated by ultracentrifugation and were characterised by western blotting, nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM). They were added to young and old MSC cultures. Real-time quantitative reverse transcription polymerase chain reactions and western blot analysis were performed to check the markers of ageing (vinculin and lamin A), pluripotency markers (Nanog and Oct4) and components of the mTOR signalling pathway (Rictor, Raptor, AKT and mTOR) in these cell populations. Subsequently, microRNA (miR)-188-3p expression was transiently inhibited in young MSCs to demonstrate the influence of mTOR2 on MSC ageing. Results Incubation with young MSC-derived extracellular vesicles decreased the levels of ageing markers and components of the mTOR pathway and increased the pluripotency markers from old MSC populations. By contrast, incubation of young MSCs with old MSC-derived extracellular vesicles generated the reverse effects. Inhibition of miR-188-3p expression in young MSCs produced extracellular vesicles that when incubated with old MSCs produced an increase in the levels of Rictor, as well as a decrease of phosphor-AKT, as indicated by a significant decrease in beta-galactosidase staining. Conclusions MSC-derived extracellular vesicles affected the behaviour of MSC cultures, based on their composition, which could be modified in vitro. These experiments represented the basis for the development of new therapies against ageing-associated diseases using MSC-derived extracellular vesicles.

Supplemental digital content is available in the text., Background Patients' experience with health care is becoming a key component for the provision of a patient-centered health care model. The aim of this study was to assess the experience with health care of patients with inflammatory arthritis and patient- and health care–related factors. Methods Patients responded to an anonymous survey provided by their treating clinical teams. The survey comprised the validated 12-item IEXPAC (Instrument to Evaluate the EXperience of PAtients with Chronic diseases) tool and demographic variables and health care–related characteristics that may affect patients' experience. Results A total of 359 of 625 surveys were returned (response rate, 57.4%). Overall, patient responses were positive (>60% gave “always/mostly” answers) for statements assessing the interaction between patients and health care professionals or patient self-management following health care professional guidance. However, positive patient responses for items regarding patient interaction with the health care system via the internet or with other patients were less than 13%. Only 25.6% of patients who had been hospitalized reported receiving a follow-up call or visit following discharge. In the bivariate analysis, experience scores were higher (better experience) in men, those seen by fewer specialists or by the same physician, and in patients treated with a fewer number of drugs or with subcutaneous/intravenous drugs. Multivariate analyses identified regular follow-up by the same physician and treatment with subcutaneous/intravenous drugs as variables associated with a better patient experience. Conclusions This study identifies areas of care for patients with inflammatory arthritis with the potential to improve patients' experience and highlights the importance of patient-physician relationships and comprehensive patient care.

To determine and analyse the organisational approach adopted by Spanish rheumatologists to osteoporosis (OP) to define strategic priorities.A group of experts designed a questionnaire on OP in the rheumatologist practice. The survey was sent to the Spanish Society of Rheumatology (SER) members. Through the Delphi round, strategic priorities were agreed upon in OP.The priorities are: 1) The SER should promote the inclusion of OP in 100% of the services and expand the training offer; 2) Rheumatology services should promote the role of the nurse in OP, promote quality indicators and referral protocols agreed with primary care in addition to promoting their training in this area; 3) The SER and Rheumatology services should promote electronic consultation, OP monographic clinics and participation in Fracture Liaison Service units.Strategic priorities in OP help identify areas of improvement at organisational, structural and quality standards level in this pathology.

Background: Bone-marrow mesenchymal stromal cells (MSCs) are multipotent self-renewal adult cells with high potential to regenerate the damaged tissues in degenerative diseases such as osteoarthritis (OA). Nevertheless, their usefulness for osteochondral Regenerative Medicine research is hampered by their proneness to senescence when in vitro cultured. Currently, MSC lines available are scarce and present limitations regarding their differentiation capacities. In addition, there is none OA MSC line available for research on this disease. Objectives: The aim of this study was to generate and characterize immortalized human OA and non-OA MSC lines for their use in osteochondral Regenerative Medicine research. Methods: For the generation of the immortalized MSC lines, SV40 large T antigen (SV40LT) and GFP-fused human telomerase reverse transcriptase (hTERT) were used. Primary MSCs derived from two hip OA patients and one hip fracture patient without OA were transduced by spinoculation at 800 xg for 45 minutes. Transgene expression was induced by valproic acid. Nuclear expression of SV40LT and GFP was tested by immunofluorescence. Proliferation and senescence were investigated through calculation of population doublings (PDs) at each passage after immortalization and β-galactosidase staining after 100 PDs for each MSC line. Maintenance of MSC characteristics in immortalized MSCs was tested by analysis of CD29, CD44, CD73, CD90, CD105, CD34 and CD45 expression by flow cytometry and cell differentiation experiments. Multi-lineage differentiation potential was analysed histochemical, immunohistochemical and molecularly. Results: Three MSC lines have been generated: two OA and one non-OA. As shown by immunofluorescence, SV40LT is expressed in the nucleoplasm of these cells, while GFP-fused hTERT is expressed in the nucleoli. A constant proliferation rate thoroughout subculturing in addition to β-galactosidase negative staining confirms that immortalized MSC lines do not senesce, unlike primary MSCs. Expression of CD29, CD44, CD73 and CD90 and lack of CD34 and CD45 was conserved in immortalized MSC lines, while CD105 expression was altered for transduction status and passage. Both OA and non-OA immortalized MSC lines maintain their multipotency (namely, osteogenic, chondrogenic and adipogenic differentiation capacity). Conclusion: Both OA and non-OA MSCs are susceptible to immortalization by SV40LT and hTERT. For they increased lifespan combined with keeping of most of primary MSC characteristics, these MSC lines are expected to be valuable tools for the research on Regenerative Medicine for OA as part of Tissue Engineering in vitro models. Acknowledgement: Xunta de Galicia and European Union (European Social Fund-ESF); Deputacion da Coruna; Rede de Investigacion en Celulas Nai e Terapia Celular (R2016/036, R2014/050 and CN2012/142) and Grupos con Potencial de Crecemento (GPC2014/048) (Xunta de Galicia); CIBER-BNN; Fundacion Espanola de Reumatologia (FER); Fondo de Investigacion en Salud (FIS) (PI17/02197). Disclosure of Interests: Maria Pineiro-Ramil: None declared, Rocio Castro-Vinuelas: None declared, Clara Sanjurjo-Rodriguez: None declared, Silvia Rodriguez-Fernandez: None declared, Tamara Hermida Gomez: None declared, Francisco Javier de-Toro-Santos: None declared, Francisco J. Blanco Consultant for: AbbVie, Bioiberica, BMS, GSK, Grunenthal, Janssen, Lilly, Pfizer, Regeneron, Roche, Sanofi, TRB Chemedica, and UCB, Isaac Fuentes-Boquete: None declared, SILVIA MARIA DiAZ-PRADO: None declared

