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When investigating a death, post-mortem identification provides with results of great legal and humanitarian significance. The effectiveness of the methods used to estimate age depends on the reference population, considering variables such as sex and ancestry. The aim of this study was to validate the Iscan method to estimate age in a Spanish forensic population, comparing the estimates obtained in dry bones and 3D reconstructions created with a surface scanner. We carried out a cross-sectional study on 109 autopsied corpses (67% male), scanning the sternal end of the right fourth rib in a 3D mesh, using an EinScan-Pro® surface scanner (precision: 0.05 mm). Two observers estimated the phases in dry bones and 3D images according to the Iscan method and to the sex of the subject. The mean age was 57.73 years (SD = 19.12 years;18–93 years). The intra-observer agreement was almost perfect in bones (κ = 0.877–0.960) and 3D images (κ = 0.954), while the inter-observer agreement was almost perfect in bones (κ = 0.813) and substantial in 3D images (κ = 0.727). The correlation with the Iscan phases was very strong in bones (Rho = 0.794–0.820; p p R2 = 0.65; SEE = ± 11.264 years; 3D images: R2 = 0.50; SEE = ± 13.537 years) from phase 4 onwards. An overestimation of age was observed in the first phases, and an underestimation in the later ones. Virtual analysis using a surface scanner in the fourth rib is a valid means of estimating age. However, the error values and confidence intervals were considerable, so the joint use of different methods and anatomical sites is recommended.

Objectives To examine the prevalence of extra-musculoskeletal manifestations (EMM) and the association between diagnostic delay and their incidence in ankylosing spondylitis (AS) and psoriatic arthritis (PsA). Methods Retrospective, cohort study comprising two single centre cohorts in Europe and one multicentre cohort in Latin America (RESPONDIA). EMMs (uveitis, inflammatory bowel disease [IBD] and psoriasis) crude prevalence was calculated across geographic area and adjusted by direct standardisation. Cox proportional hazard analysis were performed to assess the association between diagnostic delay and EMM incidence. Results Of 3553 patients, 2097 had AS and 1456 had PsA. The overall prevalence of uveitis was 22.9% (95%CI 21.1–24.8) in AS and 3.8% (95%CI 2.9–5.0) in PsA; 8.1% (95%CI 7.0–9.4) and 2.1% (1.3–2.9) respectively for IBD; 11.0% (95%CI 9.7–12.4) and 94.6% (93.0–95.9) for psoriasis; with EMM often presenting before the arthritis (uveitis 45.1% and 33.3%; IBD 37.4% and 70% in AS and PsA respectively). In the multivariable model, longer diagnostic delay (≥5 years) associated with more uveitis (HR 4.01, 95%CI 3.23–4.07) and IBD events (HR 1.85, 95%CI 1.28–2.67) in AS. Diagnostic delay was not significantly associated with uveitis (HR 1.57, 95%CI 0.69–3.59) or IBD events (HR 1.59, 95%CI 0.39–6.37) in PsA. Conclusion EMMs are more prevalent in AS than PsA and often present before the onset of the articular disease. A longer diagnostic delay is associated with the “de novo” appearance of uveitis and IBD in AS, highlighting the need to enhance diagnostic strategies to shorten the time from first symptom to diagnosis in SpA.

Resumen Objectifs: Decrire la date de survenue de l’uveite anterieure aigue (UAA) par rapport aux premiers symptomes rhumatismaux et determiner son association a l’evolution de la spondyloarthrite (SpA) en ce qui concerne l’activite, les lesions structurelles, la capacite fonctionnelle et le traitement. Methodes: Il s’agit d’une etude transversale s’appuyant sur les donnees du registre REGISPONSER (registre national des SpA de la societe espagnole de rhumatologie). Trente-et-un centres ont participe et les patients atteints de SpA selon les criteres de l’ESSG ont ete inclus entre 2004 et 2007. La classification des patients s’est faite selon la date de survenue de l’uveite par rapport aux premiers signes rhumatismaux (anterieure, simultanee ou posterieure a l’apparition des symptomes). Nous avons compare les caracteristiques cliniques, l’activite de la maladie, les lesions radiographiques et la capacite fonctionnelle entre les « UAA survenues avant/simultanement aux premiers symptomes rhumatismaux » et les « UAA survenues apres les premiers symptomes ». Pour finir, nous avons analyse l’impact de la date de survenue de l’UAA sur le recours aux anti-rhumatismaux modificateurs de la maladie conventionnels et biologiques (respectivement DMARDcs et DMARDb) Resultats: Au total, 2 367 patients ont ete inclus dans le registre REGISPONSER avec une prevalence de l’UAA de 16,2 % (379 patients). Les patients dont l’UAA precedait/accompagnait les premiers signes rhumatismaux (n=59) affichaient une meilleure capacite fonctionnelle (BASFI, OR 0,85 [0,73-0,99]) et des lesions structurelles moins marquees (BASRI au rachis, OR 0,88 [0,79-0,99]). De plus, dans ce groupe de patients, l’âge d’apparition des premiers symptomes de SpA etait plus avance (OR 1,05 [1,02-1,09]) et le delai diagnostique plus court (OR 0,90 [0,84-0,96]) comparativement aux patients ayant developpe une UAA apres l’apparition des manifestations rhumatismales (n=229). Aucune difference statistiquement significative concernant l’utilisation des DMARD n’a ete observee (27,9 % vs 23,2 % pour l’utilisation des DMARDcs et 15,3 % vs 20,3 % pour l’utilisation des DMARDb chez les patients avec une UAA survenue respectivement avant/simultanement vs apres les premiers signes rhumatismaux). Conclusion: Les patients qui presentaient un premier episode d’UAA avant/simultanement aux premiers symptomes rhumatismaux avaient une forme moins severe de la maladie (meilleure capacite fonctionnelle et dommages structuraux limites) et un delai diagnostique plus court ; cependant, la date de survenue de l’UAA n’a montre aucun effet sur les traitements administres.

