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Among the great diversity of Oligocene mammals from Quebrada Fiera (Mendoza Province, Argentina), three families of typotherian notoungulates are very abundant. Since the first paper on archaeohyracids in 2010 until the last fieldwork in 2016, numerous unpublished remains were added to the collection. The study of all these remains, together with some revised materials, allows us to provide new anatomical data and some taxonomic decisions on these groups. Within Hegetotheriidae, we present one of the most complete skulls of “Prohegetotherium schiaffinoi” known to date, providing descriptions of certain previously unknown features of the caudal cranium; MCNAM-PV 3984 is discarded as belonging to Hegetotheriopsis sulcatus, as recently suggested, and is considered as Hegetotheriinae indet., like other isolated large specimens and some teeth previously determined as Prohegetotherium sp.; and several well-preserved specimens add to the sample of the pachyrukhine Prosotherium garzoni, including a partial maxilla with erupting P2. Concerning “Archaeohyracidae”, Archaeohyrax suniensis is now better represented, recording several ontogenetic stages previously observed in the Bolivian sample of this species. Finally, within Interatheriidae, most new dental material belongs to Argyrohyrax proavus, but an isolated upper molar suggests the presence of a different Interatheriinae at Quebrada Fiera, more similar to the Bolivian Brucemacfaddenia boliviensis than to other Deseadan (late Oligocene) taxa.

Abstract Probainognathia is a derived lineage of cynodonts which encompass Mammalia as their crown-group. The rich record of probainognathians from the Carnian of Argentina contrasts with their Norian representation, with only one named species. Here we describe a new probainognathian, Tessellatia bonapartei gen. et sp. nov., from the Norian Los Colorados Formation of the Ischigualasto-Villa Unión Basin of Argentina. The new taxon, represented by a partial cranium with associated lower jaws, was analyzed through neutron and X-rays micro-tomography (μCT). The high-resolution neutron μCT data allowed the identification of a unique character combination, including features inaccessible through traditional techniques. We constructed the largest phylogenetic data matrix of non-mammalian cynodonts. The new species and its sister taxon, the Brazilian Therioherpeton cargnini, are recovered as probainognathians, closely related to Mammaliamorpha. We conducted the first quantitative paleobiogeographic analysis of non-mammalian cynodonts, focusing in probainognathians. The results indicate that Probainognathia and Mammaliamorpha originated in southwestern Gondwana (in the Brazilian Paraná Basin), which was an important center of diversification during the Triassic. Finally, the Chinese Lufeng Basin is identified as the ancestral area of Mammaliaformes. These new findings, besides adding to the knowledge of the poorly represented Norian cynodonts from the Los Colorados Formation, are significant to improve our understanding of probainognathian diversity, evolution, and paleobiogeographic history.

During the last decade, the Deseadan (late Oligocene) Quebrada Fiera locality, Mendoza Province, Argentina, has provided a large amount of mammal remains. Taxonomic studies have shown the presence of faunal elements common with other Deseadan associations from Patagonia and lower latitudes (Salla, Bolivia), as well as endemic taxa of different groups of mammals (Notohippidae, Leontiniidae, Homalodotheriidae, Hegetotheriidae, and Metatheria) and even a gastropod. In this work, we present a taxonomic and phylogenetic analysis of a set of postcranial fossils of three families of the suborder Toxodontia (Notoungulata). The postcranial elements are assigned to taxa previously recognized at Quebrada Fiera, such as the leontiniid Gualta cuyana and the homalodotheriid Asmodeus petrasnerus, but also to the family Toxodontidae that is represented by Proadinotherium sp. and another larger toxodontid; a few dental remains of Proadinotherium are also included as this is the first time that toxodontids from Quebrada Fiera are described. In the case of A. petrasnerus, an almost complete calcaneum allows us to expand the diagnosis of this taxon. The bones assigned to G. cuyana enlarge the anatomical knowledge of this species. In turn, the presence of the genus Proadinotherium extends its geographic distribution in Argentina and adds to the extra-Patagonian record of P. saltoni from Salla, Bolivia. Phylogenetic results do not differ much from previous analyses using postcranial characters, and the obtained consensus trees show low node supports. The various phylogenetic analyses performed here provide a more robust framework to interpret the relationships of the studied taxa.

