Antibodies against cyclic citrullinated peptide don’t decrease after 6 months of infliximab treatment in refractory rheumatoid arthritis

Anti-citrullinated peptide antibodies (ACPA) and the rheumatoid factor (RF) are well-established serological markers for rheumatoid arthritis (RA). ACPA are very useful in the diagnosis of RA, especially at the early stages of the disease when ACPA have a greater diagnostic value than RF. The aim of the study was to assess the influence of infliximab treatment on RF IgM and ACPA serum levels and RA activity during 6 months of treatment. Thirty-two patients with refractory RA were treated with infliximab during a 6-month period. At baseline, 3 and 6 months of treatment the patients were examined for the number swollen and tender joints out of 28 (SJC, TJC) and the visual analogue scale of arthritis activity according to the patient (VAS). Serum samples were tested for erythrocyte sedimentation rate (ESR), C-reactive protein level (CRP), ACPA and RF IgM. The disease activity score (DAS-28) parameter was also calculated at the same time. During the course of our study, we observed statistically significant improvement in ESR, CRP, TJC, SJC, VAS DAS-28, and RF IgM after 3 and 6 months of infliximab treatment when compared to the baseline, whereas the ACPA level remained unchanged after 3 and 6 months of treatment (P = 0.96 and P = 0.85). The changes in the ACPA level are not a factor for evaluation of successful infliximab treatment but the changes in RF IgM are. According to different behavior of these antibodies during infliximab treatment, we suggest that the roles of ACPA and RF in the pathogenesis of RA are different

Soccer and homosexuality: the conflicts that lie within the affective game of the coach-adolescent athlete relationship

Discussions regarding homosexuality within a sports context are mediated by emotional nuances, especially in the world of soccer, where practitioners are required to have attributes such as strength, masculinity and aggressiveness. As a consequence, this work aimed to analyze the symbolic representation of homosexual relationships between adolescent soccer players and their coaches; and, furthermore, to understand the intention behind homoerotic relationships that are established between members of the management team and its players. In this study, researchers used the life history methodology, with participation from three adolescent athletes, ages 14, 15 and 16, and three former athletes, ages 26, 28 and 45, who we called speakers. Based on the collection and analysis of research participants’ testimonies, homosexual relations were found to have occurred between athletes and coaches, or between athletes and other members of the management team, as a part of a “social contract” that is exclusively linked to their professional objectives. These relationships appear to be purely objective; authentic affective links are absent, due apparently to the transient nature of the athletes in these groups. Too, this context is usually marked by the athlete’s physical and emotional vulnerability, and the agreements he makes within this context are accompanied with moral dilemmas, because such adolescents idealize the coach as a paternal archetype.“Futebol e homossexualidade: Os conflitos que se encontram dentro do jogo afetivo da relação treinador-atleta adolescente.” As discussões a respeito da homossexualidade no contexto esportivo são mediadas por nuanças emocionais, especialmente no mundo do futebol que exige de seus praticantes atributos de força, virilidade e agressividade. Por este motivo este trabalho teve como objetivos diagnosticar existência de relações homossexuais entre atletas adolescentes da modalidade de futebol e seus técnicos e sua representação simbólica e ainda, compreender a intencionalidade das relações homoafetivas que se estabelecem entre componentes da equipe diretiva e os jogadores. Esta pesquisa é de natureza qualitativa e a técnica adotada foi a “história de vida” e a participação de três atletas adolescentes em atividade, com idade de 14, 15 e 16 anos e três ex-atletas profissionais, com idades 26, 28 e 45 anos serviram de base metodológica. A partir da análise e tratamento dos depoimentos verificou-se que ocorreram relações homossexuais nas categorias de base envolvendo técnico e atleta, ou com outros membros da equipe diretiva, como parte dos contratos sociais, ligados exclusivamente a objetivos profissionais. Estas relações parecem ser puramente objetais, não parecendo existir vínculos afetivos duradouros, aparentemente, devido à natureza transitória de atletas nesses grupos. Também, nesses ambientes, muitas vezes marcados pela vulnerabilidade física e emocional dos atletas, os acertos para as relações homossexuais são permeadas por dilemas morais, tendo em vista que os atletas adolescentes idealizam o treinador como o arquétipo paterno ideal.“El fútbol y la homosexualidad: Los conflictos que se encuentran dentro del juego afectivo de la relación atleta-entrenador de los adolescentes.” Las discusiones sobre la homosexualidad en contexto deportivo están mediadas por matices emocionales, sobre todo en el mundo del fútbol que exige a sus jugadores atributos como la fuerza, la virilidad y los jugadores. En este estudio, los investigadores utilizaron la metodología de la historia de vida, con la participación de tres atletas adolescentes, con 14, 15 y 16 años, y tres ex atletas con 26, 28 y 45 años, que llamamos ‘oradores’. Basado en la recogida y análisis de testimonios de participantes en la investigación, se encontró que las relaciones homosexuales que se han producido entre los atletas y entrenadores, o entre atletas y otros miembros del equipo de gestión, son como parte de un “contrato social” que está vinculado exclusivamente a sus objetivos profesionales. Estas relaciones parecen ser solamente como un objeto; porque a veces no hay vínculos afectivos auténticos, debido aparentemente a la naturaleza transitoria de los atletas en estos grupos. Demasiado, este contexto es generalmente marcado por la vulnerabilidad física y emocional del deportista, y los acuerdos que hace dentro de este contexto se acompañan con dilemas morales, debido a que tales adolescentes idealizan el entrenador como un arquetipo paterno. la agresividad. Por lo tanto, este estudio tuvo como objetivo diagnosticar la existencia de relaciones homosexuales entre adolescentes atletas de fútbol y sus entrenadores y la representación simbólica de estas relaciones. También comprender la intencionalidad de las relaciones homoafetivas que se intercambian entre algunos componentes del equipo directivo y(undefined

