Morphofunctional analysis of fibroblast-like synoviocytes in human rheumatoid arthritis and mouse collagen-induced arthritis

Abstract Background Fibroblast-like synoviocytes (FLS) play a prominent role in rheumatoid synovitis and degradation of the extracellular matrix through the production of inflammatory cytokines and metalloproteinases (MMPs). Since animal models are frequently used for elucidating the disease mechanism and therapeutic development, it is relevant to study the ultrastructural characteristics and functional responses in human and mouse FLS. The objective of the study was to analyze ultrastructural characteristics, Interleukin-6 (IL-6) and Metalloproteinase-3 (MMP-3) production and the activation of intracellular pathways in Fibroblast like synoviocytes (FLS) cultures obtained from patients with rheumatoid arthritis (RA) and from mice with collagen-induced arthritis (CIA). Methods FLSs were obtained from RA patients (RA-FLSs) (n = 8) and mice with CIA (CIA-FLSs) (n = 4). Morphology was assessed by transmission and scanning electron microscopy. IL-6 and MMP-3 production was measured by ELISA, and activation of intracellular signaling pathways (NF-κB and MAPK: p-ERK1/2, p-P38 and p-JNK) was measured by Western blotting in cultures of RA-FLSs and CIA-FLSs stimulated with tumor necrosis factor-alpha (TNF-α) and IL-1β. Results RA-FLS and CIA-FLS cultures exhibited rich cytoplasm, rough endoplasmic reticula and prominent and well- developed Golgi complexes. Transmission electron microscopy demonstrated the presence of lamellar bodies, which are cytoplasmic structures related to surfactant production, in FLSs from both sources. Increased levels of pinocytosis and numbers of pinocytotic vesicles were observed in RA-FLSs (p < 0.05). Basal production of MMP-3 and IL-6 was present in RA-FLSs and CIA-FLSs. Regarding the production of MMP-3 and IL-6 and the activation of signaling pathways, the present study demonstrated a lower response to IL-1β by CIA-FLSs than by RA-FLSs. Conclusion This study provides a comprehensive understanding of the biology of RA-FLS and CIA-FLS. The differences and similarities in ultrastructural morphology and important inflammatory cytokines shown, contribute to future in vitro studies using RA-FLS and CIA-FLS, in addition, they indicate that the adoption of CIA-FLS for studies should take careful and be well designed, since they do not completely resemble human diseases.

First-line biologic therapy with tumor necrosis factor inhibitors for psoriatic arthritis: a prospective observational study

ABSTRACT BACKGROUND: Psoriatic arthritis (PsA) is a chronic inflammatory disease that affects multiple joints. It is associated with psoriasis and treated with synthetic and biologic drugs. OBJECTIVE: The objective of this study was to assess the outcomes of patients who received biologic therapy with tumor necrosis factor (TNF) inhibitors in terms of effectiveness, safety, functionality, and quality of life. DESIGN AND SETTING: A prospective observational study was performed at a single center in Belo Horizonte, Brazil. METHODS: Patients with PsA who received their first TNF inhibitor treatment were followed up for 12 months. Disease activity was measured using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Clinical Disease Activity Index (CDAI). Functionality was measured using the Health Questionnaire Assessment (HAQ), and quality of life was evaluated using the European Quality of Life Five Dimensions (EQ-5D). Multiple linear regression was used to identify predictors of the clinical response at 12 months. RESULTS: A total of 143 patients treated with adalimumab or etanercept were evaluated. Most of the clinical measures were significantly improved at 12 months. However, 31%-51% of the patients did not achieve good clinical control. No differences were observed between adalimumab and etanercept, except for poor functionality at 12 months among patients treated with etanercept. The main predictors of a worse clinical response were female sex, etanercept use, poor functionality, or lower quality of life at baseline. The main adverse reactions were alopecia, headache, injection site reaction, sinusitis, flu, dyslipidemia, and infections. CONCLUSION: TNF inhibitor therapy was effective and safe. However, despite improvements in clinical measures, most patients did not achieve satisfactory control of the disease.

Biological therapy in psoriatic arthritis patients with and without previous biologic experience / Terapia biológica em pacientes com artrite psoriásica com e sem experiência prévia no uso de medicamentos biológicos

Objective: this study evaluated the biological therapy effects on disease activity, functionality, quality of life, drug survival, and safety of patients with psoriatic arthritis naïve and experienced in biological therapy. Methods: a one-year prospective observational study was performed. The outcomes assessed were drug survival, disease activity, functionality, quality of life, and safety. Multiple linear regression was used to assess predictive factors for clinical re-sponse. Results: a total of 205 patients were included, 155 of whom were biologic naïve and 50 biologic experienced. Drug survival rate was greater for naïve patients than experienced patients at 6 months, but not at 12 months. Drug survival rates were 71.5% for naïve patients and 70.0% for experienced patients at 12 months. All clinical parameters improved for both biologic naïve and experienced patients. At 12 months, 63% of naïve patients and 52% of expe-rienced patients had an improvement in their quality of life. Besides, 48% of naïve patients and 42% of experienced patients had an improvement in functionality. The axial disease improved in 67% of naïve individuals and 56% of experienced patients. Good control of peripheral disease was achieved by 49% of naïve patients and 44% of experi-enced patients. Female sex, use of etanercept or infliximab, and lower functionality or quality of life at baseline were the main predictors of poor clinical response. Conclusion: Patients' health improved after starting biological therapy. In general, biologic experienced patients had more adverse reactions and lesser effectiveness (AU)

