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Atypical femoral fractures (AFF) are rare fragility fractures in the subtrocantheric or diaphysis femoral region associated with long-term bisphosphonate (BP) treatment. The etiology of AFF is still unclear even though a genetic basis is suggested. We performed whole exome sequencing (WES) analysis of 12 patients receiving BPs for at least 5 years who sustained AFFs and 4 controls, also long-term treated with BPs but without any fracture. After filtration and prioritization of rare variants predicted to be damaging and present in genes shared among at least two patients, a total of 272 variants in 132 genes were identified. Twelve of these genes were known to be involved in bone metabolism and/or AFF, highlighting DAAM2 and LRP5, both involved in the Wnt pathway, as the most representative. Afterwards, we intersected all mutated genes with a list of 34 genes obtained from a previous study of three sisters with BP-related AFF, identifying nine genes. One of these (MEX3D) harbored damaging variants in two AFF patients from the present study and one shared among the three sisters. Gene interaction analysis using the AFFNET web suggested a complex network among bone-related genes as well as with other mutated genes. BinGO biological function analysis highlighted cytoskeleton and cilium organization. In conclusion, several genes and their interactions could provide genetic susceptibility to AFF, that along with BPs treatment and in some cases with glucocorticoids may trigger this so feared complication.

To assess the efficacy and safety of abatacept (ABA) in monotherapy (ABAMONO) versus combined-ABA, ABA plus methotrexate (ABAMTX) or ABA plus non-MTX conventional-DMARDs (ABANON-MTX), in Rheumatoid Arthritis (RA) patients with Interstitial Lung Disease (ILD) (RA-ILD).

Cancer and cancer therapies are a major factor risk for osteoporosis due to bone loss and deterioration of bone microarchitecture. Both factors contribute to a decrease in bone strength and, consequently, increased bone fragility and risk of fracture. Cancer-associated bone loss is a multifactorial process, and optimal interdisciplinary management of skeletal health, accurate assessment of bone density, and early diagnosis are essential when making decisions aimed at reducing bone loss and fracture risk in patients who have received or are receiving treatment for cancer. In this document, a multidisciplinary group of experts collected the latest evidence on the pathophysiology of osteoporosis and its prevention, diagnosis, and treatment with the support of the Spanish scientific societies SEOM, SER, SEIOMM, and SECOT. The aim was to provide an up-to-date and in-depth view of osteoporotic risk and its consequences, and to present a series of recommendations aimed at optimizing the management of bone health in the context of cancer.

OBJECTIVES: To determine cardiovascular (CV) mortality and incidence of the first CV event (CVE) in patients with chronic inflammatory rheumatic diseases (CIRD) after 5 years of follow-up. METHODS: This is an analysis of the CARdiovascular in rheMAatology (CARMA) study after 5 years of follow-up. It includes patients with RA (n = 775), AS (n = 738) and PsA (n = 721), and individuals without CIRD (n = 677) attending outpatient rheumatology clinics from 67 public hospitals in Spain. Descriptive analyses were performed for the CV mortality at 5 years. The Systematic COronary Risk Evaluation (SCORE) function at 5 years was calculated to determine the expected risk of CV mortality. Poisson models were used to estimate the incidence rates of the first CVE. Hazard ratios of the risk factors involved in the development of the first CVE were evaluated using the Weibull proportional hazard model. RESULTS: Overall, 2382 subjects completed the follow-up visit at 5 years. Fifteen patients died due to CVE. CV deaths observed in the CIRD cohort were lower than that predicted by SCORE risk charts. The highest incidence rate of CVE [7.39 cases per 1000 person-years (95% CI 4.63, 11.18)] was found in PsA patients. However, after adjusting for age, sex and CV risk factors, AS was the inflammatory disease more commonly associated with CVE at 5 years [hazard ratio 4.60 (P =0.02)], compared with those without CIRD. CONCLUSIONS: Cardiovascular mortality in patients with CIRD at 5 years of follow-up is lower than estimated. Patients with AS have a higher risk of developing a first CVE after 5 years of follow-up.