Objective: To evaluate the main outcomes of disease activity and their association with other measures of activity, damage, and quality of life in patients with idiopathic inflammatory myopathy (IIM) according to time since diagnosis and positivity to antisynthetase autoantibodies (ASAs)., Methods: Cross-sectional multicenter study within the Spanish Myo-Spain registry. Cases were classified as incident (≤ 12 months since diagnosis) and prevalent. The main outcomes of disease activity were the Myositis Disease Activity Assessment visual analogue scale (MYOACT), the Manual Muscle Test 8 (MMT-8), physician global activity (PhGA), and extramuscular activity. Other measures of activity, damage, and quality of life included patient global disease activity, MYOACT muscular, creatine phosphokinase, Health Assessment Questionnaire, physician and patient global damage, global damage of the Myositis Damage Index, and the 12-item Short-Form Health Survey (SF-12). We analyzed associations using a multivariate generalized linear model and a simple linear regression model., Results: A total of 554 patients with different diagnostic subgroups of IIM were included (136 incident and 418 prevalent cases), with 215 ASA-positive patients (58 incident and 157 prevalent cases). All measures of disease activity were higher in the incident cases (p < 0.05), except for MYOACT muscular and creatine phosphokinase, for which no differences were recorded in ASA-positive patients. No differences were found between incident and prevalent cases for measures of damage. Values for the physical component of the SF-12 were higher in the prevalent cases (p < 0.05). The multivariate model was initially significant overall for the main activity outcomes. Positivity to ASAs was positively and negatively associated with the MYOACT index and MMT-8, respectively (p < 0.05), although no association was recorded with PhGA and extramuscular activity. Prevalent cases were negatively associated with the main outcomes of activity, except with MMT-8, for which the association was positive (p < 0.05)., Conclusions: The main activity outcomes validated in polymyositis and dermatomyositis could also be used in other subtypes of IIM, such as antisynthetase syndrome. Recent diagnosis is associated with greater disease activity, as assessed based on these activity outcomes. PhGA and extramuscular activity are not modified by ASA positivity, thus supporting their preferred use for assessing treatment response in IIM with ASAs., Competing Interests: Declaration. Ethics approval and consent to participate: The study was approved by the reference Clinical Investigation Ethics Committee (Hospital La Paz, Madrid) and by the local ethics committees. All the patients gave their written informed consent before being included in the study. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background and Objective: Bibliometric studies of scientific production in Spanish Rheumatology are scarce. The aim of this study was to analyze the bibliographic production of Rheumatology Services in Spain over the period 2013-2022., Materials and Methods: Original articles and reviews with the affiliation of the first or corresponding author to a Spanish rheumatology Service/Department/Section/Unit were identified in the Web of Science Core Collection and Scopus databases. Keywords and titles were used to classify articles by field (clinical, epidemiological or basic) and pathology. International collaborations and collaborations between Autonomous Communities (AC) were identified. Quantitative bibliometric indicators were obtained (number of articles published per year, pathology and AC) and impact indicators were obtained (based on the number of citations per article). The H-index was also calculated., Results: The total number of publications was 2321, with an annual growth rate of 4.1% in the period analyzed. In 14.1% of the articles there were international collaborations, mainly with the United States and the United Kingdom, while between ACs the most numerous were between Madrid and Catalonia. The pathologies with the highest H-index were rheumatoid arthritis (RA), spondyloarthropathies (SpA), osteoarthritis and vasculitis (34, 32, 28 and 26, respectively). The H-index for the Spanish rheumatology services as a whole was 69., Discussion and Conclusions: The scientific production of rheumatology services/departments/sections/units in our country increased between 2013 and 2022. By pathology, the scientific production in RA and SpA stands out., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 Sociedad Española de Reumatología (SER), Colegio Mexicano de Reumatología (CMR) and Elsevier España, S.L.U. All rights reserved.)

Amyotrophic lateral sclerosis (ALS) is an adult-onset motor neuron disease with a mean survival time of three years. The 97% of the cases have TDP-43 nuclear depletion and cytoplasmic aggregation in motor neurons. TDP-43 prevents non-conserved cryptic exon splicing in certain genes, maintaining transcript stability, including ATG4B, which is crucial for autophagosome maturation and Microtubule-associated proteins 1A/1B light chain 3B (LC3B) homeostasis. In ALS mice (G93A), Atg4b depletion worsens survival rates and autophagy function. For the first time, we observed an elevation of LC3ylation in the CNS of both ALS patients and atg4b -/- mouse spinal cords. Furthermore, LC3ylation modulates the distribution of ATG3 across membrane compartments. Antisense oligonucleotides (ASOs) targeting cryptic exon restore ATG4B mRNA in TARDBP knockdown cells. We further developed multi-target ASOs targeting TDP-43 binding sequences for a broader effect. Importantly, our ASO based in peptide-PMO conjugates show brain distribution post-IV administration, offering a non-invasive ASO-based treatment avenue for neurodegenerative diseases., (© 2024. The Author(s).)

