Effects of different swimming intensities on the bone properties of the tibia and femur of Wistar Rats in which knee rheumatoid arthritis was induced / Efectos de las diferentes intensidades de la natación en las propiedades óseas de la tibia y fémur de Ratas Wistar con artritis reumatoide inducida en rodillas

Rheumatoid arthritis (RA) is a disease triggered by environmental and genetic factors. Research suggests that physical exercise has benefits such as delaying functional disability. In vivo studies using experimental models of arthritis can provide useful information about these benefits. to analyze the effects that different intensities of aquatic physical exercise have on the proprieties of the bones in induced arthritis in knees of Wistar rats. Male Wistar adults rats (n=20) were divided into 5 groups: Group Control Arthritis (GCA) n=4, Group control Placebo (GCP) n=4, Group Low Physical Activity (GB) n=4, Group Moderate Physical Activity (GM) n=4 and Group Intense Physical Activity (GI) n=4. The physical activity groups got an intra-articular injection of Zymosam on the right knee; the GCA received saline solution in the right knee; the GCP was submitted to the stress of the needle. The animals were submitted to aquatic activity for 30 minutes, 4 times a week for 5 weeks, and the intensity of the exercise was determined by a weight placed on their back: GB=1 %, GM=5 %, GI=15 % of their body weight. It was observed that the group GB, and the groups that did not exercise GCA and GCP, gained more weight compared to the group GM. In relation to the bone mineral content of the tibia, there was a decrease in the GM group when compared to the GCP group, whereas in the tibial bone mineral density there was a decrease in the GM group compared to the GCP, GCA, GB. As for the area of the femur, the GI group presented an increase of it compared to the GB and GM groups. It is concluded that the high intensity exercises promote better results in bone properties.

La investigación sugiere que el ejercicio físico tiene beneficios como retrasar la discapacidad funcional de la artritis reumatoide. Los estudios in vivo que utilizan modelos experimentales de artritis pueden proporcionar información útil sobre estos beneficios. Se analizaron los efectos de las intensidades del ejercicio físico acuático sobre las propiedades de los huesos, en la artritis inducida en las rodillas de ratas Wistar. Las ratas Wistar macho adultas (n = 20) se dividieron en 5 grupos: grupo de control artritis (ACG) n = 4, grupo control placebo (CGP) n = 4, grupo de actividad física baja (GB) n = 4, grupo de actividad física moderada (GM) n = 4 y grupo de actividad física intensa (GI) n = 4. Los grupos de actividad física recibieron una inyección intraarticular de Zymosam en la rodilla derecha; el GCA recibió solución salina en la rodilla derecha; el CGP fue sometido a la tensión de una aguja. Los animales fueron sometidos a actividad acuática durante 30 minutos, 4 veces a la semana durante 5 semanas, y la intensidad del ejercicio se determinó mediante un peso colocado sobre su espalda: GB = 1 %, GM = 5 %, GI = 15 % de su peso corporal. Se observó que el grupo GB, y los grupos que no ejercitaron GCA y CGP, ganaron más peso en comparación con el grupo GM. En relación con el contenido mineral óseo de la tibia, hubo una disminución en el grupo GM en comparación con el grupo GCP, mientras que en la densidad mineral del hueso tibial hubo una disminución en el grupo GM en comparación con el GCP, GCA, GB. En cuanto al área del fémur, el grupo GI presentó un aumento en comparación con los grupos GB y GM. En conclusión el ejercicio de alta intensidad promueve mejores resultados en las propiedades óseas.

Quadriceps muscle properties in rheumatoid arthritis: insights about muscle morphology, activation and functional capacity

Abstract Background: Rheumatoid arthritis (RA) is an inflammatory and chronic autoimmune disease that leads to muscle mass loss and functional capacity impairment, potentiated by physical inactivity. Despite evidences demonstrate neuromuscular impairments in RA patients, aging effects may have masked the results of similar previous studies. The aim of study was to verify (i) the effects of RA on functional capacity and muscle properties in middle-aged patients and (ii) the association between age, clinical characteristics, quadriceps muscle properties and functional capacity. Methods: Thirty-five RA women and 35 healthy age-matched women were compared with the following outcomes: (i) physical activity level through the International Physical Activity Questionnaire (IPAQ); (ii) timed-up and go (TUG) test; (iii) isometric knee extensor muscular strength; and (iv) vastus lateralis muscle activation and muscle architecture (muscle thickness, pennation angle and fascicle length) during an isometric test. An independent Student t-test and partial correlation (controlled by physical activity levels) were performed, with p < 0.05. Results: Compared with healthy women, RA presented (i) lower physical activity level (- 29.4%; p < 0.001); (ii) lower isometric knee extensor strength (- 20.5%; p < 0.001); (iii) lower TUG performance (- 21.7%; p < 0.001); (iv) smaller muscle thickness (- 23.3%; p < 0.001) and pennation angle (- 14.1%; p = 0.011). No differences were observed in muscle activation and fascicle length. Finally, the correlation demonstrated that, with exception of TUG, muscle strength and muscle morphology were not associated with age in RA, differently from healthy participants. Conclusion: Middle-aged RA patients' impairments occurred due to the disease independently of the aging process, except for functional capacity. Physical inactivity may have potentiated these losses.(AU)

¿La periodontitis crónica modifica la morbilidad de la artritis reumatoide?: aspectos clínicos y moleculares. Una revisión sistemática / Association between chronic periodontitis and rheumatoid arthritis: a systematic review

Rheumatoid arthritis (RA) and chronic periodontitis (CP) may be related due to a bidirectional etiology. The evidence shows that CP could alter the clinical course of RA. We performed a systematic search to determine if CP alters the morbidity of RA, analyzing its clinical and molecular aspects. Of 552 initial articles found, 16 were selected for a thorough review. There is a greater prevalence of CP in patients with RA. Patients with RA have significantly higher values of periodontal clinical parameters than healthy controls. Arthritis activity is significantly greater in patients who suffer from CP and decreases with nonsurgical periodontal treatment. There is a significant relationship between the severity of CP and RA activity.

