Lidiane Isabel Filippin

Sarcopenia: a predictor of mortality and the need for early diagnosis and intervention.

The term sarcopenia refers to the loss of muscle mass that occurs with aging. Sarcopenia is defined by the European Working Group on Sarcopenia in Older People (EWGSOP) as low muscle mass and low muscle function (strength and performance). Its prevalence varies depending on the definition used for it, but estimates propose a loss of approximately 8xa0% per decade until the age of 70xa0years; afterwards, the loss increases and ranges from 13 to 24xa0% per decade. Irrespective of how sarcopenia is defined, both low muscle mass and poor muscle strength are highly prevalent and important risk factors for disability and increased mortality in individuals as they age. In this review, we address age-related muscle loss and the risk factors of mortality, emphasizing the need for early diagnosis and intervention.

Collagen-induced arthritis as an animal model of rheumatoid cachexia: CIA as an animal model of RA

Rheumatoid arthritis is characterized by chronic polyarticular synovitis and presents systemic changes that impact quality of life, such as impaired muscle function, seen in up to 66% of the patients. This can progress to severely debilitating state known as rheumatoid cachexia—without loss of fat mass and body weight—for which there is little consensus in terms of diagnosis or treatment. This study aims to evaluate whether the collagen‐induced arthritis (CIA) animal model also develops clinical and functional features characteristic of rheumatoid cachexia.

Prevalence of rheumatoid cachexia in rheumatoid arthritis: a systematic review and meta-analysis: Systematic Review of RA cachexia prevalence

Low muscle mass occurs in patients with rheumatoid arthritis without weight loss; this condition is referred as rheumatoid cachexia. The aim of the current study was to perform a systematic review with meta‐analysis to determine the rheumatoid cachexia prevalence.

Motivation and adherence to psychosocial treatment for alcohol and drug use-related problems

This is a prospective cohort study of 150 individuals attending a specialized health service for substance-related disorders. The study investigated the association between motivation to remain in treatment and treatment adherence. All service users were interviewed soon after admission to the treatment program and were followed-up during the fi rst two months of treatment. A Cox Regression Model was used to estimate the hazard ratios for dropout during the two months following the admission interview. The results indicated that individuals with a primary-school education, lack of income, and low motivation toward treatment at the admission interview presented a higher risk of treatment dropout. This study showed the importance of motivation in changing addictive behavior and in adherence to treatment as essential factors for recovery.

Construction and validation of content of one instrument to assess falls in the elderly

ABSTRACT Objective To develop and validate the content of the online Questionnaire for Fall Risk Assessment in the Elderly. Methods The instrument was developed based on the International Classification of Functioning, Disability and Health (ICF) of the World Health Organization. Initially, the set of items was submitted to evaluation of judges (healthcare professionals with experience in elderly health), who could suggest inclusion or exclusion of questions from the instrument; they were also asked to rate each question according to the expected scope. At this stage, clarity and relevance levels for each item were evaluated, generating a total of Content Validity Coefficient (CtVC). Results Content Validity Coefficient values were satisfactory for both clarity (CtVC=0.76) and relevance (CtVC=0.82) of the questions. Next, a group of elderly volunteers participating in a socializing group evaluated the questionnaire for comprehension. The level of comprehension for each item was identified on a Likert scale, ranging from 0 to 5. The questionnaire was considered easy to understand by most participants (95%), with a mean of 4.75 (±0.11) points for each item. Conclusion The instrument showed acceptable psychometric qualities for screening fall risk among the elderly population. Future studies shall investigate different validation aspects of construct for this measure.