Myotonic dystrophy type 1 (DM1) is a rare neuromuscular disease caused by a CTG repeat expansion in the DMPK gene that generates toxic RNA with a myriad of downstream alterations in RNA metabolism. A key consequence is the sequestration of alternative splicing regulatory proteins MBNL1/2 by expanded transcripts in the affected tissues. MBNL1/2 depletion interferes with a developmental alternative splicing switch that causes the expression of fetal isoforms in adults. Boosting the endogenous expression of MBNL proteins by inhibiting the natural translational repressors miR-23b and miR-218 has previously been shown to be a promising therapeutic approach. We designed antimiRs against both miRNAs with a phosphorodiamidate morpholino oligonucleotide (PMO) chemistry conjugated to cell-penetrating peptides (CPPs) to improve delivery to affected tissues. In DM1 cells, CPP-PMOs significantly increased MBNL1 levels. In some candidates, this was achieved using concentrations less than two orders of magnitude below the median toxic concentration, with up to 5.38-fold better therapeutic window than previous antagomiRs. In HSA LR mice, intravenous injections of CPP-PMOs improve molecular, histopathological, and functional phenotypes, without signs of toxicity. Our findings place CPP-PMOs as promising antimiR candidates to overcome the treatment delivery challenge in DM1 therapy., Competing Interests: B.L. and R.A. are founders, and CEO and scientific consultant of Arthex Biotech, respectively. Arthex Biotech is developing antimiRs for use in the treatment of DM1., (© 2023 The Authors.)

Introduction: Limbic encephalitis (LE) can have a wide range of etiologies, most frequently infectious (especially viral) or autoimmune. Behcet's disease (BD) can present with heterogeneous neurological manifestations. However, LE is not considered a typical presentation of neuro-Behcet's disease (NBD)., Case Report: A 40-years-old male presented with new-onset subacute headaches, memory problems and apathy. A review of systems revealed an unrecorded past history of recurrent oral sores for years, recent malaise and fever, as well as an episode of bilateral panuveitis four months before presentation. His general and neurologic examination revealed slight fever, an isolated oral aphtha, anterograde amnesia and signs of bilateral retinal vasculitis. Brain magnetic resonance imaging displayed a pattern of limbic meningoencephalitis, and his cerebrospinal fluid showed mononuclear inflammation. The patient met BD diagnostic criteria. Considering LE is a very rare presentation of NBD, alternative etiologies were thoroughly assessed and excluded, including infectious, autoimmune and paraneoplastic encephalitis. Therefore, he was diagnosed with NBD, and he recovered well after immunosuppression., Discussion: Only two cases of NBD presenting with LE have been previously reported. We report a third case of this rare presentation and compare it with the previous two. We aim to highlight this association and contribute to enlarge the rich clinical spectrum of NBD.

Background: In patients with rheumatic diseases, the use of biological (b) or targeted synthetic (ts) disease-modifying antirheumatic drugs (DMARDs) after discontinuation of tumor necrosis factor inhibitors (TNFi) is known to be effective. However, data on the use of TNFi after discontinuation of non-TNFi bDMARDs or tsDMARDs (non-TNFi) are scarce. This study assessed the 4-years golimumab retention in patients with rheumatic diseases when used after discontinuation of non-TNFi., Methods: Adults with rheumatoid arthritis (RA; n = 72), psoriatic arthritis (PsA; n = 30) or axial spondyloarthritis (axSpA; n = 23) who initiated golimumab after discontinuation of non-TNFi from the Spanish registry of biological drugs (BIOBADASER) were analyzed retrospectively. The retention rate (drug survival or persistence) of golimumab up to 4 years was evaluated., Results: The golimumab retention rate was 60.7% (51.4-68.8) at year 1, 45.9% (36.0-55.2) at year 2, 39.9% (29.8-49.7) at year 3 and 33.4% (23.0-44.2) at year 4. Retention rates did not differ significantly whether golimumab was used as second, third, or fourth/subsequent line of therapy (p log-rank = 0.462). Golimumab retention rates were higher in axSpA or PsA patients than in RA patients (p log-rank = 0.002). When golimumab was administered as third or fourth/subsequent line, the 4-years retention rate after discontinuation of non-TNFi was similar to that after discontinuation of TNFi., Conclusion: In patients who discontinued non-TNFi, most of whom received golimumab as third/subsequent line of therapy, one-third of patients remained on golimumab at year 4. Retention rates were higher in patients with axSpA and PsA than in those with RA., (© 2023. The Author(s).)

