Increased frequencies of circulating CXCL10-, CXCL8- and CCL4-producing monocytes and Siglec-3-expressing myeloid dendritic cells in systemic sclerosis patients.

OBJECTIVE: To investigate the ex vivo pro-inflammatory properties of classical and non-classical monocytes as well as myeloid dendritic cells (mDCs) in systemic sclerosis (SSc) patients. METHODS: Spontaneous production of CXCL10, CCL4, CXCL8 and IL-6 was intracellularly evaluated in classical, non-classical monocytes and Siglec-3-expressing mDCs from peripheral blood of SSc patients and healthy controls (HC) through flow cytometry. In addition, production of these cytokines was determined upon toll-like receptor (TLR) 4 plus Interferon-γ (IFN-γ) stimulation. RESULTS: The frequency of non-classical monocytes spontaneously producing CXCL10 was increased in both limited (lcSSc) and diffuse cutaneous (dcSSC) subsets of SSc patients and CCL4 was augmented in dcSSc patients. The proportion of CCL4-producing mDCs was also elevated in dcSSc patients and the percentage of mDCS producing CXCL10 only in lcSSc patients. Upon stimulation, the frequency of non-classical monocytes expressing CXCL8 was increased in both patient groups and mDCs expressing CXCL8 only in lcSSc. Moreover, these parameters in unsupervised clustering analysis identify a subset of patients which are characterized by lung fibrosis and reduced pulmonary function. CONCLUSIONS: These data point towards a role of activated non-classical monocytes and mDCs producing enhanced levels of proinflammatory cytokines in SSc, potentially contributing to lung fibrosis.

Mapping and predicting mortality from systemic sclerosis.

OBJECTIVES: To determine the causes of death and risk factors in systemic sclerosis (SSc). METHODS: Between 2000 and 2011, we examined the death certificates of all French patients with SSc to determine causes of death. Then we examined causes of death and developed a score associated with all-cause mortality from the international European Scleroderma Trials and Research (EUSTAR) database. Candidate prognostic factors were tested by Cox proportional hazards regression model by single variable analysis, followed by a multiple variable model stratified by centres. The bootstrapping technique was used for internal validation. RESULTS: We identified 2719 French certificates of deaths related to SSc, mainly from cardiac (31%) and respiratory (18%) causes, and an increase in SSc-specific mortality over time. Over a median follow-up of 2.3 years, 1072 (9.6%) of 11 193 patients from the EUSTAR sample died, from cardiac disease in 27% and respiratory causes in 17%. By multiple variable analysis, a risk score was developed, which accurately predicted the 3-year mortality, with an area under the curve of 0.82. The 3-year survival of patients in the upper quartile was 53%, in contrast with 98% in the first quartile. CONCLUSION: Combining two complementary and detailed databases enabled the collection of an unprecedented 3700 deaths, revealing the major contribution of the cardiopulmonary system to SSc mortality. We also developed a robust score to risk-stratify these patients and estimate their 3-year survival. With the emergence of new therapies, these important observations should help caregivers plan and refine the monitoring and management to prolong these patients' survival.

[Portuguese recommendations for pain management by pharmocotherapy in inflammatory arthritis]. / Recomendações portuguesas para o tratamento e controlo farmacológico da dor nas artropatias inflamatórias.

OBJECTIVES: To develop Portuguese evidence-based recommendations for pain management by pharmocotherapy in inflammatory arthritis. METHODS: The Portuguese project was integrated in the multinational 3E Initiative (Evidence, Expertise, Exchange) 2010 where a total of 453 rheumatologists from 17 countries have participated. The clinical questions concerning pain were formulated and the Portuguese group added 2 more questions. A systematic literature search was performed in Medline, Embase, Cochrane Library and 2008-2009 EULAR and ACR abstracts. The selected articles were systematically reviewed and the evidence was defined according to the Oxford Levels of Evidence. In each country a group of experts joined to discuss their national recommendations. In Portugal, the national meeting was held in October 2010, where 33 rheumatologists discussed and voted by Delphi method the national recommendations. Finally, the agreement among the rheumatologists and the potential impact on their clinical practice was assessed. RESULTS: Thirteen national recommendations were formulated: pain measure scores; analgesic combination therapy; pharmacotherapy in preconception, pregnancy and lactation periods; pharmacotherapy according to comorbilities; safety of NSAIDs and/or paracetamol with methotrexate combination therapy; efficacy and safety of continuous/on-demand NSAIDs; opioids, paracetamol, corticosteroids, antidepressants, neuromodulators and muscle relaxants role and effectiveness; risk factors for the development of chronic pain and the role of topic analgesics. CONCLUSION: The portuguese recommendations for the pain management by pharmacotherapy in inflammatory arthritis were formulated according to the best evidence and supported by a panel of 63 rheumatologists. The differences between the national and international recommendations are reported in this article.

[European study of ambulatory management of heart failure by cardiologists]. / Estudio europeo del tratamiento ambulatorio de la insuficiencia cardíaca realizado por cardiólogos.