A artrite reumatoide afeta o sistema nervoso entérico? / Does the rheumatoid arthritis affect the enteric nervous system?

ABSTRACT BACKGROUND: Few studies regarding arthritic diseases have been performed to verify the presence of the neurodegeneration. Given the increased oxidative stress and extra-articular effects of the rheumatoid arthritis, the gastrointestinal studies should be further investigated aiming a better understanding of the systemic effects the disease on enteric nervous system. OBJECTIVE: To determine whether the rheumatoid arthritis affects the nitrergic density and somatic area of the nNOS- immunoreactive (IR) myenteric neurons, as well as the morphometric areas of CGRP and VIP-IR varicosities of the ileum of arthritic rats. METHODS: Twenty 58-day-old male Holtzmann rats were distributed in two groups: control and arthritic. The arthritic group received a single injection of the Freund's Complete Adjuvant in order to induce arthritis model. The whole-mount preparations of ileum were processed for immunohistochemistry to VIP, CGRP and nNOS. Quantification was used for the nitrergic neurons and morphometric analyses were performed for the three markers. RESULTS: The arthritic disease induced a reduction 6% in ileal area compared to control group. No significant differences were observed in nitrergic density comparing both groups. However, arthritic group yielded a reduction of the nitrergic neuronal somatic area and VIP-IR varicosity areas. However, an increase of varicosity CGRP-IR areas was also observed. CONCLUSION: Despite arthritis resulted in no alterations in the number of nitrergic neurons, the retraction of ileal area and reduction of nitrergic somatic and VIP-IR varicosity areas may suggest a negative impact the disease on the ENS.

RESUMO CONTEXTO: Poucos estudos sobre doenças artríticas têm sido realizados para verificar a presença de neurodegeneração. Diante do aumento do estresse oxidativo e dos efeitos extra-articulares da artrite reumatoide, estudos gastrointestinais devem ser investigados visando uma melhor compreensão dos efeitos sistêmicos da doença no sistema nervoso entérico. OBJETIVO: Determinar se a artrite reumatoide afeta a densidade nitrérgica e a área somática dos neurônios mioentéricos imunorreativos ao nNOS (nNOS-IR), bem como para as áreas morfométricas das varicosidades CGRP-IR e VIP-IR do íleo de ratos artríticos. MÉTODOS: Vinte ratos Holtzmann, com 58 dias de idade, foram distribuídos em dois grupos: controle e artrítico. O grupo artrítico recebeu uma única injeção do adjuvante completo de Freund para induzir o modelo de artrite. Os preparados totais de íleo foram processados para imuno-histoquímica ao VIP, CGRP e nNOS. A quantificação foi utilizada para os neurônios nitrérgicos e as análises morfométricas foram realizadas para os três marcadores. RESULTADOS: A doença artrítica induziu uma redução de 6% na área ileal em relação ao grupo controle. Não foram observadas diferenças significativas na densidade nitrérgica comparando os dois grupos. No entanto, o grupo artrítico produziu uma redução da área somática neuronal nitrérgica e da área das varicosidades do VIP-IR. Entretanto, foi observado um aumento das áreas das viricosidades CGRP-IR. CONCLUSÃO: Apesar da artrite não resultar em alterações no número de neurônios nitrérgicos, a retração da área ileal e a redução das áreas somática nitrérgica e das varicosidades do VIP-IR podem sugerir um impacto negativo da doença no sistema nervoso entérico.

Evaluation of the Health Assessment Questionnaire Disability Index in Chilean patients with rheumatoid arthritis / Evaluación del Health Asessment Questionnaire Disability Index (HAQDI) en pacientes chilenos con artritis reumatoide

ABSTRACT Background: The Health Assessment Questionnaire Disability Index (HAQDI) is one of the main instruments used to evaluate functional status in rheumatoid arthritis (RA). Aim: To assess the reliability and validity of the Spanish version of HAQDI in Chilean RA population. Materials and Methods: The questionnaire was applied to 98 patients with RA aged 44 ± 12 years (90% women). Reliability was assessed using Cronbach's alpha statistic for internal consistency. Construct validity was assessed by comparing total HAQDI value and eight HAQDI domains with multiple parameters of disease activity. Discriminant validity was evaluated by classifying disease activity in low, medium or high and evaluating HAQDI value in each category. Floor and ceiling effects were evaluated. To assess construct validity, principal components analysis was performed using varimax rotation. Results: There were no issues in the comprehensibility of the questionnaire. Mean HAQDI score was 1.57 ± 0.66. Standardized Cronbach's Alpha was 0.883. Correlations between Chilean HAQ domains had a p value less than 0.001, and values ranged from 0.317 to 0.597. Activity parameters, DAS 28 and CDAI were significantly correlated with HAQDI domains. Mean HAQDI values were 0.98 ± 0.59,1.45 ± 0.57, and 1.90 ± 0.56 for mild, moderate and severe disease activity. A principal components analysis identified two factors that accounted for 70.0% of total variability. Conclusions: This study shows that the Spanish version of HAQDI is reliable and valid and can be used in Chilean patients with RA.