Aim: To assess the golimumab retention rate during up to 8 years of follow up, and any associated factors., Methods: Retrospective analysis of the BIOBADASER (Spanish registry of biological drugs) database, assessing all adults who had ever started golimumab >6 months before the analysis for an approved indication (rheumatoid arthritis [RA], axial spondyloarthritis [SpA] or psoriatic arthritis [PsA])., Results: Among 885 patients (RA 267, axial SpA 370, PsA 248) receiving 944 cycles of golimumab, the retention rate of golimumab was 71.1% (95% confidence interval: 68.0-73.9) at year 1% and 37.7% (95% CI: 33.3-42.1) at year 7 and at year 8. Retention was higher when golimumab was used as the first biological drug (81.7% at year 1, 49.9% at year 7, p < 0.001). In Cox regression analysis, factors associated with golimumab retention included use as first-line therapy (hazard ratio [HR] for discontinuation 1.52 for second- and 1.79 for third/later-line vs. first-line), use in axial SpA or PsA rather than RA (HR for axial SpA vs. RA 0.59, for PsA vs. Rheumatoid arthritis 0.67), and treatment with concomitant methotrexate (HR 0.67). Factors associated with golimumab discontinuation were corticosteroid use (HR 1.46) and disease activity above median (HR 1.29) at golimumab initiation., Conclusion: Based on this retrospective analysis of the BIOBADASER registry, nearly two-fifths (37.7%) of adult rheumatology patients initiating golimumab will remain on treatment for 8 years, with a higher probability of retention in axial SpA or PsA indications and when golimumab is used as first biologic., (© 2022 The Authors. Musculoskeletal Care published by John Wiley & Sons Ltd.)

Objective: To develop a joint proposal for screening criteria of interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA) and vice versa, which serves as a guidelines in patient referral between the Rheumatology and Pneumology departments to early detection of these patients., Methods: A systematic literature review was carried out on the risk factors for the development of ILD in RA patients, and for the referral criteria to Rheumatology for suspected early RA. Based on the available evidence, screening criteria were agreed using the Delphi method by a panel of pneumologists and rheumatologists with expertise in these pathologies., Results: Screening criteria for ILD in patients with RA and for the early detection of RA in cases with ILD of unknown etiology have been developed. In both cases, a detection strategy was based on clinical risk factors. Recommendations also included the complementary tests to be carried out in the different clinical scenarios and on the periodicity that screening should be repeated., Conclusion: A selective screening strategy is recommended for the first time in the early diagnosis of patients with ILD-RA. This multidisciplinary proposal aims to solve some common clinical questions and help decision-making, although its usefulness to identify these patients with good sensitivity must be confirmed in a validation study., (Copyright © 2022. Published by Elsevier España, S.L.U.)

The aim was to identify patient- and disease-related characteristics predicting moderate-to-high disease activity in recent-onset psoriatic arthritis (PsA). We performed a multicenter observational prospective study (2-year follow-up, regular annual visits) in patients aged ≥18 years who fulfilled the CASPAR criteria and had less than 2 years since the onset of symptoms. The moderate-to-high activity of PsA was defined as DAPSA > 14. We trained a logistic regression model and random forest-type and XGBoost machine learning algorithms to analyze the association between the outcome measure and the variables selected in the bivariate analysis. The sample comprised 158 patients. At the first follow-up visit, 20.8% of the patients who attended the clinic had a moderate-to-severe disease. This percentage rose to 21.2% on the second visit. The variables predicting moderate-high activity were the PsAID score, tender joint count, level of physical activity, and sex. The mean values of the measures of validity of the machine learning algorithms were all high, especially sensitivity (98%; 95% CI: 86.89-100.00). PsAID was the most important variable in the prediction algorithms, reinforcing the convenience of its inclusion in daily clinical practice. Strategies that focus on the needs of women with PsA should be considered.