INTRODUCTION AND OBJECTIVES: This cross-sectional study examined the overall clinical characteristics and management of 1252 outpatients with heart failure in 3 countries (Spain, France and Germany). MATERIAL AND METHOD: A standardized questionnaire was used to record demographic, diagnostic, clinical and treatment data for all patients seen on one day (26 April 2001) by 465 outpatient cardiologists. RESULTS: Men accounted for 62.1% of the patients in the population, and mean age of the patients was 68.3 years. In the twelve months prior to the study 78% of the patients consulted their physician at least once because of heart failure, and 36.2% had hospital admissions. Differences between the three countries were observed in reported causes of heart failure (alone or in combination) such as ischemic heart disease (France 40.7%, Germany 41.3%, Spain 26%, P<.0001) and hypertension (France 10.7%, Germany 16.7%, Spain 43.6%, P<.0001). How-ever the proportion of patients with prior myocardial infarction was very similar (France 63.7%, Germany 69.5%, Spain 65%, P=NS). Diuretics were not prescribed in 19.7% of the patients, ACE inhibitors were not prescribed in 27.9%, and beta blockers were not prescribed in 52.3%. CONCLUSIONS: The study provides further information on the consumption of large amounts of medical resources because of heart failure. The reported etiologies differed between countries. However, the proportion of patients with prior myocardial infarction was very similar. Treatment with ACE inhibitors and beta blockers was slightly more common than previously reported, although beta blockers continue to be underused.

Estudio europeo del tratamiento ambulatorio de la insuficiencia cardíaca realizado por cardiólogos / European Study of Ambulatory Management of Heart Failure by Cardiologists

Introducción y objetivos. Se presentan los resultados globales de un estudio transversal que examina las características clínicas y el manejo de 1.252 pacientes ambulatorios diagnosticados de insuficiencia cardíaca (IC) en 3 países (España, Francia y Alemania). Material y método. Se estudiaron en un cuestionario estandarizado los datos demográficos, diagnósticos, clínicos y terapéuticos de todos los pacientes atendidos en consultorio en un mismo día (26 de abril de 2001) por 465 cardiólogos de práctica extrahospitalaria. Resultados. El 62,1% de los pacientes de la población total eran varones y la edad media fue de 68,3 años. Durante los 12 meses previos acudieron al menos a una visita médica justificada por IC el 78% de los pacientes, y se hospitalizó al 36,2%. Hubo diferencias entre los países respecto a la etiología reportada de IC (sola o en combinación): cardiopatía isquémica (Francia, el 40,7%; Alemania, el 41,3%, y España, el 26%; p < 0,0001) e hipertensión (Francia, el 10,7%; Alemania, el 16,7%, y España, el 43,6%; p < 0,0001), aunque la tasa de pacientes con infarto de miocardio previo era similar (Francia, el 63,7%; Alemania, el 69,5%, y España, el 65%; p = NS). En el 19,7% de los pacientes no se prescribieron diuréticos, en el 27,9% no se prescribieron inhibidores de la enzima de conversión de la angiotensina (IECA), y en el 52,3% no se prescribieron bloqueadores beta. Conclusiones. Este estudio proporciona información adicional respecto al gran consumo de recursos médicos de la insuficiencia cardíaca. La etiología reportada difiere entre los países, aunque la proporción de pacientes con antecedentes de infarto de miocardio es muy similar. El tratamiento con IECA y bloqueadores beta es ligeramente superior al descrito en trabajos previos, pero los bloqueadores beta siguen estando infrautilizados (AU)

Introduction and objectives. This cross-sectional study examined the overall clinical characteristics and management of 1252 outpatients with heart failure in 3 countries (Spain, France and Germany). Material and method. A standardized questionnaire was used to record demographic, diagnostic, clinical and treatment data for all patients seen on one day (26 April 2001) by 465 outpatient cardiologists. Results. Men accounted for 62.1% of the patients in the population, and mean age of the patients was 68.3 years. In the twelve months prior to the study 78% of the patients consulted their physician at least once because of heart failure, and 36.2% had hospital admissions. Differences between the three countries were observed in reported causes of heart failure (alone or in combination) such as ischemic heart disease (France 40.7%, Germany 41.3%, Spain 26%, P<.0001) and hypertension (France 10.7%, Germany 16.7%, Spain 43.6%, P<.0001). However the proportion of patients with prior myocardial infarction was very similar (France 63.7%, Germany 69.5%, Spain 65%, P=NS). Diuretics were not prescribed in 19.7% of the patients, ACE inhibitors were not prescribed in 27.9%, and beta blockers were not prescribed in 52.3%. Conclusions. The study provides further information on the consumption of large amounts of medical resources because of heart failure. The reported etiologies differed between countries. However, the proportion of patients with prior myocardial infarction was very similar. Treatment with ACE inhibitors and beta blockers was slightly more common than previously reported, although beta blockers continue to be underused (AU)