Objetivo: avaliar os efeitos da terapia biológica sobre a atividade da doença, funcionalidade, qualidade de vida, per-sistência no tratamento e segurança em pacientes com artrite psoriásica sem experiência e com experiência prévia em terapia biológica. Métodos: um estudo observacional prospectivo de um ano foi realizado. Os desfechos avaliados foram a persistência no tratamento, atividade da doença, funcionalidade, qualidade de vida e segurança. Um modelo de regressão linear múltipla foi utilizado para avaliar os fatores preditores de resposta clínica. Resultados: foram incluídos 205 pacientes, dos quais 155 não tinham e 50 tinham experiência prévia com medicamentos biológicos. As taxas de persistência no tratamento foram maiores para pacientes sem experiência prévia em comparação aos experientes em seis meses de acompanhamento, mas não em 12 meses. As taxas de persistência no tratamento foram 71,5% em pa-cientes sem experiência prévia e 70% em pacientes com experiência prévia em 12 meses. Todos os desfechos clínicos avaliados melhoraram em ambos os grupos de pacientes. Aos 12 meses, 63% dos pacientes sem experiência prévia e 52% dos pacientes com experiência prévia apresentaram melhora na qualidade de vida. Além disso, 48% dos pacientes sem experiência prévia e 42% dos pacientes com experiência prévia apresentaram melhora na funcionalidade. A do-ença axial melhorou em 67% dos pacientes sem experiência prévia e em 56% dos pacientes com experiência prévia. Um bom controle da doença articular periférica foi observado em 49% dos pacientes sem experiência prévia e em 44% dos pacientes com experiência prévia. Os principais fatores preditores de pior resposta clínica foram sexo feminino, uso de etanercepte ou infliximabe, bem como pior funcionalidade e qualidade de vida no início do estudo. Conclusão:a saúde dos pacientes melhorou após o início do tratamento com os medicamentos biológicos. Em geral, pacientes com experiência prévia com medicamentos biológicos apresentaram mais reações adversas e menor efetividade (AU)

Effect of biological disease-modifying antirheumatic drugs on body composition in patients with rheumatoid arthritis: a systematic review and meta-analysis

Abstract Background: Rheumatoid arthritis (RA) generates an inflammatory profile that predisposes to total and visceral fatty accumulation and reduced fat free mass (FFM). This metabolic disorder contributes to poor functionality, increased cardiovascular risk and higher mortality. This study aimed to address a systematic review with meta-analysis to determine the effect of biological and targeted synthetic disease-modifying antirheumatic drugs (bDMARDs and tsDMARDs) on body composition (BC) of patients with RA. Methods: The search was conducted at the electronic databases PubMed, Cochrane Library, Embase, Lilacs and grey literature. This investigation was carried until July 2021. Outcomes of interest were total weight, body mass index (BMI), fat mass (FM) and FFM. A meta-analysis comparing these outcomes in RA patients under bDMARD treatment versus controls was performed. Results: Out of 137 studies reviewed, 18 were selected: fifteen prospective cohorts, two retrospective cohorts, and one cross-sectional study. The studies comprised 1221 patients, 778 on bDMARD treatment and 443 controls, which included RA patients under conventional synthetic DMARD (csDMARD). No study addressing BC analysis in patients using tsDMARD was found. The mean age and duration of the disease was 56.7 years and 6.77 years, respectively. Ten studies demonstrated a significant increase of total weight in 88.2% of patients and 42.3% for BMI. In studies that analyzed BC by double X-ray absorptiometry (DXA), the increase in total weight and BMI correlated positively to the increase in FFM. The meta-analysis carried out in five studies showed no significant difference of the mean difference for total weight 0.12 kg (95% CI − 5.58, 5.82), BMI 0.08 kg/m2 (95% CI − 1.76, 1.92), FM − 0.08 kg (95% IC − 5.31, 5.14), and FFM − 2.08 kg (95% CI − 7.37, 3.21). Conclusion: This systematic review suggests a possible impact of bDMARDs on BC of RA patients, even though, the meta-analysis carried out in a small part of these studies was not able to confirm significant variation in BC components. Trial registration: PROSPERO code: CRD42020206949.

Guidelines on COVID-19 vaccination in patients with immune-mediated rheumatic diseases: a Brazilian Society of Rheumatology task force

Abstract Objective: To provide guidelines on the coronavirus disease 2019 (COVID-19) vaccination in patients with immune-mediated rheumatic diseases (IMRD) to rheumatologists considering specific scenarios of the daily practice based on the shared-making decision (SMD) process. Methods: A task force was constituted by 24 rheumatologists (panel members), with clinical and research expertise in immunizations and infectious diseases in immunocompromised patients, endorsed by the Brazilian Society of Rheumatology (BSR), to develop guidelines for COVID-19 vaccination in patients with IMRD. A consensus was built through the Delphi method and involved four rounds of anonymous voting, where five options were used to determine the level of agreement (LOA), based on the Likert Scale: (1) strongly disagree; (2) disagree, (3) neither agree nor disagree (neutral); (4) agree; and (5) strongly agree. Nineteen questions were addressed and discussed via teleconference to formulate the answers. In order to identify the relevant data on COVID-19 vaccines, a search with standardized descriptors and synonyms was performed on September 10th, 2021, of the MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and LILACS to identify studies of interest. We used the Newcastle-Ottawa Scale to assess the quality of nonrandomized studies. Results: All the nineteen questions-answers (Q&A) were approved by the BSR Task Force with more than 80% of panelists voting options 4—agree—and 5—strongly agree—, and a consensus was reached. These Guidelines were focused in SMD on the most appropriate timing for IMRD patients to get vaccinated to reach the adequate covid-19 vaccination response. Conclusion: These guidelines were developed by a BSR Task Force with a high LOA among panelists, based on the literature review of published studies and expert opinion for COVID-19 vaccination in IMRD patients. Noteworthy, in the pandemic period, up to the time of the review and the consensus process for this document, high-quality evidence was scarce. Thus, it is not a substitute for clinical judgment.

IL-6 levels are associated with clinical status in patients with Myasthenia Gravis / Os níveis de IL-6 estão associados com o status clínico de pacientes com Miastenia Gravis

BACKGROUND: Myasthenia gravis (MG) is an autoimmune disease marked by fluctuating course of muscle weakness. OBJECTIVES: The current study was designed to evaluate plasma levels of cytokines (IL-2, IL-4, IL-6, IL-10, TNF, IFN-γ, and IL17A) in patients with MG and controls and to investigate whether cytokines levels are associated with clinical parameters. This study was conducted at the Neuromuscular Diseases Outpatient Clinic, Hospital das Clínicas, Universidade Federal de Minas Gerais (UFMG), Brazil. METHODS: Peripheral blood was drawn, and plasma levels of cytokines were measured by cytometric bead array (CBA) in 80 treated patients with MG and 50 controls. The MG Composite (MGC) was used to evaluate muscle weakness and severity of typical motor symptoms of MG. RESULTS: Patients with MG undergoing treatment exhibit lower levels of all evaluated cytokines compared to controls. There was a negative correlation between IL-6 levels and the MG Composite score, indicating that higher levels of IL-6 were associated with better control of the disease. CONCLUSION: This exploratory study suggests that IL-6 is associated with MG clinical status, as assessed by the MGC.

