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.

Systemic lupus erythematosus: a systematic review with meta-analysis on muscle strength, muscle mass, and physical function.

To perform a systematic review with meta-analysis to verify muscle strength, muscle mass, and physical function of patients with systemic lupus erythematosus (SLE) and compare then with healthy individuals and patients with rheumatoid arthritis (RA). A systematic review with meta-analysis of observational studies published in English up to 2022 was performed using MEDLINE (via PubMed) and other relevant sources. Search strategies were based on pre-defined keywords and medical subject headings. The methodological quality of the studies was assessed using the Newcastle-Ottawa Scale. Mean difference (MD) or standardized mean difference (SMD) and 95% confidence intervals (CI) were combined using a random-effects model. Sensitivity analyses were performed when necessary. The significance level was set at p < 0.05. The systematic review included 19 studies and the meta-analysis included 11 studies. SLE patients appear to have less muscle strength assessed by handgrip than healthy controls (SLE = 21.74 kg; healthy controls = 29.34 kg; p < 0.05). SLE patients seem to have greater strength than patients with RA, but this difference was not statistically significant (RA = 17.24 kg; p = 0.210). However, in the sensitivity analysis, SLE group without deforming arthropathy showed higher muscle strength than the RA (p = 0.0001). SLE patients with deforming arthropathy have lower muscle strength compared to SLE patients without deforming arthropathy (p < 0.01). Muscle mass was similar in SLE patients compared to the RA group and healthy controls (p > 0.05). However, RA patients have a higher BMI than the two groups (p < 0.05). Patients with SLE have regular physical function. Muscle strength is affected in SLE patients. SLE patients with deforming arthropathy have less muscle strength than patients without deforming arthropathies.

A Review of Metabolomic Profiling in Rheumatoid Arthritis: Bringing New Insights in Disease Pathogenesis, Treatment and Comorbidities.

Metabolomic analysis provides a wealth of information that can be predictive of distinctive phenotypes of pathogenic processes and has been applied to better understand disease development. Rheumatoid arthritis (RA) is an autoimmune disease with the establishment of chronic synovial inflammation that affects joints and peripheral tissues such as skeletal muscle and bone. There is a lack of useful disease biomarkers to track disease activity, drug response and follow-up in RA. In this review, we describe potential metabolic biomarkers that might be helpful in the study of RA pathogenesis, drug response and risk of comorbidities. TMAO (choline and trimethylamine oxide) and TCA (tricarboxylic acid) cycle products have been suggested to modulate metabolic profiles during the early stages of RA and are present systemically, which is a relevant characteristic for biomarkers. Moreover, the analysis of lipids such as cholesterol, FFAs and PUFAs may provide important information before disease onset to predict disease activity and treatment response. Regarding therapeutics, TNF inhibitors may increase the levels of tryptophan, valine, lysine, creatinine and alanine, whereas JAK/STAT inhibitors may modulate exclusively fatty acids. These observations indicate that different disease modifying antirheumatic drugs have specific metabolic profiles and can reveal differences between responders and non-responders. In terms of comorbidities, physical impairment represented by higher fatigue scores and muscle wasting has been associated with an increase in urea cycle, FFAs, tocopherols and BCAAs. In conclusion, synovial fluid, blood and urine samples from RA patients seem to provide critical information about the metabolic profile related to drug response, disease activity and comorbidities.

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.

Morphological Parameters in Quadriceps Muscle Were Associated with Clinical Features and Muscle Strength of Women with Rheumatoid Arthritis: A Cross-Sectional Study.

BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune, inflammatory and chronic disease that may lead to loss of muscle mass, muscle strength and decreased functionality. Our objectives are to assess the quadriceps muscle morphology by ultrasound (MU) and verify its associations with clinical features, muscle strength and physical function in RA patients. METHODS: In this cross-sectional study, RA women (≥18 years) were included. Morphological parameters in quadriceps muscle consisted of the muscle thickness and pennation angle of rectus femoris (RF), vastus intermedius (VI) and vastus lateralis (VL). RA activity was measured by a 28-joint disease activity score (DAS28), muscle strength by handgrip and chair stand tests, and physical function by health assessment questionnaire (HAQ), timed-up-and-go (TUG) test and short physical performance battery (SPPB). RESULTS: Fifty-five patients were included (age: 56.73 ± 9.46 years; DAS28: 3.08 ± 1.29). Muscle thickness in RF, VI and VL were negatively associated with age (RF, p < 0.001; VI, p = 0.013; VL, p = 0.002) and disease duration (RF, p < 0.001; VI, p = 0.005; VL, p = 0.001), and were positively associated with handgrip strength (RF, p = 0.015; VI, p = 0.022; VL, p = 0.013). In addition, decreased muscle thickness in VI (p = 0.035) and a smaller pennation angle in RF (p = 0.030) were associated with higher DAS-28 scores. CONCLUSION: Quadriceps muscle morphology by ultrasound appears to be affected by age, disease duration, disease activity and muscle strength in patients with RA. MU can be a useful method to evaluate the impact of the disease on skeletal muscle.

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.

Practical screening tools for sarcopenia in patients with systemic sclerosis.

INTRODUCTION: In view of the method of diagnosing sarcopenia being complex and considered to be difficult to introduce into routine practice, the European Working Group on Sarcopenia in Older People (EWGSOP) recommends the use of the SARC-F questionnaire as a way to introduce assessment and treatment of sarcopenia into clinical practice. Only recently, some studies have turned their attention to the presence of sarcopenia in systemic sclerosis (SSc).There is no data about performance of SARC-F and other screening tests for sarcopenia in this population. OBJECTIVE: To compare the accuracy of SARC-F, SARC-CalF, SARC-F+EBM, and Ishii test as screening tools for sarcopenia in patients with SSc. METHODS: Cross-sectional study of 94 patients with SSc assessed by clinical and physical evaluation. Sarcopenia was defined according to the revised 2019 EWGSOP diagnostic criteria (EWGSOP2) with assessments of dual-energy X-ray absorptiometry, handgrip strength, and short physical performance battery (SPPB). As case finding tools, SARC-F, SARC-CalF, SARC-F+EBM and Ishii test were applied, including data on calf circumference, body mass index, limitations in strength, walking ability, rising from a chair, stair climbing, and self reported number of falls in the last year. The screening tests were evaluated through receiver operating characteristic (ROC) curves. Standard measures of diagnostic accuracy were computed using the EWGSOP2 criteria as the gold standard for diagnosis of sarcopenia. RESULTS: Sarcopenia was identified in 15 (15.9%) patients with SSc by the EWGSOP2 criteria. Area under the ROC curve of SARC-F screening for sarcopenia was 0.588 (95% confidence interval (CI) 0.420-0.756, p = 0.283). The results of sensitivity, specificity, positive likelihood ratio (+LR), negative likelihood ratio (-LR) and diagnostic Odds Ratio (DOR) with the EWGSOP2 criteria as the gold standard were 40.0% (95% CI, 19.8-64.2), 81.0% (95% CI, 71.0-88.1), 2.11 (95% CI, 0.98-4.55), 0.74 (95% CI, 0.48-1.13) and 2.84 (95% CI, 0.88-9.22), respectively. SARC-CalF and SARC-F+EBM showed better sensitivity (53.3%, 95% CI 30.1-75.2 and 60.0%, 95% CI 35.7-80.2, respectively) and specificity (84.8%, 95% CI 75.3-91.1 and 86.1%, 95% CI 76.8-92.0, respectively) compared with SARC-F. The best sensitivity was obtained with the Ishii test (86.7%, 95% CI 62.1-96.3), at the expense of a small loss of specificity (73.4%, 95% CI 62.7-81.9). Comparing the ROC curves, SARC-F performed worse than SARC-CalF, SARC-F+EBM and Ishii test as a sarcopenia screening tool in this population (AUCs 0.588 vs. 0.718, 0.832, and 0.862, respectively). Direct comparisons between tests revealed differences only between SARC-F and Ishii test for sensitivity (p = 0.013) and AUC (p = 0.031). CONCLUSION: SARC-CalF, SARC-F+EBM, and Ishii test performed better than SARC-F alone as screening tools for sarcopenia in patients with SSc. Considering diagnostic accuracy and feasibility aspects, SARC-F+EBM seems to be the most suitable screening tool to be adopted in routine care of patients with SSc.