Timed Up and Go test as a sarcopenia screening tool in home-dwelling elderly persons

Abstract Objective : to evaluate the performance of the Timed Up and Go test (TUG) as a screening tool for sarcopenia in elderly persons living in a city in the south of Brazil. Method: A cross-sectional, home-based study was conducted with 322 elderly persons. The diagnosis of sarcopenia was based on the criteria proposed by the European Working Group on Sarcopenia in Older People (EGWSOP). A Receiver Operating Characteristic (ROC) curve was constructed to assess the discriminatory power of the TUG on sarcopenia screening. Results: With a cutoff point of 7.5 seconds, the test had an area under the curve (AUC) of 0.66 (CI 0.56-0.76; p =0.002) and adequate sensitivity and negative predictive values (88.9% and 93.2%, respectively). Conclusion: Due to its ease of use and rapid execution, in addition to its low cost, this test is useful for the screening of sarcopenia, especially among elderly persons with good physical and cognitive abilities. The early identification of individuals with probable sarcopenia may allow for preventive or directive interventions for the management of this geriatric syndrome.

AB1096 Timed up and go test (TUG) for sarcopenia screening

Background Sarcopenia is a multifactorial syndrome characterized by a decrease of muscle mass and force together with functional performance impairment. Sarcopenia has been described as an independent predictor factor of health adverse outcomes such as falls, decreased quality of life, enhanced risk of death and higher treatment costs. However, there are just a few screening tolls of low cost and easy applicability to detect sarcopenia. In this context, a standard mobility assessment such as the TUG test has recently been described as a predictor of sarcopenia. Objectives To evaluate the performance of timed up and go test (TUG) as a screening toll for sarcopenia in the elderly. Methods This is a cross-sectional home study with 211 elderly participants of the South Region of Brazil. Sarcopenia diagnosis criteria was based on the European Working Group on Sarcopenia in Older People (EWGSOP). Individuals that presented low muscle mass (women: ≤6.37kg/m2 and men: ≤8.90kg/m2) added to decreased handgrip strength (women: <20kgf and men: <30kgf) and/or walking speed (≤0.8m/s) were considered sarcopenic. TUG test quantifies functional mobility through the task of getting up from a chair, walking 3m and come back to sit on the chair. Results Based on EGWSOP criteria for sarcopenia, 17.1% (n=36) received the sarcopenia diagnosis. A ROC curve was constructed to evaluate the discriminatory power of TUG (AUC: 0.73 [IC 0.67 – 0.78; p=0.0001]). TUG test presented high sensibility (88.9%) and negative predictive values (93.2%), with a cutoff point of 7.5 seconds (figure 1). Conclusions Detecting the beginning of sarcopenia could allow for early interventions and slow the syndrome process, preventing further hospitalizations and economic burden. In this context, TUG is an easy, fast and low-cost test with high sensibility for sarcopenia detection that could be used as screening toll for this syndrome. References Barbosa-Silv TG, Bielemann RM, Gonzalez MC, et al. Journal of Cachexia, Sarcopenia and Muscle. 2016; 7:136–143. Cruz-Jentoft AJ, Baeyens JP, Bauer JM, Boirie Y, Cederholm T, Landi F, et al. Age Ageing. 2010;39(4):412–23. da Silva Alexandre T, de Oliveira Duarte YA, Ferreira Santos JL, Wong R, Lebrão ML. J Nutr Health Aging. 2014;18(8):751–6. Ishii S, Tanaka T, Shibasaki K, Ouchi Y, Kikutani T, Higashiguchi T, et al. Geriatr Gerontol Int. 2014;14 Suppl 1:93–101. Malmstrom TK, Morley JE. J Am Med Dir Assoc. 2013;14(8):531–2. Martinez BP, Gomes IB, Oliveira CS, Ramos IR, Rocha MD, Forgiarini Júnior LA, et al. Clinics (Sao Paulo). 2015;70(5):369–72. Acknowledgements Conselho Nacional de Desenvolvimento Científico e Tecnolόgico (CNPq); Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS). Disclosure of Interest None declared

AB0110 The Proteasome Is Related To Muscle Wasting in Experimental Arthritis and Is Altered by Etanercept Treatment