INTRODUÇÃO: A Miastenia Gravis (MG) é uma doença autoimune caracterizada por fraqueza muscular flutuante. OBJETIVOS: avaliar os níveis plasmáticos de citocinas (IL-2, IL-4, IL-6, IL-10, TNF, IFN-γ, e IL-17A) em pacientes com MG e controles e investigar se essas citocinas estão associadas com parâmetros clínicos. Este estudo foi conduzido no ambulatório de doenças neuromusculares do Hospital das Clínicas, Universidade Federal de Minas Gerais (UFMG), Brasil. MÉTODOS: Foi coletado sangue periféricos e os níveis plasmáticos das citocinas foram medidos por citometria em 80 pacientes com MG tratados e em 50 controles. O MG composite (MGC) foi utilizado para avaliar a fraqueza muscular e a gravidade dos sintomas motores típicos da MG. RESULTADOS: Os pacientes com MG em tratamento apresentaram menores níveis de todas as citocinas avaliadas comparados ao controle. Houve uma correlação negativa entre os níveis de IL-6 e o MGC, indicando que altos níveis de IL-6 estão associados com melhor controle da doença. CONCLUSÃO: este estudo exploratório sugere que a IL-6 está associada com o status clínico da MG, quando avaliado pelo MGC.

Vitamin D and bone health in adults: a systematic review and meta-analysis / Vitamina D e saúde óssea em adultos: uma revisão sistemática e metanálise

Abstract Low bone health is associated with vitamin D deficiency in older individuals; however, this association is not well established in adults. The aim of the study was to analyze the association between serum concentrations of 25-hydroxyvitamin D and bone health in adults by systematic review and meta-analysis. The search was carried out in the LILACS, PubMed, Scopus, Web of Science, ScienceDirect databases from March 2017 to October 2018 with adult individuals (20-59 years). Bone health was evaluation performed through dual X-ray absorptiometry and serum concentrations of 25(OH)D. The random effect model was used to analyze data from bone mineral content and bone mineral. Random effects models were used and the sources of heterogeneity were explored by means of meta-regression. Thirty-five articles were selected. There was positive correlation between vitamin D and bone health in most of the evaluated sites. Correlation was observed in the analysis of subgroups for lumbar spine among men. When stratified, the studies presented high heterogeneity, which was explained by the sample size, mean serum vitamin D levels and risk of bias. Vitamin D is positively correlated to bone health in adult individuals.

Resumo A baixa saúde óssea está associada à deficiência de vitamina D em indivíduos mais velhos; no entanto, isso não está bem estabelecido em adultos. O estudo objetivou-se analisar a associação entre concentrações séricas de 25-hidroxivitamina D e baixa saúde óssea em adultos por revisão sistemática e metanálise. A pesquisa foi realizada nas bases LILACS, PubMed, Scopus, Web of Science, ScienceDirect de março de 2017 a outubro de 2018 com indivíduos adultos (20-59 anos). A avaliação da saúde óssea foi realizada através da absorciometria dupla de raios X e concentrações séricas de 25(OH)D. O modelo de efeito aleatório foi utilizado para analisar dados do conteúdo mineral ósseo e densidade mineral óssea. Modelos de efeitos aleatórios foram utilizados e a heterogeneidade foi explorada por meio de meta-regressão. Trinta e cinco artigos foram selecionados. Houve correlação positiva entre a vitamina D e a saúde óssea na maioria dos locais avaliados. Observou-se correlação na análise de subgrupos da coluna lombar entre homens. Quando estratificados, os estudos apresentaram alta heterogeneidade, explicada pelo tamanho da amostra, pelos níveis séricos médios da vitamina e pelo risco de viés. A vitamina D está positivamente correlacionada com a saúde óssea em indivíduos adultos.

Chronic use of hydroxychloroquine did not protect against COVID-19 in a large cohort of patients with rheumatic diseases in Brazil

Abstract Background: There is a lack of information on the role of chronic use of hydroxychloroquine during the SARS-CoV-2 outbreak. Our aim was to compare the occurrence of COVID-19 between rheumatic disease patients on hydroxychloroquine with individuals from the same household not taking the drug during the first 8 weeks of community viral transmission in Brazil. Methods: This baseline cross-sectional analysis is part of a 24-week observational multi-center study involving 22 Brazilian academic outpatient centers. All information regarding COVID-19 symptoms, epidemiological, clinical, and demographic data were recorded on a specific web-based platform using telephone calls from physicians and medical students. COVID-19 was defined according to the Brazilian Ministry of Health (BMH) criteria. Mann-Whitney, Chi-square and Exact Fisher tests were used for statistical analysis and two binary Final Logistic Regression Model by Wald test were developed using a backward-stepwise method for the presence of COVID-19. Results: From March 29th to May 17st, 2020, a total of 10,443 participants were enrolled, including 5166 (53.9%) rheumatic disease patients, of whom 82.5% had systemic erythematosus lupus, 7.8% rheumatoid arthritis, 3.7% Sjögren's syndrome and 0.8% systemic sclerosis. In total, 1822 (19.1%) participants reported flu symptoms within the 30 days prior to enrollment, of which 3.1% fulfilled the BMH criteria, but with no significant difference between rheumatic disease patients (4.03%) and controls (3.25%). After adjustments for multiple confounders, the main risk factor significantly associated with a COVID-19 diagnosis was lung disease (OR 1.63; 95% CI 1.03-2.58); and for rheumatic disease patients were diagnosis of systemic sclerosis (OR 2.8; 95% CI 1.19-6.63) and glucocorticoids above 10 mg/ day (OR 2.05; 95% CI 1.31-3.19). In addition, a recent influenza vaccination had a protective effect (OR 0.674; 95% CI 0.46-0.98). Conclusion: Patients with rheumatic disease on hydroxychloroquine presented a similar occurrence of COVID-19 to household cohabitants, suggesting a lack of any protective role against SARS-CoV-2 infection. Trial registration Brazilian Registry of Clinical Trials (ReBEC; RBR - 9KTWX6).

