We read with great interest the article by Hein et al., which described the meta-analysis study on the impact of disease-modifying anti-rheumatic drugs (DMARDs) therapy on skeletal muscle mass in ...rheumatoid arthritis (RA) patients. While the data presented are impressive, we add some remarks about methodological issues that should be considered. First, this meta-analysis does not include several necessary studies that have provided data on the relationship between anti-tumor necrosis factor (anti-TNF) therapy and body composition. To make the meta-analysis more comprehensive, it could be necessary to incorporate these studies into this analysis. Second, this study did not employ a representative measure of skeletal muscle mass that was adjusted for body size, such as skeletal muscle mass index (SMI). It is well recognized that skeletal muscle mass varies with body size, particularly height and body mass index. Given the heterogeneity background of body size in the studies included in this meta-analysis, it may be worthwhile to conduct an additional analysis regarding the associations between DMARDs and the adjusted measure of skeletal muscle mass such as SMI, which is recommended in several guidelines when determining and contrasting the quantity of skeletal muscle mass. Third, when determining body composition, several reports show variances between bioelectrical impedance analysis (BIA) and dual-energy X-ray absorptiometry (DEXA) in RA as well as in general. In this regard, it may not be appropriate to simultaneously perform a meta-analysis of skeletal muscle mass determined by DEXA and BIA. With the issues described above, we conclude by recommending additional investigations to strengthen the arguments presented by this valuable meta-analysis.
Objectives: Sarcopenia is characterized by loss of muscle strength and mass, leading to falls and adverse health outcomes. Our aim was to determine the prevalence of sarcopenia in patients with ...rheumatoid arthritis (RA) and to identify factors associated with sarcopenia in these patients.
Methods: A cross-sectional study of 388 consecutive women with RA was conducted, assessing muscle mass and strength, and walking speed. Falls and bone fractures sustained over the prior year were evaluated. The association between sarcopenia and RA characteristics, falls, and bone fractures was evaluated using logistic regression analyses.
Results: The prevalence of sarcopenia was 37.1% (14.7%, severe sarcopenia; 22.4%, sarcopenia), with 49.0% classified as having low muscle mass. The incidence of falls, fractures, and lower bone mineral density was higher in patients with than without sarcopenia. Age, RA duration, Steinbrocker's stage, the high Mini-Nutritional Assessment-Short Form score and the use of biological disease-modifying anti-rheumatic drugs (bDMARDs) were independent factors associated with sarcopenia.
Conclusion: We confirmed that sarcopenia develops in a significant proportion of patients with RA. Age, longer disease duration, joint destruction and malnutrition were positively associated with sarcopenia, with the use of bDMARDs being negatively associated.
Sarcopenia is an age-related disease with an increased risk of mortality. It is emerging that low serum 25-hydroxyvitamin D 25(OH)D affects the sarcopenic state in general, but in rheumatoid ...arthritis (RA), these associations are not understood although the prevalence of vitamin D insufficiency is high in RA. We conducted a cross-sectional study of older female outpatients from our cohort (KURAMA) database. We measured skeletal muscle mass, handgrip strength, and gait-speed to diagnose severe sarcopenia. The serum 25(OH)D concentration was measured using electrochemiluminescence immunoassay. A total of 156 female patients with RA (sarcopenia:44.9%, severe sarcopenia: 29.5%, and without sarcopenia: 25.6%) were enrolled. Classification of vitamin D status at a cutoff point of median 25(OH)D concentration revealed that low 25(OH)D status was associated with a high prevalence of severe sarcopenia and with low measured values of muscle mass, handgrip, and