Antecedentes: El Health Assessment Questionnaire Disability Index es uno de los principales instrumentos utilizados para evaluar incapacidad funcional en la artritis reumatoide (AR). Objetivo: Evaluar la fiabilidad y validez del HAQDI en la población chilena con AR. Material y Método: El cuestionario fue respondido por 98 pacientes con AR de 44 ± 12 años de edad (90% mujeres). La confiabilidad se evaluó usando la estadística alfa de Cronbach. La validez de constructo se evaluó comparando el valor total de HAQDI y de cada uno de sus dominios con múltiples parámetros de actividad de la enfermedad. La validez discriminante se evaluó clasificando la actividad de la enfermedad en bajo, medio o alto y evaluando el valor de HAQDI en cada categoría. Se determinaron efectos de piso y techo. Se realizó un análisis factorial utilizando rotación de varimax. Resultados: El valor promedio del HAQDI fue de 1,57 ± 0.66. El alfa estandarizado de Cronbach fue 0,883. Las correlaciones entre dominios de HAQDI tuvieron un valor p < 0,001 con valores entre 0,317 y 0,597. Los parámetros de actividad se correlacionaron significativamente con los dominios HAQDI. Se encontraron diferencias significativas entre el puntaje de HAQDI en relación con los grados de actividad de la enfermedad. Los valores medios de HAQDI fueron 0,98 ± 0,59, 1,45 ± 0,57 y 1,90 ± 0,56 para actividad leve, moderada y severa, respectivamente. El análisis de componentes principales identificó dos factores que representaron el 70.0% de la variabilidad total. Conclusiones: La versión española de HAQDI es confiable y válida en pacientes chilenos con AR.

Translation to Brazilian Portuguese, cultural adaptation and psychometric properties of 8-item ArthritisSelf-Efficacy Scale (ASES-8)

ABSTRACT BACKGROUND: Self-efficacy refers to one's belief in one's ability to organize, perform actions and face challenges in order to achieve goals and motivation. High self-efficacy improves disease coping and adherence to treatment among patients with rheumatoid arthritis. The objective of this study was to translate, culturally adapt and test the reproducibility of the 8-item Arthritis Self-Efficacy Scale (ASES-8) questionnaire for use in Brazil. DESIGN AND SETTING: Validation study conducted in university outpatient clinics. METHODS: The questionnaire was translated into Brazilian Portuguese and then back-translated into English. The final version in Portuguese was tested on 30 patients with rheumatoid arthritis and was shown to be understandable and culturally adapted. A further 32 patients with rheumatoid arthritis were evaluated three times using the questionnaire. On the first occasion, two evaluators applied the questionnaire to check inter-evaluator reproducibility. After 15 days, one of the evaluators reassessed the patients to verify intra-evaluator reproducibility. At the first assessment, to test the construct validity of ASES-8, the Numerical Pain Scale, Health Assessment Questionnaire, Beck Depression Inventory and Short Form-36 questionnaire were also applied to all the patients. RESULTS: The inter and intra-evaluator correlation coefficients for ASES-8 were high. Cronbach's alpha was higher than 0.90 for the questionnaire, indicating excellent internal consistency. There were moderate correlations between ASES-8 and most of the instruments tested, indicating good construct validity. CONCLUSION: ASES-8 was translated and adapted to the Portuguese language for Brazil. This instrument is valid, reproducible and reliable for evaluating self-efficacy among patients with rheumatoid arthritis.

Disease activity is associated with LV dysfunction in rheumatoid arthritis patients without clinical cardiovascular disease

Abstract Objectives: The cross-sectional study aimed to assess left ventricular systolic function using global longitudinal strain (GLS) by speckle-tracking echocardiography (STE) and arterial stiffness using cardio-ankle vascular index (CAVI) in Thai adults with rheumatoid arthritis (RA) and no clinical evidence of cardiovascular disease (CVD). Methods: Confirmed RA patients were selected from a list of outpatient attendees if they were 18 years (y) without clinical, ECG and echocardiographic evidence of CVD, diabetes mellitus, chronic kidney disease, and excess alcoholic intake. Controls were matched with age and sex to a list of healthy individuals with normal echocardiograms. All underwent STE and CAVI. Results: 60 RA patients (females = 55) were analysed. Mean standard deviation of patient and control ages were 50 ± 10.2 and 51 ±9.9 y, respectively, and mean duration of RA was 9.0 ± 6.8 y. Mean DAS28-CRP and DAS28-ESR were 2.9 ± 0.9 and 3.4 ± 0.9, respectively. There was no between-group differences in left ventricular ejection fraction (LVEF), LV sizes, LVMI, LV diastolic function and CAVI were within normal limits but all GLSs values was significantly lower in patients vs. controls: 17.6 ± 3.4 vs 20.4 ± 2.2 (p = 0.03). Multivariate regression analysis demonstrated significant correlations between GLSs and RA duration (p = 0.02), and GLSs and DAS28-CRP (p = 0.041). Conclusions: Patients with RA and no clinical CV disease have reduced LV systolic function as shown by lower GLSs. It is common and associated with disease activity and RA disease duration. 2D speckle-tracking GLSs is robust in detecting this subclinical LV systolic dysfunction.

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.

