Changes in physical function over time in rheumatoid arthritis patients: A cohort study.

INTRODUCTION: Self-reported disability is potentially influenced by many factors in patients with rheumatoid arthritis (RA). In this sense, we evaluated the association between self-reported disability and (1) clinical features, (2) muscle strength and (3) physical performance over time among patients with RA from two distinct patient cohorts. MATERIALS AND METHODS: Two independent prospective RA cohorts were analyzed. The Health Assessment Questionnaire (HAQ), Disease Activity Score in 28 Joints (DAS28), handgrip test, chair stand test, timed-up-and-go (TUG) test and Short Physical Performance Battery (SPPB) were performed at baseline and in follow-up. T test for independent samples, Mann-Whitney U test, Spearman correlation coefficients and linear regression with generalized estimating equations were performed to assess associations between individual constructs at baseline and over time. RESULTS: A total of 205 total RA patients were included [North American Cohort (n = 115); Brazilian Cohort (n = 90)]. At enrollment, Brazilian men had better HAQ than North American men (p<0.001). Brazilian patients overall had lower muscle strength than North American patients (p<0.05). HAQ was associated with DAS28, handgrip test, chair stand test, TUG and SPPB (p<0.001) in both cohorts. Worsening of the DAS28 and chair stand test were each associated with worsening in HAQ in longitudinal analysis over time. Worsening of handgrip was also associated in with worsening HAQ in both cohorts (p<0.05). A worse TUG test was associated with worsening in HAQ in Brazilian cohort (p<0.05) and a worse SPPB was associated with worsening in HAQ in North American cohort (p<0.05). CONCLUSION: Greater disability measured by HAQ is closely associated with disease activity, pain, muscle strength, and physical performance among RA. Worsening in self-reported disability correlate with worsening clinical factors including objectively-observed physical function.

Sarcopenia in Immune-Mediated Rheumatic Diseases-Review.

INTRODUCTION: Sarcopenia is a condition characterized by decreased muscle strength and muscle mass, which can impact physical function. Sarcopenia develops as a consequence of age-related decline (primary sarcopenia) and has a major impact on physical, social, and emotional well-being. In addition, patients with rheumatic diseases may suffer from sarcopenia independently of aging (secondary sarcopenia). Exercise, pharmacological treatments, and nutritional supplementation are some of the strategies used for the management of sarcopenia in the general population. The aim of this review is to summarize the evidence around the prevalence and impact of sarcopenia in patients with rheumatic diseases. CONCLUSIONS: From our review, we can state that sarcopenia is a common and prevalent condition among the rheumatic diseases. Furthermore, the impacts of sarcopenia are not well-appreciated, and the implementation of treatment strategies has not been widespread. Strategies such as exercise and some pharmacological treatments are effective in improving physical and functional impairment related to these conditions. FUTURE RESEARCH DIRECTIONS IN THE FIELD: New pharmacological treatments are being actively studied and may contribute in the future to the management of sarcopenia.