Background Rheumatoid arthritis is an autoimmune inflammatory disease associated with systemic complications like fatigue and muscle wasting. Muscle wasting could be related to the activation of the ubiquitin-proteasome system. Objectives To evaluate muscle loss and involvement of the proteasome in collagen-induced arthritis (CIA), with or without treatment with methotrexate or a TNF inhibitor (etanercept). Methods Male DBA1/J mice were divided into 4 groups (n=8 each): CIA (saline); ETN (etanercept, 5.5 mg/kg) and MTX (methotrexate, 35 mg/kg), treated twice a week for 6 weeks, and a healthy control group (CO). Treatments started one week after booster injection. Clinical score, hind paw oedema, and body weight were analysed during the experimental period. Gastrocnemius muscles (GA) were weighted after death and used to quantify proteasome activity, protein levels and mRNA expression of its subunits by Western blot and rtPCR. Significance was considered when p≤0.05. Results Treatments slowed disease development, observed through smaller clinical score and hindpaw edema in ETN and MTX. ETN presented higher body weight (21±1.0g) compared to MTX (19±1.3) at weeks 5 and 7. GA weight was heavier in ETN (105±12g) than CIA and MTX (80±10 and 79±10g, respectively), a result also observed after normalization of muscle with body weight. Of note, the catalytic properties of 26S proteasome showed an increase of caspase-like activity in CIA and MTX groups (150 and 200% of activity, respectively). Furthermore, muscles of MTX treated animals showed higher protein levels for proteasomal subunits PSMB8 and PSMB9 and increased gene expression for Psmb5, Psmb8 and Psmb9. In contrast, expression of Psmb6 was decreased and of Psmb9 was enhanced in CIA. Conclusions Although both drugs improved the disease score, ETN presented a stronger anti-arthritic effect and was the only treatment able to partially prevent muscle wasting. In contrast to ETN, MTX treatment did not prevent muscle loss due to CIA accompanied by persistent up-regulation of proteasome expression and activity. Acknowledgement Financial support: CAPES, CNPq, FIPE-HCPA. Disclosure of Interest None declared

AB0136 Can Nitric Oxide (NO) Regulator Drugs be Used as Treatment for Muscle Loss in Collagen-Induced Arthritis (CIA)?

Background Rheumatoid arthritis is an autoimmune disease of unknown etiology associated with progressive disability, systemic complications like fatigue and muscle weakness, early death, and socioeconomic costs [1,2]. Nitric oxide (NO) have been related with inflammation and its regulation can lead to anti-inflammatory and anti-arthritic effects in CIA as well as induce muscle repair in muscle injury [3,4]. The role of NO in CIA muscle loss has not yet been studied. Objectives How NO synthase inhibitor (NG-nitroL-arginie methy ester: L-NAME) and the NO donor (3-morpholinosydnonimine: SIN-1) affects CIA muscle loss? Methods Female Wistar rats with CIA [5] were separated in four groups: CIA (saline, n=10); L-NAME (30mg kg-1 n=10); and SIN-1 (0.3 mg kg-1, n=13), treated twice a day for 10 days after the onset of the disease, and a wildtype group (WT, n=8). Clinical score (arbitrary units – au), hind paw edema (mm), spontaneous locomotion (cm), and body weight (g) were analyzed. Ankle was collected and used for histological confirmation of the disease. Tibialis anterior (TA), gastrocnemious and soleus muscles were weighted (g). TA was used for histological analysis and immune stained for TNF-alfa, TGF-beta and IL-1beta. Serum was collected for albumin (g dL-1), total iron (μg dL-1) and ionized calcium (mg dL-1) analysis. Proper statistics were performed and p<.05 was set for critical limit. Data are in Mean ± SEM. Results Ankle histology confirmed that all CIA groups developed arthritis. In vivo analysis of hindpaw edema, clinical score, body and muscle weight, and spontaneous locomotion showed no difference among CIA groups. On the other hand, both L-NAME (48±6,5) and SIN-1 (48±6,5) groups have shown statistically decreased clinical score than saline (77±9,2) when analyzed by the area under curve. Muscle cross sectional area were higher in L-NAME (1074±315 μm) and SIN-1 (1115±303 μm) than saline (786±243 μm), however it did not reach WT diameter (1755±278 μm). Blood vessels diameter were smaller in L-NAME (287±121 μm) group compared to SIN-1 (524±169 μm) and saline (445±165 μm). Albumin was lower in all CIA groups (saline 3,8±0,2; L-NAME 3,9±0,1; SIN-1 3,7±0,1; WT 4,2±0,1), and ionized calcium had no difference among all groups. Iron was decreased in L-NAME (229±42) and SIN-1 (226±62) than WT (353±53). All CIA groups had shown increased immune cells infiltration shown by TNF-alfa, TGF-beta and IL-1beta immune staining. Conclusions The data above mentioned suggests that nitric oxide regulator drugs show good prospects as intervention for muscle loss. As was observed, even a simply drug that have main influence in vessel pressure shows preventive clinical score development and ameliorates muscle cross sectional area. The mechanism behind such findings will soon be depicted by molecular analysis. References McInnes IB, Schett G. NEJM 2011;365(23):2205-19. Alver A, et al. Clinical Biochemistry 2011;44(17-18):1385-9. Gomaa A, et al. BJP 2009;158(7):1835-47. Filippin LI, et al. Nitric Oxide 2009;21(3-4):157-63. Rosloniec EF, et al. Curr Protoc Immunol 2010; Chapter 15: Unit 15.5.1-25. Acknowledgements Financial support: CAPES, CNPq, FAPERGS, FIPE-HCPA. Disclosure of Interest None declared