gait speed. Furthermore, multivariable logistic regression analysis identified that low 25(OH)D status was associated with a high prevalence of severe sarcopenia (OR 6.00; 95% CI 1.99-18.08).The same association was observed when the cut-off value was set at 20 ng/ml. In components of sarcopenia, both low physical performance and muscle mass were associated with low 25(OH)D status. In conclusion, vitamin D status was inversely associated with severe sarcopenia, low physical performance, and low skeletal muscle mass. Modification of vitamin D status including vitamin D supplementation should be investigated as a therapeutic strategy for sarcopenic patients with RA.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Frailty is a geriatric syndrome characterized by anabolic-catabolic imbalance and multisystem dysregulation resulting in increased adverse health outcomes, and is closely related with dietary habits ...in the general population. Although chronic inflammatory diseases are thought to accelerate development of frailty, correlations between rheumatoid arthritis (RA), frailty and dietary habits have not been examined. We performed a cross-sectional study using our cohort database (KURAMA cohort), and classified 306 participants into three groups (robust, prefrail and frail) according to the Study of Osteoporotic Fracture (SOF) criteria. Multivariate logistic analysis revealed that the presence of frailty/prefrailty was significantly correlated with the disease activity score (DAS28-ESR) (OR 1.70 (1.30-2.22), p < 0.0001). Additional analyses of frailty and food intake showed that 5 foods (fish, meat, milk, vegetables and fruits) of 20 groups on the questionnaire were inversely associated with the prevalence of frail/prefrail categories. In multivariate analysis with the five nutrients, fish intake (> two times a week) was an independent covariate negatively correlated with frailty/prefrailty (OR 0.35 (0.19-0.63), p = 0.00060). In conclusion, habitual fish intake may play a key role in nutritional intervention to prevent progression of frailty and RA.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Patients with rheumatoid arthritis (RA) are prone to muscle atrophy due to inflammatory cytokines and corticosteroid use and immobility due to joint pain and deformity. Although resistance training ...is effective and safe in reversing muscle atrophy in RA, some patients are unable to perform a conventional high-load exercise program due to disease-related limitations. This study aims to examine the efficacy of individualized exercise therapy on physical function in elderly patients with RA who are at a high risk for sarcopenia.
This study is a single-center, parallel-group, two-arm, healthcare provider- and outcome assessor-blinded, superiority randomized controlled trial with a 1:1 allocation ratio. A total of 160 participants with RA between 60 and 85 years of age with a positive screening test for sarcopenia will be included. The intervention group will receive nutritional guidance and a four-month individualized exercise program in addition to the usual treatment. The control group will receive nutritional guidance in addition to the usual care. The primary endpoint will be physical function assessed using the Short Physical Performance Battery (SPPB) at 4 months. The data on outcome measures will be collected at baseline and at the two- and four-month follow-ups. Linear mixed-effects models for repeated measures will be conducted using the modified intention-to-treat analysis population.
This study will provide evidence on whether a personalized exercise program can improve physical function and quality of life in elderly patients with RA. Some limitations include limited generalizability due to the single-center study and lack of blinding of the patients to the intervention assignment because of the nature of the exercise. Physical therapists may use this knowledge in their daily practice to improve RA treatment. Tailored exercise may enhance the health outcomes of the RA population and contribute to a reduction in healthcare costs.