Prevalence and risk factors of vertebral fractures in postmenopausal RA women were assessed in 323 patients and compared with 660 age-matched women. Of patients, 24.15% had at least one vertebral fracture vs.16.06% of controls. Age, glucocorticoids and falls were the main fracture risks. Vertebral fractures were associated with disease severity. Introduction There is little quality data on the updated prevalence of fractures in rheumatoid arthritis (RA) that may have changed due to advances in the therapeutic strategy in recent years. This study was aimed at analysing the prevalence and risk factors of vertebral fractures in postmenopausal women with RA and comparing it with that of the general population. Methods We included 323 postmenopausal women diagnosed with RA from 19 Spanish Rheumatology Departments, randomly selected and recruited in 2018. Lateral radiographs of the thoracic and lumbar spine were obtained to evaluate morphometric vertebral fractures and the spinal deformity index. We analysed subject characteristics, factors related to RA, and fracture risk factors. The control group consisted of 660 age-matched Spanish postmenopausal women from the population-based Camargo cohort. Results Seventy-eight (24.15%) RA patients had at least one vertebral fracture. RA patients had increased fracture risk compared with controls (106 of 660, 16.06%) (p = 0.02). Logistic regression analysis showed that age (OR 2.17; 95% CI 1.27-4.00), glucocorticoids (OR 3.83; 95% CI 1.32-14.09) and falls (OR 3.57; 95% CI 1.91-6.86) were the independent predictors of vertebral fractures in RA patients. The subgroup with vertebral fractures had higher disease activity (DAS28: 3.15 vs. 2.78, p = 0.038) and disability (HAQ: 0.96 vs. 0.63, p = 0.049), as compared with those without vertebral fractures. Conclusion The risk of vertebral fracture in RA is still high in recent years, when compared with the general population. The key determinants of fracture risk are age, glucocorticoids and falls. Patients with vertebral fractures have a more severe RA.

OBJECTIVES: Interferon regulatory factor 5 (IRF5) is a major regulator of type I interferon induction and is also critical to produce pro-inflammatory cytokines. An influence of IRF5 genetic variants on the increased risk of immune-mediated diseases has been described. Accordingly, we aimed to evaluate the implication of IRF5 in the pathogenesis of Immunoglobulin-A vasculitis (IgAV), an inflammatory vascular pathology. METHODS: Three tag genetic variants (rs2004640, rs2070197 and rs10954213), representative of 3 different haplotype blocks within IRF5, were genotyped in 372 Caucasian patients with IgAV and 876 sex and ethnically matched healthy controls by TaqMan assays. RESULTS: No significant differences in the genotype and allele frequencies between patients with IgAV and healthy controls were observed when each IRF5 polymorphism was evaluated independently. Likewise, no significant differences between patients with IgAV and healthy controls were found when we assessed the three IRF5 polymorphisms combined, conforming haplotypes. In addition, there were no significant differences in genotype, allele and haplotype frequencies of IRF5 when patients with IgAV were stratified according to the age at disease onset or to the presence/absence of gastrointestinal or renal manifestations. CONCLUSIONS: Our results do not support an influence of IRF5 on the pathogenesis of IgAV.

Objective. The objective of the present study was to assess the efficacy of apremilast (APR) in the management of refractory oral and/or genital ulcers in patients with Behcet's disease (BD). Methods. National multicentre openlabel observational study on BD patients with recurrent oral and/or genital ulcers. In all cases orogenital ulcers were refractory to conventional therapy. APR was given and maintained at standard dose of 30 mg twice daily. The main outcome was the achievement of oral and/or genital ulcers remission. Efficacy of APR for other clinical manifestations was also evaluated. Results. We included 51 patients (35 women/16 men; mean age 44.7 +/- 13.2 years). Before APR, all patients had received several systemic conventional and/or biologic drugs. APR was initiated because of refractory oral (n=19) or genital (n=2) aphthous ulcers or both (n=30). Other manifestations found at APR onset were arthralgia/arthritis (n=16), folliculitis/pseudofolliculitis (n=14), erythema nodosum (n=3), furunculosis (n=2), paradoxical psoriasis induced by TNF-alpha-inhibitors (n=2), ileitis (n=2), deep venous thrombosis (n=2), leg ulcers (n=1), erythematosus and scaly skin lesions (n=1), fever (n=1), unilateral anterior uveitis (n=1) and neuro Behcet (n=1). After a mean follow-up of 8.5 +/- 6.9 months, most patients had experienced improvement of orogenital ulcers and prednisone dose had been successfully reduced or discontinued. APR also yielded improvement of some non-aphthous manifestations such as the cutaneous follicular and intestinal manifestations. However, the effect on musculoskeletal manifestations was variable. Conclusion. APR yielded a rapid and maintained improvement of refractory mucocutaneous ulcers of BD, even in patients refractory to several systemic drugs including biologic therapy.

