Objectives: To compare serum levels of RAS components in women with RA versus healthy females and to investigate the association between these molecules and subclinical atherosclerosis. Methods: A cross-sectional study involving female RA patients without ischemic CVD. Disease activity was assessed using the DAS28 and the CDAI. IMT of the common carotid artery was evaluated by ultrasonography. Serum levels of Ang II, Ang-(1-7), ACE and ACE2 were determined by enzyme immunoassay. Results: Fifty women with RA, mean 48.2 (7.3) years, were compared to 30 healthy women, paired by age. RA patients had higher plasma levels of Ang II (p < .01), Ang-(1-7) (p < .01), and ACE (p < .01) than controls. The ratios of ACE to ACE2 were higher in RA patients, whereas Ang II/Ang-(1-7) ratios were lower in RA patients. The presence of hypertension and the treatment with ACE inhibitors did not significantly modify serum levels of Ang II, Ang-(1-7), ACE and ACE2 in patients with RA. Seven RA patients had altered IMT, and eight patients exhibited atherosclerotic plaque. There was a negative correlation between ACE2 levels and IMT (p = .041). IMT positively correlated with age (p = .022), disease duration (p = .012) and overall Framingham risk score (p = .008). Ang II concentrations positively correlated with DAS28 (p = .034) and CDAI (p = .040). Conclusion: Patients with RA had an activation of the RAS, suggesting an association with disease activity and cardiovascular risk.Rheumatological key messages Imbalance of both RAS axes may be associated with cardiovascular risk and disease activity in rheumatoid arthritis. Ultrasonography of the carotid arteries can identify early, subclinical atherosclerotic disease in rheumatoid arthritis patients. Angiotensin-converting enzyme inhibition or angiotensin 1 receptor blockade may be beneficial for rheumatoid arthritis patients.

BACKGROUND:Identification of biomarkers associated with the diagnosis and prognosis of silicosis would be highly advantageous in the clinical setting. The aim of this study is to evaluate inflammatory and oxidative stress biomarkers in subjects exposed to silica.METHODS:A cross-sectional study of crystal craftsmen currently (n = 34) or formerly (n = 35) exposed and a group of nonexposed subjects (n = 12) was performed. Personal respirable dust samples were collected. Plasma inflammatory mediators (bone morphogenetic protein- BMP2 and chemokines CXCL16, and CCL5), oxidative stress enzymes (thiobarbituric acid reactive substances [TBARs] and superoxide dismutase [SOD]), and nitrite (NO2- ) were analyzed in parallel with nitric oxide in exhaled breath (FeNO).RESULTS:Being currently or formerly exposed to silica was related to increased levels of CXCL16 and TBARs. Currently, exposed subjects showed decreased levels of SOD. Thirty-seven craftsmen with silicosis (26 formerly and 11 currently exposed) showed higher levels of CXCL16, which was positively associated with the radiological severity of silicosis. Compared with the nonexposed, subjects with silicosis had higher levels of TBARs and those with complicated silicosis had lower levels of SOD. In multivariate analysis, higher levels of CXCL16 were associated with exposure status and radiological severity of silicosis. Smoking was not a confounder. FeNO did not distinguish between the exposure status and the presence of silicosis.CONCLUSION:CXCL16 emerged as a potential biomarker that could distinguish both silica exposure and silicosis. TBARs were elevated in exposed individuals. However, their clinical applications demand further investigation in follow-up studies of representative samples.

