Volume 8 / Number 2 / April 2017

 

 

     Page 187189

Maria Cristina Gonzalez, Steven B. Heymsfield

Bioelectrical impedance analysis for diagnosing sarcopenia and cachexia: what are we really estimating?As reference methods are not available for identifying low skeletal muscle mass in clinical practice, the European Group on Sarcopenia in Older People the Asian Working Group for Sarcopenia and the International Consensus for Cancer Cachexia guidelines accept bioelectrical impedance analysis (BIA) as an option for sarcopenia and cachexia assessment. Using different BIA equations, several components that represent ‘muscularity’ can be assessed. Total skeletal muscle mass or appendicular skeletal muscle mass normalized in relation to height (skeletal muscle mass index or appendicular skeletal muscle index, respectively) is the most common term used in the consensus. These terms are similar, but they should not be used as synonymous. Both terms can be used to define sarcopenia, but adequate equations and cut-off values should be used according to the studied population. However, there is a disagreement between the sarcopenia definition assessed by using BIA from the European Group on Sarcopenia in Older People and Cachexia Consensus, and this can lead to an overestimation of sarcopenia and, consequently, cachexia. An effort should be made to standardize the terminology employed by the Societies to define low muscularity and sarcopenia by using BIA. Future validation studies may show the need for specific cut-off values for each population using this method.

 

Gonzalez, M. C., and Heymsfield, S. B. (2017) Bioelectrical impedance analysis for diagnosing sarcopenia and cachexia: what are we really estimating?. Journal of Cachexia, Sarcopenia and Muscle, 8: 187189. doi: 10.1002/jcsm.12159.

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     Page 190201

Christopher Lipina, Harinder S Hundal

Lipid modulation of skeletal muscle mass and functionLoss of skeletal muscle mass is a characteristic feature of various pathologies including cancer, diabetes, and obesity, as well as being a general feature of ageing. However, the processes underlying its pathogenesis are not fully understood and may involve multiple factors. Importantly, there is growing evidence which supports a role for fatty acids and their derived lipid intermediates in the regulation of skeletal muscle mass and function. In this review, we discuss evidence pertaining to those pathways which are involved in the reduction, increase and/or preservation of skeletal muscle mass by such lipids under various pathological conditions, and highlight studies investigating how these processes may be influenced by dietary supplementation as well as genetic and/or pharmacological intervention.

 

Lipina, C., and Hundal, H. S. (2016) Lipid modulation of skeletal muscle mass and function. Journal of Cachexia, Sarcopenia and Muscle, 8: 190201. doi: 10.1002/jcsm.12144.

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     Page 202212

Hui Ding, Guohua Zhang, Ka Wai Thomas Sin, Zhelong Liu, Ren-Kuo Lin, Min Li, Yi-Ping Li

Activin A induces skeletal muscle catabolism via p38β mitogen-activated protein kinasesBackground
Activation of type IIB activin receptor (ActRIIB) in skeletal muscle leads to muscle atrophy because of increased muscle protein degradation. However, the intracellular signalling mechanism that mediates ActRIIB-activated muscle catabolism is poorly defined.
Methods
We investigated the role of p38β mitogen-activated protein kinases (MAPK) in mediating ActRIIB ligand activin A-activated muscle catabolic pathways in C2C12 myotubes and in mice with perturbation of this kinase pharmacologically and genetically.
Results
Treatment of C2C12 myotubes with activin A or myostatin rapidly activated p38 MAPK and its effector C/EBPβ within 1 h. Paradoxically, Akt was activated at the same time through a p38 MAPK-independent mechanism. These events were followed by up-regulation of ubiquitin ligases atrogin1 (MAFbx) and UBR2 (E3α-II), as well as increase in LC3-II, a marker of autophagosome formation, leading to myofibrillar protein loss and myotube atrophy. The catabolic effects of activin A were abolished by p38α/β MAPK inhibitor SB202190. Using small interfering RNA-mediated gene knockdown, we found that the catabolic activity of activin A was dependent on p38β MAPK specifically. Importantly, systemic administration of activin A to mice similarly activated the catabolic pathways in vivo, and this effect was blocked by SB202190. Further, activin A failed to activate the catabolic pathways in mice with muscle-specific knockout of p38β MAPK. Interestingly, activin A up-regulated MuRF1 in a p38 MAPK-independent manner, and MuRF1 did not appear responsible for activin A-induced myosin heavy chain loss and muscle atrophy.
Conclusions
ActRIIB-mediated activation of muscle catabolism is dependent on p38β MAPK-activated signalling.

 

Ding, H., Zhang, G., Sin, K. W. T., Liu, Z., Lin, R. -K., Li, M., and Li, Y. -P. (2016) Activin A induces skeletal muscle catabolism via p38β mitogen-activated protein kinases. Journal of Cachexia, Sarcopenia and Muscle, 8: 202212. doi: 10.1002/jcsm.12145.

