Abstracts of the 9th International Conference on Cachexia, Sarcopenia, and Muscle Wasting, Berlin, Germany, 10–11 December 2016 (part 2)

نویسندگان

  • Boyd J. G. Strauss
  • Ming Li Yee
  • Christopher Gilfillan
چکیده

s of the 9th International Conference on Cachexia, Sarcopenia, and Muscle Wasting, Berlin, Germany, 10–11 December 2016 (part 2) 1-39 A review of body composition, bone mineral density, and anthropometry in a cohort of 2521 women presenting for bone mineral density testing in a tertiary centre Boyd J. G. Strauss, Ming Li Yee & Christopher Gilfillan Department of Medicine, School of Clinical Sciences, Monash University Clayton, Victoria, Australia; Endocrinology Department Eastern Clinical School, Eastern Health, Melbourne, Victoria, Australia Background: Sarcopenia is defined as loss of skeletal muscle mass and function. In clinical research, measurement of skeletal muscle mass index (SMI) is based on appendicular skeletal muscle mass (kg)/height 2 (m) <2 SD below the mean of a young reference group. SMI was found to be associated with increased physical disability independent of age, ethnicity, comorbidity, and fat mass. Alternatively, SMI is reported as weight-adjusted SMI derived from values obtained from bioelectrical impedance analysis. A recent study suggests the height-adjusted SMI has better correlation with reduced muscle strength and gait speed. Methods: We assessed data on 2521 women with a variety of medical conditions who presented to a tertiary hospital for assessment of bone mineral density (BMD). Some of these women also had concurrent body composition and anthropometry performed. Aims: We aim (i) To determine the relationship between BMD, body composition, and anthropometry in the whole group and subgroups. (ii) To determine The relationship between age and decline in skeletal muscle mass and its relationship to anthropometric variables. (iii) To explore leg length (which appears constant with age) vs. height (which declines with age) in standardizing skeletal muscle measurement for body size. Results: Participants were females aged 40–97 years (mean 59 years). The majority of the patients who were referred presented on a background of breast cancer (n = 679, 27.9%), followed by screening or other causes (n = 563, 22.3%) and steroid use (n = 241, 9.6%). When analysed on regression variable plots, reduction in sitting height, biceps, thigh skin fold, total body, femoral neck BMD, and T score occurs with age. Discussion: There were no changes observed in leg length with age. This suggests that leg length may be used as an alternative to height in the calculation of skeletal muscle mass index. 1. Baumgartner RN, et al Epidemiology of sarcopenia among the elderly in New Mexico, American Journal of Epidemiology 147:8: 755-763 2. Cruz –Jentoft AJ et al, Sarcopenia: European consensus on definition and diagnosis Report of the European Working Group on Sarcopenia in Older People Age and Ageing 2010: 39: 412-423 3. Janssen et al, Low relative skeletal muscle mass (sarcopenia) in older persons is associated with functional impairment and physical disability. J. Am. Geriatr. Soc. 50, 889–896 (2002) 4. Han DS et al, Skeletal muscle mass adjusted by height correlated better with muscular functions than that adjusted by body weight in defining sarcopenia Scientific Reports 20 January 2016 1-8 1-40 Low muscle mass at initiation of anti-tumour necrosis factor therapy for inflammatory bowel disease is associated with early treatment failure Darcy Quinn Holt, Poornima Varma, Boyd Josef Gimnicher Strauss, Anton S. Rajadurai & Gregory Thomas Moore Department of Gastroenterology and Hepatology, Mon ash Health, Clayton, Victoria, Australia; School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia Goals: We sought to determine whether low muscle mass at commencement of anti-tumour necrosis factor (TNF) therapy was associated with earlier treatment failure. Background: Delayed treatment failure occurs in significant proportion of inflammatory bowel disease (IBD) patients ABSTRACTS © 2017 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society on Sarcopenia, Cachexia and Wasting Disorders Journal of Cachexia, Sarcopenia and Muscle 2017; 8: 161–183 Published online in Wiley Online Library (wileyonlinelibrary.com) DOI: 10.1002/jcsm.12182 This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. treated with TNF-alpha antagonists. Identification of predictors of loss of response may help optimize therapy. Study: A retrospective cohort study was performed of 67 patients who had undergone cross-sectional abdominal imaging at a single centre coincident with commencement of anti-TNF drugs. Analysis of the images at the third lumbar vertebra was performed using standard techniques to determine cross-sectional areas of skeletal muscle (SM), visceral adipose tissue, subcutaneous adipose tissue, and intermuscular adipose tissue. Treatment failure was defined as follows: a post-induction hospital admission or surgery for IBD, escalation of TNF dose or immunosuppressants for clinical loss of response, emergence of a new fistula, or rising Crohn’s Disease Activity Index >150. Results: Two-thirds of patients had sarcopenia. Patients with less than the gender-specific median SM area had a median time to failure of 520 (SD 135) days compared with 1100 (SD 151) days for those with greater than median SM area (P = 0.036). No difference was found in disease duration, inflammatory markers, or Crohn’s Disease Activity Index between quartiles of SM area. No relation between outcomes and measures of adipose tissue, weight, or body mass index was observed. Conclusions: Identifying low muscle mass at anti-TNF induction as a risk factor for treatment failure may contribute to a more tailored approach to IBD therapy. 