Ultrasound inflammatory parameters and Treg/Th17 cell profiles in established rheumatoid arthritis

Abstract Background: Imbalance and disfuntion in regulatory T-cells (Tregs) and IL-17 producer lymphocytes (Th17) have been implicated in the pathogenesis of rheumatoid arthritis (RA). Gray scale synovial proliferation (GS), power Doppler signal (pD) and bone erosions seen on high resolution muskuloskeletal ultrasound (MSUS) are hallmarks of destructive articular disease. Objective: To evaluate the association of peripheral Tregs and Th17 with MSUS findings in RA. Methods: RA patients (1987 ACR criteria) treated with disease-modifying antirheumatic drugs (DMARDs) were included. Lymphocytes were isolated and immunophenotyped by flow cytometry to investigate regulatory FoxP3+ T cells and IL-17+ cells. MSUS (MyLab 60, Esaote, Genova, Italy, linear probe 6-18 MHz) was performed on hand joints, and a 10-joint US score was calculated for each patient. Results: Data on lymphocytes subsets were avaiable for 90 patients. The majority of patients were Caucasian women with a median disease duration of 6 years (interquartile range: 2-13 years). Mean DAS28 was 4.28 (SD ± 1.64) and mean HAQ score was 1.11 (SD ± 0.83). There was no significant correlation of 10-joint GS score (rS = 0.122, 95% CI: - 0.124 to 0.336, P = 0.254) and 10-joint pD score (rS = 0.056, 95% CI: - 0.180 to 0.273, P = 0.602) with the mean percentage of peripheral Treg cells. Also, 10-joint GS score (rS = 0.083, 95% CI: - 0.125 to 0.302, P = 0.438) and 10-joint pD score 10 (rS = - 0.060, 95% CI: - 0.271 to 0.150, P = 0.575); did not correlate to Th17 profile. No association of bone erosions on MSUS with Treg and Th17 profiles (P = 0.831 and P = 0.632, respectively) was observed. Conclusion: In this first study addressing MSUS features and lymphocytes subtypes in established RA, data did not support an association of circulating Tregs and Th17 lymphocytes with inflammatory and structural damage findings on MSUS.

Evaluation of foot functionality in cases of rheumatoid arthritis through the FFI-BR and FHSQ-BR questionnaires: a cross-sectional observational study

ABSTRACT BACKGROUND: Rheumatoid arthritis (RA) can affect the feet, thus compromising the patient's gait and autonomy. In this study, we investigated foot disability in RA patients using the Brazilian versions of the Foot Health Status Questionnaire (FHSQ-BR) and Foot Function Index (FFI-BR). DESIGN AND SETTING: Cross-sectional, observational study conducted in a tertiary care hospital. METHODS: Two hundred individuals were studied: 100 with RA and 100 controls. Demographic variables and FFI-BR and FHSQ-BR scores were analyzed. In relation to RA patients, data on medications used and on the following clinical variables were collected: Disease Activity Score-28-ESR; erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level and rheumatoid factor (RF) level. The groups were compared and the scores and clinical variables were correlated. RESULTS: RA patients' scores in the pain, difficulty and disability domains of the FFI-BR questionnaire were worse (P < 0.0001). The FHSQ-BR showed that there were differences between RA patients and controls in relation to the pain and foot function domains: shoes (P < 0.0001), foot health (P < 0.0001), general health (P=0.0002), physical activity (P < 0.0001), social capacity (P = 0.0006) and vigor (P = 0.01). There were correlations between FFI-BR and DAS-28-ESR scores (rho = 0.45), ESR (rho = 0.27) and CRP (rho = 0.24). According to the FHSQ-BR questionnaire, there was a correlation between DAS-28-ESR and worse foot health (rho = 0.29). CONCLUSION: RA patients' scores in the foot health assessment questionnaires were worse than those of controls. A correlation between inflammatory activity and worse foot function was found.

Smoking promotes exacerbated inflammatory features in dendritic cells of Chilean rheumatoid arthritis patients / El tabaco exacerba características inflamatorias en células dendríticas de pacientes chilenos con artritis reumatoide

ABSTRACT Background: The dual potential to promote tolerance or inflammation when facing self-antigens makes dendritic cells (DCs) fundamental players in autoimmunity. There is an association between smoking and DCs maturation in patients with rheumatoid arthritis (RA). However, ethnicity is a key factor in autoimmune disorders. Aim: To evaluate phenotypic and functional alterations of DCs obtained from Chilean patients with RA as compared to healthy controls (HC). In second term, to compare the inflammatory behaviour of DCs between smoker and non-smoker patients. Material and Methods: Monocyte-derived DCs and T-cells were obtained from blood samples isolated from 30 HC and 32 RA-patients, 14 of which were currently smokers and 18 non-smokers. Several maturation surface markers were evaluated in DCs, including HLA-DR, CD40, CD80, CD83 and CD86. Furthermore, autologous co-cultures of DCs and T-cells were carried out and then T-cell proliferation, and expansion of Th1, Th17 and Tregs were analysed. Results: Compared with HC, RA-patients displayed increased HLA-DR expression in DCs, which was manifested mainly in patients with moderate-to- high disease activity scores (DAS28). Furthermore, RA-patients presented a stronger Th17-expansion and a correlation between DAS28 and Th1-expansion. Both effects were mainly observed in patients in remission or with a low DAS28. Moreover, smoker RA-patients displayed enhanced HLA-DR and CD83 expression in DCs as well as an exacerbated Th17-expansion and a correlation between DAS28 and Th1-expansion. Conclusions: These findings suggest that smoking enhances the inflammatory behaviour of DCs and the consequent Th1 and Th17-mediated response in patients with RA