Background Non-adherence to medication may lead to poorer clinical outcomes and should be prevented. Objectives We describe the frequency of non-adherence behaviors in patients with rheumatic diseases and its relationship to potentially modifiable variables. Methods Data were obtained through an anonymous survey handed to patients by physicians or nurses from 25 rheumatology clinics from Spain. Patients completed the survey anonymously at home and returned it by pre-paid post mail. Five different non-adherence behaviors were defined. Co-variables analyzed were patients’ demographics, medication characteristics, experience with healthcare (assessed with IEXPAC “Instrument to Evaluate the EXperience of PAtients with Chronic diseases” scoring 0 [worst] to 10 [best experience]), and beliefs in medicines (Beliefs About Medicines Questionnaire [BMQ], composed of a necessity and a concerns subscales and scoring -20 [weaker] to +20 [stronger beliefs]). Variables associated to non-adherence were studied with a multivariate logistic regression model. Results The survey was handed to 625 patients with rheumatic diseases, of which 336 (53.8%) returned it with the necessary data completed (mean age 55 [14] years, 64% women). Of them, 188 (56.0%) described at least one non-adherence behavior. The frequencies of the specific non-adherence behaviors were: 1) Forgetfulness in taking medication: 28.6%; 2) Taking medication at unscheduled hours: 5.6%; 3) Stopping medication when feeling well: 10.1%; 4) Stopping medication when feeling sick: 33.0% and 5) Stopping medication after reading the patients’ information leaflet: 11.5%. The frequency of at least one non-adherence behavior was similar by age, gender, educational level, working status or by number of medicines. It was slightly higher in patients needing to take their medication 3-4 times a day (63.2%) versus 1-2 times a day (52.4%, p= 0.089). IEXPAC scores were similar in patients with or without non-adherence behaviors (5.5 [2.0] in both groups, p= 0.960). BMQ overall score was lower in patients with non-adherence behaviors (4.3 versus 6.5 in those without non-adherence behaviors, p= 0.001). The frequency of non-adherence behaviors did not differ by quartiles of IEXPAC score, but it was higher in patients with lower BMQ score (Q1: 59.5%, Q2: 65.9%, Q3: 54.3%, Q4: 52.0%, p-trend = 0.014). The multivariate model (table) confirmed a relationship of non-adherence behaviors with lower BMQ beliefs scores. Conclusion Non-adherence behaviors are frequent in patients with rheumatic diseases and are mainly associated to patients’ beliefs in their medications (assessed with BMQ). This is an important aspect that can be addressed by clinical teams to improve adherence and clinical outcomes. Acknowledgement: Funded by Merck Sharp & Dohme of Spain and endorsed by 4 patients associations: ACCU, CONARTRITIS, SEISIDA, FEDE. Disclosure of Interests Maria L. Garcia Vivar: None declared, Javier de Toro-Santos: None declared, Lucia Pantoja: None declared, Cristina Lerin Lozano: None declared, Silvia Garcia-Diaz: None declared, Sabela Fernandez Employee of: MSD, Yvonne Mestre Employee of: MSD, Lidia Feo-Lucas Employee of: MSD, Luis Cea-Calvo Employee of: MSD

Background: Abatacept (CTLA4-Ig) is an approved biological therapy for the treatment of rheumatoid arthritis (RA). Similar to other biological agents, most patients (60%) respond significantly to this therapy. To date, however, the biological mechanisms underlying the lack of efficacy for this drug are unknown. Objectives: The objectives of the present study were to characterize the biological processes underlying the lack of efficacy of abatacept and to evaluate the blood transcriptome as a valid source for drug response prediction. Methods: A total of n=57 patients diagnosed with RA were recruited for this study from 16 rheumatology departments in Spain. All patients were >18 years old and, had >6 months of disease evolution. The primary clinical response to abatacept was defined at week 12 using the EULAR criteria. Good and moderate responders were aggregated into a single response group, and compared to the no response group of patients. Blood RNA was collected from all patients at baseline. From a subgroup of patients (n=31), blood RNA was also obtained at weeks 12, 24 and 48 of treatment with abatacept. Gene expression levels were determined using paired-end RNA-seq (Illumina). Differential gene expression, association to biological processes, longitudinal association analysis and building of the multigenic predictor were performed using the R software and the specialized Bioconductor libraries. The the prediction accuracy was evaluated using the ROC AUC. Results: From the 57 patients treated with abatacept, n=10 (17.5%) were good EULAR responders, n=24 (42%) moderate EULAR responders and n=23 (40.5%) non-responders at week 12 of therapy. Biological process analysis identified two significantly distinct biological profiles between responders and non-responders. In responders, we found an association to pathways associated with the effector phase of T cells (e.g. interleukin-15 and 2 signalling, P Conclusion: The analysis of blood RNA profiles of RA patients has enabled the identification of specific biological processes associated with the lack of response to abatacept. Also, we demonstrate that blood expression profiles can be predictive of the response to the drug at week 12 of therapy. Disclosure of Interests: Antonio Julia: None declared, Maria Lopez Lasanta: None declared, Antonio Gomez: None declared, Raimon Sanmarti Grant/research support from: Research support: Bristol-Myers Squibb, Speakers bureau: Speakers bureau: Bristol-Myers Squibb, Carlos Marras Fernandez Cid: None declared, Jose Manuel Pina Salvador: None declared, Susana Romero-Yuste: None declared, Raul Maria Veiga Cabello: None declared, Pilar Navarro: None declared, Carme Moragues Pastor : None declared, Silvia Martinez Pardo: None declared, Javier de Toro-Santos: None declared, Amalia Sanchez: None declared, Dacia Cerda: None declared, Alejandro Prada: None declared, Alba Erra: None declared, Jordi Monfort Speakers bureau: Bioiberica Procare Health, ANA URRUTICOECHEA-ARANA: None declared, Nuria Palau: None declared, Raquel M Lastra: None declared, Raul Tortosa: None declared, Andrea Pluma Sanjurjo: None declared, Sara Marsal: None declared