Myasthenia gravis (MG) is a neuromuscular autoimmune disease characterized by skeletal muscle weakness which can impact motor function and, furthermore, produce negative impact on the health-related quality of life (HRQOL). Objective: To evaluate the predictors for HRQOL in patients with MG. Methods: Eighty patients were evaluated with the MG Foundation of America classification and the MG Composite scale. HRQOL was estimated by the MGQOL15, while anxious and depressive symptoms were evaluated with the Hospital Anxiety and Depression Scale (HAD). Results: The mean age of patients was 41.9 years with mean illness duration of 13.5 years. Almost half of the patients (43.75%) had significant anxiety and more than a quarter (27.50%) had depressive symptoms. Factors that influenced the HRQOL in MG were skeletal muscle weakness and anxiety and depressive symptoms (p <. 001 in logistic regression model). Conclusion: Anxiety and depressive symptoms, besides motor symptoms, influence HRQOL in MG. Mental health must be a clinical focus in addition to the treatment of somatic symptoms during the course of MG. (C) 2018 Elsevier Ltd. All rights reserved.

Background Rheumatoid arthritis (RA) is an independent risk factor for cardiovascular disease (CVD). The renin-angiotensin system (RAS) is a hormonal cascade with important role in hydroelectrolytic homeostasis, blood pressure and regulation of cardiovascular remodeling. Angiotensin II (Ang II) acts as a proinflammatory mediator (1). Objectives To investigate the association of serum levels of RAS components with the presence of subclinical atherosclerosis using carotid ultrasonography in women with RA. Methods Women with RA according to ACR/EULAR 2010 or ACR 1987 criteria and without clinical ischemic CVD were included. Disease activity was assessed using the DAS28. The presence of atherosclerotic plaques and the thickness of the medium-intimal complex (EMI) of the arterial wall in the common carotid artery were evaluated by ultrasonography, Serum levels of angiotensin (Ang) II, Ang-(1-7), angiotensin converting enzyme (ECA) and ECA II were determined by enzyme immunoassay. Results 50 women with RA, mean age 48.2 years (±7.32), mean duration of disease of 15.35 years (±8.56), DAS28 of 4.02 (±1.41) and CDAI of 14.23 (±11.53) were included. Seven patients presented altered EMI, eight had atherosclerotic plaque. The prevalence of risk factors for CVD was: 12% of smoking, 12% of family history of premature CVD, 46% of arterial hypertension, 10% of diabetes, 62% of dyslipidemia, 94% of abdominal obesity and 46% of metabolic syndrome. The control group consisted of 30 healthy women, mean age of 46.3 years (±7.72). RA patients had a higher serum concentration of Ang II (p<0.01), Ang-(1-7) (p<0.01), and ACE (p<0.01) than the control group (table 1). There was a negative correlation between ECA II and EMI (p=0.041, rho -0.290). EMI correlated positively with age (p=0.022, rho 0.324), disease duration (p=0.012, rho 0.315) and overall Framingham risk (p=0.008, rho 0.368) and Ang II correlated positively with DAS28 (p=0.034, rho 0.301) and CDAI (p=0.040, rho 0.291). Conclusions Imbalance of RAS components, especially Ang II and ECA II, may be associated to CVD in RA patients. Ultrasonography of the carotid arteries can identify patients that could benefit from ECA blockade. Reference: [1] Chang Y, Wei W. Angiotensin II in inflammation, immunity and rheumatoid arthritis. Clin Exp Immunol 2015;179:137-145. doi: 10.1111/cei.12467 Acknowledgements: National Council for Scientific and Technological Development (CNPq), Foundation for Research Support of Minas Gerais (FAPEMIG) Disclosure of Interest: None declared