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     Page 213228

Félix St-Jean-Pelletier, Charlotte H Pion, Jean-Philippe Leduc-Gaudet, Nicolas Sgarioto, Igor Zovilé, Sébastien Barbat-Artigas, Olivier Reynaud, Feras Alkaterji, François C Lemieux, Alexis Grenon, Pierrette Gaudreau, Russell T Hepple, Stéphanie Chevalier, Marc Belanger, José A Morais, Mylène Aubertin-Leheudre, Gilles Gouspillou

The impact of ageing, physical activity, and pre-frailty on skeletal muscle phenotype, mitochondrial content, and intramyocellular lipids in menBackground
The exact impact of ageing on skeletal muscle phenotype and mitochondrial and lipid content remains controversial, probably because physical activity, which greatly influences muscle physiology, is rarely accounted for. The present study was therefore designed to investigate the effects of ageing, physical activity, and pre-frailty on skeletal muscle phenotype, and mitochondrial and intramyocellular lipid content in men.
Methods
Recreationally active young adult (20–30 yo; YA); active (ACT) and sedentary (SED) middle-age (50–65 yo; MA-ACT and MA-SED); and older (65 + yo; 65 + ACT and 65 + SED) and pre-frail older (65 + PF) men were recruited. Muscle biopsies from the vastus lateralis were collected to assess, on muscle cross sections, muscle phenotype (using myosin heavy chain isoforms immunolabelling), the fibre type-specific content of mitochondria (by quantifying the succinate dehydrogenase stain intensity), and the fibre type-specific lipid content (by quantifying the Oil Red O stain intensity).
Results
Only 65 + SED and 65 + PF displayed significantly lower overall and type IIa fibre sizes vs. YA. 65 + SED displayed a lower type IIa fibre proportion vs. YA. MA-SED and 65 + SED displayed a higher hybrid type IIa/IIx fibre proportion vs. YA. Sedentary and pre-frail, but not active, men displayed lower mitochondrial content irrespective of fibre type vs. YA. 65 + SED, but not 65 + ACT, displayed a higher lipid content in type I fibres vs. YA. Finally, mitochondrial content, but not lipid content, was positively correlated with indices of muscle function, functional capacity, and insulin sensitivity across all subjects.
Conclusions
Taken altogether, our results indicate that ageing in sedentary men is associated with (i) complex changes in muscle phenotype preferentially affecting type IIa fibres; (ii) a decline in mitochondrial content affecting all fibre types; and (iii) an increase in lipid content in type I fibres. They also indicate that physical activity partially protects from the effects of ageing on muscle phenotype, mitochondrial content, and lipid accumulation. No skeletal specific muscle phenotype of pre-frailty was observed.

 

 

St-Jean-Pelletier, F., Pion, C. H., Leduc-Gaudet, J. -P., Sgarioto, N., Zovilé, I., Barbat-Artigas, S., Reynaud, O., Alkaterji, F., Lemieux, F. C., Grenon, A., Gaudreau, P., Hepple, R. T., Chevalier, S., Belanger, M., Morais, J. A., Aubertin-Leheudre, M., and Gouspillou, G. (2016) The impact of ageing, physical activity, and pre-frailty on skeletal muscle phenotype, mitochondrial content, and intramyocellular lipids in men. Journal of Cachexia, Sarcopenia and Muscle, 8: 213–228. doi: 10.1002/jcsm.12139.

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     Page 229–237

Richard Matthew Dodds, Antoneta Granic, Karen Davies, Thomas B. L. Kirkwood, Carol Jagger, Avan Aihie Sayer

Prevalence and incidence of sarcopenia in the very old: findings from the Newcastle 85+ StudyIntroduction
Recognition that an older person has sarcopenia is important because this condition is linked to a range of adverse outcomes. Sarcopenia becomes increasingly common with age, and yet there are few data concerning its descriptive epidemiology in the very old (aged 85 years and above). Our aims were to describe risk factors for sarcopenia and estimate its prevalence and incidence in a British sample of the very old.
Methods
We used data from two waves (2006/07 and 2009/10) of the Newcastle 85+ Study, a cohort born in 1921 and registered with a Newcastle/North Tyneside general practice. We assessed sarcopenia status using the European Working Group on Sarcopenia in Older People (EWGSOP) definition. Grip strength was measured using a Takei digital dynamometer (Takei Scientific Instruments Ltd., Niigata, Japan), gait speed was calculated from the Timed Up and Go test, and lean mass was estimated using a Tanita-305 body fat analyzer. We used logistic regression to examine associations between risk factors for prevalent sarcopenia at baseline and incident sarcopenia at follow-up.
Results
European Working Group on Sarcopenia in Older People sarcopenia was present in 21% of participants at baseline [149/719 participants, mean age 85.5 (0.4) years]. Many participants had either slow gait speed or weak grip strength (74.3%), and hence measurement of muscle mass was frequently indicated by the EWGSOP definition. Incidence data were available for 302 participants, and the incident rate was 3.7 cases per 100 person years at risk. Low Standardized Mini-Mental State Examination, lower occupational social class, and shorter duration of education were associated with sarcopenia at baseline, while low muscle mass was associated with incident sarcopenia. Low body mass index (BMI) was a risk factor for both in a graded fashion, with each unit decrease associated with increased odds of prevalent [odds ratio (OR) 1.29, 95% confidence interval (CI): 1.21, 1.37] and incident (OR 1.20, 95% CI: 1.08, 1.33) sarcopenia.
Conclusions
To our knowledge, this is the first study to describe prevalence and incidence of EWGSOP sarcopenia in the very old. Low BMI was a risk factor for both current and future sarcopenia; indeed, there was some evidence that low BMI may be a reasonable proxy for low lean mass. Overall, the high prevalence of sarcopenia among the very old suggests that this group should be a focus for future research.