Reduced bone mineral content and density in neurofibromatosis type 1 and its association with nutrient intake

SUMMARY BACKGROUND Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disease characterized by multisystem involvement including low bone mineral density (BMD). OBJECTIVE To assess the bone phenotype of individuals with NF1 and verify its association with nutrient intake. METHODS Twenty-six adults with NF1 underwent bone phenotype assessments using dual-energy X-ray absorptiometry (DXA) and food intake evaluations. They were compared to 26 unaffected matched control patients. Weight, height, and waist circumference (WC) were measured. DXA provided total body, spine, and hip BMDs and bone mineral content (BMC) for all patients. Food intake was evaluated for energy, macro- and micro-nutrients. RESULTS Height (1.68 ± 0.1; 1.61 ± 0.1 cm; P = 0.003) and BMC (2.3 ± 0.4; 2.0 ± 0.5 kg; P = 0.046) were lower in the NF1 group. Individuals with NF1 also presented lower total body and spine BMDs (g/cm2) (1.1 ± 0.1, 1.0 ± 0.1, P = 0.036; 1.0 ± 0.1, 0.9 ± 0.1; P = 0.015, respectively). The frequency of total body bone mass below the expected level for patients' ages was higher in the NF1 group (7.7%; 34.6%, P = 0.016). There were no differences in energy consumption. No correlations between BMC and BMD with nutrient intake were observed in the NF1 group. CONCLUSIONS The NF1 group presented lower BMCs and BMDs. Although a lower consumption of calcium, iron, and vitamin A, and a higher intake of sodium and omega-6 were observed, there was no relationship between bone phenotype and nutrient intake.

RESUMO INTRODUÇÃO A Neurofibromatose tipo 1 (NF1) é uma doença genética autossômica dominante caracterizada por envolvimento neurocutâneo e multissistêmico, incluindo baixa densidade mineral óssea (DMO). OBJETIVOS Avaliar características ósseas em indivíduos com NF1 e verificar associação com a ingestão de nutrientes. METODOLOGIA 26 adultos com NF1 submeteram-se a avaliação dos parâmetros ósseos usando absorciometria com raios-X de dupla energia (DXA), além da avaliação da ingestão alimentar. O grupo NF1 foi comparado e pareado com 26 indivíduos sem a doença. Peso, estatura e circunferência da cintura foram avaliados. DXA forneceu o conteúdo mineral ósseo (CMO) e a DMO do corpo total, coluna e fêmur. A ingestão de calorias, macronutrientes e micronutrientes foi avaliada. RESULTADOS O grupo NF1 apresentou redução da estatura (1,68 ± 0,1; 1,61 ± 0,1 cm; P=0,003) e do CMO (2,3 ± 0,4; 2,0 ± 0,5 kg; P=0,046). Indivíduos com NF1 também apresentaram redução da DMO de corpo total e coluna (g/cm2) (1,1 ± 0,1, 1,0 ± 0,1, P=0,036; 1,0 ± 0,1, 0,9 ± 0,1; P=0,015, respectivamente). A frequência de indivíduos com massa óssea abaixo do esperado para a idade foi maior no grupo NF1 (7,7%; 34,6%, P=0,016). Não houve diferenças no consumo energético. Não houve correlação entre CMO e DMO com a ingestão de nutrientes no grupo NF1. CONCLUSÕES O grupo NF1 apresentou redução do CMO e da DMO. Apesar de menor consumo de cálcio, ferro e vitamina A, e maior consumo de sódio e ômega-6, não foi observada relação entre o fenótipo ósseo e a ingestão de nutrientes.

Factors associated with bone mineral content in adults: a population-based study / Fatores associados ao conteúdo mineral ósseo em adultos: estudo de base populacional

ABSTRACT Objective To determine the association among bone mineral content, sociodemographic, anthropometric and behavioral factors, and health status of Brazilian adults. Methods This was a cross-sectional, population-based study including 701 individuals from both sexes aged between 20 and 59 years. DEXA was used to evaluate dependent variable. The associations were evaluated using linear regression models stratified by sex. Results When mean bone mineral content values were compared, we found significant differences related to sex and all the independent variables evaluated. In the adjusted models, we identified an inverse association between bone mineral content and age in both sexes. Among men, to be overweight and/or obese, be highly educated, and have almost sufficiency of 25(OH)D were associated with higher bone mineral content values. On the other hand, among women, to be non-white skin color, overweight and/or obese were associated with better bone health. The main factors associated with low total bone mineral density were advanced age, white skin color, low level of formal education, eutrophy, and 25(OH)D deficiency. Conclusion Our results may help to identify adults who are at higher risk, and these findings should be used as guidelines for prevention and early diagnosis.

RESUMO Objetivo Verificar a associação entre o conteúdo mineral ósseo e fatores sociodemográficos, antropométricos, comportamentais e condições de saúde em adultos brasileiros. Métodos Estudo transversal, de base populacional, realizado com 701 indivíduos de ambos os sexos, com idade entre 20 e 59 anos. A variável dependente foi avaliada por DEXA. As associações foram avaliadas por modelos de regressão linear estratificados baseados no sexo dos indivíduos. Resultados Quando comparados os valores médios do conteúdo mineral ósseo, observamos diferença estatisticamente significante em relação aos sexos e para todas as variáveis independentes avaliadas. Nos modelos ajustados, identificamos associação inversa entre o conteúdo mineral ósseo e a idade em ambos os sexos. Entre os homens, sobrepeso e obesidade, alta escolaridade e suficiência de 25(OH)D foram associados a maiores valores de conteúdo mineral ósseo. Entre as mulheres, por sua vez, cor da pele não branca, sobrepeso e obesidade foram associados a melhor saúde óssea. Os principais fatores associados à baixa massa óssea total foram idade avançada, cor da pele branca, baixa escolaridade, eutrofia e deficiência de 25(OH)D. Conclusão Esses resultados podem auxiliar na identificação de adultos com maior risco e que devem ser alvo de medidas de prevenção e diagnóstico precoce.

