Volume 8 / Number 3 / June 2017

 

     Page 345–348

Lidia Santarpia, Franco Contaldo, Fabrizio Pasanisi

Dietary protein content for an optimal diet: a clinical viewThe dietary protein role in different clinical nutritional conditions and some physio-pathological perspectives is a current and hot topic to discuss. Recent Proceedings of the Protein Summit 2, joining more than 60 nutrition scientists, health experts, and nutrition educators, suggest to increase plant but, in particular, animal protein intake because richer in leucine and consequently more effective to influence anabolic protein metabolism. The Panel conclusions are in apparent contradiction with the nutritional ecology statements, which strongly sustain the reduction of animal origin foods in the human diet and are currently concerned about the excessive, mainly animal protein intake in western and westernized Countries. In conclusion, it is time to carefully evaluate protein and aminoacid intake accurately considering quality, digestibility, daily distribution and individual characteristics.

 

Santarpia, L., Contaldo, F., and Pasanisi, F. (2017) Dietary protein content for an optimal diet: a clinical view. Journal of Cachexia, Sarcopenia and Muscle, 8: 345–348. doi: 10.1002/jcsm.12217.

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     Page 349–369

Kerstin Boengler, Maik Kosiol, Manuel Mayr, Rainer Schulz, Susanne Rohrbach

Mitochondria and ageing: role in heart, skeletal muscle and adipose tissueAge is the most important risk factor for most diseases. Mitochondria play a central role in bioenergetics and metabolism. In addition, several lines of evidence indicate the impact of mitochondria in lifespan determination and ageing. The best-known hypothesis to explain ageing is the free radical theory, which proposes that cells, organs, and organisms age because they accumulate reactive oxygen species (ROS) damage over time. Mitochondria play a central role as the principle source of intracellular ROS, which are mainly formed at the level of complex I and III of the respiratory chain. Dysfunctional mitochondria generating less ATP have been observed in various aged organs. Mitochondrial dysfunction comprises different features including reduced mitochondrial content, altered mitochondrial morphology, reduced activity of the complexes of the electron transport chain, opening of the mitochondrial permeability transition pore, and increased ROS formation. Furthermore, abnormalities in mitochondrial quality control or defects in mitochondrial dynamics have also been linked to senescence. Among the tissues affected by mitochondrial dysfunction are those with a high-energy demand and thus high mitochondrial content. Therefore, the present review focuses on the impact of mitochondria in the ageing process of heart and skeletal muscle. In this article, we review different aspects of mitochondrial dysfunction and discuss potential therapeutic strategies to improve mitochondrial function. Finally, novel aspects of adipose tissue biology and their involvement in the ageing process are discussed.

 

Boengler, K., Kosiol, M., Mayr, M., Schulz, R., and Rohrbach, S. (2017) Mitochondria and ageing: role in heart, skeletal muscle and adipose tissue. Journal of Cachexia, Sarcopenia and Muscle, 8: 349–369. doi: 10.1002/jcsm.12217.

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     Page 370–385

Aiko Inoue, Xian Wu Cheng, Zhe Huang, Lina Hu, Ryosuke Kikuchi, Haiying Jiang, Limei Piao, Takeshi Sasaki, Kohji Itakura, Hongxian Wu, Guangxian Zhao, Yanna Lei, Guang Yang, Enbo Zhu, Xiang Li, Kohji Sato, Teruhiko Koike, Masafumi Kuzuya

Exercise restores muscle stem cell mobilization, regenerative capacity and muscle metabolic alterations via adiponectin/AdipoR1 activation in SAMP10 miceBackground
Exercise train (ET) stimulates muscle response in pathological conditions, including aging. The molecular mechanisms by which exercise improves impaired adiponectin/adiponectin receptor 1 (AdipoR1)-related muscle actions associated with aging are poorly understood. Here we observed that in a senescence-accelerated mouse prone 10 (SAMP10) model, long-term ET modulated muscle-regenerative actions.
Methods
25-week-old male SAMP10 mice were randomly assigned to the control and the ET (45 min/time, 3/week) groups for 4 months. Mice that were maintained in a sedentary condition served controls.
Results
ET ameliorated aging-related muscle changes in microstructure, mitochondria, and performance. The amounts of proteins or mRNAs for p-AMPKα, p-Akt, p-ERK1/2, p-mTOR, Bcl-XL, p-FoxO3, peroxisome proliferators-activated receptor-γ coactivator, adiponectin receptor1 (adpoR1), and cytochrome c oxidase-IV, and the numbers of CD34+/integrin-α7+ muscle stem cells (MuSCs) and proliferating cells in the muscles and bone-marrow were enhanced by ET, whereas the levels of p-GSK-3α and gp91phox proteins and apoptotic cells were reduced by ET. The ET also resulted in increased levels of plasma adiponectin and the numbers of bone-marrow (BM)-derived circulating CD34+/integrin-α7+ MuSCs and their functions. Integrin-α7+ MuSCs of exercised mice had improved changes of those beneficial molecules. These ET-mediated aged muscle benefits were diminished by adiponectin and AdipoR1 blocking as well as AMPK inhibition. Finally, recombinant mouse adiponectin enhanced AMPK and mTOR phosphorylations in BM-derived integrin-α7+ cells.
Conclusions
These findings suggest that ET can improve aging-related impairments of BM-derived MuSC regenerative capacity and muscle metabolic alterations via an AMPK-dependent mechanism that is mediated by an adiponectin/AdipoR1 axis in SAMP10 mice.