Introducción: El potencial dual que poseen para promover tolerancia o inflamación ante antígenos propios, hace de las células dendríticas (CDs) actores fundamentales en el desarrollo de autoinmunidad. Existe una asociación entre fumar y la maduración de las CDs en pacientes con artritis reumatoide (AR). No obstante, la etnicidad es un factor clave a considerar en desórdenes autoinmunes. Objetivos: Comparar las alteraciones fenotípicas y funcionales de las CDs obtenidas desde pacientes Chilenos con AR y controles sanos (CS). Además, analizamos las diferencias en el comportamiento inflamatorio que existe entre las CDs obtenidas de pacientes fumadores y CS. Materiales y Métodos: Se obtuvieron CDs derivadas de monocitos y células T desde muestras de sangre aisladas de 30 CS y 32 pacientes con AR, 14 de los cuales eran fumadores y 18 no fumadores. Se evaluaron marcadores de maduración en la superficie de las CDs: HLA-DR, CD40, CD80, CD83 y CD86. Además, se realizaron co-cultivos autólogos de células T y CDs, analizando la proliferación de células T, y la expansión de células Th1, Th17 y Tregs. Resultados: En comparación con los CS, los pacientes AR mostraron un aumento de la expresión de HLA-DR en las CDs, principalmente en los individuos con DAS28 moderado-alto. Los pacientes con AR presentaron una mayor expansión de células Th17 y una correlación entre el DAS28 y la expansión de células Th1, ambos efectos manifestados principalmente en los individuos con un DAS28 bajo o en remisión. Además, los pacientes con AR fumadores mostraron un aumento en la expresión de HLA-DR y CD83 en las CDs y una expansión de células Th17 exacerbada así como una correlación entre el DAS28 y la expansión de células Th1. Conclusiones: Nuestros resultados sugieren que fumar favorece el comportamiento inflamatorio de las CDs y en consecuencia la inducción de respuestas mediadas por células Th1 y Th17 en los pacientes Chilenos con AR.

Eficacia de medicamentos biológicos aprobados por ley 20850, para pacientes con artritis reumatoide refractaria a tratamiento / Efficacy of biological drugs approved by law N°20. 850, for patients with rheumatoid arthritis refractory to treatment

INTRODUCCIÓN: La artritis reumatoide es una enfermedad crónica, sistémica, de origen autoinmune, caracterizada por compromiso articular simétrico. Dentro de su tratamiento destacan fármacos antirreumáticos, modificadores de la enfermedad, glucocorticoides y agentes biológicos. Estos últimos, han llegado a revolucionar la progresión de la enfermedad, otorgando una mejor calidad de vida a los pacientes. CUERPO DE LA REVISIÓN: En Chile, los fármacos biológicos están asegurados para personas con artritis reumatoide refractaria a tratamiento por la ley 20.850 "Ley Ricarte Soto", que incluye los fármacos adalimumab, etanercept, abatacept y rituximab. Por lo tanto, el objetivo de esta investigación fue resumir los principales estudios que aseguran la eficacia de estos medicamentos. CONCLUSIÓN: Se ha demostrado la eficacia de los medicamentos biológicos, con clara superioridad en relación con la progresión radiológica, síntomas, alteración funcional y nivel de actividad de la enfermedad comparativamente con los placebos.

INTRODUCTION: Rheumatoid arthritis is a chronic, systemic disease of autoimmune origin, characterized by symmetrical joint involvement. Its treatment includes antirheumatic drugs, disease modifiers, glucocorticoids and biological agents. The latter have come to revolutionize the progression of the disease, giving a better quality of life to patients. REVIEW BODY: In Chile, biological drugs are insured for people with rheumatoid arthritis refractory to treatment by the 20.850 "Ricarte Soto Law", which includes the drugs adalimumab, etanercept, abatacept and rituximab. Therefore, the objective of this research was to summarize the main studies that ensure the efficacy of these medications. CONCLUSION: The efficacy of biological drugs has been demonstrated, with clear superiority in relation to radiological progression, symptoms, functional alteration and level of disease activity compared to placebos.

Association of vascular function and estimated cardiovascular risk in patients with rheumatoid arthritis / Associação entre a função vascular e o risco cardiovascular estimado em pacientes com artrite reumatoide

Abstract Objectives: Rheumatoid arthritis (RA) patients should receive cardiovascular (CV) risk assessment. For this purpose CV risk calculators are available. In addition, parameters of vascular function can be measured and used for risk prediction. Aim of the present study was to assess the association of these two concepts. Methods: 287 RA patients (58.4 ± 12.6 years) and 232 controls (49.9 ± 13.4 years) were included in this cross-sectional study. We calculated 10 year CV risk with SCORE and QRISK2. For SCORE we used the recommended multiplier of 1.5 in eligible RA patients and estimated the risk also in patients younger than 40 years (mSCORE (0-65)). Augmentation index (AIx) and central pulse pressure (PP), markers of vascular integrity and CV risk, were assessed by pulse wave analysis (PWA). Primary endpoint was the correlation of AIx and the estimated CV risk using mSCORE (0-65). Results: In RA patients AIx showed a statistically significant correlation with mSCORE (0-65) (rho = 0.3374; p < 0.0001) and QRISK2 (rho = 0.3307; p < 0.0001). The correlations of central PP with mSCORE (0-65) (rho = 0.4692; p < 0.0001) and QRISK2 (rho = 0.5828; p < 0.0001) were also statistically significant. Increasing quartiles of central PP were associated with an increased odds of being in the "high risk"category according to SCORE (OR 2.18; 95% CI 1.58-3.01) or QRISK2 (OR 2.18; 95% CI 1.75-2.72). In control patients we also found a correlation of AIx and central PP with SCORE (0-65) and QRISK2. Conclusions: Parameters of central haemodynamics correlate with calculated CV risk. However, both do not give exactly the same information. The question arises whether a combination of both concepts would result in an improved CV risk prediction.