1-41 Cushing’s syndrome: a model for sarcopenic obesity Michael Drey*, Christina M. Berr, Martin Reincke, Julia Fazel, Jochen Seissler, Jochen Schopohl, Martin Bidlingmaier, Stefanie Zopp, Nicole Reisch, Felix Beuschlein, Andrea Osswald & Ralf Schmidmaier Medizinische Klinik und Poliklinik IV, Klinikum der Universität München (LMU), Munich, Germany Background and aims: Obesity and its metabolic impairments are discussed as major risk factors for sarcopenia leading to sarcopenic obesity. Cushing’s syndrome (CS) is known to be associated with obesity and muscle atrophy. The German Cushing Registry prospectively studies phenotypic and biochemical characteristics of CS. We compared CS with matched obese controls (OC) regarding body composition, physical performance, and biochemical markers to test the hypothesis that CS could be a model for sarcopenic obesity. Methods: Analysed were 47 patients with active CS and 108 controls. By propensity score matching, 47 controls were selected by body mass index and gender as OC. Fat mass and muscle mass were measured by bioelectrical impedance analysis. Muscle function was assessed by chair rising test and hand grip strength. Multiple regression analysis was used to investigate differences in body composition, physical performance, and biochemical markers adjusted for gender and age between the groups. Results: Muscle mass did not differ between CS and OC (25.3 kg vs. 25.6 kg, P = 0.793). However, CS patients showed significantly greater chair rising time (9.5 s vs. 7.3 s, P = 0.008) and significantly lower hand grip strength (32.1 kg vs. 36.8 kg, P = 0.003). Furthermore, waist-to-hip ratio (1.0 vs. 0.9, P< 0.001) and HbA1c (6.1% vs. 5.4%, P< 0.001) adjusted for age and gender were higher in CS. CS patients with impaired fasting glucose have shown the highest limitations in hand grip strength (P = 0.025) and chair rising time (P< 0.001). Conclusions: Similar to published data in geriatrics, CS patients show impaired muscle function that cannot be explained by low muscle mass. Impaired muscle quality due to fat infiltration may be the reason. Research in sarcopenic obesity in elderly is hampered by confounding comorbidities and polymedication. As CS patients are frequently free of comorbidities and as CS is potentially curable, we suggest CS as a clinical model for further research in sarcopenic obesity. 1-42 Serum creatinine/cystatin c ratio predicts strongly both sarcopenia and poor prognosis in the elderly Takayuki Tsuneda, Hidehiko Nagasawa, Atsuhiro Shimakura & Masanobu Takata Internal Medicine, Toyama Teishin Hospital, Toyama, Japan Background: Sarcopenia develops poor prognosis in the elderly. Serum creatinine (SCr) is a major biomarker to reflect not only renal functio, but also total mass of muscle. Recently, cystatin C (CysC) is building up a renal marker without any influences of muscle mass and superior to SCr to estimate renal insufficiency. Previous reports show that low value of SCr did not reflect reserved renal function, especially in lean elderly woman with malnutrition. Therefore, we evaluated retrospectively the impact of SCr/CysC ratio for sarcopenia, the activities of daily living (ADLs), and the prognosis. Method: We enrolled 324 patients in our hospital (79 13 years old; men, 46%) and collected SCr, CysC, and albumin. For estimation of sarcopenia, we measured the area of bilateral psoas muscle normalized by height [total psoas index (TPI), mm/m] and the Hounsfield unit average calculation (HUAC, HU) as a marker of muscle density and fatty infiltration, using computed tomography (n = 195). ADL was classified by modified Rankin scale (mRS). We also analysed mortality outcome based on SCr/CysC ratio. Results: Serum creatinine/CysC ratio decreased with aging (P< 0.0001). TPI in female was smaller than that in male (P< 0.0001), without gender difference in HUAC. TPI associated with body weight (R = 0.41), and HUAC did 162 Journal of Cachexia, Sarcopenia and Muscle 2017; 8: 161–183 DOI: 10.1002/jcsm.12182 albumin (R = 0.23) and SCr/CysC ratio (R = 0.23). The lower SCr/CysC ratio was related to the greater score of mRS (P< 0.0001) with decreased HUAC (P< 0.0001). SCr/CysC ratio was superior in predicting the lower ADL (mRS ≥ 3) with 82.4% of sensitivity and 70.4% of specificity (cut-off value, 0.705) to TPI or HUAC, assessed by receiver operating characteristic analysis (area under the curve: 0.83, 0.60, and 0.73, respectively). According to Kaplan–Meier analysis, the low SCr/CysC ratio (<0.70) associated with unfavourable prognosis because of all causes (P< 0.0001). Conclusion: Our study indicated that the SCr/CysC ratio might predict poor prognosis as well as the degree of sarcopenia in the elderly. 