 


Inoue, A., Cheng, X. W., Huang, Z., Hu, L., Kikuchi, R., Jiang, H., Piao, L., Sasaki, T., Itakura, K., Wu, H., Zhao, G., Lei, Y., Yang, G., Zhu, E., Li, X., Sato, K., Koike, T., and Kuzuya, M. (2016) Exercise restores muscle stem cell mobilization, regenerative capacity and muscle metabolic alterations via adiponectin/AdipoR1 activation in SAMP10 mice. Journal of Cachexia, Sarcopenia and Muscle, 8: 370–385. doi: 10.1002/jcsm.12217.

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     Page 386–404

Elena Conte, Giulia Maria Camerino, Antonietta Mele, Michela De Bellis, Sabata Pierno, Francesco Rana, Adriano Fonzino, Roberta Caloiero, Laura Rizzi, Elena Bresciani, Khoubaib Ben Haj Salah, Jean-Alain Fehrentz, Jean Martinez, Arcangela Giustino, Maria Addolorata Mariggiò, Mauro Coluccia, Domenico Tricarico, Marcello Diego Lograno, Annamaria De Luca, Antonio Torsello, Diana Conte, Antonella Liantonio

Growth hormone secretagogues prevent dysregulation of skeletal muscle calcium homeostasis in a rat model of cisplatin-induced cachexiaBackground
Cachexia is a wasting condition associated with cancer types and, at the same time, is a serious and dose-limiting side effect of cancer chemotherapy. Skeletal muscle loss is one of the main characteristics of cachexia that significantly contributes to the functional muscle impairment. Calcium-dependent signaling pathways are believed to play an important role in skeletal muscle decline observed in cachexia, but whether intracellular calcium homeostasis is affected in this situation remains uncertain. Growth hormone secretagogues (GHS), a family of synthetic agonists of ghrelin receptor (GHS-R1a), are being developed as a therapeutic option for cancer cachexia syndrome; however, the exact mechanism by which GHS interfere with skeletal muscle is not fully understood.
Methods
By a multidisciplinary approach ranging from cytofluorometry and electrophysiology to gene expression and histology, we characterized the calcium homeostasis in fast-twitch extensor digitorum longus (EDL) muscle of adult rats with cisplatin-induced cachexia and established the potential beneficial effects of two GHS (hexarelin and JMV2894) at this level. Additionally, in vivo measures of grip strength and of ultrasonography recordings allowed us to evaluate the functional impact of GHS therapeutic intervention.
Results
Cisplatin-treated EDL muscle fibres were characterized by a ~18% significant reduction of the muscle weight and fibre diameter together with an up-regulation of atrogin1/Murf-1 genes and a down-regulation of Pgc1-a gene, all indexes of muscle atrophy, and by a two-fold increase in resting intracellular calcium, [Ca2+]i, compared with control rats. Moreover, the amplitude of the calcium transient induced by caffeine or depolarizing high potassium solution as well as the store-operated calcium entry were ~50% significantly reduced in cisplatin-treated rats. Calcium homeostasis dysregulation parallels with changes of functional ex vivo (excitability and resting macroscopic conductance) and in vivo (forelimb force and muscle volume) outcomes in cachectic animals. Administration of hexarelin or JMV2894 markedly reduced the cisplatin-induced alteration of calcium homeostasis by both common as well as drug-specific mechanisms of action. This effect correlated with muscle function preservation as well as amelioration of various atrophic indexes, thus supporting the functional impact of GHS activity on calcium homeostasis.
Conclusions
Our findings provide a direct evidence that a dysregulation of calcium homeostasis plays a key role in cisplatin-induced model of cachexia gaining insight into the etiopathogenesis of this form of muscle wasting. Furthermore, our demonstration that GHS administration efficaciously prevents cisplatin-induced calcium homeostasis alteration contributes to elucidate the mechanism of action through which GHS could potentially ameliorate chemotherapy-associated cachexia.

 


Conte, E., Camerino, G. M., Mele, A., De Bellis, M., Pierno, S., Rana, F., Fonzino, A., Caloiero, R., Rizzi, L., Bresciani, E., Ben Haj Salah, K., Fehrentz, J.-A., Martinez, J., Giustino, A., Mariggiò, M. A., Coluccia, M., Tricarico, D., Lograno, M. D., De Luca, A., Torsello, A., Conte, D., and Liantonio, A. (2017) Growth hormone secretagogues prevent dysregulation of skeletal muscle calcium homeostasis in a rat model of cisplatin-induced cachexia. JJournal of Cachexia, Sarcopenia and Muscle, 8: 386–404. doi: 10.1002/jcsm.12217.