Objective: Systemic lupus erythematosus (SLE) is associated to boosted atherosclerosis development and a higher cardiovascular disease risk. This study aimed to delineate the role of anti-double stranded DNA (anti-dsDNA) antibodies on the molecular profile and the activity of immune and vascular cells, as well as on their enhanced cardiovascular risk. Approach and Results: Eighty SLE patients were included. Extensive clinical/analytical evaluation was performed, including cardiovascular disease parameters (endothelial function, proatherogenic dyslipidemia, and carotid intima-media thickness). Gene and protein expression profiles were evaluated in monocytes from patients diagnosed positive or negative for anti-dsDNA antibodies by using NanoString and cytokine arrays, respectively. NETosis and circulating inflammatory profile was assessed in both neutrophils and plasma. Positivity and persistence of anti-dsDNA antibodies in SLE patients were associated to endothelial dysfunction, proatherogenic dyslipidemia, and accelerated atherosclerosis. In parallel, anti-dsDNA antibodies were linked to the aberrant activation of innate immune cells, so that anti-dsDNA(+) SLE monocytes showed distinctive gene and protein expression/activity profiles, and neutrophils were more prone to suffer NETosis in comparison with anti-dsDNA(−) patients. Anti-dsDNA(+) patients further displayed altered levels of numerous circulating mediators related to inflammation, NETosis, and cardiovascular risk. In vitro, Ig-dsDNA promoted NETosis on neutrophils, apoptosis on monocytes, modulated the expression of inflammation and thrombosis-related molecules, and induced endothelial activation, at least partially, by FcR (Fc receptor)-binding mechanisms. Conclusions: Anti-dsDNA antibodies increase the cardiovascular risk of SLE patients by altering key molecular processes that drive a distinctive and coordinated immune and vascular activation, representing a potential tool in the management of this comorbidity.

Objectives To determine groups of factors (clusters) potentially associated with the patient global assessment (measured with the Bath Ankylosing Spondylitis Patient Global Score (BAS-G)), and to quantify the contribution of each cluster to the patient's well-being. Methods This was a cross-sectional study in patients with a diagnosis of ankylosing spondylitis (AS) from the national, multicentre Spanish REGISPONSER-AS registry. A hierarchical cluster analysis was conducted to group the potential factors (sociodemographic, socioeconomic, patient-reported outcomes, physical exploration variables and depression) associated with the BAS-G. The contribution of each cluster to the variability of the BAS-G was evaluated using a multivariate linear regression model and the determination coefficient (R2) for each cluster. Results A total of 681 patients with complete data were included. Three clusters of variables potentially associated with the BAS-G were found: cluster 1 contained the Maastricht Ankylosing Spondylitis Enthesitis Score (MASES), depression, sex (female) and university studies; cluster 2 included the Graffar scale, age and body mass index; and cluster 3 contained the Bath Ankylosing Spondylitis Functional Index (BASFI), the individual items of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), pain during the last week, nocturnal pain and the number of swollen joints. A total of 6.8% of the variability of the BAS-G was explained by cluster 1, 0.5% was explained by cluster 2, and 60.8% was explained by cluster 3. Conclusion The BAS-G is mostly explained by pain and function, while demographic and socioeconomic factors are weakly associated with the BAS-G. Depression also has a weak effect on this score.