The study protocol was retrospectively registered at the University hospital Medical Information Network-Clinical Trial Repository (UMIN-CTR) (registration number: UMIN000044930, https://www.umin.ac.jp/ctr/index-j.htm ) on January 4, 2022.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Interleukin 17 (IL-17) is a pleiotropic cytokine that acts on both immune and non-immune cells and is generally implicated in inflammatory and autoimmune diseases. Although IL-17 as well as their ...source, mainly but not limited to Th17 cells, is also abundant in the inflamed intestine, the role of IL-17 in inflammatory bowel disease remains controversial. In the present study, by using IL-17 knockout (KO) mice, we investigated the role of IL-17 in colitis, with special focus on the macrophage subpopulations. Here we show that IL-17KO mice had increased susceptibility to DSS-induced colitis which was associated with decrease in expression of mRNAs implicated in M2 and/or wound healing macrophages, such as IL-10, IL-1 receptor antagonist, arginase 1, cyclooxygenase 2, and indoleamine 2,3-dioxygenase. Lamina propria leukocytes from inflamed colon of IL-17KO mice contained fewer CD11b+Ly6C+MHC Class II+ macrophages, which were derived, at least partly, from blood monocytes, as compared to those of WT mice. FACS-purified CD11b+ cells from WT mice, which were more abundant in Ly6C+MHC Class II+ cells, expressed increased levels of genes associated M2/wound healing macrophages and also M1/proinflammatory macrophages. Depletion of this population by topical administration of clodronate-liposome in the colon of WT mice resulted in the exacerbation of colitis. These results demonstrate that IL-17 confers protection against the development of severe colitis through the induction of an atypical M2-like macrophage subpopulation. Our findings reveal a previously unappreciated mechanism by which IL-17 exerts a protective function in colitis.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objective
Pain is one of the main symptoms of patients with rheumatoid arthritis (RA). Pain in RA is caused by specific physical changes, such as joint destruction, and is therefore used as a disease ...activity marker. Although pain can also be influenced by emotional factors, neither the effect of emotional health nor the indirect effect of the physical state mediated by emotional health on pain has been quantified.
Methods
A total of 548 patients with RA participated. Emotional health was assessed using the Hospital Anxiety and Depression Scale (HADS). Measures routinely used in practice were used to evaluate the physical state and pain. To quantify the effects of the physical state on emotional health, and the effects of both physical and emotional health on pain, we used structural equation modeling, with emotional health, physical state, and pain as latent variables.
Results
The prevalence of anxiety and depression (HADS score ≥8 for each) among patients with RA was 18.7% and 29.4%, respectively. Emotional health was significantly influenced by the physical state (β = 0.21). Pain was affected by physical (β = 0.54) and emotional health (β = 0.29). The effect of the physical state on pain was mediated by emotional health, with this mediation effect (β = 0.06) accounting for 10.2% of the total effect.
Conclusion
The magnitude of pain in RA is determined by the mediation effect of emotional health as well as the direct physical state. Our findings suggest that emotional factors should be taken into account when assessing RA disease activity.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Although mental disorder is one of the most common comorbidities of rheumatoid arthritis (RA) and is known as a critical influence on RA remission rates, there is little knowledge regarding a ...possible therapeutic strategy for depression or anxiety in a RA population. Most recently, clinical evidence of dietary improvement for depression has emerged in a general population, but the relationship between dietary habits and mental disorder has not been investigated in RA. The purpose of this study is to elucidate clinical associations between mental disorder (depression/anxiety), dietary habits and disease activity/physical function in patients with RA. A cross-sectional study was performed with 267 female outpatients from the KURAMA database. Using the Hospital Anxiety and Depression Scale (HADS), we classified the participants into three groups by depression state, and their characteristics were compared. Using the 20-items on the self-reported food frequency questionnaire, we investigated the relationship between dietary habits and depression or anxiety, adopting a trend test and a multivariate standardized linear regression analysis for the HADS score of depression or that of anxiety as a dependent variable. According to the classified stage of depression, current disease activity (DAS28-CRP: 28-Joint RA Disease Activity Score-C-reactive protein) and the health assessment questionnaire disability Index (HAQ-DI) were significantly increased. Trend analyses revealed that the depression score was inversely associated with the consumption of three food (fish, vegetables and fruit) out of twenty as was the anxiety score with only fish intake. Furthermore, multiple linear regression analysis revealed that the depression score was negatively associated with frequent fish intake (greater than or equal to 3 times per week) (Estimate -0.53, p = 0.033), HAQ-DI score within normal range (Estimate -0.88, p less than or equal to 0.001) and MTX use (Estimate -0.60, p less than or equal to 0.023). For the anxiety score, multivariate analysis showed similar but not significant associations with variables except for HAQ-DI score. In a RA population, both depression and anxiety had a significant and negative association with HAQ-DI score, and depression rather than anxiety had negative association with frequent fish intake. Modification of dietary habits such as increased fish consumption may have a beneficial effect on the depression state in RA patients.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objectives
To study the perceptions and behavioural changes related to the coronavirus disease 2019 (COVID-19) in patients with rheumatoid arthritis (RA) and determine their associations with patient ...characteristics, such as health literacy.