Background The experience of patients with healthcare has been associated to important outcomes. Objectives We describe the experience with healthcare of patients with rheumatic diseases from Spain self-reported through IEXPAC, a validated questionnaire, and the influence of demographic and health care-related factors. Methods The IEXPAC scale (“Instrument to Evaluate the EXperience of PAtients with Chronic diseases”, http://www.iemac.es/iexpac/) was developed and validated in Spain by health care professional and social organizations, experts in quality of healthcare and chronic patients (1). It consists of 12 items with Likert responses from “always” to “never” and yields an overall score from 0 (worst) to 10 (best experience). Three factors with sub-scores derive from the scale: Factor 1 (productive interactions, average of items 1, 2, 5 and 9, on patient-health care professionals relationship), Factor 2 (new relational model, average of items 3, 7 and 11, on the use of new technologies and contact with other patients) and Factor 3 (self-management, patients’ ability to self-care, average of items 4, 6, 8 and 10). Data were obtained through an anonymous survey to patients from 25 Spanish hospitals. Bivariate comparisons and a multivariate analysis were made to explore the association between scores and demographic and health care-related characteristics. Results 625 patients received the survey, 359 (57.4%) returned it (mean age 55 years, 67% women). The percentage of patients who responded “always” or “nearly always” to the different statements is displayed in table 1. Mean overall IEXPAC score was 5.5 (SD 2.0), sub-scores were: productive interactions: 7.5 (2.5); new relational model: 1.7 (2.1); self-care: 6.5 (2.5). Overall score was higher (better experience) in men (p= 0.022), in those needing follow-up in a different region (p= 0.004), seen by a lower number of physicians (p= 0.025), seen by the same physician each time (p Conclusion Through IEXPAC, patients with rheumatic diseases identified areas of improvement in healthcare, especially those related with access to reliable information and services, interaction with other patients and continuity of health care after hospital discharge. Better experience was associated to being seen by lower number of specialists or being followed-up by the same physician each time, and also with treatment with SC/IV drugs, maybe in relation to the more personalized care these patients receive. Acknowledgement Funded by MSD of Spain and endorsed by 4 patients associations: ACCU, CONARTRITIS, SEISIDA, FEDE. We thank the participant patients for providing this valuable information by completing the survey. Disclosure of Interests Javier de Toro-Santos: None declared, Maria L. Garcia Vivar: None declared, Lucia Pantoja: None declared, Cristina Lerin Lozano: None declared, Silvia Garcia-Diaz: None declared, Yvonne Mestre Employee of: MSD, Sabela Fernandez Employee of: MSD, Luis Cea-Calvo Employee of: MSD

Background Research results in the field of hand OA are currently limited due to the unavailability of tissue samples and lack of animal models replicating the features of the disease in humans. Cellular in vitro models are important tools to elucidate molecular mechanisms and pathways that are involved in hand OA. Specifically, induced pluripotent stem cells (iPSc) are considered ideal tools for this purpose since they allow the use of unlimited cells with chondrogenic differentiation potential. However, there are not studies published generating iPSc from patients with hand OA. Objectives To generate and characterize iPSc-lines from patients with radiographic hand OA and healthy donors, which can be used as cellular models of the disease, for studying the pathogenesis of the disease in vitro and for testing new drugs. Methods Patients with hand OA (non erosive hand OA with right thumb OA) and a healthy control were selected for the study. Using the explant culture technique, fibroblasts from skin biopsies of these patients were isolated. Transcriptional factors Oct4, Sox2, Klf4 and c-Myc were used for the reprogramming process; which was performed by using a non-integrating method, the Sendai virus. Cell lines obtained were morphologically, phenotypically and functionally characterized. To evaluate weather these iPSc lines could be used as cellular model of hand OA, presence of single nucleotide polymorphisms (SNPs) within the genes ALDH1A2 and SMAD3 were studied by Sanger sequencing, before and after reprogramming. Variants rs3204689 and rs12901499 respectively have been associated with severe OA of the hand (Styrkarsdottir et al., 2014; Shu-Thao Gao et al., 2018). Finally, chondrogenic differentiation capacity of the “healthy” and “ill” iPSc-lines was studied by means of histological techniques. Results Fibroblasts were isolated from one patient with radiographic hand OA and one healthy donor. Three weeks after reprogramming, embryonic stem cell-like colonies emerged in culture. These cells showed positivity for alkaline phosphatase activity (fig. 1A) and the pluripotency markers Tra1-81 and Nanog (fig. 1B). Molecular analyses showed high relative expression levels of the pluripotency-related genes OCT4, SOX2, NANOG and CRIPTO in the iPSc. These cells were also able to give rise to cells from the three germ layers (fig. 1C). Indeed, during mesodermal differentiation, spontaneously beating cardiomyocytes were seen in culture. Regarding SNPs studies, cells from the patient with hand OA were homozygous for the at-risk allele in both genes studied, both before and after reprogramming (fig. 1D). The “ill” iPSc-line (MOAFiPS 15/645#7) showed worse chondrogenic differentiation than the “healthy” iPSc-line (NFiPS 15/637#7), as shown by the micromasses collagen and proteoglycan content (fig. 1E). Conclusion The generation of one iPSc-line form patients with hand OA is reported for the first time. The presence of the at-risk alleles within the ALDH1A2 and SMAD3 genes were maintained after fibroblast reprogramming. The iPSC lines obtained shown differences in their chondrogenic differentiation capacity, showing their usefulness to model hand OA in vitro, and to deeper study the role of these genetic variants in the pathogenesis of hand OA. References [1] Styrkarsdottir U, et al. (2014). Nat Genet. 46(5):498-502. [2] Shu-Tao Gao, et al. (2018) Ther Clin Risk Manag. 14: 929–936. Acknowledgement FER; ISCIII (PI17/02197); CIBER-BBN; REDICENT; GPC (Xunta de Galicia); Diputacion Coruna; Xunta de Galicia y Fondo Social Europeo, Servicio de Genetica Hospital Teresa Herrera; Servicio Radiofisica Centro Oncologico de Galicia, Universidade da Coruna. Disclosure of Interests Rocio Castro-Vinuelas: None declared, Clara Sanjurjo-Rodriguez: None declared, Maria Pineiro-Ramil: None declared, Tamara Hermida Gomez: None declared, Isaac Fuentes-Boquete: None declared, Javier de Toro-Santos: None declared, Francisco J. Blanco Consultant for: AbbVie, Bioiberica, BMS, GSK, Grunenthal, Janssen, Lilly, Pfizer, Regeneron, Roche, Sanofi, TRB Chemedica, and UCB, SILVIA MARIA DIAZ-PRADO: None declared