Objectives: To evaluate the effect of potential confounders on the association between sex and disease impact in recent-onset psoriatic arthritis., Methods: We performed a multicentre observational prospective study (2-year follow-up, regular annual visits). The study population comprised patients aged ≥18 years who fulfilled the CASPAR criteria and less than 2 years since the onset of symptoms. The dataset was generated using data for each patient at the 3 visits (baseline, first year, and second year of follow-up) matched with the PsAID values at each of the 3 visits. Once variables associated with both PsAID ≥4 and sex were selected, those that led to a difference of >10% between the adjusted and crude estimations were identified as potential confounders in the association between sex and PsAID. Lastly, the final multivariate logistic regression model estimating the association between sex and PsAID was defined., Results: The dataset contained 418 observations (158 at baseline, 135 at the first follow-up visit, and 125 at the second visit). The confounders identified in the multivariate model were HAQ, global pain, level of physical activity, and joint pattern at diagnosis. After adjustment for these variables, no statistically significant association was observed between female sex and PsAID ≥4., Conclusions: The association between female sex and greater disease impact could be explained by the influence of other variables, specifically higher HAQ score, greater intensity of pain, differences in the level of physical activity and in the joint pattern at diagnosis (lower frequency of the spondylitis pattern in women).

Aims: Interstitial lung disease (ILD) is frequent in patients with rheumatoid arthritis (RA) and is associated with significant morbidity and mortality. The aim of this review was to identify the different screening methods for ILD in patients with RA., Methods: We ran a systematic search in Pubmed, Embase and Cochrane Library up to April 2020 and did a hand search of the references of the retrieved articles. The search was limited to humans and articles published in English, Spanish or French. We selected studies with any design where: (a) the population included adult patients with RA; (b) the intervention was any screening method for ILD; and (c) validity or reliability of the screening method were evaluated, or a screening method was described. Two reviewers independently screened the articles by title and abstract and subsequently extracted the information using a specific data extraction form., Results: 25 studies were included with a total of 2593 patients. The most frequently used tool for ILD screening was high resolution computed tomography (HRCT) of the lung. Electronic auscultation, biochemical markers, bronchoalveolar lavage (BAL), pulmonary function tests (PFTs) and lung ultrasonography were also evaluated. Across the different studies, electronic auscultation and lung ultrasonography achieved higher accuracy than PFTs, BAL and biochemical markers., Conclusions: HRCT resulted as the most sensitive tool for ILD screening in patients with RA. Given its harmlessness and high sensitivity, lung ultrasonography may become the first-choice tool in the future., (Copyright © 2021 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.)

Objectives: To evaluate which patient and disease characteristics are associated with the perception of high-impact disease (PsAID ≥4) in recent-onset psoriatic arthritis., Methods: We performed a multicenter observational prospective study (2-year follow-up, regular annual visits). The study population comprised patients aged ≥18 years who fulfilled the CASPAR criteria and less than 2 years since the onset of symptoms. The dataset was generated using data for each patient at the 3 visits (baseline, first year, and second year of follow-up) matched with the PsAID values at each of the 3 visits. PsAID was categorized into two groups (<4 and ≥4). We trained a logistic regression model and random forest-type and XGBoost machine learning algorithms to analyze the association between the outcome measure and the variables selected in the bivariate analysis. A k-fold cross-validation with k = 5 was performed., Results: The sample comprised 158 patients. Of the patients who attended the clinic, 45.8% scored PsAID ≥4 at baseline; 27.1%, at the first follow-up visit, and in 23.0%, at the second follow-up visit. The variables associated with PsAID ≥4 were, in decreasing order of importance: HAQ, pain, educational level, and physical activity. Higher HAQ (logistic regression coefficient 10.394; IC95% 7.777,13.011), higher pain (5.668; 4.016, 7.320), lower educational level (-2.064; -3.515, -0.613) and high level of physical activity (1.221; 0.158, 2.283) were associated with a higher frequency of PsAID ≥4. The mean values of the measures of validity of the algorithms were all ≥85%., Conclusions: Despite the higher weight given to pain when scoring PsAID, we observed a greater influence of physical function on disease impact., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022. Published by Elsevier Inc.)