Objective: To evaluate potential associations between clinical features and inflammatory markers in patients with amyotrophic lateral sclerosis (ALS). Methods: A consecutive series of 68 patients (39 males and 29 females) with sporadic ALS were subjected to a comprehensive clinical assessment and blood draw. A subset of these patients underwent a new assessment within 6-12 months after the baseline visit. In addition, a group of 62 subjects composed by age and sex-matched healthy subjects (38 males and 24 females) was enrolled in this study. Peripheral blood was drawn and plasma levels of chemokines and cytokines were measured by cytometric bead array and enzyme-linked immunosorbent assay. Results: Our sample was composed by patients with ALS with an average age of 58 (+/- 12.3) years old and 3 (+/- 2.7) years of disease length at the baseline visit. Patients with ALS presented increased plasma levels of interleukin (IL)-6 and IL-8 in comparison with controls. After multivariate analysis, higher levels of IL-6 and lower levels of IL-2 were significantly associated with increased likelihood of ALS diagnosis. When evaluating the subset of patients assessed longitudinally, we did not find any significant difference in the levels of inflammatory markers between the two time points. Older age at ALS onset was the only factor associated with a faster rate of disease progression. Conclusions: IL-6 levels could discriminate between ALS and controls and may be regarded as a potential biomarker of ALS diagnosis. An increase in IL-2 levels was associated with a protective effect on the odds of ALS diagnosis. Older age at ALS onset predicted a fast rate of disease progression.

Background Rheumatoid arthritis (RA) patients have loss of muscle mass. The balance between muscle protein synthesis and degradation is regulated by cytokines and growth factors, named myokines, such as irisin and myostatin. Myokines are mainly expressed by skeletal muscle and exert systemic effects promoting crosstalk among different tissues. Irisin increases cortical bone mass and its low levels are related to muscle atrophy and obesity[,1, 2 while myostatin is a negative regulator of muscle growth and regeneration and has a direct role in osteoclastogenesis of inflammatory bone destruction[.3, 4 Objectives To evaluate serum levels of irisin and myostatin and body composition of RA patients and controls. Methods 122 female patients with RA, mean age 53 years, mean disease activity score (DAS28) 4.09, mean disease duration 11.2 years and mean body mass index 27.33 kg/m2 were included. 69 age and sex-matched healthy subjects were enrolled as control group. Irisin (Phoenix Pharmaceuticals) and myostatin (R and D Systems) serum levels were evaluated by ELISA. Fat mass index (FMI;Kg/m2) and appendicular lean mass index (ALMI;Kg/m2) were assessed by total body dual-energy x-ray absorptiometry. Student’s t test and Spearman correlation were performed. Significance was set at p<0.05. Results RA patients had decreased serum levels of irisin (25,61±8,25 vs 30,36±10,95 ng/ml; p<0.05) and myostatin (3011,28±1271,11 vs 4049,08±1610,01 pg/ml; p<0.05), decreased ALMI (6,09±0,88 vs 6,50±1,10; p<0.05) and increased FMI (11,26±3,30 vs 9,44±2,65; p<0.05), compared to controls. No correlations were observed among irisin and myostatin levels and ALMI and FMI. Of the 122 RA patients, 40 were analysed for the use of biologic medication. Serum levels of irisin and myostatin were different between RA patients treated and non-treated with biologics (table 1). Conclusions RA patients presented loss of lean mass and gain of fat mass, as well as lower irisin and myostatin serum levels, in comparison with controls. Additionally, the use of biologic medication by patients impacted on myokines serum levels. Further analyses are needed for a better comprehension of irisin and myostatin roles in RA, and to verify their correlation to other RA features. References [1] Colaianni G, et al. Proc Natl Acad Sci2015;112(39):12157–62. [2] Chang J, et al. Geriatr Gerontol Int. 2017;17(11):2266–2273. [3] Huang Z, et al. Cell Signal2011;23(9):1441–6. [4] Dankbar B, et al. Nat Med2015;21(9):1085–90. Disclosure of Interest None declared