 

Dodds, R. M., Granic, A., Davies, K., Kirkwood, T. B. L., Jagger, C., and Sayer, A. A. (2016) Prevalence and incidence of sarcopenia in the very old: findings from the Newcastle 85+ Study. Journal of Cachexia, Sarcopenia and Muscle, 8; 229–237. doi: 10.1002/jcsm.12157.

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     Page 238–244

Charlotte Beaudart, Emmanuel Biver, Jean-Yves Reginster, René Rizzoli, Yves Rolland, Ivan Bautmans, Jean Petermans, Sophie Gillain, Fanny Buckinx, Nadia Dardenne, Olivier Bruyère

Validation of the SarQoL®, a specific health-related quality of life questionnaire for SarcopeniaBackground
A specific self-administrated health-related quality of life questionnaire for sarcopenia, the Sarcopenia and Quality Of Life (SarQoL®), has been recently developed. This questionnaire is composed of 55 items translated into 22 questions and organized into seven domains of quality of life. The objective of the present work is to evaluate the psychometric properties (discriminative power, validity, reliability, floor and ceiling effects) of the SarQoL® questionnaire.
Methods
Sarcopenic subjects were recruited in an outpatient clinic in Liège, Belgium and were diagnosed according to the algorithm developed by the European Working Group on Sarcopenia in Older People. We compared the score of the SarQoL® between sarcopenic and non-sarcopenic subjects using a logistic regression after adjustment for potential confounding variables. Internal consistency reliability was determined using Cronbach's alpha coefficient; construct validity was assessed using convergent and divergent validities. Test–retest reliability was verified after a two-week interval using the intra-class correlation coefficient (ICC). At last, floor and ceiling effects were also tested.
Results
A total of 296 subjects with a median age of 73.3 (68.9–78.6) years were recruited for this study. Among them, 43 were diagnosed sarcopenic. After adjustment for potential confounding factors, the total score and the scores of the different dimensions of the SarQoL® questionnaire were significantly lower for sarcopenic than for non-sarcopenic subjects (54.7 (45.9–66.3) for sarcopenic vs. 67.8 (57.3 – 79.0) for non sarcopenic, OR 0.93 (95%CI 0.90–0.96)). Regarding internal consistency, the Cronbach's alpha coefficient was 0.87. The SarQoL® questionnaire data showed good correlation with some domains of the Short-Form 36 (SF-36) and the EuroQoL 5-dimension (EQ-5D) questionnaires and with the mobility test. An excellent agreement between the test and the retest was found with an ICC of 0.91 (95% CI 0.82–0.95). At last, neither floor nor ceiling effects were detected.
Conclusions
The SarQoL® questionnaire is valid, consistent, and reliable and can therefore be recommended for clinical and research purposes. However, its sensitivity to change needs to be assessed in future longitudinal studies.

 

Beaudart, C., Biver, E., Reginster, J. -Y., Rizzoli, R., Rolland, Y., Bautmans, I., Petermans, J., Gillain, S., Buckinx, F., Dardenne, N., and Bruyère, O. (2016) Validation of the SarQoL®, a specific health-related quality of life questionnaire for Sarcopenia. Journal of Cachexia, Sarcopenia and Muscle, 8: 238–244. doi: 10.1002/jcsm.12149.

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     Page 245–250

Leandro dos Santos, Edilson S. Cyrino, Melissa Antunes, Diana A. Santos, Luís B. Sardinha

Sarcopenia and physical independence in older adults: the independent and synergic role of muscle mass and muscle functionBackground
The loss of skeletal muscle mass (MM) or muscle function (MF) alone increases the risk for losing physical independence in older adults. We aimed to examine the independent and synergic associations of low MM and low MF, both criteria of sarcopenia, with the risk for losing projected physical independence in later life (+90?years old).
Methods
Cross-sectional analyses were conducted in 3493 non-institutionalized older adults (1166 males). Physical independence was assessed with a 12-item composite physical function scale. Logistic regression was used to estimate the odds-ratio (OR) for being at risk for losing physical independence.
Results
Approximately 30% of the participants were at risk for losing physical independence at 90?years of age. Independent analysis demonstrated that participants with low MM had 1.65 (95%CI: 1.27–2.31) increased odds for being at risk for losing physical independence and participants with low MF had 6.19 (95%CI 5.08–7.53) increased odds for being at risk. Jointly, having a low MM and a low MF increased the risk for losing physical independence to 12.28 (95%CI 7.95 to 18.96).
Conclusions
Although low MM represents a risk factor for losing physical independence, low MF seems to play a more dominant role in this relationship, with the presence of both sarcopenia criteria representing a substantial risk for losing physical independence in later life.