The role of proteasome in muscle wasting of experimental arthritis

Abstract Background Rheumatoid arthritis is an autoimmune inflammatory disease that often leads patients to muscle impairment and physical disability. This study aimed to evaluate changes in the activity of proteasome system in skeletal muscles of mice with collagen-induced arthritis (CIA) and treated with etanercept or methotrexate. Methods Male DBA1/J mice were divided into four groups (n = 8 each): CIA-Vehicle (treated with saline), CIA-ETN (treated with etanercept, 5.5 mg/kg), CIA-MTX (treated with methotrexate, 35 mg/kg) and CO (healthy control group). Mice were treated two times a week for 6 weeks. Clinical score and hind paw edema were measured. Muscles were weighted after euthanasia and used to quantify proteasome activity, gene (MuRF-1, PMSα4, PSMβ5, PMSβ6, PSMβ7, PSMβ8, PSMβ9, and PSMβ10), and protein (PSMβ1, PSMβ5, PSMβ1i, PSMβ5i) expression of proteasome subunits. Results Both treatments slowed disease development, but only CIA-ETN maintained muscle weight compared to CIA-MTX and CIA-Vehicle groups. Etanercept treatment showed caspase-like activity of 26S proteasome similar to CO group, while CIA-Vehicle and CIA-MTX had higher activity compared to CO group (p: 0.0057). MuRF-1 mRNA expression was decreased after etanercept administration compared to CIA-Vehicle and CO groups (p: 0.002, p: 0.007, respectively). PSMβ8 and PSMβ9 mRNA levels were increased in CIA-Vehicle and CIA-MTX compared to CO group, while CIA-ETN presented no difference from CO. PMSβ6 mRNA expression was higher in CIA-Vehicle and CIA-MTX groups than in CO group. Protein levels of the PSMβ5 subunit were increased in CO group compared to CIA-Vehicle; after both etanercept and methotrexate treatments, PSMβ5 expression was higher than in CIA-Vehicle group and did not differ from CO group expression (p: 0.0025, p: 0.001, respectively). The inflammation-induced subunit β1 (LMP2) was enhanced after methotrexate treatment compared to CO group (p: 0.043). Conclusions The results of CIA-Vehicle show that arthritis increases muscle proteasome activation by enhanced caspase-like activity of 26S proteasome and increased PSMβ8 and PSMβ9 mRNA levels. Etanercept treatment was able to maintain the muscle weight and to modulate proteasome so that its activity and gene expression were compared to CO after TNF inhibition. The protein expression of inflammation-induced proteasome subunit was increased in muscle of CIA-MTX group but not following etanercept treatment. Thus, anti-TNF treatment may be an interesting approach to attenuate the arthritis-related muscle wasting.

Physical frailty in patients with systemic sclerosis.

INTRODUCTION: Systemic sclerosis (SSc) is a chronic disease characterized by autoimmunity, vasculopathy and fibrosis of several organs, such as skin, lungs, and heart. During the disease course, patients with SSc are prone to accumulating multiple organ damage and increasing their vulnerability to adverse outcomes. This increased vulnerability to adverse outcomes when exposed to a stressor among people of the same age is known as frailty. One of the most used definitions of frailty is the physical frailty phenotype (PFP), including 5 components: unintentional weight loss, exhaustion, muscle weakness, slow walking speed, and low physical activity. There is scarce data about frailty in patients with SSc. OBJECTIVES: To determine the prevalence and clinical profile of PFP in a sample of patients with SSc. To investigate the diagnostic accuracy of the Fatigue, Resistance, Ambulation, Illness and Loss of weight (FRAIL) scale, Edmonton frailty scale (EFS) and Short Physical Performance Battery (SPPB) using the PFP as the reference standard. METHODS: Cross-sectional study including 94 patients with SSc according to the 2013 ACR-EULAR classification criteria or the criteria suggested by Le Roy and Medsger for early disease. Gastrointestinal symptoms were assessed by the UCLA GIT 2.0 questionnaire, malnutrition was defined according to European Society of Clinical Nutrition and Metabolism (ESPEN) recommendations, and physical performance was assessed by SPPB. PFP assessment was according to the original definition, except for physical activity domain, assessed with the International Physical Activity Questionnaire (IPAQ). FRAIL scale and EFS were also applied to the same individuals. For diagnostic assessment of FRAIL, EFS and SPPB, we estimated the area under the receiver operating characteristic curve (AUC), considering PFP as the reference standard and dichotomizing the results in frail vs. non-frail. RESULTS: According to PFP, 33 patients (35.1%) were considered frail and 53 patients (56.4%) pre-frail. According to FRAIL scale, 27 patients (28.7%) were considered frail and 53 patients (56.4%) pre-frail. According to EFS, 28 patients (29.7%) were classified as vulnerable and 15 (15.9%) as frail: mild in 8 (8.5%), moderate in 5 (5.3%) and severe in 2 (2.1%). According to SPPB, 19 patients (20.2%) were considered frail. The AUC against PFP was: 0.829 (95% CI 0.743-0.916) for FRAIL scale, 0.859 (95% CI 0.784-0.934) for EFS and 0.791 (95% CI 0.697-0.885) for SPPB. The PFP was associated with current use of glucocorticoids (p=0.011), UCLA GIT 2.0 score (p=0.001), HAQ (p<0.0001), patient and physician-assigned VAS (p<0.0001, both), malnutrition (p=0.007), hospitalizations in the past year (p=0.008) and dependence on BADL and IADL (p=0.027 and p<0.0001, respectively). The PFP was not associated with gender (p=0.679), age (p=0.303), disease duration (p=0.504), Rodnan skin score (p=0.918), diffuse subtype (p=0.116), polypharmacy (p=845) and sarcopenia (p=0.328). CONCLUSION: Frailty is prevalent in patients with long-standing SSc and is associated with disability, limitations in daily activities and hospitalizations in the past year. Also, malnutrition and more severe gastrointestinal symptoms were more common in frail patients. Both FRAIL scale and EFS showed excellent diagnostic accuracy against PFP as the reference standard, however the FRAIL scale presents a higher sensitivity and seems to be more feasible and practical than EFS and SPPB in clinical practice.