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     Page 405–416

Ashok Narasimhan, Sunita Ghosh, Cynthia Stretch, Russell Greiner, Oliver F. Bathe, Vickie Baracos, Sambasivarao Damaraju

Small RNAome profiling from human skeletal muscle: novel miRNAs and their targets associated with cancer cachexiaBackground
MicroRNAs (miRs) are small non-coding RNAs that regulate gene (mRNA) expression. Although the pathological role of miRs have been studied in muscle wasting conditions such as myotonic and muscular dystrophy, their roles in cancer cachexia (CC) are still emerging.
Objectives
The objectives are (i) to profile human skeletal muscle expressed miRs; (ii) to identify differentially expressed (DE) miRs between cachectic and non-cachectic cancer patients; (iii) to identify mRNA targets for the DE miRs to gain mechanistic insights; and (iv) to investigate if miRs show potential prognostic and predictive value.
Methods
Study subjects were classified based on the international consensus diagnostic criteria for CC. Forty-two cancer patients were included, of which 22 were cachectic cases and 20 were non-cachectic cancer controls. Total RNA isolated from muscle biopsies were subjected to next-generation sequencing.
Results
A total of 777 miRs were profiled, and 82 miRs with read counts of =5 in 80% of samples were retained for analysis. We identified eight DE miRs (up-regulated, fold change of =1.4 at P?<?0.05). A total of 191 potential mRNA targets were identified for the DE miRs using previously described human skeletal muscle mRNA expression data (n?=?90), and a majority of them were also confirmed in an independent mRNA transcriptome dataset. Ingenuity pathway analysis identified pathways related to myogenesis and inflammation. qRT-PCR analysis of representative miRs showed similar direction of effect (P?<?0.05), as observed in next-generation sequencing. The identified miRs also showed prognostic and predictive value.
Conclusions
In all, we identified eight novel miRs associated with CC.

 

Narasimhan, A., Ghosh, S., Stretch, C., Greiner, R., Bathe, O. F., Baracos, V., and Damaraju, S. (2017) Small RNAome profiling from human skeletal muscle: novel miRNAs and their targets associated with cancer cachexia. Journal of Cachexia, Sarcopenia and Muscle, 8: 405–416. doi: 10.1002/jcsm.12217.

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     Page 417–427

Tito Borner, Myrtha Arnold, Johan Ruud, Samuel N. Breit, Wolfgang Langhans, Thomas A. Lutz, Anders Blomqvist, Thomas Riediger

Anorexia-cachexia syndrome in hepatoma tumour-bearing rats requires the area postrema but not vagal afferents and is paralleled by increased MIC-1/GDF15Background
The cancer-anorexia-cachexia syndrome (CACS) negatively affects survival and therapy success in cancer patients. Inflammatory mediators and tumour-derived factors are thought to play an important role in the aetiology of CACS. However, the central and peripheral mechanisms contributing to CACS are insufficiently understood. The area postrema (AP) and the nucleus tractus solitarii are two important brainstem centres for the control of eating during acute sickness conditions. Recently, the tumour-derived macrophage inhibitory cytokine-1 (MIC-1) emerged as a possible mediator of cancer anorexia because lesions of these brainstem areas attenuated the anorectic effect of exogenous MIC-1 in mice.
Methods
Using a rat hepatoma tumour model, we examined the roles of the AP and of vagal afferents in the mediation of CACS. Specifically, we investigated whether a lesion of the AP (APX) or subdiaphragmatic vagal deafferentation (SDA) attenuate anorexia, body weight, muscle, and fat loss. Moreover, we analysed MIC-1 levels in this tumour model and their correlation with tumour size and the severity of the anorectic response.
Results
In tumour-bearing sham-operated animals mean daily food intake significantly decreased. The anorectic response was paralleled by a significant loss of body weight and muscle mass. APX rats were protected against anorexia, body weight loss, and muscle atrophy after tumour induction. In contrast, subdiaphragmatic vagal deafferentation did not attenuate cancer-induced anorexia or body weight loss. Tumour-bearing rats had substantially increased MIC-1 levels, which positively correlated with tumour size and cancer progression and negatively correlated with food intake.
Conclusions
These findings demonstrate the importance of the AP in the mediation of cancer-dependent anorexia and body weight loss and support a pathological role of MIC-1 as a tumour-derived factor mediating CACS, possibly via an AP-dependent action.

 

 

Borner, T., Arnold, M., Ruud, J., Breit, S. N., Langhans, W., Lutz, T. A., Blomqvist, A., and Riediger, T. (2017) Anorexia-cachexia syndrome in hepatoma tumour-bearing rats requires the area postrema but not vagal afferents and is paralleled by increased MIC-1/GDF15. Journal of Cachexia, Sarcopenia and Muscle, 8: 417–427. doi: 10.1002/jcsm.12169.