Background: Musculoskeletal disorders cause in Spain 23% of temporary work disability (TD). They are the first cause of permanent work disability (PD). A study of early intervention by a rheumatologist reduced TD days reduced PD. Using the “Fit for Work” European coalition led by AbbVie, the program was implemented nationwide. Objectives: To analyze the variation in the duration of sick leaves in patients referred to an early intervention program in relation to the delay on the referral from primary care and from the Occupational Health service of our hospital. Methods: Cross-sectional observational study of a hospital cohort of patients referred for 34 consecutive months to the Rheumatology Early Intervention program due to TDdue to musculoskeletal pathologies. Patients whoseTD had a traumatic or surgical origin, or with incomplete information were excluded from the analysis. We created 4 groups of patients according to the time elapsed from the start of the TD until the referral to our office: 0 to 15 days, 15 to 30 days, 30-60 days or> 90 days. We compared the patients referred from primary care with those referred from occupational health. Results: For the analysis we included 394 patients, 63.3% women, with a mean age (±D.E.) of 48.5 (±9.8) years. We analyzed the most frequent pathologies: back pain (33.5%), shoulder pain (19.8%) and neck pain (8.4%). 85.8% came from primary care, 10.2% from occupational health and 4.1% from other units. The median time between referral and 1st consultation was 6 days. We found statistically significant differences in the total duration of TD among the patients referred to consultation in the first 30 days compared to those sent later in the 3 pathologies (decreasing the duration of TD between 50 and 100 days in low back pain, between 44 and 54 days in shoulder pain and between 13 and 20 days in neck pain). In back pain we found statistically significant differences in the duration of the TD after the 1st consultation, obtaining an average decrease in the duration of the TD between 42 and 52 days. In shoulder pain and neck pain an important decrease is observed without reaching statistical significance, probably related to the sample size. Regarding the patients referred from occupational health, the median time between TD and referral was 2.5 days. The pathology most frequently evaluated was low back pain (60% of cases), finding statistically significant differences in the total duration of TD, with a mean decrease in the duration of TD of 59 days compared to the general population. Conclusion: Early intervention by rheumatologists in patients with TD due to musculoskeletal disorders reduces the duration of the processes, saving costs to the health system. Disclosure of Interests: None declared

Our group focuses on the study of mesenchymal stem cells (MSCs) from human umbilical cord stroma or Warthons jelly and their directed differentiation toward chondrocyte-like cells capable of regenerating damaged cartilage when transplanted into an injured joint. This study aimed to determine whether lactogenic hormone prolactin (PRL) or 3, 3', 5-triiodo-L-thyronine (T3), the active thyroid hormone, modulates chondrogenesis in our in vitro model of directed chondrogenic differentiation, and whether Wnt signalling is involved in this modulation. MSCs from human umbilical cord stroma underwent directed differentiation toward chondrocyte-like cells by spheroid formation. The addition of T3 to the chondrogenic medium increased the expression of genes linked to chondrogenesis like collagen type 2, integrin alpha 10 beta 1, and Sox9 measured by quantitative real time polymerase chain reaction (qRT-PCR) analysis. Levels of collagen type 2 and aggrecane analyzed by immunohistochemistry, and staining by Safranin O were increased after 14 days in spheroid culture with T3 compared to those without T3 or only with PRL. B-catenin, Frizzled, and GSK-3β gene expressions were significantly higher in spheroids cultured with chondrogenic medium (CM) plus T3 compared to CM alone after 14 days in culture. The increase of chondrogenic differentiation was inhibited when the cells were treated with T3 plus ML151, an inhibitor of the T3 steroid receptor. This work demonstrates, for first time, that T3 promotes differentiation towards chondrocytes-like cells in our in vitro model, that this differentiation is mediated by steroid receptor co-activator 2 (SRC2) and does not induce hypertrophy. J. Cell. Biochem. 117: 2097-2108, 2016. © 2016 Wiley Periodicals, Inc.