Objectif Analyser l’association potentielle entre la presence de HLA-B27 et les differentes comorbidites observees chez les patients atteints de spondyloarthrite axiale. Methodes Une etude comparative transversale incluant des patients ayant une spondyloarthrite axiale et issus du registre COMOSPA ; COMOSPA est un registre international qui regroupe un grand nombre de variables anthropometriques et cliniques provenant de 3984 patients atteints de spondyloarthrite. Le registre comprend egalement les comorbidites les plus frequemment observees au cours de la spondyloarthrite comme l’obesite, l’hypertention, le diabete, l’hyperlipidemie, la cardiopathie ischemique, l’AVC, l’insuffisance renale, les neoplasmes, l’ulcere gastro-duodenal, la diverticulite, la bronchopneumopathie chronique obstructive et l’osteoporose. Une analyse descriptive et un modele de regression logistique multiple ont ete realises en incluant toutes les variables evaluees. Resultats Un total de 2370 patients repondant aux criteres ASAS pour la spondyloarthrite axiale ont ete inclus dans cette etude. Parmi eux, 1858 (78,4 %) etaient positifs pour le HLA-B27. Les patients souffrant de spondyloarthrite axiale et HLA-B27 positifs etaient majoritairement de sexe masculin, avec une maladie de plus longue duree, un pourcentage superieur de spondylarthrites ankylosantes averees, une CRP plus elevee mais egalement un tabagisme et une consommation excessive d’alcool plus marques comparativement aux patients HLA-B27 negatifs. A noter cependant qu’une forme plus active de la maladie selon le BASDAI, BASFI et l’ADAS-CRP a ete rapportee chez les patients negatifs pour le HLA-B27 comparativement aux patients positifs. La seule association observee entre les comorbidites et la positivite pour le HLA-B27 a ete la presence de l’osteoporose, meme apres ajustement dans l’analyse multivariee sur toutes les variables etudiees. Conclusion L’association observee entre le HLA-B27 et l’osteoporose dans la spondyloarthrite axiale pourrait avoir un interet tout particulier si l’on considere l’impact de l’osteoporose sur le phenotype de ces patients.

The impact of the COVID-19 pandemic and lockdown may affect suicide risk and behavior. We compared suicide-related presentations during the national quarantine with pre-COVID data. This observational incidence study compared all suicide-related presentations at the University Hospital Reina Sofia emergency department (ED) in Cordoba, Spain, for the lockdown period from 15 March to 15 May 2020, with the same period in 2019. Descriptive and inferential analyses of case characteristics between 2019 and 2020 periods were conducted, and a multivariable logistic regression model developed. Results: Despite a decrease in overall ED cases during the lockdown, the number of suicide-related presentations stayed the same and represented a significantly larger proportion of cases in comparison to the pre-COVID period (0.42 vs. 0.87%, in 2019 and 2020, respectively; p < .001). The number presenting alone more than doubled during the COVID lockdown, increasing to 42.9% compared with 19.4% in 2019 (p = .002). An increase in presentations with a family history of suicide was also found. Conclusions: Suicide cases represented an increased proportion of ED cases during the lockdown. Presenting to ED alone, having a family history of suicide, habitual drug consumption, and hospital admission to ICU differentiated cases between pre and during COVID periods. These findings should be considered in light of the second wave and further implementation of lockdown measures.

Heart failure (HF) is the leading cause of hospitalization for aging populations in Western countries, and is showing an increasing mortality. The aim of this study was to assess the probable long-term mortality risk factors for patients admitted because of HF. Retrospective study of a cohort of 202 patients consecutively hospitalized because of HF and followed up for a maximum period of 5 years. Clinical and epidemiological factors and their relationship to in-hospital and long-term mortality were analyzed. In-hospital mortality was 16%.The independent predictors were: age >75 years (HR?=?2.68, 95%?IC: 1.65-4.36, p?=?0.001); cognitive impairment (HR?=?2.77, 95%?IC: 1.40-5.48, p?=?0.004); Barthel index =60 (HR?=?0.54, 95%?IC: 0.37-0.78, p?=?0,009); creatinine levels >1.16 mg/dl at admission (HR?=?1.57, 95%?IC: 1.12-2.20, p?=?0.009); and number of diagnostics >10 on discharge (HR?=?1. 64, 95%?IC: 1.14-2.36, p?=?0.007). Accumulated mortality at 12, 24, 36 and 48 months after hospital discharge were 43%, 51%, 67% and 70%, respectively; the independent predictors for this were: age >75 years (HR?=?2.55, 95%?IC: 1.56-4.15, p?75 years (HR?=?2.68, 95%?IC: 1.65-4.36, p?=?0.001); cognitive impairment (HR?=?2.77, 95%?IC: 1.40-5.48, p?=?0.004); Barthel index =60 (HR?=?0.54, 95%?IC: 0.37-0.78, p?=?0,009); creatinine levels >1.16 mg/dl at admission (HR?=?1.57, 95%?IC: 1.12-2.20, p?=?0.009); and number of diagnostics >10 on discharge (HR?=?1. 64, 95%?IC: 1.14-2.36, p?=?0.007). Accumulated mortality at 12, 24, 36 and 48 months after hospital discharge were 43%, 51%, 67% and 70%, respectively; the independent predictors for this were: age >75 years (HR?=?2.55, 95%?IC: 1.56-4.15, p?1.16 mg/dl at admission (HR?=?1.57, 95%?IC: 1.12-2.20, p?=?0.009); and number of diagnostics >10 on discharge (HR?=?1. 64, 95%?IC: 1.14-2.36, p?=?0.007). Accumulated mortality at 12, 24, 36 and 48 months after hospital discharge were 43%, 51%, 67% and 70%, respectively; the independent predictors for this were: age >75 years (HR?=?2.55, 95%?IC: 1.56-4.15, p?10 on discharge (HR?=?1. 64, 95%?IC: 1.14-2.36, p?=?0.007). Accumulated mortality at 12, 24, 36 and 48 months after hospital discharge were 43%, 51%, 67% and 70%, respectively; the independent predictors for this were: age >75 years (HR?=?2.55, 95%?IC: 1.56-4.15, p?75 years (HR?=?2.55, 95%?IC: 1.56-4.15, p?1.16 mg/dl on admission (HR?=?1.59, 95%?IC: 1.12-2.24, p?=?0.009); systolic blood pressure >140 mm Hg on admission (HR?=?0.56, 95%?IC: 0.40-0.80, p?140 mm Hg on admission (HR?=?0.56, 95%?IC: 0.40-0.80, p?10 on discharge (HR?=?1. 49, 95%?IC: 1.03-2.16, p?=?0.033). Clinical and epidemiological factors related to in-hospital and long-term mortality could help to improve the management of patients with HF.