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     Page 428–436

Merry-Lynn Noelle McDonald, Sungho Won, Manuel Mattheisen, Peter J. Castaldi, Michael H. Cho, Erica Rutten, Megan Hardin, Wai-Ki Yip, Stephen I. Rennard, David A. Lomas, Emiel F.M. Wouters, Alvar Agusti, Richard Casaburi, Christoph P. Lange, George O'Connor, Craig P. Hersh, Edwin K. Silverman

Body mass index change in gastrointestinal cancer and chronic obstructive pulmonary disease is associated with Dedicator of Cytokinesis 1Background
There have been a number of candidate gene association studies of cancer cachexia-related traits, but no genome-wide association study (GWAS) has been published to date. Cachexia presents in patients with a number of complex traits, including both cancer and COPD. The objective of the current investigation was to search for a shared genetic aetiology for change in body mass index (?BMI) among cancer and COPD by using GWAS data in the Framingham Heart Study.
Methods
A linear mixed effects model accounting for age, sex, and change in smoking status was used to calculate ?BMI in participants over 40?years of age with three consecutive BMI time points (n?=?4162). Four GWAS of ?BMI using generalized estimating equations were performed among 1085 participants with a cancer diagnosis, 204 with gastrointestinal (GI) cancer, 112 with lung cancer, and 237 with COPD to test for association with 418?365 single-nucleotide polymorphisms (SNPs).
Results
Two SNPs reached a level of genome-wide significance (P?<?5?×?10-8) with ?BMI: (i) rs41526344 within the CNTN4 gene, among COPD cases (ß?=?0.13, P?=?4.3?×?10-8); and (ii) rs4751240 in the gene Dedicator of Cytokinesis 1 (DOCK1) among GI cancer cases (ß?=?0.10, P?=?1.9?×?10-8). The DOCK1 SNP association replicated in the ?BMI GWAS among COPD cases (ßmeta-analyis?=?0.10, Pmeta-analyis?=?9.3?×?10-10). The DOCK1 gene codes for the dedicator of cytokinesis 1 protein, which has a role in myoblast fusion.
Conclusions
In sum, one statistically significant common variant in the DOCK1 gene was associated with ?BMI in GI cancer and COPD cases providing support for at least partially shared aetiology of ?BMI in complex diseases.

 


McDonald, M.-L. N., Won, S., Mattheisen, M., Castaldi, P. J., Cho, M. H., Rutten, E., Hardin, M., Yip, W. -K., Rennard, S. I., Lomas, D. A., Wouters, E. F. M., Agusti, A., Casaburi, R., Lange, C. P., O'Connor, G., Hersh, C. P., and Silverman, E. K. (2017) Body mass index change in gastrointestinal cancer and chronic obstructive pulmonary disease is associated with Dedicator of Cytokinesis 1. Journal of Cachexia, Sarcopenia and Muscle, 8: 428–436. doi: 10.1002/jcsm.12217.

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     Page 437–446

Sorrel T. Burden, Debra J. Gibson, Simon La, James Hill, Mark Pilling, Mattias Soop, Aswatha Ramesh, Chris Todd

Pre-operative oral nutritional supplementation with dietary advice versus dietary advice alone in weight-losing patients with colorectal cancer: single-blind randomized controlled trialBackground
Pre-operative weight loss has been consistently associated with increased post-operative morbidity. The study aims to determine if pre-operative oral nutritional supplements (ONSs) with dietary advice reduce post-operative complications.
Methods
Single-blinded randomized controlled trial. People with colorectal cancer scheduled for surgery with pre-operative weight loss >1?kg/3–6?months were randomized by using stratified blocks (1:1 ratio) in six hospitals (1 November 2013–28 February 2015). Intervention group was given 250?mL/day ONS (10.1?KJ and 0.096?g protein per mL) and dietary advice. Control group received dietary advice alone. Oral nutritional supplements were administered from diagnosis to the day preceding surgery. Research team was masked to group allocation. Primary outcome was patients with one or more surgical site infection (SSI) or chest infection; secondary outcomes included percentage weight loss, total complications, and body composition measurements. Intention-to-treat analysis was performed with both unadjusted and adjusted analyses. A sample size of 88 was required.
Results
Of 101 participants, (55 ONS, 46 controls) 97 had surgery. In intention-to-treat analysis, there were 21/45 (47%) patients with an infection—either an SSI or chest infection in the control group vs. 17/55 (30%) in the ONS group. The odds ratio of a patient incurring either an SSI or chest infection was 0.532 (P?=?0.135 confidence interval 0.232 to 1.218) in the unadjusted analysis and when adjusted for random differences at baseline (age, gender, percentage weight loss, and cancer staging) was 0.341 (P?=?0.031, confidence interval 0.128 to 0.909). Pre-operative percentage weight loss at the first time point after randomization was 4.1% [interquartile range (IQR) 1.7–7.0] in ONS group vs. 6.7% (IQR 2.6–10.8) in controls (Mann–Whitney U P?=?0.021) and post-operatively was 7.4% (IQR 4.3–10.0) in ONS group vs. 10.2% (IQR 5.1–18.5) in controls (P?=?0.016).
Conclusions
Compared with dietary advice alone, ONS resulted in patients having fewer infections and less weight loss following surgery for colorectal cancer. We have demonstrated that pre-operative oral nutritional supplementation can improve clinical outcome in weight losing patients with colorectal cancer.

 


Burden, S. T., Gibson, D. J., Lal, S., Hill, J., Pilling, M., Soop, M., Ramesh, A., and Todd, C. (2017) Pre-operative oral nutritional supplementation with dietary advice versus dietary advice alone in weight-losing patients with colorectal cancer: single-blind randomized controlled trial. Journal of Cachexia, Sarcopenia and Muscle, 8: 437–446. doi: 10.1002/jcsm.12217.