1-43 Sarcopenia, vitamin D, and functional status in mild Alzheimer’s disease and community-dwelling older adults Odete Vicente de Sousa & Teresa Freitas do Amaral Faculdade de Ciências da Nutrição e Alimentação, Universidade do Porto, Porto, Portugal; UNIFAI – Instituo de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal; Hospital de Magalhães Lemos E.P.E., Porto, Portugal; UISPA – LAETA/INEGI, Faculdade de Engenharia, Universidade do Porto, Porto, Portugal Background: The knowledge on the association of sarcopenia, vitamin D, and functional status with Alzheimer’s disease (AD) is limited. The present study aims to evaluate the association of sarcopenia, vitamin D, and functional factors with mild AD. Methods: A case–control study was conducted among 79 mild AD community-dwelling older adults (32 men; age: 78.2 6.6 years) and 32 non-AD community-dwelling older adults (seven men; age: 72.3 7.4 years). Nutrition status was assessed using MNA® score, serum 25-hydroxyvitamin D3 [25(OH)D3] and bioimpedance analysis. Sarcopenia was defined according to EWGSOP 2010 criteria. Functional status using gait speed, handgrip strength, and Barthel index was determined. Multivariate backward logistic regression analyses were carried out. Results: Thirty-three AD patients (41.7%) and three (9.3%) controls showed sarcopenia. Among the sarcopenic AD patients, 54.5% were classified as undernourished and the remaining at undernutrition risk. All the sarcopenic controls were non-undernourished. Sixty-five AD patients (82.3%) and 20 (62.5%) controls had serum 25(OH)D3 deficiency (20.1–30.0 ng/mL). Sarcopenia [OR = 7.75, 95% confidence interval (CI) 1.59–37.74, P = 0.011], gait speed (OR 16.94, CI 95% 3.93–72.90, P< 0.001), and Barthel index (OR 7.93, CI 95% 2.41–26.06, P = 0.001) were associated with AD. Conclusion: A high proportion of AD patients (95%) and controls (90.6%) had 25(OH)D3 insufficiency (<30 ng/mL). Sarcopenia, low gait speed, and dependence were strongly associated with AD. Conflict of interest: The authors have reported no conflicts of interest. This article has no sponsorship. 1-44 Electronically administered patient reported outcomes (ePROs) in sarcopenic older patients: the SARA clinical data platform novel approach to clinical trials SusannaDel Signore, Gianluca Zia, StefaniaDel Signore&Waly Dioh Bluecompanion ltd, London, UK; Biophytis, Romainville, France Sarcopenia was recently recognized as an independent condition by the International Classification of Disease, Tenth Revision, Clinical Modification under the code M62.84. Although no candidate drug has received yet marketing authorization for (ageing related) sarcopenia, US and EU regulatory experts do strengthen the importance of testing patient-reported outcomes aside from objective measurements of mobility function and body composition, to demonstrate clinical efficacy in sarcopenia. Rationale: Standard designed clinical trials may be inadequate for collecting good quality long-term clinical data in older adults. Concomitant chronic diseases and poly-therapy-related exclusion criteria often prevent enrolling a representative sample of the target population. Rigid visit and investigation scheduling negatively affects compliance and retention rate while increasing the risk of biased results. Administering PROs to older patients via remotely connected devices as an approach for good quality clinical data is now being tested in SARA-OBS, an EU/US study assessing the 6month rate of change in physical function and body composition of 300 community dwelling older patients with low SPPB, at risk of mobility disability and physical dependence. SARA clinical data platform is based on a semi-permanent clinical trial infrastructure, centred on geographic areas and their clinical investigation centres. A digital platform integrates different source data: clinical data, DXA, physical activity recording, biomarkers (via a Biobank), and PROs. At study end, data could be retrieved for secondary research in sarcopenia, for example, answering additional, not prespecified questions from regulators. The clinical trial platform is enabled by novel information and communication technologies, allowing friendly secure communication with patients and continuous data collection from home, minimizing travels to the investigational site. This approach succeeds to empower patient’s role in clinical research by providing simplified communication with the study staff. A dedicated website as entry portal and an adaptive data warehouse complete the SARA clinical data platform infrastructure. 163 Journal of Cachexia, Sarcopenia and Muscle 2017; 8: 161–183 DOI: 10.1002/jcsm.12182 1-45 Psoas muscle measurements are inferior to total skeletal muscle measurements in the assessment of sarcopenia in ovarian cancer Iris J. Rutten, Jorne Ubachs, Roy F. P. M. Kruitwagen, Regina G. H. Beets-Tan, Steven W. M. Olde Damink & Toon van Gorp Department of Radiology, Maastricht University Medical Centre, Maastricht, The Netherlands; Department of Obstetrics and Gynaecology, Maastricht University Medical Centre, Maastricht, The Netherlands; Department of General Surgery, Maastricht University Medical Centre, Maastricht, The Netherlands Background: Computed tomography measurements of total skeletal muscle area can detect changes and predict overall survival (OS) in patients with advanced ovarian cancer. This study investigates whether assessment of psoas muscle area reflects total muscle area and data collected can be used to assess sarcopenia in ovarian cancer patients. Methods: Ovarian cancer patients (n = 150) treated with induction chemotherapy and interval debulking were enrolled retrospectively in this longitudinal study. Muscle was measured cross-sectionally with computed tomography in three ways: (i) software quantification of total skeletal muscle area (SMA); (2) software quantification of psoas muscle area (PA); and (3) manual measurement of length and width of the psoas muscle to derive the psoas surface area (PLW). Pearson correlation between the different methods was studied. Patients were divided into two groups based on the extent of change in muscle area, and agreement was measured with kappa coefficients. Cox regression was used to test predictors for OS. Results: Correlation between SMA and both psoas muscle area measurements was poor (r = 0.52 and 0.39 for PA and PLW, respectively). After categorizing patients into muscle loss or gain, kappa agreement was also poor for all comparisons (all κ< 0.40). In regression analysis, SMA loss was predictive of poor OS [hazard ratio 1.698 (95%CI 1.038–2.778), P = 0.035]. No relationship with OS was seen for PA or PLW loss. Conclusions: Change in psoas muscle area is not representative of the total muscle area change and should not be used to substitute total skeletal muscle to predict survival in patients with ovarian cancer. 