The purpose of this prospective study was to compare the clinical and structural findings following the arthroscopic repair of partial-thickness (exceeding 50%) articular-sided rotator cuff tears using either a single-row or a double-row suture bridge fixation. Fifty patients were included in this study. The patients were randomly placed into two groups: 25 underwent the single-row (Group I) and 25 a double-row suture bridge fixation (Group II). The clinical outcomes were assessed using ASES and Constant shoulder scores, both preoperatively and at the end of follow-up. The pain level was evaluated using the visual analogue scale (VAS), preoperatively, at 6 months and at the end of follow-up. All patients underwent preoperative MRI to identify the rotator cuff tear, and postoperatively at 12 months to evaluate tendon integrity. The average follow-up was 32.5 months. The mean ASES scores increased from 35.9 to 96.7 in Group I and from 35.3 to 93.4 in Group II; the mean Constant shoulder scores increased from 55.6 to 97.8 in Group I and from 57.5 to 97.3 in Group II. There were no significant differences between the two groups. The average preoperative pain level decreased from 7.4 to 3 at 6 months and to 0.4 at the end of the Group I; and from 7.6 to 3 at 6 months and 0.8 in Group II. There was no significant difference between the two groups. At 12 months, the MRI assessments showed two retears in Group I (8%) and one retear in Group II (4%). Arthroscopic repair of partial-thickness articular rotator cuff tears that exceed 50% of tendon thickness with a single-row transtendon repair or double-row suture bridge provides functional improvement and pain relief regardless of the repair technique used. There were no differences in clinical results between both techniques. Level II; prospective comparative study.

Espondilitis anquilosante; Artritis; Epidemiología Espondilitis anquilosant; Artritis; Epidemiologia Ankylosing spondylitis; Arthritis; Epidemiology Aims To explore the clinical and radiographical characteristics of axial psoriatic arthritis (PsA) and to compare it with ankylosing spondylitis (AS) with psoriasis. Methods Cross-sectional study from the national multicentre registry REGISPONSER where participants fulfilled the European Spondyloarthropathy Study Group spondyloarthritis criteria at entry. Clinical, laboratory and radiographical characteristics between patients classified as axial PsA and AS with psoriasis by their rheumatologist are compared according to HLA-B27 status. Results Of 2367 patients on REGISPONSER, n=405 had PsA, of whom 27% (n=109) had axial involvement as per the treating rheumatologist. 30% (n=26/86) of axial PsA were HLA-B27 positive. In the AS group, 9% (127/1422) had a history of psoriasis and were more frequently male, with longer diagnostic delay and more anterior uveitis than those with axial PsA who had more peripheral involvement and nail disease. Patients with HLA-B27-negative axial PsA reported less inflammatory pain and structural damage compared with AS with psoriasis. By contrast, HLA-B27-positive axial PsA shared clinical characteristics similar to AS and psoriasis although with a lower BASRI score. In the multivariable analysis, patients with AS and psoriasis were independently associated with HLA-B27 positivity (OR 3.34, 95% CI 1.42 to 7.85) and lumbar structural damage scored by BASRI (OR 2.14, 95% CI 1.4 to 3.19). Conclusion The more prevalent axial PsA phenotype is predominantly HLA-B27 negative and presents different clinical and radiological manifestations when compared with AS with psoriasis. There is great heterogeneity in what rheumatologists consider axial PsA from a clinical and imaging perspective, highlighting the need for research into possible genetic drivers and a consensus definition. HM-O is supported by the National Institute for Health Research Leeds Biomedical Research Centre. The REGISPONSER registry is funded by an unrestricted grant from the Spanish Society for Rheumatology. There was no specific funding for the current analysis.