Inflammatory bowel disease; Patients experience; Chronic disease Malaltia intestinal inflamatòria; Experiència dels pacients; Malalties cròniques Enfermedad intestinal inflamatoria; Experiencia de los pacientes; Enfermedades crónicas To assess inflammatory bowel disease (IBD) patients' experience of chronic illness care and the relationship with demographic and healthcare-related characteristics.This cross-sectional survey used the Instrument to Evaluate the EXperience of PAtients with Chronic diseases (IEXPAC) questionnaire to identify parameters associated with a better healthcare experience for IBD patients. IEXPAC questionnaire responses are grouped into 3 factors - productive interactions, new relational model, and patient self-management, scoring from 0 (worst) to 10 (best experience). Scores were analyzed by bivariate comparisons and multiple linear regression models.Surveys were returned by 341 of 575 patients (59.3%, mean age 46.8 (12.9) years, 48.2% women). Mean (SD) IEXPAC score was 5.9 (2.0); scores were higher for the productive interactions (7.7) and patient self-management factors (6.7) and much lower for the new relational model factor (2.2). Follow-up by a nurse, being seen by the same physician, and being treated with a lower number of medicines were associated with higher (better) overall patient experience score, and higher productive interactions and self-management factor scores. A higher productive interactions score was also associated with patients receiving medication subcutaneously or intravenously. Higher new relational model scores were associated with follow-up by a nurse, affiliation to a patients' association, receiving help from others for healthcare, a lower number of medicines and a higher educational level.In patients with IBD, a better overall patient experience was associated with follow-up by a nurse, being seen by the same physician, and being treated with a lower number of medicines.

Objective: The objective of the current work was to assess the frequency of non-adherence behaviors and potential association with patients’ experience with healthcare and beliefs in medicines self-reported by patients with four different chronic conditions. Methods: Patients responded anonymously to a survey comprising five non-adherence behaviors (based on physician and patient input), an assessment of patients’ experience with healthcare using the validated Instrument to Evaluate the EXperience of PAtients with Chronic diseases (IEXPAC), and a validated Spanish version of the Beliefs about Medicines Questionnaire (BMQ). Associations of non-adherence behavior were analyzed using logistic regression models. Results: Of 1530 respondents, 53.1% reported ≥1 non-adherence behavior. Non-adherence rates were 59.8% in diabetes mellitus (DM), 56.0% in rheumatic disease, 55.6% in inflammatory bowel disease, and 42.8% in human immunodeficiency virus (HIV) infection patients (p < .001). IEXPAC and BMQ scores were higher in adherent vs. non-adherent patients. In multivariate analysis, non-adherence behavior was strongly associated with lower overall BMQ, lower BMQ Necessity scores and higher BMQ Concerns scores (p < .001 for all), and with a lower IEXPAC self-management score (p = .007), but not with the overall IEXPAC score. Non-adherence was more frequent in DM patients compared with HIV infection patients (p < .001). Conclusions: Patients’ beliefs in medicines-a lower perception for the necessity of medication, and higher concerns in taking medication-and low patient self-management experience score were associated with non-adherence behavior. These are modifiable aspects that need to be addressed to increase medication adherence in chronic disease.

[Abstract] Objective: To investigate, in Spanish patients with rheumatic diseases treated with subcutaneous biological drugs, their sources of information, which sources they consider most relevant, and their satisfaction with the information received in the hospital. Methods: Rheumatologists from 50 hospitals handed out an anonymous survey to 20 consecutive patients with rheumatoid arthritis, axial spondyloarthritis or psoriatic arthritis treated with subcutaneous biologicals. The survey was developed ad hoc by 4 rheumatologists and 3 patients, and included questions with closed-ended responses on sources of information and satisfaction. Results: The survey was handed-out to 1,000 patients, 592 of whom completed it (response rate: 59.2%). The rheumatologist was mentioned as the most important source of information (75%), followed by the primary care physician, nurses, and electronic resources; 45.2% received oral and written information about the biological, 46.1% oral only, and 6.0% written only; 8.7% stated that they had not been taught to inject the biological. The percentage of patients satisfied with the information received was high (87.2%), although the satisfaction was lower in relation to safety. If the information came from the rheumatologist, the satisfaction was higher (89.6%) than when coming from other sources (59.6%; P

Objective The aim of this study was to explore perceptions of patients with rheumatic diseases treated with subcutaneous (SC) biological drugs on the impact on daily life and satisfaction with current therapy, including preferred attributes. Methods A survey was developed ad hoc by four rheumatologists and three patients, including Likert questions on the impact of disease and treatment on daily life and preferred attributes of treatment. Rheumatologists from 50 participating centers were instructed to handout the survey to 20 consecutive patients with rheumatoid arthritis (RA), axial spondyloarthritis (ax-SpA), or psoriatic arthritis (PsA) receiving SC biological drugs. Patients responded to the survey at home and sent it to a central facility by prepaid mail. Results A total of 592 patients returned the survey (response rate: 59.2%), 51.4% of whom had RA, 23.8% had ax-SpA, and 19.6% had PsA. Patients reported moderate-to-severe impact of their disease on their quality of life (QoL) (51.9%), work/daily activities (49.2%), emotional well-being (41.0%), personal relationships (26.0%), and close relatives’ life (32.3%); 30%–50% patients reported seldom/never being inquired about these aspects by their rheumatologists. Treatment attributes ranked as most important were the normalization of QoL (43.6%) and the relief from symptoms (35.2%). The satisfaction with their current antirheumatic therapy was high (>80% were “satisfied” or “very satisfied”), despite moderate/severe impact of disease. Conclusion Patients with rheumatic diseases on SC biological therapy perceive a high disease impact on different aspects of daily life, despite being highly satisfied with their treatment; the perception is that physicians do not frequently address personal problems. Normalization of QoL is the most important attribute of therapies to patients.