Resumo Objetivos: Os pacientes com artrite reumatoide (AR) devem receber uma avaliação do risco cardiovascular (CV). Para esse fim, existem as calculadoras de risco CV. Além disso, parâmetros da função vascular podem ser medidos e usados para predição do risco. O objetivo deste estudo foi avaliar a associação entre esses dois conceitos. Métodos: Foram incluídos neste estudo transversal 287 pacientes com AR (58,4 ± 12,6 anos) e 232 controles (49,9 ± 13,4 anos). Calculou-se o risco CV em 10 anos com o Score e o QRISK2. No Score, usou-se o multiplicador recomendado de 1,5 em pacientes com AR elegíveis e estimou-se também o risco em pacientes com menos de 40 anos [mScore (0-65)]. O índice de aumento (AIx) e a pressão de pulso (PP) central, marcadores da integridade vascular e risco CV, foram avaliados pela análise de onda de pulso (PWA). O desfecho primário foi a correlação entre o AIx e o risco CV estimado com o mScore (0-65). Resultados: Em pacientes com AR, o AIx mostrou correlação estatisticamente significativa com o mScore (0-65) (rho = 0,3374; p < 0,0001). A correlação entre o AIx e o QRISK2 também foi significativa (rho = 0,3307, p < 0,0001). As correlações entre a PP central e o mScore (0-65) (rho = 0,4692; p < 0,0001) e QRISK2 (rho = 0,5828; p < 0,0001) também foram estatisticamente significativas. Os quartis incrementais da PP central estiveram associados a uma maior probabilidade de estar na categoria de "alto risco"de acordo com o Score (OR 2,18; IC 95% 1,58 a 3,01) ou QRISK2 (OR 2,18; IC 95% 1,75-2,72). Nos pacientes do grupo controle também se encontrou uma correlação entre o AIx e a PP central no Score (0-65) e no QRISK2. Conclusões: Os parâmetros de hemodinâmica central se correlacionam com o risco CV calculado. No entanto, ambos não fornecem exatamente as mesmas informações. Pergunta-se se uma combinação de ambos os conceitos resultaria em uma melhor predição do risco CV.

Falls and their association with physical tests, functional capacity, clinical and demographic factors in patients with rheumatoid arthritis / Ocorrência de quedas e sua associação com testes físicos, capacidade funcional e aspectos clínicos e demográficos em pacientes com artrite reumatoide

ABSTRACT Objective: To evaluate the occurrence of falls reported by rheumatoid arthritis patients and its relation to disease activity, functional capacity and physical fitness. Materials and methods: A cross-sectional study constituted by a sample of 97 rheumatoid arthritis patients from the city of Marília (SP) from 2012 to 2013, were assessed for disease activity. Instruments validated for Brazilian population in order to evaluate physical and functional capacity were used. Data analysis was carried out with descriptive statistics, Spearman correlation and Chi-squared test, considering p < 0.05. Results: 88.7% were female subjects with a mean age of 56 (±11.7) years. The median duration of rheumatoid arthritis was 10 years (P25 = 6 and P75 = 17) and the mean of disease activity was 3.6 (±1.3), what was considered a moderate activity. In the last 12 months 37.1% of patients experienced at least one fall, with a total of 52 episodes, and fear of falling was reported by 74.2% of them, but this was not associated to the occurrence of a fall (χ 2 = 1.19, p = 0.27). Gender, number of medications, age, disease activity, duration of rheumatoid arthritis, functional capacity, and physical tests showed no associations with history of falls in the past year. Conclusion: It was observed that the occurrence of falls and the fear of falling are quite common in this population. The occurrence of falls in this sample of rheumatoid arthritis patients bears no relation to disease activity, functional capacity, or physical fitness tests.

RESUMO Objetivo: Avaliar a ocorrência de quedas reportadas por pacientes com artrite reumatoide (AR) e sua associação com a atividade da doença, capacidade funcional e aptidão física. Material e métodos: Estudo transversal com uma amostra de 97 pacientes com AR em Marília (SP), entre 2012 e 2013. Foram usados instrumentos validados na população brasileira para avaliar capacidade física e funcional. Análise dos dados com estatística descritiva, correlações de Spearman e qui-quadrado, considerado p < 0,05. Resultados: Dos pacientes, 88% eram mulheres, média de 56, anos (± 11,7), duração mediana da AR de 10 anos (P25 = 6 e P75 = 17) e média da atividade da doença 3,6 (± 1,3). Nos últimos 12 meses, 37,1% tiveram pelo menos uma queda (total 52 episódios), 74,2% relataram medo de cair, porém sem associação com a ocorrência de quedas (χ2 = 1,19, p = 0,27). Sexo, quantidade de medicamentos, idade, atividade da doença, duração da AR, capacidade funcional e testes físicos não estão associados com história de queda no último ano. Conclusões: Observou-se que a ocorrência de quedas e o medo de cair é frequente nessa população. A ocorrência de quedas nessa amostra de pacientes com AR não está relacionada à atividade da doença, à capacidade funcional e a testes de aptidão física.