Vitamin D supplementation modulates autophagy in the pristane-induced lupus model

Abstract Introduction/objectives: Clinical evidence of skeletal muscle involvement is not uncommon in systemic lupus erythematosus (SLE). Because of the poor understanding of signaling pathways involved in SLE muscle wasting, the aim of this study was to evaluate the effects of vitamin D supplementation on skeletal muscle in mice with pristane-induced lupus. Methods: Balb/c mice with lupus-like disease induced by pristane injection were randomized into three groups: pristane-induced lupus (PIL; n = 10), pristane-induced lupus + vitamin D supplementation (PIL + VD; n = 10) and healthy controls (CO; n = 8). Physical function was evaluated on days 0, 60, 120 and 180. The tibialis anterior and gastrocnemius muscles were collected to evaluate myofiber cross-sectional area (CSA) and protein expression. Results: The PIL + VD group showed lower muscle strength compared to the CO and PIL groups at different time points. PIL mice showed similar myofiber CSA compared to CO and PIL + VD groups. LC3-II expression was higher in PIL compared to CO and PIL + VD groups. MyoD expression was higher in PIL mice compared to PIL + VD, while myostatin expression was higher in PIL + VD than PIL group. Myogenin expression levels were decreased in the PIL + VD group compared with the CO group. The Akt, p62 and MuRF expressions and mobility assessment showed no significance. Conclusions: Changes in skeletal muscle in PIL model happen before CSA reduction, possibly due to autophagy degradation, and treatment with Vitamin D has a impact on physical function by decreasing muscle strength and time of fatigue.. Vitamin D supplementation has a potential role modulating physical parameters and signaling pathways in muscle during pristane-induced lupus model.

The effects of resistance training with blood flow restriction on muscle strength, muscle hypertrophy and functionality in patients with osteoarthritis and rheumatoid arthritis: A systematic review with meta-analysis.