1-46 Loss of lean mass after stroke: results from the prospective observational study on body composition in acute stroke (BoSSS) Charlotte Pietrock, Nadja Scherbakov, Jochen B. Fiebach, Nicole Ebner, Anja Sandek, Miroslava Valentova, Stephan von Haehling, Stefan D. Anker & Wolfram Doehner Center for Stroke Research Berlin (CSB), Charité University Medical School, Berlin, Germany; German Center for Cardiovascular Diseases (DZHK), Partner Site, Berlin; Innovative Clinical Trials, Department of Cardiology and Pneumology University Medical Centre Göttingen, Germany; Department of Cardiology, Charité University Medical School, Berlin, Germany Introduction: The structural and functional deterioration of skeletal muscle in paretic stroke patients has a strong impact on clinical outcome after stroke. Using dual-energy X-ray absorptiometry (DEXA) to analyse changes in body composition, this study aimed to assess long-term loss and remodelling processes of skeletal muscles of stroke patients. Methods: A total of 131 patients with acute ischemic stroke who were admitted to a university centre and stroke unit (age: 67 13 years; 80 men, 51 women; BMI: 27 4 kg/m, mean NIHSS: 4 3) were studied in a prospective longitudinal observational study. DEXA was used to assess fat and lean tissue, and appendicular lean mass of the affected (paralytic) vs. non-affected body side was studied. DEXA studies were performed immediately at the time of acute stroke (4 2 days) and at 1 (12.8 0.9months, n = 67) and 2 year (24.9 1.3months, n = 44) follow-up (FU). Patients (34%, n = 44) with acute stroke received thrombolytic therapy at admission to the hospital. Volume of early ischemic injury was analysed using the quantitative topographic Alberta stroke programme early CT score (ASPECTS), which revealed an average of 8.6 1.4 points. Results: The baseline examination showed a trend towards reduction of lean mass of the paretic arms and/or legs compared with the non-paretic arms and/or legs (P = 0.0551). Significantly less lean mass was found in the paretic arms and/or legs compared with the non-paretic arms and/or legs at 1 and 2 year FU (both P< 0.001). There was no significant change in lean mass in the non-paretic arms and/ or legs at 1 and 2 year FU (P = 0.4198 and P = 0.3484, respectively). Additionally, at 1 and 2 year FU, reduction of BMI was observed in patients without thrombolytic therapy (both P< 0.001). In contrast, no reduced BMI and no loss of lean mass were observed during 2 year FU in patients who received thrombolytic therapy (all P> 0.16). Patients without thrombolytic therapy showed significantly less lean mass in the paretic arms and/or legs compared with that in the non-paretic arms and/or legs (P = 0.009). At 1 year FU, patients with an initial ASPECTS ≤8 points, indicating a higher volume of brain injury, showed significantly less lean mass in the paretic arms and/or legs compared with that in the non-paretic arms and/or legs in contrast with patients with a score of ≥9 points (P< 0.05). Conclusion: Muscle wasting was observed in patients after acute stroke in the paretic limb, but not in the non-paretic limb, and was continuously observed after 2 years of FU. Tissue wasting was particularly present in patients without thrombolytic therapy and in this with higher volume of brain injury. 164 Journal of Cachexia, Sarcopenia and Muscle 2017; 8: 161–183 DOI: 10.1002/jcsm.12182 1-47 The influence of operative stress, systemic inflammation, and sepsis on computed tomography body composition variables Michael Ramage, Graeme W. Couper, James A. Ross, Christopher D.A. Deans, Richard J. E. Skipworth & Kenneth C. H. Fearon* Clinical Surgery, Royal Infirmary of Edinburgh, Edinburgh, UK; NHS Lothian, Royal Infirmary of Edinburgh, Edinburgh, UK; Tissue Injury and Repair Group, Chancellor’s Building, University of Edinburgh, Edinburgh, UK Introduction: Computed tomography (CT) planimetry at the L3 level can identify sarcopenia and prognosticate morbidity and mortality in cancer patients. The deleterious impact of neoadjuvant chemotherapy on CT-derived lean body mass has been assessed previously. However, the impact of systemic inflammation (SI) on CT-derived body composition variables has not been investigated. Methods: Pre-operative staging and post-operative portal venous phase CT scans of oesophageal cancer patients who underwent Ivor Lewis esophagectomy and then subsequently developed sepsis secondary to anastomotic leak (n = 14; M : F 12 : 2; median age 67 years) were analysed. Body composition variables were collected using validated semi-automated analysis software (Matlab). Results: There were no significant differences in L3 skeletal muscle area [median 149.7 cm (range 82.5–203.2) vs. 156.1 cm (112.6–205.5); P = 0.11] or subcutaneous adipose tissue area [210.4 cm (93.1–696.9) vs. 