Intra-articular injection with triamcinolone hexacetonide in patients with rheumatoid arthritis: prospective assessment of goniometry and joint inflammation parameters / Injeção intra-articular de hexacetonido de triancinolona em pacientes com artrite reumatoide: avaliação prospectiva da goniometria e parâmetros de inflamação articular

Abstract Objectives: To evaluate local joint variables after intra-articular injection with triamcinolone hexacetonide in rheumatoid arthritis patients. Methods: We blindly and prospectively (baseline, 1, 4, 12 and 24 weeks) evaluated metacarpophalangeal, wrist, elbow, shoulder, knee and ankle joints after triamcinolone hexacetonide intra-articular injection by the following outcome measures: visual analogue scale 0–10 cm (VAS) for rest pain (VASR); VAS for movement pain (VASM); VAS for joint swelling (VASSw); flexion (FlexG) and extension (ExtG). Results: 289 patients (635 joints) were studied. VASSw (p < 0.001) and VASR (0.001 < p < 0.016) improved from T0 to T4, T12 and T24 for all joints. VASM improved from T0 to T4 (p < 0.021) for all joints; T0 to T12 (p < 0.023) for MCF and knee; T0 to T24 (p < 0.019) only for MCF and knee. FlexG improved from T0 to T4 (p < 0.001) for all joints; T0 to T12 (p < 0.001) and T0 to T24 (p < 0.02) only for MCF and knee. ExtG improved from T0 to T4 (p < 0.001) for all joints except for elbow; T0 to T12 (p = 0.003) for wrist, metacarpophalangeal and knee; and T0 to T24 (p = 0.014) for MCF and knee. Conclusion: VASSw responded better at short and medium term after IAI with triamcinolone hexacetonide in our sample of RA patients.

Resumo Objetivos: Avaliar variáveis articulares locais após a injeção intra-articular (IIA) de hexacetonido de triancinolona (HT) em pacientes com artrite reumatoide (AR). Métodos: Avaliaram-se de modo cego e prospectivo (inicial, 1, 4, 12 e 24 semanas) as articulações metacarpofalângica (MCF), punho, cotovelo, ombro, joelho e tornozelo após a IIA de HT à procura das seguintes medidas de desfecho: escala visual analógica (EVA) de 0 a 10 cm para dor em repouso (EVAr); EVA para dor ao movimento (EVAm); EVA para inchaço das articulações (EVAi); flexão (FlexG) e extensão (ExtG). Resultados; Estudaram-se 289 pacientes (635 articulações). A EVAi (p < 0,001) e a EVAr (0,001 < p < 0,016) melhoraram de T0 a T4, T12 e T24 em todas as articulações. A EVAm melhorou de T0-T4 (p < 0,021) em todas as articulações; T0-T12 (p < 0,023) na MCF e no joelho; T0-T24 (p < 0,019) apenas na MCF e no joelho. A FlexG melhorou de T0-T4 (p < 0,001) em todas as articulações; T0-T12 (p < 0,001) e T0-T24 (p < 0,02) apenas na MCF e no joelho. A ExtG melhorou de T0-T4 (p < 0,001) em todas as articulações, exceto no cotovelo; T0-T12 (p = 0,003) no punho, na MCF e no joelho; e T0-T24 (p = 0,014) na MCF e no joelho. Conclusão: A EVAi respondeu melhor em curto e médio prazos após a IIA de HT na presente amostra de pacientes com AR.

Anti-CCP antibodies are not a marker of severity in established rheumatoid arthritis: a magnetic resonance imaging study / O anti-CCP não é um marcador de gravidade da artrite reumatoide estabelecida: um estudo de ressonância magnética

ABSTRACT Introduction: The presence of anti-CCP is an important prognostic tool of rheumatoid arthritis (RA). But research is still ongoing on its relationship with disease activity and functional capacity. Objectives: To study the relationship between anti-CCP and disease activity, functional capacity and structural damage indexes, by means of conventional radiography (CR) and magnetic resonance imaging (MRI), in cases of established RA. Methods: Cross-sectional study with RA patients with 1–10 disease duration. Participants underwent clinical evaluation with anti-CCP. Disease activity was assessed using the Clinical Disease Activity Index (CDAI), and functional capacity through the Health Assessment Questionnaire (HAQ). CR analysis was carried out by the Sharp van der Heijde index (SvdH), and MRI analysis by RAMRIS (Rheumatoid Arthritis Magnetic Resonance Image Scoring). Results: We evaluated 56 patients, with a median (IqR) age of 55 (47.5–60) years; 50 (89.3%) participants were female and 37 (66.1%) were positive for anti-CCP. Medians (IqR) of CDAI, HAQ, SvdH and RAMRIS were 14.75 (5.42–24.97) 1.06 (0.28–1.75), 2 (0–8) and 15 (7–35), respectively. There was no association between anti-CCP and CDAI, HAQ and SvdH and RAMRIS scores. Conclusion: Our results have not established an association of anti-CCP with the severity of disease. To date, we cannot corroborate anti-CCP as a prognostic tool in patients with established RA.

RESUMO Introdução: A presença do anti-CCP constitui importante ferramenta prognóstica da artrite reumatoide (AR), mas ainda se investiga sua relação com a atividade da doença e a a capacidade funcional. Objetivos: Estudar a relação do anti-CCP com os índices de atividade da doença, de capacidade funcional e de dano estrutural, por meio de radiografia convencional (RC) e de ressonância magnética (RM), em AR estabelecida. Métodos: Estudo transversal com pacientes com AR, com um a 10 anos de doença. Os participantes foram submetidos à avaliação clínica com pesquisa do anti-CCP. A atividade de doença foi avaliada por meio do Clinical Disease Activity Index (CDAI) e a capacidade funcional por meio do Health Assessment Questionnaire (HAQ). A análise da RC foi feita pelo índice de Sharp van der Heijde (SmvH) e da RM pelo Sistema de Pontuação de Imagem por Ressonância Magnética na Artrite Reumatoide (RAMRIS, Rheumatoid Arthritis Magnetic Resonance Image Scoring). Resultados: Foram avaliados 56 pacientes, com mediana (IIq) de 55 (47,5-60,0) anos, 50 (89,3%) do sexo feminino e 37 (66,1%) anti-CCP positivos. As medianas (IIq) do CDAI, do HAQ, de SmvH e do RAMRIS foram de 14,75 (5,42-24,97), 1,06 (0,28-1,75), 2 (0-8) e 15 (7-35), respectivamente. Não houve associação do anti-CCP com o CDAI, com o HAQ e com os escores SmvH e RAMRIS. Conclusão: Nossos resultados não estabeleceram a associação do anti-CCP com a gravidade da doença. Até o momento, não podemos corroborar o anti-CCP como uma ferramenta prognóstica em AR estabelecida.