 

dos Santos, L., Cyrino, E. S., Antunes, M., Santos, D. A., and Sardinha, L. B. (2016) Sarcopenia and physical independence in older adults: the independent and synergic role of muscle mass and muscle function. Journal of Cachexia, Sarcopenia and Muscle, 8; 245–250. doi: 10.1002/jcsm.12160.

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     Page 251–258

Ming Yang, Xiaoyi Hu, Haozhong Wang, Lei Zhang, Qiukui Hao, Birong Dong

Sarcopenia predicts readmission and mortality in elderly patients in acute care wards: a prospective studyObjectives
The aim of this study is to assess the prevalence of sarcopenia and investigate the associations between sarcopenia and long-term mortality and readmission in a population of elderly inpatients in acute care wards.
Methods
We conducted a prospective observational study in the acute care wards of a teaching hospital in western China. The muscle mass was estimated according to a previously validated anthropometric equation. Handgrip strength was measured with a handheld dynamometer, and physical performance was measured via a 4 m walking test. Sarcopenia was defined according to the recommended diagnostic algorithm of the Asia Working Group for Sarcopenia. The survival status and readmission information were obtained via telephone interviews at 12, 24, and 36 months during the 3 year follow-up period following the baseline investigation.
Results
Two hundred and eighty-eight participants (mean age: 81.1 ± 6.6 years) were included. Forty-nine participants (17.0%) were identified as having sarcopenia. This condition was similar in men and women (16.9% vs. 17.5%, respectively, P = 0.915). During the 3 year follow-up period, 49 men (22.7%) and 9 women (16.4%) died (P = 0.307). The mortality of sarcopenic participants was significantly increased compared with non-sarcopenic participants (40.8% vs. 17.1%, respectively, P < 0.001). After adjusting for age, sex and other confounders, sarcopenia was an independent predictor of 3 year mortality (adjusted hazard ratio: 2.49; 95% confidential interval: 1.25–4.95) and readmission (adjusted hazard ratio: 1.81; 95% confidential interval: 1.17–2.80).
Conclusions
Sarcopenia, which is evaluated by a combination of anthropometric measures, gait speed, and handgrip strength, is valuable to predict hospital readmission and long-term mortality in elderly patients in acute care wards.


Yang, M., Hu, X., Wang, H., Zhang, L., Hao, Q., and Dong, B. (2016) Sarcopenia predicts readmission and mortality in elderly patients in acute care wards: a prospective study. Journal of Cachexia, Sarcopenia and Muscle, 8; 251–258. doi: 10.1002/jcsm.12163.

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     Page 259–266

Jinhee Kim, Yunhwan Lee, Seunghee Kye, Yoon-Sok Chung, Okhee Lee

Association of serum vitamin D with osteosarcopenic obesity: Korea National Health and Nutrition Examination Survey 2008–2010Background
Serum vitamin D levels have been reported to be associated with individual components of body composition. However, the relationship between serum vitamin D and combined indices of adverse body composition is largely unknown. This cross-sectional study examined the association between serum vitamin D and osteosarcopenic obesity in a nationally representative sample of middle-aged and older adults.
Methods
We analysed the Korea National Health and Nutrition Examination Surveys (IV and V) conducted in 2008–2010, consisting of 5908 (2485 men, 3423 women) aged =?50?years. Serum vitamin D levels were determined by radioimmunoassay, and body composition was evaluated by dual-energy x-ray absorptiometry. The association between serum vitamin D levels and the number of abnormalities in body composition, including osteosarcopenic obesity, a low bone and muscle mass with concurrent high fat mass, was analysed by multinomial logistic regression adjusting for covariates.
Results
In men, after controlling for covariates, higher vitamin D levels were associated with a significantly reduced likelihood of the number of phenotypes of adverse body composition (P for trend?<?0.05). Those in the highest tertile group of serum vitamin D levels, compared with those in the lowest tertile, were less likely to have adverse body composition, numbering one (odds ratio [OR]?=?0.67, 95% confidence interval [CI]: 0.49, 0.92), two (OR?=?0.49, 95% CI: 0.33, 0.73), and three (osteosarcopenic obesity; OR?=?0.42, 95% CI: 0.26, 0.67). In women, those in the highest tertile group of serum vitamin D levels, compared with those in the lowest tertile, were less likely to have osteosarcopenic obesity (OR?=?0.55, 95% CI: 0.33, 0.93). Vitamin D deficiency (<20?ng/mL) in men was significantly associated with an increased likelihood of a higher number of adverse body composition, especially for osteosarcopenic obesity (OR?=?2.08, 95% CI: 1.42, 3.03). Vitamin D deficient women, compared with those having normal levels of serum vitamin D, were also more likely to demonstrate osteosarcopenic obesity (OR?=?1.99, 95% CI: 1.30, 3.05).
Conclusions
A high serum vitamin D level in mid- and late-life was associated with reduced odds of multiple adverse body composition, especially osteosarcopenic obesity, suggesting potential health benefits of maintaining adequate levels of vitamin D.