219.2 cm (97.8– 346.2); P = 0.55] between preand post-operative scans. There was a significant reduction in visceral adipose tissue area [179.0 cm (51.7–380.5) vs. 154.1 cm (40.7–364.9); P = 0.041], but this is explained by the removal of the surgical specimen. However, there was a significant reduction in skeletal muscle density (in Hounsfield units) between pre-and post-operative scans [36.8 (20.0–49.7) vs. 27.5 (15.5–46.1); P = 0.026], whereas there were significant increases in both visceral adipose tissue density ( 97.7 [ 104.8 to 74.6] vs. 88.8 [ 98.6 to 71.30]; P = 0.002) and subcutaneous adipose tissue density ( 102.77 [ 111.71 to 87.86] vs. 86.44 [ 97.00 to 71.14]; P = 0.001). Conclusion: The lack of change in skeletal muscle area between preand post-operative scans would support the reliability of L3 CT planimetry to assess sarcopenia across repeated assessments. In the early phase, operative stress and SI (sepsis) are associated with alterations in tissue density, likely explained by an increase in tissue oedema and/or altered blood flow affecting contrast uptake. Care must be taken when interpreting skeletal muscle density/myosteatosis in the presence of SI, as CT-derived body composition will be affected by the patient’s condition. 1-48 Albuminuria and hemodynamics in patients with heart failure referred for transplantation Piotr Rozentryt, Jacek Niedziela, Jolanta U. Nowak, Bartosz Hudzik, Marek Gierlotka, Andrzej Lekston, Michał Hawranek, Ewa Jankowska, Stephan von Haehling, Wolfram Doehner, Stefan D. Anker & Mariusz Gąsior III Department of Cardiology, Silesian Centre for Heart Disease, Silesian Medical University, Zabrze, Poland; Department of Heart Diseases, Wroclaw Medical University, Wroclaw, Poland; Department of Innovative Clinical Trials, University Medical Center Göttingen (UMG), Göttingen, Germany; Applied Cachexia Research, Department of Cardiology, Charite Medical School—Campus VirchowKlinikum, Berlin, Germany Background: Both albuminuria and reduced kidney function are important prognosticators in heart failure (HF). Reduction of filtration in HF was shown to be linked with elevated venous pressure and low cardiac output. Much less is known on the reasons of for albuminuria in HF. The relations between albumin loss into urine and invasively assessed hemodynamic characteristics have never been studied in HF. Aim: We intended to analyse the relation between degree of albuminuria and hemodynamic characteristics measured invasively using Swan–Ganz catheter. Material and methods: In the 244 patients with HF with reduced ejection fraction referred for qualification to heart transplantation (age: 51 10 years, 12% female: LVEF: 24 11%, NYHA class: 3.0 0.7), we measured mean right atrial (RA), pulmonary artery (PA) and capillary wedge (PCWP) pressures as well as cardiac output (CO) using termodilution technique. Albumin excretion was measured taking advantage of standard method from morning urine sample and expressed in milligrammes per 1 g of excreted creatinine (UA). Clinical, laboratory, and hemodynamic characteristics of patients with different UA values were compared. We used logistic regression to estimate the association of various variables on the risk of UA above median value as compared with UA bellow median. Results: The median UA was 1.64mg/g of creatinine. The group with higher UA was not different with respect to age, BMI, NYHA class, LVEF, hsCRP, NTproBNP, MDRD, and per cent-recommended dosages of beta-blockers, ACEI/ARB, and aldosterone antagonist. The group with UA above median had higher RA (8 3 vs. 3 1mmHg, P< 0.0001), PA (30 11 vs. 23 9mmHg, P = 0.01), and PCWP (20 10 vs. 14 7mmHg, P< 0.0001) higher dose of furosemide equivalent (121 75 vs. 101 57mg). There was also more women in this group. The CO was not different (5.1 4.2 vs. 4.6 2.2 L/min, P = 0.69). In univariate analysis, higher UA was associated with sex, OR = 0.60, 95%CI: 0.36–0.99, P = 0.04 (male vs. female); weight loss during HF, OR = 2.45, 95%CI: 1.07–5.57, P = 0.03 (per 1% increase); NTproBNP, OR = 1.22, 95% CI: 1.08–1.37, P = 0.002 (per 1000 pg/mL increase); and dose of loop diuretics, OR = 1.20, 95% CI: 1.00–1.45, P = 0.04 (per 40mg of furosemide equivalent increment). 165 Journal of Cachexia, Sarcopenia and Muscle 2017; 8: 161–183 DOI: 10.1002/jcsm.12182 In multivariable analysis comprising parameters with P< 0.2 on univariate analysis, no parameter was predictive of higher UA. Conclusion: Higher albuminuria in patients with HF parallel elevated filling pressures, but we failed to confirm the independent association of these variables with UA. 1-49 Fractional urinary excretion of potassium, treatment pattern, and mortality in heart failure Piotr Rozentryt, Jacek Niedziela, Jolanta U. Nowak, Bartosz Hudzik, Przemysław Leszek, Tomasz Rywik, Ewa Jankowska, Wolfram Doehner, Stephan von Haehling, Stefan D. Anker & Mariusz Gąsior III Department of Cardiology, Silesian Centre for Heart Disease, Silesian Medical University, Zabrze, Poland; Department of Heart Failure and Transplantology, Institute of Cardiology, Warsaw, Poland; Applied Cachexia Research, Department of Cardiology, Charite Medical School—Campus Virchow-Klinikum, Berlin, Germany; Department of Innovative Clinical Trials, University Medical Center Göttingen (UMG), Göttingen, Germany Introduction: Fractional urinary excretion of potassium (FUEK) tells us what percentage of potassium filtered within glomerulus is finally lost into urine. It can be taken as a surrogate of renin–angiotensin–aldosterone (RAA) activity on the