[Abstract] Objective. To determine the clinical profile, degree of involvement and management in patients with knee, hip or hand osteoarthritis. Methods. Observational study (health centres from 14 autonomous regions, n = 363 primary care physicians), involving patients with clinical and/or radiological criteria from the American College of Rheumatology, consecutively selected (n = 1258). Sociodemographic variables, clinical and radiological findings, comorbidity and therapeutic management were analysed. Results. Mean age was 68.0 ± 9.5 years old; 77.8% were women and 47.6% obese. Distribution by location was 84.3% knee, 23.4% hip, and 14.7% hands. All patients reported pain. The most frequent radiographic Kellgren-Lawrence grade was stage III for knee and hip (42.9% and 51.9%, respectively), and III (37.2%) and II (34.5%) for hip. Time since onset of osteoarthritis symptoms was 9.4 ± 7.5 years, with a mean age at onset of around 60 years and a family history of osteoarthritis in 66.0%. The most frequent comorbidities were hypertension (55.1%), depression/anxiety (24.7%) and gastroduodenal diseases (22.9%). A total of 97.6% of the patients received pharmacological treatment, with oral analgesics (paracetamol) (70.5%) and oral NSAIDs (67.9%) being the most frequent drugs. Bilateral osteoarthritis was present in 76.9% of the patients with knee osteoarthritis, 59.3% in hip and 94.7% in hands. Female gender and time since onset were associated with bilateral knee and hip osteoarthritis. Conclusions. The profile of the osteoarthritis patient is female, >65 years old, overweight/obese, with a comorbidity, frequent symptoms and moderate radiologic involvement. Most of the patients had bilateral osteoarthritis, associated with female gender and time since onset of disease. Paracetamol was the most common pharmacological treatment. [Resumen] Objetivo. Determinar el perfil clínico, afectación y tratamiento en pacientes con artrosis de rodilla, cadera y manos. Material y método. Estudio observacional (Centros de Salud de 14 Comunidades Autónomas, n = 363 médicos). Se incluyen pacientes con criterios clínicos/radiológicos de artrosis del American College of Rheumatology, seleccionados consecutivamente (n = 1258). Se analizan variables sociodemográficas, hallazgos clínico-radiológicos, comorbilidad y tratamiento. Resultados. La media de edad fue 68,0 ± 9,5 años, 77,8% eran mujeres y 47,6% tenían obesidad. Un 84,3% tenían artrosis de rodilla, 23,4% de cadera y 14,7% de manos. Todos los pacientes referían dolor. El grado radiológico de Kellgren-Lawrence más frecuente en rodilla y mano fue el III (42.9% y 51.9%, respectivamente), y en cadera grado III (37,2%) y II (34,5%). El tiempo de evolución de los síntomas de artrosis fue 9,4 ± 7,5 años, con edad de inicio alrededor de 60 años. El 66% de los pacientes tenían antecedentes de artrosis. Las comorbilidades más frecuentes son: hipertensión (55,1%), depresión/ansiedad (24,7%) y patología gastroduodenal (22,9%). Un 97,6% recibían tratamiento farmacológico, los más utilizados son: analgésicos orales (paracetamol) (70,5%) y AINES orales (67,9%). Presentaban afectación bilateral el 76,9% de pacientes con artrosis de rodilla, 59,3% en cadera y 94,7% en manos. El sexo femenino y mayor tiempo de evolución se asocian a afectación bilateral en rodilla y cadera. Conclusiones. El perfil del paciente artrósico es de mujer >65 años, con sobrepeso-obesidad, comorbilidad, clínica frecuente y afectación radiológica moderada. La mayoría presentan afectación bilateral, asociada al sexo femenino y tiempo de evolución. El paracetamol es el fármaco más utilizado.

Resumen En los ultimos anos, la ensenanza universitaria ha experimentado un profundo cambio como consecuencia de la creacion del Espacio Europeo de Educacion Superior. Se ha pasado de un modelo centrado en el profesor, basado en la transmision de conocimientos a traves de las clases magistrales, a otro centrado en el alumno, basado en la adquisicion de competencias y que otorga gran importancia al aprendizaje autonomo. Esta transformacion comporta la necesidad de reorganizar la actividad academica y de emplear nuevas herramientas docentes, como las metodologias activas de aprendizaje, mas acordes con las exigencias actuales. En este articulo se exponen los ejes vertebradores del Espacio Europeo de Educacion Superior y se describen diversas experiencias de innovacion docente en el marco de Reumacademia y de 3 universidades espanolas.

In recent years, university education has undergone profound changes as a result of the creation of the European Space for Higher Education. It has gone from a teacher-centred model, based on the transmission of knowledge through lectures, to being student-centred, based on the acquisition of skills and attaching great importance to independent learning. This transformation involves the need to reorganise academic activity and employ new teaching tools, such as active learning methodologies, more in line with current requirements. In this article, the backbones of the European Space for Higher Education are presented, and diverse experiences of teaching innovation described under Reumacademia and from three Spanish universities.