Introduction: The aim of the study was to compare the prevalence of comorbidities between patients with axial and peripheral phenotypes and to evaluate the role of psoriasis in such comorbidities. Methods: Patients from the cross-sectional Assessment in SpondyloArthritis Inter-national Society (ASAS)-COMOSPA study were classified as having either the axial (presence of sacroiliitis on X-ray or MRI) or peripheral phenotype (absence of sacroiliitis AND presence of peripheral involvement). Patients with each phenotype were divided into two groups depending on the presence or history of psoriasis. Pair-wise comparisons among the four groups (axial/peripheral phenotype with/without psoriasis) were conducted through univariate logistic regressions and generalized linear mixed models using disease duration and sex as fixed effects and country as random effect. Results: A total of 3291 patients were included in this analysis. The peripheral involvement with psoriasis phenotype showed the highest prevalence of hypertension (44.9%), dyslipidaemia (34%) and diabetes (8.8%), while the axial involvement without psoriasis phenotype exhibited the lowest prevalence of dyslipidaemia (14.2%), diabetes (4.1%) and stroke (0.9%). Among patients with psoriasis, the axial phenotype showed a significantly lower prevalence of hypertension (OR: 0.51, 95% CI: 0.35–0.75) and lower prevalence of Framingham score ⩾15 (OR: 0.57, 95% CI: 0.38–0.85) than patients with peripheral involvement after adjusting for disease duration, sex and country. Among patients with the axial phenotype, patients with psoriasis showed a higher prevalence of hypertension (OR 1.76, 1.40–2.20), dyslipidaemia (OR: 1.99, 95% CI: 1.56–2.53), diabetes (OR: 2.05, 95% CI: 1.39–3.02) and Framingham score ⩾15 (OR: 2.00, 95% CI: 1.57–2.55) than non-psoriatic patients. No differences were found across groups concerning bone metabolism disorders. Conclusion: Both the peripheral phenotype and psoriasis are independently associated with an increased prevalence of cardiovascular risk factors. No differences were found for bone metabolism disorders.

Aim: The main objective of this study was to determine the prevalence of real DDIs between immunosuppressants and other drugs in transplant patients. Methods: We conducted a prospective, observational 1-year study at a tertiary hospital, including all transplanted patients. We evaluated data from monitoring blood concentrations of immunosuppressive drugs and adverse drug events (ADEs) caused by DDIs. The DDIs were classified as C, D, or X according to their Lexi-Interact rating (C = monitor therapy, D = consider therapy modification, X = avoid combination). The clinical importance of real DDIs was expressed in terms of patient outcomes. The data were analyzed using Statistical Package for Social Sciences (SPSS) package v. 25.0 (IBM Corp., Armonk, NY, USA). Results: A total of 309 transplant patients were included. Their mean age was 52.0 ± 14.7 years (18–79) and 69.9% were male. The prevalence of real DDIs was 21.7%. Immunosuppressive drugs administered with anti-fungal azoles and tacrolimus (TAC) with nifedipine have a great clinical impact. Real DDIs caused ADEs in 22 patients. The most common clinical outcome was nephrotoxicity (1.6%; n=5), followed by hypertension (1.3%; n=4). Suggestions for avoiding category D and X DDIs included: changing the immunosuppressant dosage, using paracetamol instead of non-steroidal anti-inflammatory drugs, and interrupting atorvastatin. The number of drugs prescribed and having been prescribed TAC was associated with an increased risk of real DDIs. Conclusion: There are many potential DDIs described in the literature but only a small percentage proved to be real DDIs, based on the patients´ outcomes.

The physician's duty of confidentiality is based on the observance of the patient's privacy and intimacy and on the importance of respecting both of these rights, thus creating a relationship of confidence and collaboration between doctor and patient. The main objective of this work consists of analyzing the aspects that are related to the confidentiality of patients' data with respect to the training, conduct and opinions of doctors from different Clinical Management Units of a third-level hospital via a questionnaire. The present study aimed to define the problem and determine whether the opinions of these professionals correspond to those observed in a previous work conducted at the same center. Of the 200 questionnaires that were collected, 62.5% were from consultants and the rest were from residents (37.5%) with an average of 14.4 ± 12.5 years in professional practice. The respondents noted habitual situations in which confidentiality was breached in the reference hospital (74%). The section on their attitudes and behaviors towards situations related to confidentiality showed a slightly lower average score than that of their medical knowledge; significant differences in these scores were observed between the consultants and residents as well as between the extreme age groups (≤ 30 vs. ≥ 51 years) and years of professional practice, thus more inadequate attitudes were consistently noted in younger doctors who had fewer years of experience. Finally, the respondents answered that the training of doctors in the aspects of healthcare law and ethics was the most important measure that the hospital could adopt regarding confidentiality practices.