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     Page 447–456

Mariëlle P.K.J. Engelen, V. Suzanne Klimberg, Arianna Allasia, Nicolaas EP Deutz

Presence of early stage cancer does not impair the early protein metabolic response to major surgeryBackground
Combined bilateral mastectomy and reconstruction is a common major surgical procedure in women with breast cancer and in those with a family history of breast cancer. As this large surgical procedure induces muscle protein loss, a preserved anabolic response to nutrition is warranted for optimal recovery. It is unclear whether the presence of early stage cancer negatively affects the protein metabolic response to major surgery as this would mandate perioperative nutritional support.
Methods
In nine women with early stage (Stage II) breast malignancy and nine healthy women with a genetic predisposition to breast cancer undergoing the same large surgical procedure, we examined whether surgery influences the catabolic response to overnight fasting and the anabolic response to nutrition differently. Prior to and within 24?h after combined bilateral mastectomy and reconstruction surgery, whole body protein synthesis and breakdown rates were assessed after overnight fasting and after meal intake by stable isotope methodology to enable the calculation of net protein catabolism in the post-absorptive state and net protein anabolic response to a meal.
Results
Major surgery resulted in an up-regulation of post-absorptive protein synthesis and breakdown rates (P?<?0.001) and lower net protein catabolism (P?<?0.05) and was associated with insulin resistance and increased systemic inflammation (P?<?0.01). Net anabolic response to the meal was reduced after surgery (P?<?0.05) but higher in cancer (P?<?0.05) indicative of a more preserved meal efficiency. The significant relationship between net protein anabolism and the amount of amino acids available in the circulation (R2?=?0.85, P?<?0.001) was independent of the presence of non-cachectic early stage breast cancer or surgery.
Conclusions
The presence of early stage breast cancer does not enhance the normal catabolic response to major surgery or further attenuates the anabolic response to meal intake within 24?h after major surgery in patients with non-cachectic breast cancer. This indicates that the acute anabolic potential to conventional feeding is maintained in non-cachectic early stage breast cancer after major surgery.

 

Engelen, M. P. K. J., Klimberg, V. S., Allasia, A., and Deutz, N. E. (2017) Presence of early stage cancer does not impair the early protein metabolic response to major surgery. Journal of Cachexia, Sarcopenia and Muscle, 8: 447–456. doi: 10.1002/jcsm.12217.

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     Page 457–456

Koji Amano, Isseki Maeda, Tatsuya Morita, Mika Baba, Tomofumi Miura, Takashi Hama, Ichiro Mori, Nobuhisa Nakajima, Tomohiro Nishi, Hiroki Sakurai, Satofumi Shimoyama, Takuya Shinjo, Hiroto Shirayama, Takeshi Yamada, Shigeki Ono, Taketoshi Ozawa, Ryo Yamamoto, Naoki Yamamoto, Hideki Shishido, Hiroya Kinoshita

C-reactive protein, symptoms and activity of daily living in patients with advanced cancer receiving palliative careBackground
The association between C-reactive protein (CRP) level, symptoms, and activities of daily living (ADL) in advanced cancer patients is unclear.
Methods
Secondary data analysis of a multicenter prospective cohort study consisted of 2426 advanced cancer patients referred to palliative care settings was conducted to examine the cross-sectional relationships between CRP level, symptoms, and ADL disabilities. Laboratory data, symptoms, ADL, and manual muscle testing (MMT) results were obtained at baseline. Participants were divided into four groups: low (CRP < 1 mg/dl), moderate (1 = < CRP <5 mg/dl), high (5 = < CRP < 10 mg/dl), and very high CRP (10 mg/dl = < CRP). The proportions of eight symptoms, five ADL disabilities, and three categories of MMT according to the CRP groups were tested by chi-square tests. Multiple-adjusted odd ratios (ORs) were calculated by using ordinal logistic regression after adjustment for age, gender, site of primary cancer, metastatic disease, performance status, chemotherapy, and setting of care.
Results
A total of 1702 patients were analysed. Positive rates of symptoms and ADL disabilities increased with increasing CRP level. In the very high-CRP group, rates of positivity for anorexia, fatigue, and weight loss were 89.8%, 81.0%, and 79.2%, respectively, and over 70% of patients received assistance for bathing, dressing, going to the toilet, and transfer. The grade of MMT also deteriorated with increasing CRP level. Adjusted ORs for the accumulated symptoms significantly increased with increasing CRP level in the moderate-CRP, high-CRP, and very high-CRP groups [1.6 (95% confidence interval 1.2–2.0), P < 0.001; 2.5 (1.9–3.2), P < 0.001; 3.5 (2.7–4.6), P < 0.001, respectively]. Adjusted ORs for the accumulated ADL disabilities significantly increased in the very high-CRP groups [2.1 (1.5–2.9), P < 0.001].
Conclusions
Associations between CRP level, symptoms, and ADL were observed in advanced cancer patients receiving palliative care.