Patients with rheumatoid arthritis (RA) have a significantly increased risk of sexual dysfunction. However, it is not properly included in commonly used questionnaires to assess health-related quality of life in RA. Qualisex is a questionnaire developed in France to assess the impact of RA on patients´ sexual function. Our aim was to adapt and validate this questionnaire for use with Spanish RA patients. Two independent translations and a backward translation were obtained. The final version was tested in a pilot study with 10 RA patients to detect any aspects that could hinder interpretation. The validity and reliability of the linguistically validated questionnaire were studied in a multicenter cross-sectional study, with a longitudinal component for reliability estimation. 125 RA patients were included. The response process, discrimination, internal consistency, internal structure, convergent validity (correlation with MGH-SFQ questionnaire, DAS-28, physician global assessment, patient global health assessment, RAID, HAQ, HADS and SF-12 © ) and reliability were analyzed. The inclusion of two extra items was proposed in the pilot study. The validity analysis detected responses for item 10 that were not coherent with responses for the rest of items. The Cronbach alpha coefficient was 0.971. The highest correlation (0.665) was obtained with MGH-SFQ (questionnaire measuring sexual functioning), followed by RAID (0.516). The intra-class correlation was 0.880 (95% CI 0.815; 0.923), higher than 0.85, which indicates excellent reliability. All parameters used to assess this questionnaire show highly acceptable values. Qualisex allows for a global score of RA patients' sexual functioning and can be self-administered., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Very few data are available on predictors of minimal disease activity (MDA) in patients with recent-onset psoriatic arthritis (PsA). Such data are crucial, since the therapeutic measures used to change the adverse course of PsA are more likely to succeed if we intervene early. In the present study, we used predictive models based on machine learning to detect variables associated with achieving MDA in patients with recent-onset PsA., Methods: We performed a multicenter observational prospective study (2-year follow-up, regular annual visits). The study population comprised patients aged ≥18 years who fulfilled the CASPAR criteria and less than 2 years since the onset of symptoms. The dataset contained data for the independent variables from the baseline visit and from follow-up visit number 1. These were matched with the outcome measures from follow-up visits 1 and 2, respectively. We trained a random forest-type machine learning algorithm to analyze the association between the outcome measure and the variables selected in the bivariate analysis. In order to understand how the model uses the variables to make its predictions, we applied the SHAP technique. We used a confusion matrix to visualize the performance of the model., Results: The sample comprised 158 patients. 55.5% and 58.3% of the patients had MDA at the first and second follow-up visit, respectively. In our model, the variables with the greatest predictive ability were global pain, impact of the disease (PsAID), patient global assessment of disease, and physical function (HAQ-Disability Index). The percentage of hits in the confusion matrix was 85.94%., Conclusions: A key objective in the management of PsA should be control of pain, which is not always associated with inflammatory burden, and the establishment of measures to better control the various domains of PsA., (© 2022. The Author(s).)

Background: Spondyloarthritis (SpA) is one of the most common extraintestinal manifestations of inflammatory bowel disease (IBD). Diagnostic delay must be avoided., Aims: We assessed the validity of SpA screening criteria (any of the following characteristics: chronic low back pain with onset before 45 years of age; inflammatory lower back pain or alternating buttock pain; arthritis; heel enthesitis; dacylitis; HLA-B27 positivity; sacroiliitis on imaging)., Methods: This was a multicenter cross-sectional observational study in IBD patients aged ≥18 years. After evaluating the SpA screening criteria, the gastroenterologists referred the participants to the rheumatologists, who determined whether the patient fulfilled the screening criteria and carried out the necessary tests for SpA diagnosis., Results: 35 (11.7%) out of 300 patients were diagnosed with SpA. The combination with the best balance between sensitivity and specificity (91.4% and 72.1%, respectively, when applied by the rheumatologists; 80% and 78.9%, when applied by the gastroenterologists) for SpA screening, was fulfillment of any of the following: chronic low back pain with onset before age 45 years, inflammatory low back pain or alternating buttock pain, arthritis, or dactylitis., Conclusion: This is one of the first studies to validate SpA screening criteria in IBD patients in routine clinical practice., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest related to this work., (Copyright © 2021. Published by Elsevier Ltd.)

Objective: Axial osteoarthritis (OA) is a common cause of back and neck pain, however, few studies have examined its prevalence. The aim was to estimate the prevalence and the characteristics of symptomatic axial OA in Spain., Methods: EPISER2016 is a cross-sectional multicenter population-based study of people aged 40 years or older. Subjects were randomly selected using multistage stratified cluster sampling. Participants were contacted by telephone to complete rheumatic disease screening questionnaires. Two phenotypes were analyzed, patients with Non-exclusive axial OA (NEA-OA) and Exclusive axial OA (EA-OA). To calculate the prevalence and its 95% confidence interval (CI), the sample design was considered and weighting was calculated according to age, sex and geographic origin., Results: Prevalence of NEA-OA by clinical or clinical-radiographic criteria was 19.17% (95% CI: 17.82-20.59). The frequency of NEA-OA increased with age (being 3.6 times more likely in patients aged 80 s or more than in those between 40 and 49 years) and body mass index. It was significantly more frequent in women, as well as in the center of Spain. It was less frequent in those with a higher level of education. Lumbar OA was more frequent than cervical OA. This difference grew with increasing age and was not associated with gender. It was also greater in overweight and obese subjects., Conclusions: This is the first study on the prevalence of axial OA phenotypes in Europe describing the associated socio-demographic, anthropometric, and lifestyle variables., (© 2021. The Author(s).)