kidney. In heart failure (HF), RAA system is up-regulated and degree of activity is associated with poor outcome. In clinical practice, only part of patients receive RAA-inhibiting therapy at dosages recommended by guidelines. The relation between FUEK, mortality, and treatment quality in this population has never been assessed. Aim: We wanted to determine the association of FUEK and mortality in HF patients treated with various dosages of recommended drugs. Material and methods: In the 380 HF patients (age: 52 11 years, female: 14%, NYHA: 2.7 0.7, LVEF: 24 7%), we measured FUEK from spot morning urine sample. The patients were all treated with angiotensin-converting enzyme inhibitors (ACEI), beta-blockers (BB), aldosterone antagonists (AA), and loop diuretics LD at dosages: ACEI: 59 48%, BB: 56 30%, AA: 112 58%, and LD: 101 83mg of furosemide equivalent. During the follow-up of 3 years, 106 patients (27.9%) have died. We used Kaplan–Maier method to assess the cumulative probability of death for each tertile of FUEK. Next, we constructed Cox proportional hazard models to estimate the unadjusted risk of death for tertiles of FE and the risk after adjustment for treatment pattern. Results: Figure 1 shows Kaplan–Maier curves for mortality at tertiles of FUEK. The hazard ratio of mortality 95% confidence intervals for middle and upper tertile of FUEK relative to the bottom in unadjusted and adjusted models are shown in Table 1. Tertiles of FUEK (HR 95% CI) Bottom Middle Upper Unadjusted model 1.0 1.59 (0.94–2.68), P=0.08 2.17 (1.33–3.54), P=0.002 Adjusted for MDRD 1.0 1.51 (0.89–2.55), P=0.12 1.74 (1.03–2.94), P=0.03 Adjusted for percent recommended dose of ACEI, BB, AA, the dose of LD, MDRD, and urinary sodium 1.0 1.25 (0.67–2.35), P=0.48 1.79 (0.99–3.24), P=0.052 Conclusion: In HF patients, high FUEK may be associated of elevated risk independent of treatment pattern. Whether high FUEK reflects undertreatment remains to be established. Figure 4 The Kaplan–Maier curves for 3 year mortality in tertiles of fractional urinary excretion of potassium. 1-50 Bioelectrical impedance analysis as an objective nutritional assessment’s method in patients undergoing palliative care: preliminary study Teresa Małecka-Massalska, Monika Prendecka, Radoslaw Mlak, Przemysław Matras, Mariusz Teter, Beata Kolano-Janeczek & Waldemar Wójcik Department of Human Physiology, Medical University of Lublin, Lublin, Poland; Department of General and Transplant Surgery and Nutritional Treatment, Medical University of Lublin, Lublin, Poland; Hospice of the Good Samaritan in Lublin, Lublin, Poland; Institute of Electronics and Information Technology, Technical University of Lublin, Lublin, Poland Background and Objective: Nutritional deficits have a significant impact on mortality, morbidity, and quality of life in cancer patients. Bioelectrical impedance (BIA) has been established as an easy-to-use, non-invasive, reproducible and thus valuable tool in the evaluation of body composition and nutritional status. BIA evaluates body components such as resistance (R) and reactance (Xc) by recording a voltage drop in applied current. The phase angle (PA) calculated as index of capacitance (Xc/R) has been found to be a prognostic indicator in several neoplasms: lung, pancreatic, colon, and breast cancers. This study was conducted to investigate the 166 Journal of Cachexia, Sarcopenia and Muscle 2017; 8: 161–183 DOI: 10.1002/jcsm.12182 role of Xc, R, and PA as an malnutrition markers of cancer patients. Methods: We evaluated 12 palliative women (cancer patients hospitalized in Hospice of the Good Samaritan in Lublin, Poland) and 15 healthy volunteers matched by body mass index, age, and sex as a control group—between November 2014 and January 2015. Palliative patients and control group underwent a baseline nutritional assessment: subjective global assessment and BIA. BIA was conducted at 50 kHz. Results: Reactance was found to be significantly lower in palliative patients than in the control group [medians (and 95%CIs) respectively: 2.12 (1.71–2.97) vs. 5.55 (5.18–6.07), P< 0.0001]. Similarly, PA was found to be significantly lower in palliative patients than in the control group [medians (and 95%CIs) respectively: 18.55 (9.40–30.69) vs. 49.68 (45.24– 53.38), P< 0.0001]. No significant differences were found during R analysis: P = 0.4945. Conclusion: Palliative patients have altered tissue electrical properties expressed by BIA parameters. BIA could be an alternative method to Subjective Global Assessment measurement and may provide more objectively assess nutritional status of patients with different cancers treated in palliative care units. However, further observations in larger sample sizes are needed to validate use of parameters of BIA as a nutritional marker or prognostic factor in clinical practice. 