 

Amano, K., Maeda, I., Morita, T., Baba, M., Miura, T., Hama, T., Mori, I., Nakajima, N., Nishi, T., Sakurai, H., Shimoyama, S., Shinjo, T., Shirayama, H., Yamada, T., Ono, S., Ozawa, T., Yamamoto, R., Yamamoto, N., Shishido, H., and Kinoshita, H. (2017) C-reactive protein, symptoms and activity of daily living in patients with advanced cancer receiving palliative care. Journal of Cachexia, Sarcopenia and Muscle, 8: 457–456. doi: 10.1002/jcsm.12217.

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     Page 466–474

Esmee M. Reijnierse, Nynke de Jong, Marijke C. Trappenburg, Gerard Jan Blauw, Gillian Butler-Browne, Helena Gapeyeva, Jean-Yves Hogrel, Jamie S. McPhee, Marco V. Narici, Sarianna Sipilä, Lauri Stenroth, Rob C. van Lummel, Mirjam Pijnappels, Carel G.M. Meskers, Andrea B. Maier

Assessment of maximal handgrip strength: how many attempts are needed?Background
Handgrip strength (HGS) is used to identify individuals with low muscle strength (dynapenia). The influence of the number of attempts on maximal HGS is not yet known and may differ depending on age and health status. This study aimed to assess how many attempts of HGS are required to obtain maximal HGS.
Methods
Three cohorts (939 individuals) differing in age and health status were included. HGS was assessed three times and explored as continuous and dichotomous variable. Paired t-test, intraclass correlation coefficients (ICC) and Bland–Altman analysis were used to test reproducibility of HGS. The number of individuals with misclassified dynapenia at attempts 1 and 2 with respect to attempt 3 were assessed.
Results
Results showed the same pattern in all three cohorts. Maximal HGS at attempts 1 and 2 was higher than at attempt 3 on population level (P < 0.001 for all three cohorts). ICC values between all attempts were above 0.8, indicating moderate to high reproducibility. Bland–Altman analysis showed that 41.0 to 58.9% of individuals had the highest HGS at attempt 2 and 12.4 to 37.2% at attempt 3. The percentage of individuals with a maximal HGS above the gender-specific cut-off value at attempt 3 compared with attempts 1 and 2 ranged from 0 to 50.0%, with a higher percentage of misclassification in middle-aged and older populations.
Conclusions
Maximal HGS is dependent on the number of attempts, independent of age and health status. To assess maximal HGS, at least three attempts are needed if HGS is considered to be a continuous variable. If HGS is considered as a discrete variable to assess dynapenia, two attempts are sufficient to assess dynapenia in younger populations. Misclassification should be taken into account in middle-aged and older populations.

 

Reijnierse, E. M., de Jong, N., Trappenburg, M. C., Blauw, G. J., Butler-Browne, G., Gapeyeva, H., Hogrel, J.-Y., McPhee, J. S., Narici, M. V., Sipilä, S., Stenroth, L., van Lummel, R. C., Pijnappels, M., Meskers, C. G. M., and Maier, A. B. (2017) Assessment of maximal handgrip strength: how many attempts are needed?. Journal of Cachexia, Sarcopenia and Muscle, 8: 466–474. doi: 10.1002/jcsm.12217.

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     Page 475–481

Jessica M. Scott, David S. Martin, Robert Ploutz-Snyder, Timothy Matz, Timothy Caine, Meghan Downs, Kyle Hackney, Roxanne Buxton, Jeffrey W. Ryder, Lori Ploutz-Snyder

Panoramic ultrasound: a novel and valid tool for monitoring change in muscle massBackground
The strong link between reduced muscle mass and morbidity and mortality highlights the urgent need for simple techniques that can monitor change in skeletal muscle cross-sectional area (CSA). Our objective was to examine the validity of panoramic ultrasound to detect change in quadriceps and gastrocnemius size in comparison with magnetic resonance imaging (MRI) in subjects randomized to 70?days of bed rest (BR) with or without exercise.
Methods
Panoramic ultrasound and MRI images of the quadriceps and gastrocnemius muscles were acquired on the right leg of 27 subjects (26 male, 1 female; age: 34.6?±?7.8?years; body mass: 77.5?±?10.0?kg; body mass index: 24.2?±?2.8?kg/m2; height: 179.1?±?6.9?cm) before (BR-6), during (BR3, 7, 11, 15, 22, 29, 36, 53, 69), and after (BR+3, +6, +10) BR. Validity of panoramic ultrasound to detect change in muscle CSA was assessed by Bland–Altman plots, Lin's concordance correlation coefficient (CCC), sensitivity, specificity, positive predictive value, and negative predictive value.
Results
Six hundred ninety-eight panoramic ultrasound CSA and 698 MRI CSA measurements were assessed. Concordance between ultrasound and MRI was excellent in the quadriceps (CCC: 0.78; P?<?0.0001), whereas there was poor concordance in the gastrocnemius (CCC: 0.37; P?<?0.0006). Compared with MRI, panoramic ultrasound demonstrated high accuracy in detecting quadriceps atrophy and hypertrophy (sensitivity: 73.7%; specificity: 74.2%) and gastrocnemius atrophy (sensitivity: 83.1%) and low accuracy in detecting gastrocnemius hypertrophy (specificity: 33.0%).
Conclusions
Panoramic ultrasound imaging is a valid tool for monitoring quadriceps muscle atrophy and hypertrophy and for detecting gastrocnemius atrophy

 

Scott, J. M., Martin, D. S., Ploutz-Snyder, R., Matz, T., Caine, T., Downs, M., Hackney, K., Buxton, R., Ryder, J. W., and Ploutz-Snyder, L. (2017) Panoramic ultrasound: a novel and valid tool for monitoring change in muscle mass. Journal of Cachexia, Sarcopenia and Muscle, 8: 475–481. doi: 10.1002/jcsm.12217.