[Abstract] The integrity of the articular cartilage is necessary for the proper functioning of the diarthrodial joint. The self-repair capacity of this tissue is very limited and, currently, there is no effective treatment capable of restoring it. The degradation of the articular cartilage leads to osteoarthritis (OA), a leading cause of pain and disability mainly among older people. Different cell treatments have been developed with the aim of forming a repair tissue with the characteristics of native articular cartilage, including cellular therapy and tissue engineering. Cell therapy-based approaches include bone marrow-stimulating techniques, implants of periosteum and perichondrium, ostechondral grafting and implantation of chondrogenic cells as chondrocytes, mesenchymal stem cells or induced pluripotent stem cells. In tissue engineering-based approaches cell-free scaffolds capable of recruiting endogenous cells or chondrogenic cell-loaded scaffolds may be used. However, despite the numerous treatments available nowadays, no technique has been able to consistently regenerate native articular cartilage in clinical trials. Although many cell therapy and tissue engineering studies have shown promising results and clinical improvement, these treatments generate a fibrocartilaginous tissue different from native articular cartilage. More research is needed to improve cell-based approaches and prove its efficacy. Xunta de Galicia; R2014/050 Ministerio de Economía y Competitividad; RTC-2016-5386-1

Health Administration; Public Health; Quality of Life Research Administración sanitaria; Salud pública; Investigación de calidad de vida Administració sanitària; Salut pública; Investigació sobre la qualitat de vida Background Patient experience is acknowledged as a principal aspect of quality healthcare delivery, and it has implications with regard to outcomes. Objectives Our objective was to evaluate the healthcare experience of patients with chronic diseases to identify patient-perceived healthcare gaps and to assess the influence of demographic and healthcare-related variables on patient experiences. Methods A cross-sectional survey was delivered to adult patients with chronic diseases: diabetes mellitus (DM), human immunodeficiency virus (HIV) infection, inflammatory bowel disease (IBD) or rheumatic diseases. Patient experiences were assessed with the Instrument for Evaluation of the Experience of Chronic Patients (IEXPAC) questionnaire, with possible scores ranging from 0 (worst) to 10 (best experience). Results Of the 2474 patients handed the survey, 1618 returned it (response rate 65.4%). Patients identified gaps in healthcare related mainly to access to reliable information and services, interaction with other patients and continuity of healthcare after hospital discharge. The mean ± standard deviation (SD) IEXPAC score was 6.0 ± 1.9 and was higher for patients with HIV (6.6 ± 1.7) than for those with rheumatic disease (5.5 ± 2.0), IBD (5.9 ± 2.0) or DM (5.9 ± 1.9) (p

Calcium gluconate extravasation is a process, which, while not common, occurs more frequently in neonatal intensive care units. The aim of this study is to present a number of cases of calcium gluconate extravasation, which have occurred in our hospital, and to carry out a review of those clinical cases published in the literature to obtain relevant epidemiological data.Data were gathered on the medical histories of 5 patients who presented lesions secondary to calcium gluconate extravasation in our center. A review of the literature was also performed to include clinical cases of calcium gluconate extravasation already published.Data were collected on 60 cases published in 37 articles. Most patients (55%) were neonates. The average age of these neonates was 8 days. The commonest location of injuries was the back of the hand and wrist (42%). The 2 most frequent symptoms were the appearance of erythema (65%) and swelling/edema (48%) followed by the appearance of skin necrosis (47%), indurated skin (33%), and yellow-white plaques or papules (33%). Most cases are cured within a period of 3 to 6 months. Fifty percent of patients required surgery, and in 13% of cases, skin grafts were performed. The most frequent histological finding was the presence of calcium deposits. Other histological findings described were the presence of necrosis, lymphohistiocytic infíltrate, and granulomas. Most histological findings were located in the dermis. Most x-rays showing calcium deposits had been performed at 3 to 4 weeks.Calcium gluconate extravasation is a process, which, although infrequent, is associated with serious skin and soft-tissue lesions, mainly affecting infants. Further studies are needed to determine possible specific procedures to be carried out in these cases.

Background Systemic Lupus Erythematosus (SLE) is an autoimmune systemic rheumatic disease that, in our area, presents hematologic manifestations in approximately 70% of cases1. Some of them are very rare so there are no large series whose analysis could provide relevant information. Objectives To study the characteristics of patients with Hemophagocytic Syndrome (HS) in a large sample of SLE patients. Methods SLE patients from RELESSER database were studied. We analysed SLE manifestations present at 12 different domains (mucocutaneous, renal, musculoskeletal, constitutional, hematologic, vascular, cardiac, respiratory, neuropsychiatric, gastrointestinal, ophthalmic and serological) before, during and after HS diagnosis and until the last available assessment. We also studied activity (SELENA-SLEDAI) and damage (SLICC/ACR DI) indices at those moments.We evaluated the treatment received, HS recurrences and the number of deaths by this entity. Results 3,656 SLE patients (≥4 ACR criteria) from 45 Rheumatology Units across Spain were studied. Seven patients ( Clinically, 100% of the patients presented fever and alterations of the liver profile, 85.8% cytopenias and 71.5% dermatological manifestations. Respiratory manifestations and hemolytic anemia were present in 57.2% of the cases, both; lymph nodes and coagulopathy in 42.9%. Hepatomegaly was detected in 28.6%, as well as neuropsychiatric, digestive and renal manifestations. Splenomegaly was detected in 14.3%. The mean hemoglobin level was 8.6 (± 1.1) g/dl, platelets 85,585 (± 83,390)/mm3, ferritin 7,410 (± 6,470) ng/ml and triglycerides 404.7 (± 235.6) mg/dl. All patients were admitted and undergonebone marrow study, requiring a mean of 2.2 (± 1.5) treatment lines, using 2.8 (± 1.7) drugs. One patient died during the HS episode by the HS itself and another 2 patients had 2 and 3 recurrences, respectively. The following table shows the characteristics of each patient. Conclusions HS is a rare life-threatening SLE manifestation. It must be suspected in SLE patients with persistent fever who do not respond to antibiotics, cytopenias and evidence of multiorgan involvement. Relapses and death are common in HS associated to SLE. References Pego-Reigosa JM, Rua-Figueroa I, Lopez-Longo FJ, Galindo-Izquierdo M, Calvo-Alen J, Olive-Marques A, et al. Analysis of disease activity and response to treatment in a large Spanish cohort of s with systemic lupus erythematosus. Lupus 2015;24:720–9. Acknowledgements Work supported by Spanish Society of Rheumatology, FIS/ISCIII (PI11/02857), BIOCAPS from the European Union 7th Framework Programme/REGPOT-2012–2013.1 (316265), GSK, Roche, Novartis, UCB. Disclosure of Interest None declared