 

Kim, J., Lee, Y., Kye, S., Chung, Y. -S., and Lee, O. (2016) Association of serum vitamin D with osteosarcopenic obesity: Korea National Health and Nutrition Examination Survey 2008–2010. Journal of Cachexia, Sarcopenia and Muscle, 8; 259–266. doi: 10.1002/jcsm.12154.

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     Page 267–276

Tim Snijders, Joshua P. Nederveen, Sophie Joanisse, Marika Leenders, Lex B. Verdijk, Luc J.C. van Loon, Gianni Parise

Muscle fibre capillarization is a critical factor in muscle fibre hypertrophy during resistance exercise training in older menBackground
Adequate muscle fibre perfusion is critical for the maintenance of muscle mass; it is essential in the rapid delivery of oxygen, nutrients and growth factors to the muscle, stimulating muscle fibre growth. Muscle fibre capillarization is known to decrease substantially with advancing age. However, whether (relative) low muscle fibre capillarization negatively impacts the muscle hypertrophic response following resistance exercise training in older adults is unknown.
Methods
Twenty-two healthy older men (71 ± 1 years) performed 24 weeks of progressive resistance type exercise training. To assess the change in muscle fibre characteristics, percutaneous biopsies from the vastus lateralis muscle were taken before and following 12 and 24 weeks of the intervention programme. A comparison was made between participants who had a relatively low type II muscle fibre capillary-to-fibre perimeter exchange index (CFPE; LOW group) and high type II muscle fibre CFPE (HIGH group) at baseline. Type I and type II muscle fibre size, satellite cell, capillary content and distance between satellite cells to the nearest capillary were determined by immunohistochemistry.
Results
Overall, type II muscle fibre size (from 5150 ± 234 to 6719 ± 446 µm2, P < 0.05) and satellite cell content (from 0.058 ± 0.006 to 0.090 ± 0.010 satellite cells per muscle fibre, P  < 0.05) had increased significantly in response to 24 weeks of resistance exercise training. However, these improvements where mainly driven by differences in baseline type II muscle fibre capillarization, whereas muscle fibre size (from 5170 ± 390 to 7133 ± 314 µm2, P < 0.05) and satellite cell content (from 0.059 ± 0.009 to 0.102 ± 0.017 satellite cells per muscle fibre, P  < 0.05) increased significantly in the HIGH group, no significant changes were observed in LOW group following exercise training. No significant changes in type I and type II muscle fibre capillarization were observed in response to 12 and 24 weeks of resistance exercise training in both the LOW and HIGH group.
Conclusions
Type II muscle fibre capillarization at baseline may be a critical factor for allowing muscle fibre hypertrophy to occur during prolonged resistance exercise training in older men.

 

Snijders, T., Nederveen, J. P., Joanisse, S., Leenders, M., Verdijk, L. B., van Loon, L. J. C., and Parise, G. (2016) Muscle fibre capillarization is a critical factor in muscle fibre hypertrophy during resistance exercise training in older men. Journal of Cachexia, Sarcopenia and Muscle, 8; 267–276. doi: 10.1002/jcsm.12137.

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     Page 277–284

Sheng-Chih Huang, Jin-Fu Wu, Suchada Saovieng, Wei-Horng Chien, Ming-Fen Hsu, Xiao-Fei Li, Shin-Da Lee, Chih-Yang Huang, Chih-Yang Huang, Chia-Hua Kuo

Doxorubicin inhibits muscle inflammation after eccentric exerciseBackground
Doxorubicin, a widely used anti-tumour drug, is known to cause muscle loss in cancer patients.
Methods
Following an acute dose of doxorubicin injection (2.5 mg/kg per body weight), we examined macrophage distribution in rat soleus muscle challenged by eccentric exercise (downhill running). Long-term doxorubicin treatment (one injection every 3 days) on muscle mass and survival were also determined.
Results
Under non-exercised condition, increased tumour necrosis factor (TNF)-alpha mRNA and decreased IL-10 mRNA were observed in soleus muscle of doxorubicin-treated rats, compared with saline-treated control rats. However, increases in inflammation score (leukocyte infiltration), nitrotyrosine level, and M1 macrophage (CD68+) invasion in exercised soleus muscle were absent in doxorubicin-treated rats, whereas increased M2 macrophage (CD163+) localization in exercised muscle was less affected by doxorubicin. Despites coenzyme Q (Q10) supplementation significantly elevated TNF-alpha mRNA, nitrotyrosine, and anti-oxidant gamma-glutamylcysteine synthetase (GCS) levels in non-exercised soleus muscle, these pro-inflammatory responses were also abolished in doxorubicin-treated rats. Results from long-term doxorubicin treatment show a significant muscle loss followed by an accelerated death, which cannot be reversed by Q10 supplementation.
Conclusions
(i) Doxorubicin impairs inflammation mechanism by depleting M1 macrophage in exercised skeletal muscle; (ii) Muscle loss and accelerated death during prolonged doxorubicin treatment cannot be reversed by Q10 supplementation.