Purpose: We assessed the efficacy and safety of biologic therapy in severe and refractory Peripheral Ulcerative Keratitis (PUK). Design: Open-label multicenter study of biologic-treated patients with severe PUK refractory to conventional immunosuppressive drugs. Subjects: We studied 34 patients (44 affected eyes) (24 women/10 men; mean age, 55.26 +/- 17.4 years). PUK was associated with a well-defined condition in 29 of them (rheumatoid arthritis [n = 20], psoriatic arthritis [n = 2], inflammatory bowel disease [n = 2], Beh,cet disease [n = 1], granulomatosis with polyangiitis [n = 1], microscopic polyangiitis [n = 1], systemic lupus erythematosus [n = 1] and axial spondyloarthritis [n = 1]). Besides topical and oral systemic glucocorticoids, patients had received: methylprednisolone pulses [n = 9], and conventional immunosuppressive drugs, mainly methotrexate [n = 18], and leflunomide [n = 7]. Eleven patients had required ocular surgery prior to biologic therapy. Methods: Following biologic therapy, baseline main outcomes were compared with those found at 1st week, 1st and 6th months and 1st year. Main outcome measures: Efficacy and safety of biologic therapy. Efficacy was analyzed by the assessment of corneal inflammation (corneal thinning, central keratolysis and ocular perforation); other causes of ocular surface inflammation (scleritis, episcleritis); intraocular inflammation (uveitis); visual acuity and glucocorticoid sparing effect. Results: The first biologic agents used were anti-TNFa drugs (n = 25); adalimumab (n = 16), infliximab (n = 8), etanercept (n = 1), and non-TNFa agents (n = 9); rituximab (n = 7), tocilizumab (n = 1) belimumab (n = 1) and abatacept (n = 1). During the follow-up, switching to a second biologic agent was required in 12 of the 25 (48%) patients treated with anti-TNF alpha drugs. However, no switching was required in those undergoing biologic therapy different from anti-TNF alpha agents. The main outcome variables showed a rapid and maintained improvement after a mean follow-up of 23.7 +/- 20 months. Major adverse effects were tachyphylaxis, relapsing respiratory infections, supraventricular tachycardia, pulmonary tuberculosis and death, one each. Conclusions: Biologic therapy is effective and relatively safe in patients with severe and refractory PUK. Nonanti-TNF alpha agents appear to be effective in these patients. (C) 2020 Elsevier Inc. All rights reserved.

El experimento fue conducido para determinar los coeficientes de digestibilidad y la energía digestible del Arachis pintoi, Stylozanthes guianensis, Erythrina poeppigiana, Centrocema macrocarpum y Pueraria phaseoloides. Se empleo el método directo, usando el mismo forraje como único alimento. El experimento tuvo dos fases, una de adaptación y una de colección de heces, con una duración de 15 y 5 días, respectivamente. Se utilizaron 25 cuyes machos en etapa de crecimiento distribuidos de tal manera que 5 cuyes correspondieron a cada leguminosa tropical evaluada. Los coeficientes de digestibilidad de los nutrientes del Arachis pintoi (51,96, 56,80, 29,46 y 71,32 por ciento de digestibilidad de la materia seca, proteína cruda, fibra cruda y extracto libre de nitrógeno, respectivamente) fueron cuantitativamente superiores a los otros tratamientos a excepción de la ceniza. Asimismo, los valores de energía digestible (en base seca) obtenidos fueron mayores en el Arachis pintoi (2,20 Kcal/g) que los otros forrajes. This study was carried out to determine the digestibility coefficients and digestible energy of Arachis pintoi, Stylozanthes guianensis, Erythrina poeppigiana, Centrocema macrocarpum and Pueraria phaseoloides. The direct method was used, using the same forage as the only food. The experiment had two phases, one for adaptation and one of faeces collection, with duration of 15 and 5 days, respectively. We used 25 male guinea pigs in growth stage distributed in order to get 5 guinea pigs for each tropical legume evaluated. The digestibility coefficients of nutrients were numerically higher for Arachis pintoi (51,96, 56,80, 29,46 y 71,32 percent of the dry matter, crude protein, crude fiber and nitrogen free extract digestibility, respectively) than for all the other treatments, except for the ash. Likewise, digestible energy values (in dry basis) were greater for Arachis pintoi (2,20 kcal/g) than for all other forages.