1-52 Estimation of different body composition parameters in obese patients using bioelectrical impedance Nadja Vasiljevic, Dragana Davidovic, Nikolina Banjanin, Branko Jakovljevic, Milos Maksimovic & Jagoda Jorga Institute of Hygiene and Medical Ecology, Faculty of Medicine, University of Belgrade, Belgrade11000, Serbia Background and Aims: The assessment of nutritional status is an initial step in the treatment of obese persons. The aim of this study was to evaluate the anthropometric characteristics and body composition variables in relation to sex and age, in obese patients. Methods: The study involved 498 subjects of both sexes who applied to the Department of Nutrition for MNT for obesity. The anthropometric evaluations, as well as the measuremen by using Tanita BC 418 MA bioelectric impedance, were carried out for all patients. On that basis, FM and FFM parameters were obtained, and then the value of FM index (FMI) and FFM index (FFMI) was calculated. Results: The test sample consisted of 76% of females and 24% males. Among them, the highest prevalence was of first degree obesity 37.1%. Body composition analysis has shown that the FFM values differ significantly with respect to these three categories of nutritional status, in both sexes and regarding the age (P< 0.001). FFMI values were also significantly different within these three groups (P< 0.001) in both sexes. When the differences were analysed in relation to age, it was indicated, in male participants, that with the age increase, FFMI values declined significantly (P< 0.02), and they were the lowest in the group of patients older than 60 years. In the oldest group of tested women, the values of FMI were significantly higher (P< 0.007). Conclusions: The assessment of nutritional status in people who are on MNT for obesity is necessary, but the estimation of body composition is essential as well, and that fact becomes clear through monitoring FFM and FFMI, as well as FM and FMI. It is particularly important to assess these in the elderly and in order to prevent and monitor sarcopenic obesity. 1-54 Correlation between handgrip strength and muscle mass with biochemical and body composition parameters Cristina Garagarza, Ana Laura Flores & Ana Valente Nephrocare, Lisbon, Portugal; Faculty of Medicine, Universidad de Colima, Colima, México Background and Aim: Hemodialysis (HD) patients are vulnerable to multiple metabolic and nutritional derangements leading to changes in body composition. Several methods to assess muscle reserves have been used; one of this is the handgrip strength (HGS), a simple and reliable method that evaluates muscle strength, and it has been used as a nutritional marker. The aim of this study was to evaluate the correlation of HGS with biochemical parameters and body composition in HD patients. Methods: Single-centre, cross-sectional study, where 155 patients in HD were included. Body composition was assessed through bioimpedance spectroscopic. HGS was measured with a hydraulic hand dynamometer in the opposite hand to the vascular access. Protein intake was assessed through normalized protein catabolic rate (nPCR). Albumin and total protein were also evaluated. Data were analysed by sex. P value <0.05 was considered statistically significant. IBM SPSS version 20 (IBM, Chicago, IL, USA) was used to perform statistical analysis. Results: Men constitute 60.6% in the study population, and the mean age was 64.4 14.7 years. We found a positive correlation of HGS with lean tissue mass, lean tissue index, and body cell mass and a negative correlation between HGS, age, and OH/ECW in both genders. Albumin presented a positive correlation, and magnesium showed a negative correlation with HGS but only in men. nPCR, total protein, and HD vintage were not correlated with HGS in any of the two groups. Conclusions: Muscle strength is positively correlated with muscle mass; therefore, the muscle strength can be a good marker to determinate changes in muscle mass. Gender 167 Journal of Cachexia, Sarcopenia and Muscle 2017; 8: 161–183 DOI: 10.1002/jcsm.12182 influences strength as it is usually higher in men, even in patients in HD, and the HGS tends to decrease with aging. In summary, muscle strength is not only about muscle size; there are other entities that may be associated, as age, sex, and biochemical parameters. 1-55 The desmosomal component, plakoglobin, forms novel complexes in skeletal muscle, whose dissociation promotes atrophy Yara Eid Mutlak, Alexandra Volodin, Anna Parnis & Shenhav Cohen Technion Institute of Technology, Haifa, Israel Skeletal muscle atrophy occurs during fasting and inactivity, naturally with aging, and in many human diseases including diabetes and cancer. During atrophy, there is a major loss of muscle mass and strength, primarily because of the accelerated destruction of the muscle’s contractile machinery, the myofibrils, by the proteasome. We have previously shown that plakoglobin is a new constituent of skeletal muscle, which binds to the insulin receptor and the p85 regulatory subunit of PI3K to enhance the insulin signaling, PI3K/Akt cascade, and glucose uptake. Using tandem native purification approach, biochemical fractionation procedures, and mass spectrometry, we now surprisingly demonstrate that plakoglobin forms distinct complexes in skeletal muscle, which contain components of the dystroglycan complex, the insulin receptor and p85/PI3K, and the intermediate filament protein, desmin. Our data indicate that dystroglycan complex integrity is coupled to signal transmission via the insulin receptor and that the desmosomal component plakoglobin is critical for the stability of both structures. Interestingly, in muscles from diabetic mice, where signaling through the IGF-1 and insulin receptors is impaired, plakoglobin-containing complexes are compromised. However, overexpression of plakoglobin alone enhanced the stability of these structures. Thus, dissociation of plakoglobin-containing complexes may be an early event leading to reduced PI3K/Akt signaling, accelerated proteolysis, and atrophy. 