Digital ulcers predict a worse disease course in patients with systemic sclerosis

Objective: Systemic sclerosis (SSc) is a systemic autoimmune disease with high morbidity and significant mortality. There is a great need of predictors that would allow risk stratification of patients with SSc and ultimately initiation of treatment early enough to ensure optimal clinical results. In this study, we evaluated whether a history of digital ulcers (HDU) at presentation may be a predictor of vascular outcomes and of overall clinical worsening and death in patients with SSc. Methods: Patients from the EULAR Scleroderma Trials and Research (EUSTAR) database, satisfying at inclusion the 1980 American College of Rheumatology classification criteria for SSc, who had a follow-up of at least 3 years since baseline or who have died, were included in the analysis. HDU at presentation as a predictor of disease worsening or death was evaluated by Cox proportional hazards regression analysis. Results :3196 patients matched the inclusion criteria (male sex 13.2%, 33.4% diffuse subset). At presentation, 1092/3196 patients had an HDU (34.1%). In multivariable analysis adjusting for age, gender and all parameters considered potentially significant, HDU was predictive for the presence of active digital ulcers (DUs) at prospective visits (HR (95% CI)): 2.41(1.91 to 3.03), p<0.001, for an elevated systolic pulmonary arterial pressure on heart ultrasound (US-PAPs):1.36 (1.03 to 1.80), p=0.032, for any cardiovascular event (new DUs, elevated US-PAPs or LV failure):3.56 (2.26 to 5.62), p<0.001, and for death (1.53 (1.16 to 2.02), p=0.003). Conclusions :In patients with SSc, HDU at presentation predicts the occurrence of DUs at follow-up and is associated with cardiovascular worsening and decreased survival

Update of EULAR recommendations for the treatment of systemic sclerosis

The aim was to update the 2009 European League against Rheumatism (EULAR) recommendations for the treatment of systemic sclerosis (SSc), with attention to new therapeutic questions. Update of the previous treatment recommendations was performed according to EULAR standard operating procedures. The task force consisted of 32 SSc clinical experts from Europe and the USA, 2 patients nominated by the pan-European patient association for SSc (Federation of European Scleroderma Associations (FESCA)), a clinical epidemiologist and 2 research fellows. All centres from the EULAR Scleroderma Trials and Research group were invited to submit and select clinical questions concerning SSc treatment using a Delphi approach. Accordingly, 46 clinical questions addressing 26 different interventions were selected for systematic literature review. The new recommendations were based on the available evidence and developed in a consensus meeting with clinical experts and patients. The procedure resulted in 16 recommendations being developed (instead of 14 in 2009) that address treatment of several SSc-related organ complications: Raynaud's phenomenon (RP), digital ulcers (DUs), pulmonary arterial hypertension (PAH), skin and lung disease, scleroderma renal crisis and gastrointestinal involvement. Compared with the 2009 recommendations, the 2016 recommendations include phosphodiesterase type 5 (PDE-5) inhibitors for the treatment of SSc-related RP and DUs, riociguat, new aspects for endothelin receptor antagonists, prostacyclin analogues and PDE-5 inhibitors for SSc-related PAH. New recommendations regarding the use of fluoxetine for SSc-related RP and haematopoietic stem cell transplantation for selected patients with rapidly progressive SSc were also added. In addition, several comments regarding other treatments addressed in clinical questions and suggestions for the SSc research agenda were formulated. These updated data-derived and consensus-derived recommendations will help rheumatologists to manage patients with SSc in an evidence-based way. These recommendations also give directions for future clinical research in SSc