RESUMO O objetivo deste estudo foi revisar sistematicamente a literatura sobre a eficácia do Nintendo Wii na melhora de desfechos funcionais e de saúde de indivíduos com doença de Parkinson. A revisão foi desenvolvida seguindo o PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses), com buscas nas bases de dados MEDLINE, SciELO, LILACS e PEDro mediante estratégia de busca composta pela combinação dos termos “Wii”, “Doença de Parkinson”, “reabilitação” e “fisioterapia”, seguida de busca manual. Os critérios de inclusão foram: estudos experimentais ou quase-experimentais relacionados a intervenções envolvendo o uso do Nintendo Wii para melhora de desfechos funcionais em indivíduos com doença de Parkinson, publicados até fevereiro de 2016, sem restrição de idioma. A qualidade metodológica dos estudos foi avaliada pela escala PEDro. Dos 701 estudos encontrados, foram selecionados sete que atenderam aos critérios de inclusão, a maioria (57,14%) apresentava qualidade metodológica ruim e era do tipo quase-experimental. Os resultados sugerem que o uso do Wii parece eficaz para melhora de desfechos funcionais (equilíbrio, mobilidade, desempenho motor e independência) e de saúde (diminuição do risco de quedas), sendo mais consistentes os resultados para melhora do equilíbrio. São necessários estudos com melhor qualidade metodológica para o estabelecimento das evidências e, ainda, padronizações sobre os tipos de jogos, intensidade e frequência adequados para cada tipo de paciente com DP.

This study aimed to evaluate changes in body composition, i.e. overweight, obesity, fat accumulation and low lean body mass and plasma levels of adipokines in patients with MG. The study enrolled 80 patients with MG, and 62 controls. Body fat mass and body lean mass was analyzed by dual-energy X-ray absorptiometry technique (DXA). Plasma levels of leptin were analyzed by Luminex® and adiponectin and resistin were analyzed by ELISA. The mean age of patients with MG was 41.9years, with 13.5years of length of illness, and mean cumulative dose of glucocorticoids 38,123mg. Our results showed that the frequency of obesity is higher in MG patients than in controls, and patients with MG presented higher body fat mass, android body adiposity and total body fat than controls. MG patients presented lower levels of resistin and higher levels of leptin in comparison with controls. There were no differences in the plasma levels of adiponectin. Higher total body fat and lower body lean mass were associated with increased severity of MG symptoms. This result points to the relevance of estimation of body composition in planning long-term care of MG patients.

This current study aimed to evaluate the frequency of low bone mass, osteopenia, and osteoporosis in patients with myasthenia gravis (MG) and to investigate the possible association between bone mineral density (BMD) and plasma levels of bone metabolism markers. Eighty patients with MG and 62 controls BMD were measured in the right femoral neck and lumbar spine by dual-energy X-ray absorptiometry. Plasma concentrations of osteocalcin, osteopontin, osteoprotegerin, tumor necrosis factor (TNF-α), interleukin (IL)-1β, IL-6, dickkopf (DKK-1), sclerostin, insulin, leptin, adrenocorticotropic hormone, parathyroid hormone, and fibroblast growth factor (FGF-23) were analyzed by Luminex®. The mean age of patients was 41.9 years, with 13.5 years of length of illness, and a mean cumulative dose of glucocorticoids 38,123 mg. Patients had significant reduction in BMD of the lumbar, the femoral neck, and in the whole body when compared with controls. Fourteen percent MG patients had osteoporosis at the lumbar spine and 2.5% at the femoral neck. In comparison with controls, patients with MG presented lower levels of osteocalcin, adrenocorticotropic hormone, parathyroid hormone, sclerostin, TNF-α, and DKK-1 and higher levels of FGF-23, leptin, and IL-6. There was a significant negative correlation between cumulative glucocorticoid dose and serum calcium, lumbar spine T-score, femoral neck BMD, T-score, and Z-score. After multivariate analysis, higher TNF-α levels increased the likelihood of presenting low bone mass by 2.62. MG patients under corticotherapy presented low BMD and altered levels of bone markers.