Ghrelin plasma levels, gastric ghrelin cell density and bone mineral density in women with rheumatoid arthritis

Generalized bone loss can be considered an extra-articular manifestation of rheumatoid arthritis (RA) that may lead to the occurrence of fractures, resulting in decreased quality of life and increased healthcare costs. The peptide ghrelin has demonstrated to positively affect osteoblasts in vitro and has anti-inflammatory actions, but the studies that correlate ghrelin plasma levels and RA have contradictory results. We aimed to evaluate the correlation between total ghrelin plasma levels, density of ghrelin-immunoreactive cells in the gastric mucosa, and bone mineral density (BMD) in twenty adult women with established RA with 6 months or more of symptoms (mean age of 52.70±11.40 years). Patients with RA presented higher ghrelin-immunoreactive cells density in gastric mucosa (P=0.008) compared with healthy females. There was a positive relationship between femoral neck BMD and gastric ghrelin cell density (P=0.007). However, these same patients presented a negative correlation between plasma ghrelin levels and total femoral BMD (P=0.03). The present results indicate that ghrelin may be involved in bone metabolism of patients with RA. However, the higher density of ghrelin-producing cells in the gastric mucosa of these patients does not seem to induce a corresponding elevation in the plasma levels of this peptide.

Sensory disturbance and polyneuropathy in rheumatoid arthritis patients with foot deformity / Perturbações sensitivas e polineuropatia em pacientes com artrite reumatoide com deformidade do pé

Abstract Introduction Our aim in this study was to present the results of sensory evaluation tests and electrophysiological evaluations in rheumatoid arthritis (RA) patients with foot deformity and to determine their relation with general health status and lower extremity functionality. Materials and methods Fifty-one patients with RA diagnosis and foot deformity were included in the study. Demographic and disease characteristics of the patients were recorded, and a detailed neurological examination was performed. Superficial sensation, pain, heat, vibration, and two-point discrimination sensation were evaluated in each foot, and their sum was used to determine the sensory deficits index (SDI) of 0–10. The presence of polyneuropathy was evaluated with electrophysiological methods. The Health Assessment Questionnaire and mobility and walking subscales of the Arthritis Impact Measurement Scales-2 were used to assess general health status and lower extremity functionality, respectively. According to the sensory examination and electromyography results, patients were compared in terms of their general health status and lower extremity functional status. Results Sensory disturbance was detected in 39 patients (74%) during the examination; however, 27 patients (52.9%) had polyneuropathy determined electrophysiologically. In patients with sensory deficits, statistically significant deterioration was detected in general health and foot functionality, including mobility and walking, when compared to patients with a normal sensory evaluation. Conclusions Even in the presence of normal electrophysiological tests, sensory dysfunction alone seems to be associated with severe disability in general health status and foot functionality when compared to patients with a normal sensory examination.

Resumo Introdução O objetivo deste estudo foi apresentar os resultados dos testes de avaliação sensitiva e do exame eletrofisiológico em pacientes com artrite reumatoide (AR) com deformidade do pé e determinar a sua relação com o estado geral de saúde e o aspecto funcional dos membros inferiores. Materiais e métodos Foram incluídos no estudo 51 pacientes com diagnóstico de AR e deformidade do pé. Foram registradas as características demográficas e da doença de cada indivíduo e foi feito um exame neurológico detalhado. Foi avaliada a sensibilidade superficial, dolorosa, térmica e vibratória e aplicado o teste de discriminação de dois pontos em cada um dos pés. A soma dos escores foi usada para determinar o índice de déficits sensitivos (IDS) de 0‐10. A presença de polineuropatia foi avaliada com métodos eletrofisiológicos. Foram usados o Health Assessment Questionnaire e as subescalas mobilidade e deambulação da Arthritis Impact Measurement Scales‐2 para avaliar o estado geral de saúde e o aspecto funcional de membros inferiores, respectivamente. De acordo com os resultados dos exames de eletromiografia e de sensibilidade, os pacientes foram comparados em relação ao seu estado geral de saúde e estado funcional de membros inferiores. Resultados Foram detectados distúrbios sensitivos em 39 pacientes (74%) durante o exame; contudo, 27 (52,9%) tinham polineuropatia determinada eletrofisiologicamente. Em pacientes com déficits sensitivos, foi detectada deterioração estatisticamente significativa no estado geral de saúde e no aspecto funcional do pé, inclusive na mobilidade e deambulação, quando comparados com os pacientes com uma avaliação sensitiva normal. Conclusão Mesmo na presença de testes eletrofisiológicos normais, a disfunção sensitiva isolada parece estar associada a incapacidade grave no estado geral de saúde e ao aspecto funcional do pé em comparação com pacientes com um exame sensitivo normal.