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     Page 482–489

Julie A. Pasco, Mohammadreza Mohebbi, Kara L. Holloway, Sharon L. Brennan-Olsen, Natalie K. Hyde, Mark A. Kotowicz

Musculoskeletal decline and mortality: prospective data from the Geelong Osteoporosis StudyBackground
We aimed to examine the relationship between musculoskeletal deterioration and all-cause mortality in a cohort of women studied prospectively over a decade.
Methods
A cohort of 750 women aged 50–94?years was followed for a decade after femoral neck bone mineral density (BMD) and appendicular lean mass (ALM) were measured using dual energy X-ray absorptiometry, in conjunction with comorbidities, health behaviour data, and other clinical measures. The outcome was all-cause mortality identified from the Australian National Deaths Index. Using Cox proportional hazards models and age as the time variable, mortality risks were estimated according to BMD groups (ideal-BMD, osteopenia, and osteoporosis) and ALM groups (T-scores?>?-1.0 high, -2.0 to -1.0 medium, <-2.0 low).
Results
During 6712 person years of follow-up, there were 190 deaths, the proportions increasing with diminishing BMD: 10.7% (23/215) ideal-BMD, 23.5% (89/378) osteopenia, 49.7% (78/157) osteoporosis; and with diminishing ALM: 17.0% (59/345) high, 26.2% (79/301) medium, 50.0% (52/104) low. In multivariable models adjusted for smoking, polypharmacy, and mobility, compared with those with ideal BMD, mortality risk was greater for those with osteopenia [hazard ratio (HR) 1.77, 95% confidence interval (CI) 1.11–2.81] and osteoporosis (HR 2.61, 95%CI 1.60–4.24). Similarly, compared with those with high ALM, adjusted mortality risk was greater for medium ALM (HR 1.36, 95%CI 0.97–1.91) and low ALM (HR 1.65, 95%CI 1.11–2.45). When BMD and ALM groups were tested together in the model, BMD remained a predictor of mortality (HR 1.74, 95%CI 1.09–2.78; HR 2.82, 95%CI 1.70–4.70; respectively), and low ALM had borderline significance (HR 1.52, 95%CI 1.00–2.31), which was further attenuated after adjusting for smoking, polypharmacy, and mobility.
Conclusions
Poor musculoskeletal health increased the risk for mortality independent of age. This appears to be driven mainly by a decline in bone mass. Low lean mass independently exacerbated mortality risk, and this appeared to operate through poor health exposures.

 

Pasco, J. A., Mohebbi, M., Holloway, K. L., Brennan-Olsen, S. L., Hyde, N. K., and Kotowicz, M. A. (2016) Musculoskeletal decline and mortality: prospective data from the Geelong Osteoporosis Study. Journal of Cachexia, Sarcopenia and Muscle, 8: 482–489. doi: 10.1002/jcsm.12217.

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     Page 490–499

Elisa Fabbri, Nancy Chiles Shaffer, Marta Gonzalez-Freire, Michelle D. Shardell, Marco Zoli, Stephanie A. Studenski, Luigi Ferrucci

Early body composition, but not body mass, is associated with future accelerated decline in muscle qualityBackground
Muscle quality (MQ) or strength-to-mass ratio declines with aging, but the rate of MQ change with aging is highly heterogeneous across individuals. The identification of risk factors for accelerated MQ decline may offer clues to identity the underpinning physiological mechanisms and indicate targets for prevention and treatment. Using data from the Baltimore Longitudinal Study of Aging, we tested whether measures of body mass and body composition are associated with differential rates of changes in MQ with aging.
Methods
Participants included 511 men and women, aged 50 years or older, followed for an average of 4 years (range: 1–8). MQ was operationalized as ratio between knee-extension isokinetic strength and CT-thigh muscle cross-sectional area. Predictors included body mass and body composition measures: weight (kg), body mass index (BMI, kg/m2), dual-energy x-ray absorptiometry-measured total body fat mass (TFM, kg) and lean mass (TLM, kg), and body fatness (TFM/weight). Covariates were baseline age, sex, race, and body height.
Results
Muscle quality showed a significant linear decline over the time of the follow up (average rate of decline 0.02 Nm/cm2 per year, P < .001). Independent of covariates, neither baseline body weight (P = .756) nor BMI (P = .777) was predictive of longitudinal rate of decline in MQ. Instead, higher TFM and lower TLM at baseline predicted steeper longitudinal decline in MQ (P = .036 and P < .001, respectively). In particular, participants with both high TFM and low TLM at baseline experienced the most dramatic decline compared with those with low TFM and high TLM (about 3% per year vs. 0.5% per year, respectively). Participants in the higher tertile of baseline body fatness presented a significantly faster decline of MQ than the rest of the population (P = .021). Similar results were observed when body mass, TFM, and TLM were modeled as time-dependent predictors.
Conclusions
Body composition, but not weight nor BMI, is associated with future MQ decline, suggesting that preventive strategies aimed at maintaining good MQ with aging should specifically target body composition features.