Factors associated with bone mineral density in adults: a cross-sectional population-based study / Fatores associados à densidade mineral óssea em adultos: um estudo transversal baseado em população / Factores asociados con la densidad mineral ósea en adultos: un estudio transversal basado en población

Abstract Objective: This study aimed to analyze the association between lumbar spine, femoral neck, total hip bone mineral density (biophysical bone health assessment parameter), and sociodemographic, anthropometric, behavioral, and health condition factors in Brazilian adults. Method: This is a cross-sectional, population-based study performed with individuals of both genders, aged between 20 and 59 (n=701). The dependent variables were evaluated by Dual Energy X-ray Absorptiometry. The independent variables were evaluated through a questionnaire, anthropometric evaluation and blood collection. The association between bone mineral density and the independent variables was evaluated by linear regression analysis. All analyses were stratified by gender. Results: Men presented higher bone mineral density than women. Bone mineral density was inversely associated with age range and directly associated with nutritional status in both genders and in the three bone sites analyzed. In addition, 25 Hydroxyvitamin D deficient status among men and contraceptive use among women were associated with lower bone mineral density, and a significant association was only found with lumbar spine bone mineral density in women. Conclusion: The factors associated with bone health among men were age, skin color, nutritional status, and vitamin D status. For women, the associated factors with bone health were age, skin color, nutritional status and contraceptive use.

Resumo Objetivo: Este estudo tem como objetivo analisar a associação entre coluna lombar, colo femoral, densidade mineral óssea total do quadril (parâmetro biofísico de avaliação da saúde óssea) e fatores sociodemográficos, antropométricos, comportamentais e de condição de saúde nos adultos brasileiros. Método: Este é um estudo transversal, baseado em população, realizado com indivíduos de ambos os gêneros, com idades entre 20 e 59 anos (n=701). As variáveis dependentes foram avaliadas por Absorciometria com Raios-X de Dupla Energia. As variáveis independentes foram avaliadas por meio de um questionário, avaliação antropométrica e coleta de sangue. A associação entre densidade mineral óssea e variáveis independentes foi avaliada por análise de regressão linear. Todas as análises foram estratificadas por gênero. Resultados: Os homens apresentaram densidade mineral óssea mais alta do que as mulheres. A densidade mineral óssea foi inversamente associada à faixa etária e diretamente associada ao estado nutricional em ambos os gêneros e nos três locais ósseos analisados. Além disso, o estado de deficiência de 25-Hidroxivitamina D entre os homens e o uso de contraceptivos entre as mulheres foram associados a uma densidade mineral óssea mais baixa, e uma associação significativa só foi encontrada com a densidade mineral óssea da coluna lombar nas mulheres. Conclusão: Os fatores associados à saúde óssea entre os homens foram idade, cor da pele, estado nutricional e estado da vitamina D. Para as mulheres, os fatores associados à saúde óssea foram idade, cor da pele, estado nutricional e uso de contraceptivos.

Resumen Objetivo: Este estudio tiene como fin analizar la asociación entre columna lumbar, cuello femoral, densidad mineral ósea total de la cadera (parámetro biofísico de evaluación de la salud ósea) y factores sociodemográficos, antropométricos, comportamentales y de condición de salud en los adultos brasileños. Método: Este es un estudio transversal, basado en población, llevado a cabo con individuos de ambos géneros, con edades entre 20 y 59 años (n=701). Las variables dependientes fueron evaluadas por Absorciometría con Rayos X de Doble Energía. Las variables independientes fueron evaluadas mediante un cuestionario, evaluación antropométrica y recolección de sangre. La asociación entre densidad mineral ósea y variables independientes fue valorado por análisis de regresión lineal. Todos los análisis fueron estratificados por género. Resultados: Los varones presentaron densidad mineral ósea más alta que las mujeres. La densidad mineral ósea estuvo inversamente asociada con el rango de edad y directamente asociada con el estado nutritivo en ambos géneros y en los tres sitios óseos analizados. Además, el estado de deficiencia de 25-Hidroxivitamina D entre los hombres y el uso de contraceptivos entre las mujeres estuvieron asociados con una densidad mineral ósea más baja, y una asociación significativa solo fue encontrada con la densidad mineral ósea de la columna lumbar en las mujeres. Conclusión: Los factores asociados con la salud ósea entre los varones fueron edad, color de la piel, estado nutritivo y estado de la vitamina D. Para las mujeres, los factores asociados con la salud ósea fueron edad, color de la piel, estado nutritivo y uso de contraceptivos.

Concurrent validity of handgrip strength between the jamar and bulb dynamometers in women with rheumatoid arthitis / Validade concorrente da força de preensão palmar entre os dinamômetros Jamar e de bulbo em mulheres com artrite reumatoide / Validez concurrente de la fuerza de prensión palmar entre los dinamómetros Jamar y de bulbo en mujeres con artritis reumatoide

Abstract Introduction: Rheumatoid arthritis (RA) is a progressive disease that causes deformation and constant joint damage. Handgrip strength (HGS) has been used by several health professionals in clinical practice as a mechanism for assessing muscle strength and overall performance. Objective: To perform the concordance analysis of handgrip strength measurements using a pneumatic dynamometer (Bulb) and a hydraulic dynamometer (Jamar) in women with rheumatoid arthritis. Method: The HGS measurements by the two dynamometers followed the norms of the American Society of Hand Therapists. The concordance between measurements was performed by the Bland-Altman method. Significance level was 5%. Results: In total, 41 women (60.63 ± 8.35 years) participated in the study. Analysis showed that the measures between the two dynamometers were not concordant (bias = 9.04, p < 0.01), there was a linear relationship between the difference of the measures and the mean (r = 0.73, p < 0.01), and the limits of agreement were very extensive (−2.74 to 20.81). Conclusion: Assuming that the rheumatoid arthritis compromises the hands, with a consequent decrease in HGS, further exploration of the subject is suggested in future studies to define the best measure for clinical practice at the different levels of health care. However, since there are many different dynamometers, we suggest to better explore the agreement between the measurements obtained by them in populations under different conditions.