Resume Objectifs Cette etude avait pour objectifs : (1) de comparer la prevalence de la maladie cardiovasculaire et des facteurs de risque cardiovasculaire entre les differents phenotypes de la spondyloarthrite (SpA) ; (2) d’evaluer les differences en matiere de maladie cardiovasculaire et de facteurs de risque cardiovasculaire entre deux zones geographiques – le nord de l’Europe vs les pays mediterraneens ; (3) d’identifier les facteurs predictifs d’un score de Framingham eleve en fonction des caracteristiques cliniques de la SpA et de la zone geographique. Methodes Analyse derivee de l’etude observationnelle, transversale, multicentrique internationale Asas-Comospa. La maladie cardiovasculaire et les facteurs de risque cardiovasculaire ont ete compares selon le phenotype de la SpA et la zone geographique. Les facteurs associes a un haut risque cardiovasculaire (score de Framingham eleve) ont ete determines a partir d’un modele de regression logistique multiple. Resultats Les facteurs de risque cardiovasculaire et de maladie cardiovasculaire les plus frequents etaient respectivement le tabagisme (31,2 %) et une cardiopathie ischemique (3,2 %). En ce qui concerne les phenotypes de la SpA, on notait chez les patients atteints de SpA axiale une prevalence significativement moins elevee (p Conclusion D’apres nos resultats, le phenotype de la SpA et la zone geographique sont associes a la prevalence des facteurs de risque cardiovasculaire et au risque cardiovasculaire lui-meme observes chez les patients de la cohorte Asas-Comospa.

Background: This prospective multicenter study developed an integrative clinical and molecular longitudinal study in Rheumatoid Arthritis (RA) patients to explore changes in serologic parameters following anti-TNF therapy (TNF inhibitors, TNFi) and built on machine-learning algorithms aimed at the prediction of TNFi response, based on clinical and molecular profiles of RA patients.Methods: A total of 104 RA patients from two independent cohorts undergoing TNFi and 29 healthy donors (HD) were enrolled for the discovery and validation of prediction biomarkers. Serum samples were obtained at baseline and 6 months after treatment, and therapeutic efficacy was evaluated. Serum inflammatory profile, oxidative stress markers and NETosis-derived bioproducts were quantified and miRNomes were recognized by next-generation sequencing. Then, clinical and molecular changes induced by TNFi were delineated. Clinical and molecular signatures predictors of clinical response were assessed with supervised machine learning methods, using regularized logistic regressions.Results: Altered inflammatory, oxidative and NETosis-derived biomolecules were found in RA patients vs. HD, closely interconnected and associated with specific miRNA profiles. This altered molecular profile allowed the unsupervised division of three clusters of RA patients, showing distinctive clinical phenotypes, further linked to the TNFi effectiveness. Moreover, TNFi treatment reversed the molecular alterations in parallel to the clinical outcome. Machine-learning algorithms in the discovery cohort identified both, clinical and molecular signatures as potential predictors of response to TNFi treatment with high accuracy, which was further increased when both features were integrated in a mixed model (AUC: 0.91). These results were confirmed in the validation cohort.Conclusions: Our overall data suggest that: 1. RA patients undergoing anti-TNF-therapy conform distinctive clusters based on altered molecular profiles, which are directly linked to their clinical status at baseline. 2. Clinical effectiveness of anti-TNF therapy was divergent among these molecular clusters and associated with a specific modulation of the inflammatory response, the reestablishment of the altered oxidative status, the reduction of NETosis, and the reversion of related altered miRNAs. 3. The integrative analysis of the clinical and molecular profiles using machine learning allows the identification of novel signatures as potential predictors of therapeutic response to TNFi therapy.