Methods
This cross-sectional study was conducted from September to November of 2020 and included 400 outpatients with RA aged 18 and above. We measured self-reported perceptions as outcomes, such as awareness, knowledge and behaviours related to COVID-19. Health literacy and other characteristics as exposures were investigated using self-report questionnaires and electronic health records. To analyse the association between patient factors and the outcomes, multivariable linear and logistic regression models were performed.
Results
In total, 365 patients completed the survey. More than half (51%) of patients reported that they were ‘very worried’ about possible infection with COVID-19, whereas over 80% believed the possibility of getting COVID-19 was low. In the multivariable analyses, patients with low health literacy had limited knowledge about COVID-19 and did not change daily routines and perform preventive measures.
Conclusions
In this pandemic, healthcare providers may need to be aware of more vulnerable individuals and share COVID-19 related information promptly and effectively with their patients.
Key Points
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This cross-sectional study aimed to investigate the perceptions and behavioural changes related to COVID-19 in patients with RA.
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All patients were aware of COVID-19 and most of them worried about getting infected.
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Health literacy, age, sex, disease activity and rheumatic drugs were associated with perceptions and behaviours related to COVID-19.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
To clarify the relationship between dietary habit and disease activity of rheumatoid arthritis (RA).
This study enrolled RA patients who met the ACR/EULAR 2010 classification criteria from Kyoto ...University Rheumatoid Arthritis Management Alliance (KURAMA) cohort in 2015. 22-item food frequency questionnaire (FFQ) was taken for the measurement of dietary habit in a single-institution cohort of RA (Kyoto University Rheumatoid Arthritis Management Alliance: KURAMA) in 2015. The disease activities of RA using the Disease Activity Score calculated based on the erythrocyte sedimentation rate (DAS28-ESR), Simplified Disease Activity Index (SDAI), Health Assessment Questionnaire (HAQ), and serum matrix metalloproteinase-3 (MMP-3) level, the use of disease-modifying anti-rheumatic drugs (DMARDs), disease duration, rheumatoid factor, anti-cyclic citrullinated antibody, and body mass index were also examined. All of them were combined and statistically analyzed.
441 RA patients (81% women; mean age 65 years; mean disease duration 15 years) were enrolled from the KURAMA cohort. Average Disease Activity Score-28 using the erythrocyte sedimentation rate (DAS28-ESR) was 2.7. Univariate analysis showed that intake frequency of vegetables had a statistically significant negative correlation with disease activity markers, such as DAS28-ESR (ρ = -0.11, p<0.01), Simplified Disease Activity Index (SDAI) (ρ = -0.16, p<0.001), matrix metalloproteinase-3 (MMP-3) (ρ = -0.21, p<0.0001), and Health Assessment Questionnaire (HAQ) (ρ = -0.13, p<0.01). Factor analysis with varimax rotation was done to simplify the relevance of disease activity to various food items. 22 foods were categorized into five dietary patterns: "seafoods", "vegetables/fruits", "meats/fried foods", "snacks", and "processed foods". The multivariate analysis adjusted for clinically significant confounders showed that "seafoods" had statistically significant negative correlations with DAS28-ESR (β = -0.15, p<0.01), SDAI (β = -0.18, p<0.001), MMP-3 (β = -0.15, p<0.01), and HAQ (β = -0.24, p<0.0001). "Vegetables/fruits" had statistically significant negative correlations with SDAI (β = -0.11 p<0.05), MMP-3 (β = -0.12, p<0.01), and HAQ (β = -0.11, p<0.05).
These results suggest that high intake frequency of vegetables/fruits and/or seafoods might correlate with low disease activity.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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