1-56 ACE-2494, a systemically acting transforming growth factor-β superfamily ligand trap, prevents and restores muscle loss and weakness in disuse atrophy mice Jia Li, Maureen Frederics, Rajasekhar N. V. S. Suragani, Scott R. Pearsall & Ravindra Kumar Acceleron Pharma, Cambridge, MA, USA Background and Aims: Skeletal muscle atrophy is a debilitating and a common disorder effecting ~30 million people in the USA. There is a need for treatments that could accelerate the rate of rehabilitation and reduce overall healthcare costs. We have developed ACE-2494, a GDF ligand trap that was previously demonstrated to increase muscle mass in wild-type mice. This study sought to determine its preventative and therapeutic effects in a model of disuse atrophy mice. Here, an immobilization mouse model was utilized to specifically induce tibialis anterior muscle atrophy and tibiae bone loss. Methods: Thirty-two 12-week-old C57BL/6J male mice were immobilized for 14 days via stapling the unilateral hindlimb. Mice were randomized to receive either vehicle or ACE2494 (10mg/kg) twice per week by subcutaneous delivery. Treatments were carried out either during the 14 day immobilization or during 14 day remobilization. Muscle strength was assessed by performing isometric contraction. Alteration of myocyte morphology was determined by minimal Feret’s diameter. Area bone mineral density (aBMD) was measured by dual-energy X-ray absorptiometry. All data were normalized to vehicle-treated unstapled hindlimb to evaluate muscle alterations during immobilization and remobilization. Results: Fourteen-day immobilization caused a significant reduction in muscle weight, peak tetanic force, myocyte size, and aBMD ( 10%, 7%, 17%, and 7%, respectively). Fourteen-day remobilization was not able to restore the decrease. However, with ACE-2494 intervention, muscle rehabilitation was greatly accelerated with ~14% muscle hypertrophy accompanied with ~14% higher force generation. Myocyte area was also fully recovered. During the 14 day immobilization, ACE-2494 treatment resulted in enlarged muscle fibre size by ~28% and restored the loss in aBMD to control levels. Conclusions: ACE-2494 restored and prevented muscle loss, muscle weakness, and bone loss in disuse atrophy mice. This study provides proof of concept for potential treatments against human disorders involving muscle atrophy. Reference: 1.Dyle MC, et al. (2014) Systems-based discovery of tomatidine as a natural small molecule inhibitor of skeletal muscle atrophy. J Biol Chem 289(21):14913–14924. 2.Pearsall RS, et al. (2015) ACE-2494, a novel GDF ligand trap, increases muscle mass upon systemic administration in mice. The 20th International Congress of the World Muscle Society. 1-57 Compensatory anabolic signaling in the sarcopenia of experimental chronic arthritis Robert D. Little, Iván Prieto-Potin, Sandra Pérez-Baos, Amanda Villalvilla, Paula Gratal, Flavia Cicuttini, Raquel Largo & Gabriel Herrero-Beaumont Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Alfred Hospital, Melbourne, Australia; Bone and Joint Research Unit, Service of Rheumatology, IIS-Fundación Jiménez Díaz, Autonomous University of Madrid, Madrid, Spain; Red Temática de Investigación Cooperativa de Envejecimiento y Fragilidad (RETICEF)-Instituto de Salud Carlos III, Madrid, Spain 168 Journal of Cachexia, Sarcopenia and Muscle 2017; 8: 161–183 DOI: 10.1002/jcsm.12182 Background and Aims: Inflammatory activity in rheumatoid arthritis may alter the regulation of muscle mass leading to a secondary sarcopenia, commonly termed rheumatoid cachexia (RC). The mechanisms and response to muscle atrophy in RC are poorly understood. We aimed to characterize the alterations to muscle structure and the relative expression of a range of anabolic and catabolic regulatory factors. Methods: Twenty male, adult rabbits were randomly assigned to antigen-induced arthritis (AiA) or control groups. Animals were weighed weekly, and serum, tibialis anterior, gastrocnemius, and extensor digitorum longus muscles were collected. Muscle sections underwent haematoxylin and eosin staining for total cross-sectional area and diameter, RAM11, Pax7 immunohistochemistry to identify macrophages and satellite cells, respectively, and immunofluorescence to calculate myonuclei. Gene expression of muscular IL-1β, IL-6, TNF, CCL-2, myostatin, MuRF-1, and atrogin-1 were quantified. Protein levels of myostatin, Pax7, pSTAT1, and pSTAT3 were measured. Myostatin was also determined in synovial tissue and circulation, alongside serum C-reactive protein (CRP). Results: Antigen-induced arthritis rabbits exhibited significantly less weight gain than controls and increase in serum CRP. AiA rabbit muscles were lighter and showed a reduction in CSD and increased number of myonuclei. Atrogin-1 and MuRF-1 were up-regulated in the AiA group alongside a two-fold increase in IL-1β mRNA despite a decrease in CCL-2 and a reduction in TNF and equivalent IL-6 mRNA levels. We observed a decrease in pSTAT3, unchanged pSTAT1, and increased Pax7 levels. AiA rabbits showed reduced myostatin mRNA and protein from gastrocnemii and a decrease in synovial myostatin with a congruent reduction in serum. Conclusions: Chronic arthritis induced an RC-like secondary sarcopenia with increased muscle protein breakdown. Elevated serum CRP and muscle IL-1βmay indicate a systemic inflammatory state with a compensatory anabolic effort suggested by myonuclear expansion, increased Pax7, reduced pSTAT3, and serum, synovial, and muscular myostatin. 1-58 Deciphering the pathophysiology of the tuberculosis wasting syndrome from the pathogenicity of Mycobacterium tuberculosis

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عنوان ژورنال:

دوره 8  شماره 

صفحات  -

تاریخ انتشار 2017