ObjectivesTo characterise splicing machinery (SM) alterations in leucocytes of patients with rheumatoid arthritis (RA), and to assess its influence on their clinical profile and therapeutic response.MethodsLeucocyte subtypes from 129 patients with RA and 29 healthy donors (HD) were purified, and 45 selected SM elements (SME) were evaluated by quantitative PCR-array based on microfluidic technology (Fluidigm). Modulation by anti-tumour necrosis factor (TNF) therapy and underlying regulatory mechanisms were assessed.ResultsAn altered expression of several SME was found in RA leucocytes. Eight elements (SNRNP70, SNRNP200, U2AF2, RNU4ATAC, RBM3, RBM17, KHDRBS1 and SRSF10) were equally altered in all leucocytes subtypes. Logistic regressions revealed that this signature might: discriminate RA and HD, and anti-citrullinated protein antibodies (ACPAs) positivity; classify high-disease activity (disease activity score-28 (DAS28) >5.1); recognise radiological involvement; and identify patients showing atheroma plaques. Furthermore, this signature was altered in RA synovial fluid and ankle joints of K/BxN-arthritic mice. An available RNA-seq data set enabled to validate data and identified distinctive splicing events and splicing variants among patients with RA expressing high and low SME levels. 3 and 6 months anti-TNF therapy reversed their expression in parallel to the reduction of the inflammatory profile. In vitro, ACPAs modulated SME, at least partially, by Fc Receptor (FcR)-dependent mechanisms. Key inflammatory cytokines further altered SME. Lastly, induced SNRNP70-overexpression and KHDRBS1-overexpression reversed inflammation in lymphocytes, NETosis in neutrophils and adhesion in RA monocytes and influenced activity of RA synovial fibroblasts.ConclusionsOverall, we have characterised for the first time a signature comprising eight dysregulated SME in RA leucocytes from both peripheral blood and synovial fluid, linked to disease pathophysiology, modulated by ACPAs and reversed by anti-TNF therapy.

To evaluate the impact of the number of comorbidities on the outcome measures after two years of follow-up in patients with Ankylosing Spondylitis (AS) and to determine whether the number of comorbidities influences the retention rate of the first anti-TNF.This was an observational and prospective study conducted during 2 years of follow-up in the REGISPONSER-AS registry. The patients were divided into three groups according to the number of comorbidities at baseline (0, 1 or ≥2). Linear regression models adjusted for disease duration, age, sex and smoking were constructed to evaluate the association between the number of comorbidities and the Patient Reported Outcomes (PRO) scores. The impact of the number of comorbidities on PROs over two years of follow-up was evaluated using mixed models for repeated measures adjusted for disease duration, age, sex and smoking. Finally, the retention rate of the first anti-TNF antibody across the three groups was evaluated using a log-rank test.Patients with two or more comorbidities showed higher scores at baseline and during the two years of follow-up for the Global VAS, BASDAI, ASDAS, and BASFI and worse scores for the physical component of the SF12. A higher probability of discontinuation of the first anti-TNF was found in patients with 2 or more comorbidities compared with the patients in the other groups (38.2% vs. 26.6% vs. 25.4% for ≥2 comorbidities, 0 and 1 comorbidity, respectively), although these differences were not significant (log-rank test: p-value = 0.180).In patients with AS, the presence of 2 or more comorbidities was associated with worse scores on the outcome measures test after two years of follow-up and a greater tendency of discontinuation for the first anti-TNF.

Funder: Europeo de Desarrollo Regional de la Unión Europea, Funder: Rheumatic Diseases Network, OBJECTIVE: To analyze the relationship between complement component 3 (C3) and the prevalence of cardiometabolic risk factors and disease activity in the rheumatic diseases having the highest rates of cardiovascular morbidity and mortality: rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA). METHODS: This is a cross-sectional study including 200 RA, 80 PsA, 150 axSpA patients and 100 healthy donors. The prevalence of cardiometabolic risk factors [obesity, insulin resistance, type 2 diabetes mellitus, hyperlipidemia, apolipoprotein B/apolipoprotein A (apoB/apoA) and atherogenic risks and hypertension] was analyzed. Serum complement C3 levels, inflammatory markers and disease activity were evaluated. Cluster analysis was performed to identify different phenotypes. Receiver operating characteristic (ROC) curve analysis to assess the accuracy of complement C3 as biomarker of insulin resistance and disease activity was carried out. RESULTS: Levels of complement C3, significantly elevated in RA, axSpA and PsA patients, were associated with the prevalence of cardiometabolic risk factors. Hard clustering analysis identified two distinctive phenotypes of patients depending on the complement C3 levels and insulin sensitivity state. Patients from cluster 1, characterized by high levels of complement C3 displayed increased prevalence of cardiometabolic risk factors and high disease activity. ROC curve analysis showed that non-obesity related complement C3 levels allowed to identify insulin resistant patients. CONCLUSIONS: Complement C3 is associated with the concomitant increased prevalence of cardiometabolic risk factors in rheumatoid arthritis and spondyloarthritis. Thus, complement C3 should be considered a useful marker of insulin resistance and disease activity in these rheumatic disorders.