 

Fabbri, E., Chiles Shaffer, N., Gonzalez-Freire, M., Shardell, M. D., Zoli, M., Studenski, S. A., and Ferrucci, L. (2017) Early body composition, but not body mass, is associated with future accelerated decline in muscle quality. Journal of Cachexia, Sarcopenia and Muscle, 8: 490–499. doi: 10.1002/jcsm.12217.

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     Page 500–507

Serpil Muge Deger, Ping Wang, Rachel Fissell, Charles D. Ellis, Cindy Booker, Feng Sha1, Jennifer L. Morse, Thomas G. Stewart, John C. Gore, Edward D. Siew, Jens Titze, Talat Alp Ikizler

Tissue sodium accumulation and peripheral insulin sensitivity in maintenance hemodialysis patientsBackground
Recent data suggest that sodium (Na+) is stored in the muscle and skin without commensurate water retention in maintenance hemodialysis (MHD) patients. In this study, we hypothesized that excessive Na+ accumulation would be associated with abnormalities in peripheral insulin action.
Methods
Eleven MHD patients and eight controls underwent hyperinsulinemic–euglycemic–euaminoacidemic clamp studies to measure glucose (GDR) and leucine disposal rates (LDR), as well as lower left leg 23Na magnetic resonance imaging to measure Na+ concentration in the muscle and skin tissue.
Results
The median GDR and LDR levels were lower, and the median muscle Na+ concentration was higher in MHD patients compared with controls. No significant difference was found regarding skin Na+ concentration between group comparisons. Linear regression revealed inverse relationships between muscle Na+ concentration and GDR and LDR in MHD patients, whereas no relationship was observed in controls. There was no association between skin Na+ content and GDR or LDR in either MHD patients or controls.
Conclusions
These data suggest that excessive muscle Na+ content might be a determinant of IR in MHD patients, although the causality and mechanisms remain to be proven.

 

Deger, S. M., Wang, P., Fissell, R., Ellis, C. D., Booker, C., Sha, F., Morse, J. L., Stewart, T. G., Gore, J. C., Siew, E. D., Titze, J., and Ikizler, T. A. (2017) Tissue sodium accumulation and peripheral insulin sensitivity in maintenance hemodialysis patients. Journal of Cachexia, Sarcopenia and Muscle, 8: 500–507. doi: 10.1002/jcsm.12217.

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     Page 508–511

Nicole Ebner, Stephan von Haehling

Highlights from the 9th Cachexia ConferenceThis article highlights updates of pathways as well as pre-clinical and clinical studies into the field of wasting disorders that were presented at the 9th Cachexia Conference held in Berlin, Germany, December 2016. This year, some interesting results from clinical trials and different new therapeutic targets were shown. This article presents the biological and clinical significance of different markers and new diagnostic tools and cut-offs of detecting skeletal muscle wasting. Effective treatments of cachexia and wasting disorders are urgently needed in order to improve the patients' quality of life and their survival.

 

Ebner, N., and von Haehling, S. (2017) Highlights from the 9th Cachexia Conference. Journal of Cachexia, Sarcopenia and Muscle, 8: 508–511. doi: 10.1002/jcsm.12217.

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     Page 512–513

Josef Finsterer, Marlies Frank

Management of statin myopathyno abstract

 

Finsterer, J., and Frank, M. (2017) Management of statin myopathy. Journal of Cachexia, Sarcopenia and Muscle, 8: 512–513. doi: 10.1002/jcsm.12207.

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     Page 514–515

Amirhossein Sahebkar, Maciej Banach

Response letter: Management of statin-induced myopathies: Much demands and still (almost) empty hands!no abstract

 

Sahebkar, A., and Banach, M. (2017) Response letter: Management of statin-induced myopathies: Much demands and still (almost) empty hands!. Journal of Cachexia, Sarcopenia and Muscle, 8: 514–515. doi: 10.1002/jcsm.12215.

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     Page 516–517

Junichi Ishida, Masakazu Saitoh, Jochen Springer

Single-nucleotide polymorphisms in cachexia-related genes: Can they optimize the treatment of cancer cachexia?no abstract

 

Ishida, J., Saitoh, M., and Springer, J. (2017) Single-nucleotide polymorphisms in cachexia-related genes: Can they optimize the treatment of cancer cachexia?. Journal of Cachexia, Sarcopenia and Muscle, 8: 516–517. doi: 10.1002/jcsm.12214.

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     Page 518–519

Masakazu Saitoh, Junichi Ishida, Jochen Springer

Physical activity for the prevention and treatment of sarcopenic obesityno abstract

 

Saitoh, M., Ishida, J., and Springer, J. (2017) Physical activity for the prevention and treatment of sarcopenic obesity. Journal of Cachexia, Sarcopenia and Muscle, 8: 518–519. doi: 10.1002/jcsm.12216.

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