Predictors of disease worsening defined by progression of organ damage in diffuse systemic sclerosis: a European Scleroderma Trials and Research (EUSTAR) analysis.

Objectives Mortality and worsening of organ function are desirable endpoints for clinical trials in systemic sclerosis (SSc). The aim of this study was to identify factors that allow enrichment of patients with these endpoints, in a population of patients from the European Scleroderma Trials and Research group database. Methods Inclusion criteria were diagnosis of diffuse SSc and follow-up over 12\ub13 months. Disease worsening/organ progression was fulfilled if any of the following events occurred: new renal crisis; decrease of lung or heart function; new echocardiography-suspected pulmonary hypertension or death. In total, 42 clinical parameters were chosen as predictors for the analysis by using (1) imputation of missing data on the basis of multivariate imputation and (2) least absolute shrinkage and selection operator regression. Results Of 1451 patients meeting the inclusion criteria, 706 had complete data on outcome parameters and were included in the analysis. Of the 42 outcome predictors, eight remained in the final regression model. There was substantial evidence for a strong association between disease progression and age, active digital ulcer (DU), lung fibrosis, muscle weakness and elevated C-reactive protein (CRP) level. Active DU, CRP elevation, lung fibrosis and muscle weakness were also associated with a significantly shorter time to disease progression. A bootstrap validation step with 10 000 repetitions successfully validated the model. Conclusions The use of the predictive factors presented here could enable cohort enrichment with patients at risk for overall disease worsening in SSc clinical trial

Phenotypes Determined by Cluster Analysis and Their Survival in the Prospective European Scleroderma Trials and Research Cohort of Patients With Systemic Sclerosis

Objective: Systemic sclerosis (SSc) is a heterogeneous connective tissue disease that is typically subdivided into limited cutaneous SSc (lcSSc) and diffuse cutaneous SSc (dcSSc) depending on the extent of skin involvement. This subclassification may not capture the entire variability of clinical phenotypes. The European Scleroderma Trials and Research (EUSTAR) database includes data on a prospective cohort of SSc patients from 122 European referral centers. This study was undertaken to perform a cluster analysis of EUSTAR data to distinguish and characterize homogeneous phenotypes without any a priori assumptions, and to examine survival among the clusters obtained. / Methods: A total of 11,318 patients were registered in the EUSTAR database, and 6,927 were included in the study. Twenty‐four clinical and serologic variables were used for clustering. / Results: Clustering analyses provided a first delineation of 2 clusters showing moderate stability. In an exploratory attempt, we further characterized 6 homogeneous groups that differed with regard to their clinical features, autoantibody profile, and mortality. Some groups resembled usual dcSSc or lcSSc prototypes, but others exhibited unique features, such as a majority of lcSSc patients with a high rate of visceral damage and antitopoisomerase antibodies. Prognosis varied among groups and the presence of organ damage markedly impacted survival regardless of cutaneous involvement. / Conclusion: Our findings suggest that restricting subsets of SSc patients to only those based on cutaneous involvement may not capture the complete heterogeneity of the disease. Organ damage and antibody profile should be taken into consideration when individuating homogeneous groups of patients with a distinct prognosis

Autoantibody Production in Anti-TNF- -Treated Patients

Targeting tumor necrosis factor alpha (TNF-alpha) has offered an additional therapeutic strategy against several rheumatic inflammatory disorders. The current use of TNF-alpha inhibitors allows physicians who manage these diseases and patients themselves to testify to an extraordinary efficacy, even though caution for possible adverse events must be maintained. Among these, the occurrence of autoimmune phenomena, encompassing new autoantibody formation and triggering of clinical manifestations, continues to be noted in published reports. Here, we review the current knowledge regarding the autoimmune phenomena linked to anti-TNF-alpha therapy in patients with rheumatic inflammatory disorders