AB0135 Aerobic Exercise in Inclined Treadmill Reduce Fatigue in Collagen-Induced Arthritis

Background Rheumatoid arthritis (RA) patients suffer from joint pain and decreased physical capacity, like muscle wasting and fatigue. Fatigue is a clinical manifestation reported by 40-80% of patients with RA and is regarded as an important feature of the disease. Aerobic exercise may be beneficial for treating this feature in RA patients, however the mechanisms involved are still unclear. Objectives To evaluate the effect of aerobic exercise training on the endurance exercise performance in collagen-induced arthritis (CIA) mice. Methods Male DBA1/J mice with CIA [1] were randomly divided into 3 groups: wildtype with exercise (WT-EXE, n=4), CIA exercised (CIA-EXE, n=5) and CIA non-exercised (CIA, n=4). Endurance exercise performance test (fatigue) was analyzed in all groups prior to booster injection and each 15 days after protocol started. Eighteen days after the disease induction (booster), WT and CIA-EXE were submitted to training on an inclined treadmill (θ=5°), 45 minutes a day, 5 days per week for 6 weeks at 60% of their own endurance exercise performance. Variables analyzed were disease score, hindpaw nociception, body weight (g), fatigue (by endurance exercise performance in min) and relative muscle weight (muscle weight in mg divided by total animal weight in g). Data was analyzed with ANOVA Two-Way followed by Bonferroni and independent sample t-test and p<0.05 was considered significant. All data are represented as Mean ± SEM. Results Body weight was significantly higher in WT-EXE compared with CIA after 4 and 6 weeks of exercise. At week 6 of exercise, CIA-EXE had higher body weight than CIA. Fatigue test at 4 and 6 weeks of experiment was significantly different among all experimental groups; WT-EXE and CIA had, respectively, the highest and the lowest fatigue velocity. Gastrocnemius muscle weight was significantly heavier in control group than in CIA-EXE and CIA. Nociception and clinical score of arthritis did not differ between CIA-EXE and CIA. Conclusions Inclined aerobic exercise appears as an interesting intervention in RA to treat decreased physical capacity. Collagen-induced arthritis animals demonstrated decreased endurance, and consequently increased fatigue, characteristics of a good animal model to study fatigue. The exercise protocol used in this study was able to improve this feature, demonstrating that interventions used to treat physical disabilities in RA are also valid in this model. Further studies are necessary to clarify the mechanisms behind fatigue, especially when combining exercise training and common treatments of RA. References Rosloniec EF, et al. Curr Protoc Immunol 2010; Chapter 15: Unit 15.5.1-25. Acknowledgements Financial support: CAPES, CNPq, FAPERGS, FIPE-HCPA. Disclosure of Interest None declared