INTRODUCTION: Rheumatoid arthritis(RA) and osteoarthritis(OA) patients showed systemic manifestations that may lead to a reduction in muscle strength, muscle mass and, consequently, to a reduction in functionality. On the other hand, moderate intensity resistance training(MIRT) and high intensity resistance training(HIRT) are able to improve muscle strength and muscle mass in RA and OA without affecting the disease course. However, due to the articular manifestations caused by these diseases, these patients may present intolerance to MIRT or HIRT. Thus, the low intensity resistance training combined with blood flow restriction(LIRTBFR) may be a new training strategy for these populations. OBJECTIVE: To perform a systematic review with meta-analysis to verify the effects of LIRTBFR on muscle strength, muscle mass and functionality in RA and OA patients. MATERIALS AND METHODS: A systematic review with meta-analysis of randomized clinical trials(RCTs), published in English, between 1957-2021, was conducted using MEDLINE(PubMed), Embase and Cochrane Library. The methodological quality was assessed using Physiotherapy Evidence Database scale. The risk of bias was assessed using RoB2.0. Mean difference(MD) or standardized mean difference(SMD) and 95% confidence intervals(CI) were pooled using a random-effects model. A P<0.05 was considered statistically significant. RESULTS: Five RCTs were included. We found no significant differences in the effects between LIRTBFR, MIRT and HIRT on muscle strength, which was assessed by tests of quadriceps strength(SMD = -0.01[-0.57, 0.54], P = 0.96; I² = 58%) and functionality measured by tests with patterns similar to walking(SMD = -0.04[-0.39, 0.31], P = 0.82; I² = 0%). Compared to HIRT, muscle mass gain after LIRTBFR was reported to be similar. When comparing LIRTBFR with low intensity resistance training without blood flow restriction(LIRT), the effect LIRTBFR was reported to be higher on muscle strength, which was evaluated by the knee extension test. CONCLUSION: LIRTBFR appears to be a promising strategy for gains in muscle strength, muscle mass and functionality in a predominant sample of RA and OA women.

Development of new adjusted equations to estimate the skeletal muscle mass stratified by nutritional status for patients with rheumatoid arthritis: a methodological study / Desenvolvimento de novas equações ajustadas para estimativa da massa muscular esquelética estratificada pelo estado nutricional para pacientes com artrite reumatoide: um estudo metodológico

Abstract Our objective was to adjust and validate predictive equations for appendicular skeletal muscle mass (ASM) in patients with Rheumatoid Arthritis (RA). Whole-body DXA data in 90 RA patients were used for measurement of ASM (kg). The prediction equation anthropometric for muscle mass proposed by Lee et al was used to generate estimates of ASM. Appendicular skeletal muscle mass index (ASMI, kg/m2) was calculated. Frequency analysis, Paired student's t-test, Linear regression, Pearson correlation, Intraclass correlation coefficients, and Bland-Altman scatter were performed. The statistical significance considered was p<0.05. Lee's equation was overestimated by 30% when compared with ASMI by DXA. When stratified by nutritional status, Lee's equation overestimated the ASMI by 30% in overweight patients and by 50% in obese patients when compared with DXA (p<0.05). These adjusted equations estimated values for ASMI were closer to those obtained by DXA than those estimated by the original Lee's equation (p<0.05). This greater concordance was confirmed by the observed interclass correlation coefficients and by Bland-Altman scatter graphs. In conclusion, the prediction of muscle mass in RA patients may be performed with equations that consider the nutritional status of patients.

Resumo Nosso objetivo foi ajustar e validar equações preditivas para massa muscular esquelética apendicular (ASM) em pacientes com Artrite Reumatoide (AR). Dados de DXA de corpo inteiro em 90 pacientes com AR foram usados ​​para medição de ASM (kg). A equação de predição antropométrica de massa muscular proposta por Lee et al foi utilizada para gerar estimativas de ASM. Índice de massa muscular esquelética apendicular (ASMI, kg / m2) foi calculada. Análise de frequência, Teste t de Student pareado, Regressão linear, Correlação de Pearson, Coeficientes de correlação intraclasse e Dispersão de Bland-Altman foram realizados. A significância estatística considerada foi p<0,05. A equação de Lee superestimou em 30% quando comparada com a ASMI da DXA. Quando estratificada por estado nutricional, a equação de Lee superestimou o ASMI em 30% em pacientes com sobrepeso e em 50% em pacientes obesos em comparação com DXA (p<0,05). Esses valores estimados de equações ajustadas para ASMI foram mais próximos daqueles obtidos por DXA do que aqueles estimados pela equação de Lee original (p<0,05). Essa maior concordância foi confirmada pelos coeficientes de correlação interclasses observados e pelos gráficos de dispersão de Bland-Altman. Em conclusão, a predição da massa muscular em pacientes com AR pode ser realizada com equações que consideram o estado nutricional dos pacientes.