Objectives: The aim of the study was to evaluate the plasma levels of inflammatory mediators in subjects exposed to silica, with and without silicosis compared with unexposed control group; and to check the association between inflammatory mediators with pulmonary function, quality of life, functional capacity, and dyspnea grade. Methods: Inflammatory mediators were measured by enzyme-linked immunosorbent assay. There were 30 subjects exposed to silica and 24 control group. Results: Interleukin-6 plasma levels were higher in subjects exposed to silica with and without silicosis than in the control group. There was a positive correlation between radiological severity and the quality of life, whereas there was a negative correlation between radiological severity and pulmonary function. A negative correlation between sTNFR1 plasma level and functional capacity was found. Interleukin-10 was negatively correlated with the quality of life total score and was positively correlated with the functional capacity and pulmonary function.

Myasthenia Gravis (MG) is an autoimmune disease characterized by fluctuating muscle weakness. The MG treatment with corticosteroids is initially made; however, its prolonged use is associated with risk of osteoporosis. Objectives: To define the osteoporosis prevalence in patients with MG and biomarkers measure in peripheral blood from patients with MG and compare to healthy individuals (CG) without use of corticosteroids. Patients and methods: bone densitometry was performed in the right femoral neck and lumbar spine by DXA technique and the plasma concentrations of TNF, IL-1β, IL-6, OPG, FGF-23, ACTH, DKK1, insulin, leptin, osteocalcin, osteopontin and SOST were analyzed by Luminex®. Results: 90 MG patients with 42.57 years (mean), presented 13.73 years of time of disease and mean cumulative dose of corticosteroids 38130.98 mg. The patients had significant reduction in bone mineral density (BMD) of the lumbar, the femoral neck and in the whole body. In MG patients, 14.5% had osteoporosis at the lumbar spine and 3% at the femoral neck. The presence of lumbar spine osteopenia was 10.5% and 21% at the femoral neck. The low bone mass for age in the lumbar spine was 4% and 5% in the femoral neck. Leptin, OPN, insulin and OPG were higher in patients compared with the CG and DDK1 was reduced in the MG patients. There was a negative correlation between femoral neck BMD and the cumulative dose of corticosteroids. Conclusion: This study demonstrated that MG patients under corticotherapy presented low bone mineral density and impairment in bone metabolism proteins.

Objective: To evaluate the plasma levels of CCL2, CCL3, CCL11, CCL24, tumor necrosis factor alpha, sTNFR1, and sTNFR2 in subjects exposed to silica (SES) with and without silicosis compared with unexposed reference control group, and their associations with the radiological severity and duration of exposure to silica.Methods: Fifty-seven SES; 36 with silicosis and 22 subjects in control group, were included in the study.Results: CCL3, CCL24, sTNFR1, and sTNFR2 were increased in SES and in SES with silicosis than in controls. There were no differences in the levels of CCL2, CCL11, or tumor necrosis factor alpha. The sTNFR2 level was greater in SES with silicosis than in SES without silicosis. There was a positive correlation between sTNFR1 and sTNFR2 and the radiological severity and time of exposure to silica. sTNFR2 was associated with all categories of radiological severity.Conclusion: sTNFR2 is associated with silicosis severity and early exposure to silica.

A silicose representa um importante problema de saúde pública em todo o mundo, sobretudo nos países em desenvolvimento, sendo a principal causa de invalidez entre as doenças respiratórias ocupacionais. É uma pneumoconiose fibrótica, irreversível e potencialmente fatal, causada pela inalação de poeira contendo sílica cristalina. O diagnóstico é estabelecido através da história clínica e ocupacional de exposição à sílica, na presença de alterações radiológicas. Estudos experimentais e clínicos sugerem que a inalação da poeira da sílica está associada a um processo inflamatório pulmonar e sistêmico, mesmo em indivíduos que não desenvolveram silicose. Até o momento não existem exames laboratoriais específicos para o diagnóstico da doença, de modo que o conhecimento de marcadores biológicos associados à imunopatologia da silicose pode ser importante na detecção precoce da instalação e desenvolvimento da doença. O presente artigo traz uma revisão de estudos que investigaram os possíveis biomarcadores inflamatórios da doença no sangue e no lavado bronco-alveolar de humanos e de modelos experimentais.