Objectives: To identify patient- and disease-related characteristics that make it possible to predict higher disease severity in recent-onset PsA., Methods: We performed a multicenter observational prospective study (2-year follow-up, regular annual visits). The study population comprised patients aged ≥ 18 years who fulfilled the CASPAR criteria and less than 2 years since the onset of symptoms. Severe disease was defined at each visit as fulfillment of at least 1 of the following criteria: need for systemic treatment, Health Assessment Questionnaire (HAQ) > 0.5, polyarthritis. The dataset contained data for the independent variables from the baseline visit and follow-up visit number 1. These were matched with the outcome measures from follow-up visits 1 and 2, respectively. We trained a logistic regression model and random forest-type and XGBoost machine learning algorithms to analyze the association between the outcome measure and the variables selected in the bivariate analysis., Results: The sample comprised 158 patients. At the first follow-up visit, 78.2% of the patients who attended the clinic had severe disease. This percentage decreased to 76.4% at the second visit. The variables predicting severe disease were patient global pain, treatment with synthetic DMARDs, clinical form at diagnosis, high CRP, arterial hypertension, and psoriasis affecting the gluteal cleft and/or perianal area. The mean values of the measures of validity of the machine learning algorithms were all ≥ 80%., Conclusion: Our prediction model of severe disease advocates rigorous control of pain and inflammation, also addressing cardiometabolic comorbidities, in addition to actively searching for hidden psoriasis., Competing Interests: DS-M received honoraria from Galapagos for an educational event. AL received payment or honoraria for speakers’ bureaus and educational events, support for attending meetings, and participation on Advisory Boards from Novartis, Pfizer, Amgen, Janssen, and Lilly. EG received payment for presentations, support for attending meetings, and participation on Advisory Boards from Novartis, Pfizer, Amgen, Janssen, Lilly, AbbVie, MSD, Roche, and UCB. JP received payment for presentations, support for attending meetings, and participation on Advisory Boards from Janssen, Novartis, and Lilly. JB received payment for a presentation from Amgen and support for attending meetings from AbbVie and Pfizer. BJ received payment for speaker bureau, support for attending meetings, and participation on Advisory Boards from Novartis, UCB, and Amgen. JR received consulting fees, payment for presentations, support for attending meetings, and participation on Advisory Boards from MSD, Novartis, AbbVie, Pfizer, Janssen, Amgen, UCB, and Lilly. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Queiro, Seoane-Mato, Laiz, Galindez Agirregoikoa, Montilla, Park, Pinto Tasende, Bethencourt Baute, Joven Ibáñez, Toniolo, Ramírez and Pruenza García-Hinojosa.)

Myotonic dystrophy type 1 is a debilitating neuromuscular disease causing muscle weakness, myotonia, and cardiac dysfunction. The phenotypes are caused by muscleblind-like (MBNL) protein sequestration by toxic RNA in the DM1 protein kinase ( DMPK ) gene. DM1 patients exhibit a pathogenic number of repetitions in DMPK , which leads to downstream symptoms. Another disease characteristic is altered microRNA (miRNA) expression. It was previously shown that miR-23b regulates the translation of MBNL1 into protein. Antisense oligonucleotide (AON) treatment targeting this miRNA can improve disease symptoms. Here, we present a refinement of this strategy targeting a miR-23b binding site on the MBNL1 3' UTR in DM1 model cells and mice by using AONs called blockmiRs. BlockmiRs linked to novel cell-penetrating peptide chemistry showed an increase in MBNL1 protein in DM1 model cells and HSA LR mice. They also showed an increase in muscle strength and significant rescue of downstream splicing and histological phenotypes in mice without disturbing the endogenous levels of other miR-23b target transcripts., Competing Interests: We declare that R.A., B.L., and E.C.-H. are co-inventors in patent PCT/EP2017/073685, currently licensed to Arthex Biotech, of which R.A. and B.L. are co-founders and R.A. is scientific consultant., (© 2022 The Author(s).)