 

Huang, S. -C., Wu, J. -F., Saovieng, S., Chien, W. -H., Hsu, M. -F., Li, X. -F., Lee, S. -D., Huang, C. -Y., Huang, C. -Y., and Kuo, C. -H. (2016) Doxorubicin inhibits muscle inflammation after eccentric exercise. Journal of Cachexia, Sarcopenia and Muscle, 8; 277–284. doi: 10.1002/jcsm.12148.

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     Page 285297

Jeroen L.A. van Vugt, Stef Levolger, Arvind Gharbharan, Marcel Koek, Wiro J. Niessen, Jacobus W.A. Burger, Sten P. Willemsen, Ron W.F. de Bruin, Jan N.M. IJzermans

A comparative study of software programmes for cross-sectional skeletal muscle and adipose tissue measurements on abdominal computed tomography scans of rectal cancer patientsBackground
The association between body composition (e.g. sarcopenia or visceral obesity) and treatment outcomes, such as survival, using single-slice computed tomography (CT)-based measurements has recently been studied in various patient groups. These studies have been conducted with different software programmes, each with their specific characteristics, of which the inter-observer, intra-observer, and inter-software correlation are unknown. Therefore, a comparative study was performed.
Methods
Fifty abdominal CT scans were randomly selected from 50 different patients and independently assessed by two observers. Cross-sectional muscle area (CSMA, i.e. rectus abdominis, oblique and transverse abdominal muscles, paraspinal muscles, and the psoas muscle), visceral adipose tissue area (VAT), and subcutaneous adipose tissue area (SAT) were segmented by using standard Hounsfield unit ranges and computed for regions of interest. The inter-software, intra-observer, and inter-observer agreement for CSMA, VAT, and SAT measurements using FatSeg, OsiriX, ImageJ, and sliceOmatic were calculated using intra-class correlation coefficients (ICCs) and Bland–Altman analyses. Cohen's κ was calculated for the agreement of sarcopenia and visceral obesity assessment. The Jaccard similarity coefficient was used to compare the similarity and diversity of measurements.
Results
Bland–Altman analyses and ICC indicated that the CSMA, VAT, and SAT measurements between the different software programmes were highly comparable (ICC 0.979–1.000, P < 0.001). All programmes adequately distinguished between the presence or absence of sarcopenia (κ = 0.88–0.96 for one observer and all κ = 1.00 for all comparisons of the other observer) and visceral obesity (all κ = 1.00). Furthermore, excellent intra-observer (ICC 0.999–1.000, P < 0.001) and inter-observer (ICC 0.998–0.999, P < 0.001) agreement for all software programmes were found. Accordingly, excellent Jaccard similarity coefficients were found for all comparisons (mean ≥ 0.964).
Conclusions
FatSeg, OsiriX, ImageJ, and sliceOmatic showed an excellent agreement for CSMA, VAT, and SAT measurements on abdominal CT scans. Furthermore, excellent inter-observer and intra-observer agreement were achieved. Therefore, results of studies using these different software programmes can reliably be compared.

 


van Vugt, J. L. A., Levolger, S., Gharbharan, A., Koek, M., Niessen, W. J., Burger, J. W. A., Willemsen, S. P., de Bruin, R. W. F., and IJzermans, J. N. M. (2016) A comparative study of software programmes for cross-sectional skeletal muscle and adipose tissue measurements on abdominal computed tomography scans of rectal cancer patients. Journal of Cachexia, Sarcopenia and Muscle, 8; 285297. doi: 10.1002/jcsm.12158.