Resumo Introdução: Artrite reumatóide (AR) é uma doença progressiva que causa deformação e comprometimento articular. A força de preensão palmar (FPP) tem sido usada por vários profissionais de saúde, na prática clínica, para avaliar força muscular e desempenho. Objetivo: Analisar a concordância das medidas de força de preensão palmar usando o dinamômetro pneumático (Bulbo) e hidráulico (Jamar) em mulheres com artrite reumatoide. Método: As medidas de FPP pelos dois dinamômetros seguiram as normas da American Society of Hand Therapists. A concordância entre as medidas foi por meio do método de Bland-Altman. Nível de significância de 5%. Resultados: Participaram 41 mulheres (60,63 ± 8,35 anos). A análise entre os dois dinamômetros demonstrou não haver concordância (bias = 9,04, p < 0,01), com uma relação linear entre a diferença das medidas e a média (r = 0,73, p < 0,01) e, os limites de concordância foram muito extensos (-2,74 to 20,81). Conclusão: Como a artrite reumatoide compromete as mãos com consequente diminuição da FPP, é importante explorar melhor este tema para definir a melhor medida para a prática clínica nos diferentes níveis de atenção à saúde. No entanto, devido ao grande número de tipo de dinamômetros, sugere-se novos estudos sobre a concordância destas medidas em populações de diferentes condições.

Resumen Introducción: La artritis reumatoide (AR) es una enfermedad progresiva que causa deformación y compromiso articular. La fuerza de prensión palmar (FPP) ha sido utilizada por varios profesionales de la salud, en la práctica clínica, para evaluar la fuerza muscular y el rendimiento. Objetivo: Analizar la concordancia de las medidas de fuerza de prensión palmar usando el dinamómetro neumático (Bulbo) e hidráulico (Jamar) en mujeres con artritis reumatoide. Método: Las medidas de FPP por los dos dinamómetros siguieron las normas de la American Society of Hand Therapists. La concordancia entre las medidas fue mediante el método de Bland-Altman. Nivel de significancia del 5%. Resultados: Participaron 41 mujeres (60,63 ± 8,35 años). El análisis entre los dos dinamómetros demostró no haber concordancia (bias = 9,04, p < 0,01), con una relación lineal entre la diferencia de las medidas y la media (r = 0,73, p < 0,01), los límites de concordancia fueron muy extensos (-2,74 a 20,81). Conclusión: Como la artritis reumatoide compromete las manos con consecuente disminución de la FPP, es importante explorar mejor este tema para definir la mejor medida para la práctica clínica en los diferentes niveles de atención a la salud. Sin embargo, debido al gran número de dinamómetros, se sugiere nuevos estudios sobre la concordancia de estas medidas en poblaciones de diferentes condiciones.

High frequency of methotrexate intolerance in longstanding rheumatoid arthritis: using the methotrexate intolerance severity score (MISS)

Abstract Background: Methotrexate (MTX) intolerance is frequent, and its early identification may impact treatment, leading to timely changes in medication that may promote patient compliance and better control of rheumatoid arthritis (RA). The objective of this study was to identify the frequency of, and risk factors for, MTX intolerance using the Brazilian Portuguese version of the Methotrexate Intolerance Severity Score (MISS) questionnaire in patients with RA. Methods: This cross-sectional study was performed between April 2018 and April 2019 and enrolled patients with RA in regular use of oral or subcutaneous MTX for at least 3 months. Patients were invited to answer the Brazilian Portuguese version of the MISS questionnaire, and MTX intolerance was defined by a score ≥ 6 points. Age, sex, disease duration, time of MTX use, dose, route of administration, concomitant medications, comorbidities, smoking, and Disease Activity Score for 28joint (DAS28) data were collected from institutional medical records. Results: Among 120 patients, 103 (85.8%) were female, the mean age was 61 (±12.5) years, the mean duration of disease was 16 (±10.3) years, and the average duration of MTX use was 7 (±5.5) years. The frequency of MTX intolerance was 21.6%. The most frequent symptoms reported after the use of MTX were nausea (92.3%), abdominal pain (46.1%), and vomiting (30.7%). Behavioral symptoms occurred in 96.1% of patients with MTX intolerance, the most frequent being restlessness and irritability. Patients who used corticosteroids were more likely to develop MTX intolerance than those not using corticosteroids (odds ratio = 2.73; 95% confidence interval, 1.06 to 7.06; p = 0.038). Conversely, increasing age showed marginally significant association with decreased risk of MTX intolerance (p = 0.059). Conclusions: The use of the MISS questionnaire disclosed high frequencies of anticipatory, associative, and behavioral symptoms in MTX-intolerant patients, and the use of corticosteroid increases the risk of MTX intolerance. We suggest that the MISS questionnaire be used routinely in clinical practice.(AU)

Revisiting hydroxychloroquine and chloroquine for patients with chronic immunity-mediated inflammatory rheumatic diseases

Abstract Hydroxychloroquine and chloroquine, also known as antimalarial drugs, are widely used in the treatment of rheumatic diseases and have recently become the focus of attention because of the ongoing COVID-19 pandemic. Rheumatologists have been using antimalarials to manage patients with chronic immune-mediated inflammatory rheumatic diseases for decades. It is an appropriate time to review their immunomodulatory and anti-inflammatory mechanisms impact on disease activity and survival of systemic lupus erythematosus patient, including antiplatelet effect, metabolic and lipid benefits. We also discuss possible adverse effects, adding a practical and comprehensive approach to monitoring rheumatic patients during treatment with these drugs.(AU)

Impacto da educação na saúde de pacientes com artrite reumatoide - estudo piloto / Impact of education on rheumatoid arthritis patients' health - pilot study