Estado nutricional antropométrico e associação com pressão arterial em crianças e adolescentes: um estudo populacional / Anthropometric nutritional status and association with blood pressure in children and adolescents: a population-based study

OBJETIVOS: Avaliar o estado nutricional de crianças e de adolescentes por meio de indicadores antropométricos e avaliar a associação desses resultados com a pressão arterial. MÉTODOS: Foram incluídos neste estudo crianças e adolescentes entre quatro e 19 anos de idade, oriundos de escolas rurais e urbanas de um município do Rio Grande do Sul. Foram excluídos aqueles que recusaram (ou cujos pais recusaram) participar ou não assinaram o termo de consentimento livre e esclarecido, ou nos quais não foi possível realizar as medidas antropométricas ou da pressão arterial. Foram mensurados peso, estatura, circunferência da cintura, pregas cutâneas e pressão arterial, e foi calculado o índice de massa corporal. Os dados foram descritos por média, desvio padrão, amplitude de variação, frequências absolutas e relativas. Foi realizada estratificação por sexo, índice de massa corporal e obesidade central, para analisar a influência destas variáveis sobre as demais. O Qui-quadrado de Pearson foi utilizado para avaliar as associações. O nível de significância foi de p<0,05. RESULTADOS: No período da coleta de dados estavam matriculados nas escolas do município 7.082 crianças e adolescentes dentro da faixa etária determinada, os quais foram convidados a participar. Após aplicação dos critérios de exclusão, 5.936 crianças/adolescentes foram incluídos no estudo. A amostra apresentou prevalência de excesso de peso de 30,3%, obesidade central 31,1% e excesso de gordura corporal 8,7%. O excesso de peso foi maior em crianças de escolas particulares (44,1%) quando comparadas com escolas estaduais (29,5%) e municipais (29,9%) (p<0,001). Foram encontradas associações estatisticamente significativas de hipertensão arterial com sobrepeso, obesidade e obesidade central (p<0,001). CONCLUSÕES: A prevalência de excesso de peso foi elevada e a hipertensão arterial associou-se com sobrepeso, obesidade e obesidade central nas crianças e adolescentes da população estudada.

AIMS: To evaluate the nutritional status of children and adolescents by anthropometric indicators and to evaluate the association of these results with blood pressure. METHODS: Children and adolescents between four and 19 years of age from rural and urban schools of a municipality of Rio Grande do Sul were included in this study. Those who refused (or whose parents refused) to participate or did not sign the consent form, or in whom it was not possible to carry out the anthropometric or blood pressure measurements, were excluded. Weight, height, waist circumference, skin folds and blood pressure were measured, and the body mass index was calculated. Data were described by mean, standard deviation, amplitude of variation, absolute and relative frequencies. Stratification by gender, body mass index and central obesity was performed to analyze the influence of these on the other variables. Pearson's Chi-square was used to evaluate the associations. The level of significance was p<0.05. RESULTS: At the time of data collection, 7,082 children and adolescents within the age group were enrolled in the municipal schools, and they were invited to participate. After applying the exclusion criteria, 5,936 children/adolescents were included in the study. The sample presented prevalence of overweight of 30.3%, central obesity 31.1% and excess body fat 8.7%. Overweight was higher in children from private schools (44.1%) than in state schools (29.5%) and municipal schools (29.9%) (p<0.001). There were statistically significant associations of high blood pressure with overweight, obesity, and central obesity (p<0.001). CONCLUSIONS: Prevalence of overweight was high and hypertension was associated with overweight, obesity and central obesity in children and adolescents of the studied population.