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     Page 298–304

Michael P. Chu, Jessica Lieffers, Sunita Ghosh, Andrew Belch, Neil S. Chua, Amelie Fontaine, Randeep Sangha, Robert A. Turner, Vickie E. Baracos andMichael B. Sawyer

Skeletal muscle density is an independent predictor of diffuse large B-cell lymphoma outcomes treated with rituximab-based chemoimmunotherapyBackground
While much cancer research focuses on tumours and their microenvironment, malignancies cause widespread physiologic changes. Cancer and treatment-related sarcopenia, measured with quantitative imaging or as a decrease in overall body mass, are indicative of poor prognosis in elderly diffuse large B-cell lymphoma (DLBCL) patients, skeletal muscle radiodensity (SMD) may be a better prognostic marker. SMD, a measure of muscle radiation attenuation on CT imaging, is more prognostic than sarcopenia or International Prognostic Index (IPI) scores in follicular lymphoma and multiple solid organ malignancies. Low SMD appears to correlate with fat accumulation in muscle and is associated with inflammation. This study set out to examine SMD's prognostic ability in DLBCL.
Methods
All DLBCL patients treated with rituximab-containing therapy between 2004 and 2009 were compared to determine SMD's prognostic ability in this single centre, retrospective study. Pre-treatment CT scans were used to measure SMD and muscle cross-sectional area. Primary endpoints included progression free (PFS) and overall survival (OS) while objective response rates (ORR) were secondary.
Results
Of 224 evaluable patients, 116 were identified as having low SMD. Low SMD predicted poorer 5 year PFS, 60 vs. 81% (p = 0.001) and OS, 58 vs. 86% (p < 0.0001). SMD's prognostic ability retained significance in multivariate analysis taking into consideration the Revised International Prognostic Index (R-IPI) and sex. Although high SMD was not predictive of ORR (95.4 vs. 91.4%, p = 0.17), it was strongly associated with radiographic complete response (85 vs. 66%, p = 0.0007). Contrary to previous findings, sarcopenia did not predict for poorer OS but suggested improved OS in elderly DLBCL patients (HR 0.38, p = 0.01).
Conclusions
SMD is a novel prognostic (and potentially treatment predictive) marker independent of R-IPI in DLBCL. It presents an inexpensive yet complementary assessment to R-IPI for prognosticating DLBCL outcomes.

 


Chu, M. P., Lieffers, J., Ghosh, S., Belch, A., Chua, N. S., Fontaine, A., Sangha, R., Turner, R. A., Baracos, V. E., and Sawyer, M. B. (2016) Skeletal muscle density is an independent predictor of diffuse large B-cell lymphoma outcomes treated with rituximab-based chemoimmunotherapy. Journal of Cachexia, Sarcopenia and Muscle, 8; 298–304. doi: 10.1002/jcsm.12161.

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     Page 305–316

Oliver Klassen, Martina E. Schmidt, Cornelia M. Ulrich, Andreas Schneeweiss, Karin Potthoff, Karen Steindorf, Joachim Wiskemann

Muscle strength in breast cancer patients receiving different treatment regimesBackground
Muscle dysfunction and sarcopenia have been associated with poor performance status, an increased mortality risk, and greater side effects in oncologic patients. However, little is known about how performance is affected by cancer therapy. We investigated muscle strength in breast cancer patients in different adjuvant treatment settings and also compared it with data from healthy individuals.
Methods
Breast cancer patients (N = 255) from two randomized controlled exercise trials, staged 0–III and aged 54.4 ± 9.4 years, were categorized into four groups according to their treatment status. In a cross-sectional design, muscle function was assessed bilaterally by isokinetic dynamometry (0°, 60°, 180°/s) as maximal voluntary isometric contraction (MVIC) and maximal isokinetic peak torque (MIPT) in shoulder rotators and knee flexors and extensors. Additionally, muscular fatigue index (FI%) and shoulder flexibility were evaluated. Healthy women (N = 26), aged 53.3 ± 9.8 years, were tested using the same method. Analysis of covariance was used to estimate the impact of different cancer treatments on skeletal muscle function with adjustment for various clinical and socio-demographic factors.
Results
Consistently, lower muscle strength was measured in shoulder and knee strength in patients after chemotherapy. On average, patients had up to 25% lower strength in lower extremities and 12–16% in upper extremities in MVIC and MIPT during cancer treatment compared with healthy women. No substantial difference between patient groups in shoulder strength, but significantly lower shoulder flexibility in patients with radical mastectomy was measured. Chemotherapy-treated patients had consistently higher FI%. No serious adverse events were reported.
Conclusions
Breast cancer patients showed markedly impaired muscle strength and joint dysfunctions before and after anticancer treatment. The significant differences between patients and healthy individuals underline the need of exercise therapy as early as possible in order to prevent or counteract the loss of muscle function after curative surgery as well as the consequences of neo-/adjuvant chemotherapy.

 

Klassen, O., Schmidt, M. E., Ulrich, C. M., Schneeweiss, A., Potthoff, K., Steindorf, K., and Wiskemann, J. (2016) Muscle strength in breast cancer patients receiving different treatment regimes. Journal of Cachexia, Sarcopenia and Muscle, 8; 305–316. doi: 10.1002/jcsm.12165.