[Abstract] This study aimed to generate a minimum list of structural and functional anatomical items about the pelvis/hip, knee, ankle/foot, gait, and lower limb innervation, which are most relevant to the practice of rheumatology. To determine their perceived relevance to clinical practice, seven members of the Mexican Clinical Anatomy Task Force compiled an initial list of 470 anatomical items. Ten local and international experts according to a 0-10 Likert scale ranked these items. Of the original list, 101 (21.48%) items were considered relevant (global rate >40). These included 36/137 (26.27%) pelvis and hip items, 25/82 (30.48%) knee items, 22/168 (13.98%) ankle/foot items, 11/68 (16.17%) neurologic items, and 7/15 (46.66%) gait-related items. We propose that these 101 anatomical items of the lower extremity, when added to the 115 anatomic items of the upper extremity and spine we previously reported, may represent an approximation to the minimal anatomical knowledge central to the competent practice of rheumatology. The meager representation of ankle and foot items may reflect a lesser emphasis in these anatomical regions during rheumatologic training. Attention to these and related items during rheumatologic training and beyond may sharpen the rheumatologist's ability in the differential diagnosis of regional pain syndromes as well as strengthen an endangered art: the rheumatologic physical examination.

The purpose of this study was to investigate cartilage repair of in vitro lesion models using human bone marrow mesenchymal stromal cells (hBMSCs) with different collagen (Col) scaffolds. Lesions were made in human cartilage biopsies. Injured samples were pre-treated with interleukin 1β (IL1β) for 24 h; also, samples were not pre-treated. hBMSCs were seeded on different types of collagen scaffolds. The resulting constructs were placed into the lesions, and the biopsies were cultured for 2 months in chondrogenic medium. Using the modified ICRSII scale, neotissues from the different scaffolds showed ICRS II overall assessment scores ranging from 50% (fibrocartilage) to 100% (hyaline cartilage), except for the Col I +Col II +HS constructs (fibrocartilage/hyaline cartilage, 73%). Data showed that hBMSCs cultured only on Col I +Col II +HS scaffolds displayed a chondrocyte-like morphology and cartilage-like matrix close to native cartilage. Furthermore, IL1β pre-treated biopsies decreased capacity for repair by hBMSCs and decreased levels of chondrogenic phenotype of human cartilage lesions.

[Abstract] Mesenchymal stem cells are being the focus of connective tissue technology and regenerative medicine, presenting a good choice cell source for improving old and well recognized techniques of cartilage defect repair. For instance, the autologous chondrocyte transplantation using new concepts of regenerative medicine. The present study investigated the risk of xenogenicity of human synovial membrane-derived MSCs, injected into the monkeys using intravenous and intra-articular administration. The animal models used were adult monkeys Rhesus which had been injured into the left knee to create an Osteoarthritis (OA) animal model. CD105+-MSCs were injected twice into the OA monkeys with an interval of one week between them. The animals were euthanized one month after treatment. Immunohistochemistry analysis of different organs: spleen, heart, fat, liver, gut, pancreas, lung, skeletal muscle and kidney from the animals revealed that CD105+-MSCs migrated towards the injured knee joint. MSCs naive were found statistically significant increased in the injured knee in front of healthy one. CD105+-MSCs were negatives for CD68 and the area where CD105+-MSCs were found presented SDF-1 increased levels in front of healthy knee. We concluded that a characterized MSCs subset could be a safe alternative for cell therapy in clearly localized pathologies. Instituto de Salud Carlos III; PI11/02799

Carlos M González,1 Loreto Carmona,2 Javier de Toro,3 Enrique Batlle-Gualda,4 Antonio I Torralba,5 María J Arteaga,6 Luis Cea-Calvo6 1Department of Rheumatology, Gregorio Marañón Hospital, 2Instituto de Salud Musculoesquelética, Madrid, 3Department of Rheumatology, Hospital Universitario A Coruña, A Coruña, 4Department of Rheumatology, Hospital Universitario de Sant Joan d’Alacant, Alicante, 5Coordinadora Nacional de Artritis, 6Medical Affairs Department, Merck Sharp & Dohme, Madrid, Spain Objective: The aim of this study was to explore perceptions of patients with rheumatic diseases treated with subcutaneous (SC) biological drugs on the impact on daily life and satisfaction with current therapy, including preferred attributes. Methods: A survey was developed ad hoc by four rheumatologists and three patients, including Likert questions on the impact of disease and treatment on daily life and preferred attributes of treatment. Rheumatologists from 50 participating centers were instructed to handout the survey to 20 consecutive patients with rheumatoid arthritis (RA), axial spondyloarthritis (ax-SpA), or psoriatic arthritis (PsA) receiving SC biological drugs. Patients responded to the survey at home and sent it to a central facility by prepaid mail. Results: A total of 592 patients returned the survey (response rate: 59.2%), 51.4% of whom had RA, 23.8% had ax-SpA, and 19.6% had PsA. Patients reported moderate-to-severe impact of their disease on their quality of life (QoL) (51.9%), work/daily activities (49.2%), emotional well-being (41.0%), personal relationships (26.0%), and close relatives’ life (32.3%); 30%–50% patients reported seldom/never being inquired about these aspects by their rheumatologists. Treatment attributes ranked as most important were the normalization of QoL (43.6%) and the relief from symptoms (35.2%). The satisfaction with their current antirheumatic therapy was high (>80% were “satisfied” or “very satisfied”), despite moderate/severe impact of disease. Conclusion: Patients with rheumatic diseases on SC biological therapy perceive a high disease impact on different aspects of daily life, despite being highly satisfied with their treatment; the perception is that physicians do not frequently address personal problems. Normalization of QoL is the most important attribute of therapies to patients. Keywords: rheumatic diseases, quality of life, emotional well-being, biological drugs, patient’s satisfaction