Cardiovascular (CV) disease is one of the main causes of morbi-mortality in spondyloarthritis (SpA), partially explained by traditional CV risk factors. Information on lipoprotein(a) [Lp(a)], a non-conventional risk factor, in SpA is scarce. In this study we assessed the prevalence of hyperlipoproteinaemia(a) in SpA patients and analysed the possible related factors.

Objective: Interstitial lung disease (ILD) is one of the most serious complications of rheumatoid arthritis (RA). In the present study, we aimed to assess the efficacy of abatacept (ABA) in patients with ILD associated to RA. Methods: National multicenter, non-controlled, open-label registry study of RA patients with ILD treated with ABA. Results: 63 patients (36 women) with RA-associated ILD undergoing ABA therapy were studied. The mean +/- standard deviation age at the time of the study was 63.2 +/- 9.8 years. The median duration of RA and ILD from diagnosis were 6.8 and 1 year, respectively. RA was seropositive in 55 patients (87.3%). In 15 (23.8%) of 63 patients the development of ILD was closely related to the administration of synthetic or biologic disease modifying anti-rheumatic drugs. After a follow-up of 9.4 +/- 3.2 months, two-thirds of patients remained stable whereas one-quarter experienced improvement in the Modified Medical Research Council scale. At that time forced vital capacity remained stable in almost two-thirds of patents and improved in one out of five patients assessed. Also, diffusing capacity of the lung for carbon monoxide remained stable in almost two-thirds and showed improvement in a quarter of the patients assessed. At 12 months, 50% of the 22 patients in whom chest HRCT scan was performed due persistence of respiratory symptoms showed stabilization, 8 (36.4%) improvement and 3 worsening of the HRCT scan pattern. Eleven of 63 patients had to discontinue ABA, mainly due to adverse events. Conclusion: ABA appears to be an effective in RA-associated ILD. (C) 2018 Elsevier Inc. All rights reserved.

This article focuses on the analysis of some factors that would be widening the gap between the dynamism on the agricultural sector and progress related to reduce rural poverty. This is analyzed in relation to the different countries capacity about the progress on these two dimensions, poverty and growth. Here begin the question about what are the ways to create a new research agenda and political discussion in the current trends in agricultural and rural development on Latin America. From this perspective, the article refers to the origin of the initial hypothesis, which proposes a vision of the impact of development models on rural poverty that dominated the region. Then, a synthesis of main results obtained in each of the eight countries where the studies were conducted. Thirdly, the main conclusion of this work. Finally, we present the public policy agenda, main issues to overcome situations of rural poverty., Este artículo está centrado en el análisis de algunos de los factores que estarían ampliando la brecha entre el dinamismo del sector agropecuario y los avances en la reducción de la pobreza rural. Esta brecha es analizada en relación a la capacidad que tuvieron los distintos países estudiados en avanzar en estas dos dimensiones: pobreza y crecimiento. Desde aquí nace la pregunta sobre cuáles son las formas de crear una nueva agenda de investigación y de discusión política, en el marco de las actuales tendencias del desarrollo agropecuario y rural en América Latina. Desde esta óptica, el artículo hace referencia al origen de la hipótesis inicial, que plantea una visión sobre el impacto de los modelos de desarrollo sobre la pobreza rural que han predominado en la Región. Luego, se hace una síntesis de los principales resultados obtenidos en cada uno de los ocho países donde se realizaron los estudios. En tercer lugar, se presentan las principales conclusiones de este trabajo. Por último, se muestra la agenda de políticas públicas con aspectos claves para superar situaciones de pobreza rural.

Objective To estimate cut-off points and to establish response criteria for the Hospital Universitario La Princesa Index (HUPI) in patients with chronic polyarthritis. Methods Two cohorts, one of early arthritis (Princesa Early Arthritis Register Longitudinal PEARL] study) and other of long-term rheumatoid arthritis (Estudio de la Morbilidad y Expresión Clínica de la Artritis Reumatoide EMECAR]) including altogether 1200 patients were used to determine cut-off values for remission, and for low, moderate and high activity through receiver operating curve (ROC) analysis. The areas under ROC (AUC) were compared to those of validated indexes (SDAI, CDAI, DAS28). ROC analysis was also applied to establish minimal and relevant clinical improvement for HUPI. Results The best cut-off points for HUPI are 2, 5 and 9, classifying RA activity as remission if =2, low disease activity if >2 and =5), moderate if >5 and