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     Page 317–326

David P. J. van Dijk, Maikel J. A. M. Bakens, Mariëlle M. E. Coolsen, Sander S. Rensen, Ronald M. van Dam, Martijn J. L. Bours, Matty P. Weijenberg, Cornelis H. C. Dejong, Steven W. M. Olde Damink

Low skeletal muscle radiation attenuation and visceral adiposity are associated with overall survival and surgical site infections in patients with pancreatic cancerBackground
Cancer cachexia and skeletal muscle wasting are related to poor survival. In this study, quantitative body composition measurements using computed tomography (CT) were investigated in relation to survival, post-operative complications, and surgical site infections in surgical patients with cancer of the head of the pancreas.
Methods
A prospective cohort of 199 patients with cancer of the head of the pancreas was analysed by CT imaging at the L3 level to determine (i) muscle radiation attenuation (average Hounsfield units of total L3 skeletal muscle); (ii) visceral adipose tissue area; (iii) subcutaneous adipose tissue area; (iv) intermuscular adipose tissue area; and (v) skeletal muscle area. Sex-specific cut-offs were determined at the lower tertile for muscle radiation attenuation and skeletal muscle area and the higher tertile for adipose tissues. These variables of body composition were related to overall survival, severe post-operative complications (Dindo–Clavien ≥ 3), and surgical site infections (wounds inspected daily by an independent trial nurse) using Cox-regression analysis and multivariable logistic regression analysis, respectively.
Results
Low muscle radiation attenuation was associated with shorter survival in comparison with moderate and high muscle radiation attenuation [median survival 10.8 (95% CI: 8.8–12.8) vs. 17.4 (95% CI: 14.7–20.1), and 18.5 (95% CI: 9.2–27.8) months, respectively; P < 0.008]. Patient subgroups with high muscle radiation attenuation combined with either low visceral adipose tissue or age <70 years had longer survival than other subgroups (P = 0.011 and P = 0.001, respectively). Muscle radiation attenuation was inversely correlated with intermuscular adipose tissue (rp = −0.697, P < 0.001). High visceral adipose tissue was associated with an increased surgical site infection rate, OR: 2.4 (95% CI: 1.1–5.3; P = 0.027).
Conclusions
Low muscle radiation attenuation was associated with reduced survival, and high visceral adiposity was associated with an increase in surgical site infections. The strong correlation between muscle radiation attenuation and intermuscular adipose tissue suggests the presence of ectopic fat in muscle, warranting further investigation. CT image analysis could be implemented in pre-operative risk assessment to assist in treatment decision-making.

 

 

van Dijk, D. P. J., Bakens, M. J. A. M., Coolsen, M. M. E., Rensen, S. S., van Dam, R. M., Bours, M. J. L., Weijenberg, M. P., Dejong, C. H. C., and Olde Damink, S. W. M. (2016) Low skeletal muscle radiation attenuation and visceral adiposity are associated with overall survival and surgical site infections in patients with pancreatic cancer. Journal of Cachexia, Sarcopenia and Muscle, 8; 317–326. doi: 10.1002/jcsm.12155.

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     Page 302–312

Rizhen Yu, Ji-an Chen, Jing Xu, Jin Cao, Yanlin Wang, Sandhya S. Thomas, Zhaoyong Hu

Suppression of muscle wasting by the plant-derived compound ursolic acid in a model of chronic kidney diseaseBackground
Muscle wasting in chronic kidney disease (CKD) and other catabolic disorders contributes to morbidity and mortality, and there are no therapeutic interventions that regularly and safely block losses of muscle mass. We have obtained evidence that impaired IGF-1/insulin signalling and increases in glucocorticoids, myostatin and/or inflammatory cytokines that contribute to the development of muscle wasting in catabolic disorders by activating protein degradation.
Methods
Using in vitro and in vivo models of muscle wasting associated with CKD or dexamethasone administration, we measured protein synthesis and degradation and examined mechanisms by which ursolic acid, derived from plants, could block the loss of muscle mass stimulated by CKD or excessive levels of dexamethasone.
Results
Using cultured C2C12 myotubes to study muscle wasting, we found that exposure to glucocorticoids cause loss of cell proteins plus an increase in myostatin; both responses are significantly suppressed by ursolic acid. Results from promoter and ChIP assays demonstrated a mechanism involving ursolic acid blockade of myostatin promoter activity that is related to CEBP/δ expression. In mouse models of CKD-induced or dexamethasone-induced muscle wasting, we found that ursolic acid blocked the loss of muscle mass by stimulating protein synthesis and decreasing protein degradation. These beneficial responses included decreased expression of myostatin and inflammatory cytokines (e.g. TGF-β, IL-6 and TNFα), which are initiators of muscle-specific ubiquitin-E3 ligases (e.g. Atrogin-1, MuRF-1 and MUSA1).
Conclusions
Ursolic acid improves CKD-induced muscle mass by suppressing the expression of myostatin and inflammatory cytokines via increasing protein synthesis and reducing proteolysis.

 

Yu, R., Chen, J., Xu, J., Cao, J., Wang, Y., Thomas, S. S., and Hu, Z. (2016) Suppression of muscle wasting by the plant-derived compound ursolic acid in a model of chronic kidney disease. Journal of Cachexia, Sarcopenia and Muscle, 8; 302–312. doi: 10.1002/jcsm.12162.

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