Objetivo: Grupos de orientação para pacientes com artrite reumatoide (AR) têm boa aceitação, mas benefícios controversos no tratamento dessa doença. Este estudo visa a avaliar seu impacto sobre a qualidade de vida e a dor em pacientes com AR. Métodos: Ensaio clínico piloto de intervenção em grupos de orientação que incluiu 15 pacientes com AR. Foram realizados 12 encontros de duas horas por semanas, que abordaram ações educativas sobre a doença, o tratamento, medidas de proteção articular e conservação de energia, atividades terapêuticas ocupacionais e oficinas de vivências. Foramutilizados a escala visual analógica de dor (EVA dor) e o sistemadescritivo em três níveis de cinco dimensões do EuroQol e sua escala visual analógica (EQ-5D-3L e EQ-VAS) para avaliação da qualidade de vida. Resultados: Catorze (93%) pacientes eram do gênerofeminino, com idade média 61,27 anos, tempo médio de doença de 19,93 anos. Treze (87%) deles apresentavam deformidades articulares em mãos pela AR. Houve melhora significativa no domínio cuidadospessoais do EQ-5D-3L (p=0,046) e tendência à redução da dor(EVA dor) e melhora da qualidade de vida (EQ-5D-3L e EQVAS),sem significância estatística (P>0,05). Conclusões: Apesar dopequeno número de pacientes incluídos neste estudo piloto, a melhora dos cuidados pessoais, da autopercepção da dor e da qualidade devida dos pacientes sugere que houve impacto positivo da educação, das atividades terapêuticas ocupacionais e do compartilhamento devivências entre os pacientes com AR

Background: Educational groups of patients with rheumatoid arthritis (RA) have good acceptance, but controversial benefits for its treatment. This study aims to evaluate quality of life and pain in RA patient attending education groups. Methods: Pilot clinical intervention study of educational groups including 15 RA patients. Twelve weekly appointments lasting two hours each were held. They addressed educational actions on the disease treatment, joint protection and energy conservation measures, occupational therapeutic activities and workshops on sharing experiences. The pain visual analogue scale (VAS-pain) and the 5 domain-three-dimensional descriptive system of EuroQol (EQ-5D-3L) and its visual analogue scale (EQ-VAS) were applied to assess pain and quality of life. Results: Fourteen (93%) patients were female, with a mean age of 61,27 years, mean disease time of 19,93 years. Thirteen (87%) of them had hand joint deformities due to RA. There was a significant improvement in the personal care domain of the EQ-5D-3L (P= 0,046) and a tendency to pain reduction (VAS-pain) and improvement of quality of life (EQ-5D-3L and EQVAS index), without statistical significance (P>0.05). Conclusion: Despite the evaluation of few RA patients, the improvement of patients' personal care, pain self-perception and quality of life suggests that there was a positive impact of education, occupational therapy interventions and sharing experiences among patients with RA

Força de preensão palmar e desempenho funcional em mulheres de meia-idade e idosas com artrite reumatoide / Fuerza de prensión manual y rendimiento funcional en mujeres de mediana edad y ancianas con artritis reumatoide / Handgrip strength and functional performance in middle-aged and older women with rheumatoid arthritis

RESUMO A força de preensão palmar em mulheres com artrite reumatoide pode estar comprometida devido à presença de deformidades e restrições funcionais impostas pela doença. Existem poucas informações na literatura sobre a diferença de força de preensão e funcionalidade em mulheres adultas e idosas com artrite reumatoide. O objetivo foi comparar a força de preensão palmar, capacidade funcional, e fadiga entre mulheres adultas (meia idade) e idosas com artrite reumatoide e verificar a associação destas variáveis nas duas faixas etárias. Participaram mulheres com artrite reumatoide, acima de 45 anos, com marcha independente, divididas em grupo de adultas (45 a 59 anos) e idosas (60 anos e mais). Foram mensuradas a força de preensão palmar (dinamômetro Jamar®), capacidade funcional (velocidade de marcha) e fadiga (Functional Assessment of Chronic Illness Therapy); feitas comparações entre grupos de idade pelo teste t-Student independente, e associação entre as variáveis, em cada grupo, pelo teste de correlação de Pearson. Foi verificado nível de significância de 5% e a força de preensão palmar foi maior no grupo de idosas (p=0,01). No grupo de adultas, houve associação entre capacidade funcional e fadiga (r=0,53; p=0,01) e no grupo de idosas, houve associação entre força de preensão palmar e velocidade de marcha (r=0,51; p=0,02). Os resultados demonstraram que as idosas estavam em melhores condições musculares. Parâmetros indicados, como marcadores de desempenho funcional e muscular em idosas demonstraram estar associados, confirmando o uso destes marcadores nesta condição específica.

RESUMEN La fuerza de prensión manual en mujeres con artritis reumatoide puede verse comprometida debido a la presencia de deformidades y restricciones funcionales impuestas por la enfermedad. Hay poca información en la literatura sobre la diferencia en la fuerza de agarre y la funcionalidad en mujeres adultas y mayores con artritis reumatoide. El objetivo fue comparar la fuerza de la empuñadura, la capacidad funcional y la fatiga entre mujeres adultas (de mediana edad) y ancianas con artritis reumatoide y verificar la asociación de estas variables en ambos grupos de edad. Participaron mujeres con artritis reumatoide, mayores de 45 años, con marcha independiente, divididas en grupos de adultos (45 a 59 años) y ancianos (60 años y más). Se midieron la fuerza de agarre de la mano (dinamómetro Jamar®), la capacidad funcional (velocidad de marcha) y la fatiga (Evaluación funcional de la terapia de enfermedades crónicas). Se realizaron comparaciones entre grupos de edad mediante la prueba t de Student independiente, y la asociación entre las variables en cada grupo mediante la prueba de correlación de Pearson. Nivel de significancia del 5%. La fuerza de agarre fue mayor en el grupo de ancianos (p=0.01). En el grupo de adultos, hubo una asociación entre la capacidad funcional y la fatiga (r=0.53; p=0.01), y en el grupo de ancianos, hubo una asociación entre la fuerza de prensión y la velocidad de la marcha (r=0.51; p=0.02). Los resultados mostraron que las mujeres mayores estaban en mejor condición muscular. Los parámetros indicados como marcadores de rendimiento funcional y muscular en mujeres de edad avanzada se asociaron, lo que confirma el uso de estos marcadores en esta condición específica.