Objective: To estimate the prevalence of gout in Spain., Methods: Cross-sectional, population-based study of people aged 20 years or older. First, randomly selected individuals were contacted by telephone and rheumatic disease screening questionnaires were conducted. If the first screening was positive, medical records were then reviewed and/or a phone questionnaire was conducted by a rheumatologist, followed by an appointment if necessary. Newly diagnosed cases had to fulfil the ACR/EULAR 2015 criteria. To calculate the prevalence and its 95% CI, the sample design was taken into account and weighing was calculated according to age, sex and geographic origin., Results: In all, 4916 individuals were included, 1361 had a positive screening result for gout (59 of them reported a prior diagnosis). Of these, 51 were classified as missing and 95 were classified as gout cases. An additional case was detected through a positive screening for fibromyalgia and Sjögren's syndrome, although a previous gout diagnosis was confirmed by a review of the medical records. Of the 96 gout cases, 31 (32%) were de novo diagnoses. The estimated weighted prevalence of gout was 2.4% (95% CI 1.95-2.95), with a higher prevalence in men (4.55% [95%CI 3.65-5.65]) than women (0.38% [95%CI 0.19-0.76])., Conclusion: EPISER2016 is the first population-based study to estimate the prevalence of gout in Spain. Undiagnosed patients accounted for a substantial proportion of cases, highlighting the need for population-approaches when estimating the prevalence of infra-diagnosed diseases. Reliable national approaches are key to obtaining accurate estimates of diseases to better aid healthcare and workforce planning., (Copyright © 2021 Société française de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.)

Introduction: The Spanish Society of Rheumatology carried out the EPISER2000 study in 2000 to determine the prevalence of osteoarthritis and other rheumatic diseases in the Spanish population. Recent sociodemographic changes and lifestyle habits in Spain justified updating the epidemiological data on osteoarthritis and other rheumatic diseases (EPISER2016-study)., Objective: To estimate the prevalence of symptomatic osteoarthritis of the cervical spine, lumbar spine, hip, knee and hand in the adult population in Spain., Material and Methods: Cross-sectional population-based study. A multistage and stratified random cluster sampling was carried out. The participants were contacted by telephone to complete an osteoarthritis screening questionnaire. A rheumatologist confirmed or discarded the diagnosis. The ACR-clinical-criteria were used to diagnose hand-osteoarthritis and the ACR-clinical-radiological criteria to diagnose knee- and hip-osteoarthritis. To estimate the prevalence and its 95% confidence interval, weights were calculated according to the probability of selection in each of the sampling stages., Results: The prevalence of osteoarthritis in Spain in one or more of the locations studied was 29.35%. The prevalence of cervical-osteoarthritis was 10.10% and of lumbar-osteoarthritis 15.52%. Both are more frequent in women and at older ages, as well as in people with low levels of education and obesity. The prevalence of hip-osteoarthritis was 5.13%, that of knee-osteoarthritis 13.83%, these are associated with female sex, overweight and obesity. The prevalence of hand osteoarthritis was 7.73%. It is more frequent in women, who are obese, with a low educational level and who are older., Conclusion: The EPISER2016 study is the first to analyse the prevalence of symptomatic osteoarthritis in 5 locations (cervical, lumbar, knee, hip and hands) in Spain. Lumbar spine osteoarthritis is the most prevalent., (Copyright © 2020. Published by Elsevier España, S.L.U.)

Myotonic dystrophy type 1 (DM1) is a rare neuromuscular disease caused by expansion of unstable CTG repeats in a non-coding region of the DMPK gene. CUG expansions in mutant DMPK transcripts sequester MBNL1 proteins in ribonuclear foci. Depletion of this protein is a primary contributor to disease symptoms such as muscle weakness and atrophy and myotonia, yet upregulation of endogenous MBNL1 levels may compensate for this sequestration. Having previously demonstrated that antisense oligonucleotides against miR-218 boost MBNL1 expression and rescue phenotypes in disease models, here we provide preclinical characterization of an antagomiR-218 molecule using the HSA LR mouse model and patient-derived myotubes. In HSA LR , antagomiR-218 reached 40-60 pM 2 weeks after injection, rescued molecular and functional phenotypes in a dose- and time-dependent manner, and showed a good toxicity profile after a single subcutaneous administration. In muscle tissue, antagomiR rescued the normal subcellular distribution of Mbnl1 and did not alter the proportion of myonuclei containing CUG foci. In patient-derived cells, antagomiR-218 improved defective fusion and differentiation and rescued up to 34% of the gene expression alterations found in the transcriptome of patient cells. Importantly, miR-218 was found to be upregulated in DM1 muscle biopsies, pinpointing this microRNA (miRNA) as a relevant therapeutic target., Competing Interests: B.L., R.A., J.M.F.-C., and E.C.-H. are inventors in patent PCT/EP2017/073685. This patent is currently licensed to Arthex Biotech, of which B.L. and R.A. are founders and CEO and scientific consultant, respectively. B.L. and R.A. each hold more than 5% ownership of Arthex, a company with related interests., (© 2021 The Author(s).)