Objective To evaluate whether the presence of psoriasis influences the clinical expression, disease activity and disease burden in both axial and peripheral phenotypes of spondyloarthritis (SpA). Methods Patients from the Spanish REGISPONSER registry classified as having SpA according to the ESSG criteria were included. Patients were classified as psoriatic or non-psoriatic depending on the presence of cutaneous or nail psoriasis; thereafter, they were classified as having either axial [presence of radiographic sacroiliitis OR inflammatory back pain (IBP)] or peripheral phenotype (absence of radiographic sacroiliitis AND absence of IBP AND presence of peripheral involvement). Pair-wise univariate and multivariate analyses among the four groups (psoriatic/non-psoriatic axial phenotypes and psoriatic/non-psoriatic peripheral phenotypes) were performed with adjustment for treatment intake. Results A total of 2296 patients were included in the analysis. Among patients with axial phenotype, psoriasis was independently associated (P Conclusion These findings suggest that, among all patients with SpA, psoriasis is associated with differences in clinical expression of SpA, a greater disease burden and increased use of drugs.

BACKGROUND: The objective of the current study was to determine whether overnight pulse oximetry in patients with amyotrophic lateral sclerosis is prognostic of the onset of awake respiratory failure and hospital admissions. METHODS: This was an observational study in a cohort of subjects with amyotrophic lateral sclerosis. The study included subjects with a baseline SpO2 ≥ 94% on home overnight pulse oximetry testing. Patients age ≥ 80 y and those with comorbidities and with poor short-term prognosis or sleep apnea were excluded. The subjects were classified as nocturnal desaturators according to percentage of sleep time with SpO2 10%. RESULTS: A total of 76 subjects were included: 40 men (53%), mean ± SD age 60 ± 14.4 y, mean ± SD body mass index 25.7 ± 4.60 kg/m2, and spinal presentation in 63.2%. After overnight pulse oximetry, 20 subjects (26%) were classified as desaturators and 56 (74%) as non-desaturators. In the first year, the subjects with nocturnal desaturation had respiratory failure more often compared with the subjects without desaturation (35% vs 10.91%; P = .02) and had a higher risk of developing respiratory failure during the course of the study (hazard ratio 2.48; P = .030). The desaturator group also had a higher rate of ≥ 1 admission (40% vs 7.3%; P = .01) and a higher likelihood of respiratory-related hospitalization (hazard ratio 2.41; P = .02). Median survival was almost 1 year less if T90 > 10% was observed in the overnight pulse oximetry: 21 months versus 32 months survival if T90 was ≤ 10%. CONCLUSIONS: In subjects with amyotrophic lateral sclerosis, nocturnal desaturation conferred a higher risk of respiratory failure and poorer prognosis. Even in the absence of other clinical criteria, early pulse oximetry should be performed and the need for nocturnal ventilatory support assessed.

Background and importance The risk of drug interactions in transplant patients is extremely high as they are polymedicated. The characteristics of immunosuppressants constitute an added risk. There are many potential drug–drug interactions (DDIs) but it would be interesting to know which ones are real and have clinical outcomes. Aim and objectives The main objective of the study was to determine the prevalence of real DDIs between immunosuppressants and other drugs in transplant patients. Secondary objectives were to evaluate clinical impact, categorise the type of DDIs, identify drugs involved and propose alternative therapeutic strategies. Material and methods A prospective, observational 1 year study (February 2018 to February 2019) was conducted at a third level hospital, including all new transplanted patients. DDIs were detected by a computer application. To determine real clinical DDIs, patient medical records were reviewed, looking for data on monitoring blood concentrations of immunosuppressive drugs and adverse drug events (ADEs) caused by DDIs. DDIs were classified in C, D or X according to the Lexi interact score (C=monitor therapy, D=consider therapy modification, X=avoid combination). The clinical importance of the real DDIs was expressed in terms of patient outcomes: percentage of patients with ADEs due to real DDIs. Data were analysed using SPSS V.17.0 (Chicago, Illinois, USA). Results A total of 309 transplant patients were included with a mean age of 52±14 years (13–79) and 69.9% were men. The prevalence of real DDIs was 21.68%. The number of real DDIs between immunosuppressants and other drugs was 71. The largest type of real DDIs was category D (52 (73.23%)). Immunosuppressive drugs administered with antifungal azoles and tacrolimus with nifedipine had a great clinical impact due to the fluctuation in trough immunosuppressant blood concentrations (C0) of the immunosuppressants. The most common clinical outcomes were nephrotoxicity (12%), hyperkalaemia (10%) and hypertension (5%). Suggestions to avoid D and X for real DDIs included: immunosuppressant dose change, consider therapy modification and using paracetamol instead of non-steroidal anti-inflammatory drugs. A statistically significant linear correlation was detected between number of prescribed drugs and real and clinically important DDIs. Conclusion and relevance There are many potential interactions described in the literature but only a small percentage have been proved to be real DDIs, based on patient outcomes, which were detected by determining the variations in C0 of immunosuppressants and ADEs caused by DDIs. Few patients suffered ADEs due to the close pharmacokinetic monitoring of immunosuppressants. The results allow us to identify the pharmacological groups that caused real DDIs. References and/or acknowledgements No conflict of interest.