ABSTRACT The handgrip strength in women with rheumatoid arthritis may be compromised, considering the presence of deformities and functional restrictions imposed by the disease. There is insufficient information on the difference in handgrip strength and functionality among middle-aged and older women with rheumatoid arthritis. The aim was to compare handgrip strength, functional capacity and fatigue among middle-aged and older women with rheumatoid arthritis and to verify the association of these variables in the different age groups. Women with rheumatoid arthritis, older than 45 years, with independent gait, were divided into groups of middle-aged (45-59 years) and older women (60 years and over). Handgrip strength (Jamar® dynamometer), functional capacity (gait speed) and fatigue (Functional Assessment of Chronic Illness Therapy) were measured. Statistical comparisons were made between groups by the independent Student's t-test and the association between variables in each group by Pearson's correlation test. The significance level considered was 5%. There was a significant difference in handgrip strength between groups (p=0.01). In the adult group, there was an association between functional capacity and fatigue (r=0.53, p=0.01) and in the elderly women group, there was an association between handgrip strength and gait speed (r=0.51, p=0.02). The results showed that the older women were in better muscle conditions. Parameters indicated as markers of functional and muscle performance in elderly women were shown to be associated, confirming the use of these markers in this specific condition.

Body composition indices in Brazilian adults: age-specific and sex-specific percentile curves

ABSTRACT Objective To establish percentile curves for measures and indices of body composition by age and sex and compare them with data from other ethnic groups. Subjects and methods Cross-sectional, population-based study with adults aged 20-59 years (n = 689). Percentile curves adjusted by a third degree polynomial function were constructed for skeletal mass index (SMI), fat mass index, body fat, and load-capacity metabolic indices (LCMI) based on dual-energy X-ray absorptiometry (DXA). Results SMIweight and SMIBMI showed decline from the third decade of life in both sexes, whereas SMIheight was not able to identify lean mass loss over the ages studied. There was a slight drop at the end of the fifth decade (50-59 years) in men. Among Americans and Chinese, the 50th percentile curve of SMIheight showed an earlier decline. The estimates of adiposity and LCMI curves peaked between 40-49 years and Americans and Chinese maintained an upward curve throughout adulthood. Conclusion The data and curves showed that the SMI adjusted for BMI and body weight were more adequate in detecting the decline of lean mass in adults due to aging. In contrast, SMIheight had a positive correlation with age and its curve increased throughout the evaluated age groups. The results contribute to the evaluation to the nutritional status of adults and to the prevention and treatment of outcomes related to adiposity and deficit lean mass.

High prevalence of obesity in rheumatoid arthritis patients: association with disease activity, hypertension, dyslipidemia and diabetes, a multi-center study

Abstract Introduction: Rheumatoid arthritis (RA) is a well-documented independent risk factor for cardiovascular disease. Obesity may provide an additional link between inflammation and accelerated atherosclerosis in RA. Objective: To evaluate the association between obesity and disease parameters and cardiovascular risk factors in RA patients. Method: Cross-sectional study of a cohort of RA patients from three Brazilian teaching hospitals. Information on demographics, clinical parameters and the presence of cardiovascular risk factors was collected. Blood pressure, weight, height and waist circumference (WC) were measured during the first consultation. Laboratory data were retrieved from medical records. Obesity was defined according to the NCEP/ATPIII and IDF guidelines. The prevalence of obesity was determined cross-sectionally. Disease activity was evaluated using the DAS28 system (remission < 2.6; low 2.6—3.1; moderate 3.2-5.0; high >5.1). Results: The sample consisted of 791 RA patients aged 54.7 ± 12.0 years, of whom 86.9% were women and 59.9% were Caucasian. The mean disease duration was 12.8 ± 8.9 years. Three quarters were rheumatoid factor-positive, the mean body mass index (BMI) was 27.1 ±4.9, and the mean WC was 93.5 ± 12.5 cm. The observed risk factors included dyslipidemia (34.3%), type-2 diabetes (15%), hypertension (49.2%) and family history of premature cardiovascular disease (16.5%). BMI-defined obesity was highly prevalent (26.9%) and associated with age, hypertension and dyslipidemia. Increased WC was associated with diabetes, hypertension, dyslipidemia and disease activity. Conclusion: Obesity was highly prevalent in RA patients and associated with disease activity.

Methotrexate use, not interleukin 33, is associated with lower carotid intima-media thickness in patients with rheumatoid arthritis

Abstract Background: Rheumatoid arthritis is a risk factor for early mortality due to cardiovascular disease. Interleukin-33 appears to protect against the development of atherosclerosis. The purpose of this study was to investigate the relationship between serum levels of interleukin-33 and its soluble receptor with the presence of subclinical carotid atherosclerosis in rheumatoid arthritis patients. Methods: Rheumatoid arthritis patients without atherosclerotic disease were subjected to clinical and laboratory assessments, including carotid ultrasound. Interleukin-33 and its soluble receptor serum levels were measured by ELISA. Results: 102 patients were included. The prevalence of carotid plaques was 23.5% and the median intima-media thickness was 0.7 mm. The median interleukin-33 and its soluble receptor concentration was 69.1 and 469.8 pg/ml. No association was found between serum interleukin-33 or its soluble receptor and intima-media thickness or plaque occurrence. Each 0.1 mm increase of intima-media thickness raised the odds of plaque occurrence by 5.3-fold, and each additional year of rheumatoid arthritis duration increased the odds of plaque occurrence by 6%. Each additional year in patients age and each one-point increase in the Framingham Risk Score were associated with a 0.004 mm and 0.012 mm increase in intima-media thickness. Methotrexate use was associated with a 0.07 mm reduction in intima-media thickness. Conclusions: Interleukin-33 and its soluble receptor were not associated with subclinical atherosclerosis. Traditional risk factors for atherosclerosis and rheumatoid arthritis duration were associated with intima-media thickness and plaque occurrence; methotrexate use was associated with a lower intima-media thickness.