Article first published online:  13 August 2019

Marcello Maggio, Fulvio Lauretani

Prevalence, incidence, and clinical impact of cognitive–motoric risk syndrome in Europe, USA, and Japan: facts and numbers update 2019
A new syndrome called the ‘motoric–cognitive risk’ (MCR) syndrome has recently been proposed in older persons. According to this definition, the parallel impairment in muscle and brain function is more predictive for identifying subjects at risk of dementia than impairment a in single system alone. Epidemiological studies suggest that among older persons, enrolled in worldwide population‐based studies, 10% are affected by this syndrome, which confers a higher risk of future disability. In detail, the prevalence of MCR in Europe is around 8.0%, 7.0% in the United States, and 6.3% in Japan. The incidence of the MCR syndrome is estimated to be 65.2 per 1000 person years in adults aged 60 years or older. Many studies reported negative outcomes of the syndrome in older persons, emphasizing its clinical impact. In particular, in almost all longitudinal studies, MCR produces a three‐time increased risk of future dementia. In Europe, data from the InCHIANTI study report an increased risk of 2.74 [1.54–4.86], which is 2.49 [1.52–4.10] in the United States and 3.27 [1.55–6.90] in Japan. The studies in different continents are also consistent in showing an increased risk of all‐cause mortality, which is 1.50–1.87 in the Europeans and 1.69 [1.08–2.02] for incident disability in Japan. For the identification of the MCR syndrome, different tests and procedures have been proposed, with a final ‘core‐battery’ that includes gait speed, dual‐task gait speed, the Montreal Cognitive Assessment and Trail Making Test A and B. The criteria used to select this core‐battery were based on the best accuracy for identifying older persons at risk of negative outcomes such as dementia, falls, aging‐related disabilities, and sensitivity to interventions. The selection of these tests will allow to start studies aimed to better capture older persons at higher risk of mobility and cognitive disability. By these tests, it will be possible to better evaluate the effect of treatment composing of tailored physical exercise, nutritional suggestions, and medical therapy to overturn negative effect of both cognitive and motoric frailty. This article provides an overview of the current knowledge of the MCR syndrome.

Maggio, M., and Lauretani, F. ( 2019) Prevalence, incidence, and clinical impact of cognitive–motoric risk syndrome in Europe, USA, and Japan: facts and numbers update 2019, Journal of Cachexia, Sarcopenia and Muscle, 10: 953– 955. https://doi.org/10.1002/jcsm.12476.

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     Article first published online:  15 September 2019

Juergen Bauer, John E. Morley, Annemie M.W.J. Schols, Luigi Ferrucci, Alfonso J. Cruz‐Jentoft, Elsa Dent, Vickie E. Baracos,, Jeffrey A. Crawford, Wolfram Doehner, Steven B. Heymsfield, Aminah Jatoi, Kamyar Kalantar‐Zadeh, Mitja Lainscak, Francesco Landi, Alessandro Laviano, Michelangelo Mancuso, Maurizio Muscaritoli, Carla M. Prado, Florian Strasser, Stephan von Haehling, Andrew J.S. Coats, Stefan D. Anker

Sarcopenia: A Time for Action. An SCWD Position Paper
The term sarcopenia was introduced in 1988. The original definition was a “muscle loss” of the appendicular muscle mass in the older people as measured by dual energy x‐ray absorptiometry (DXA). In 2010, the definition was altered to be low muscle mass together with low muscle function and this was agreed upon as reported in a number of consensus papers. The Society of Sarcopenia, Cachexia and Wasting Disorders supports the recommendations of more recent consensus conferences, i.e. that rapid screening, such as with the SARC‐F questionnaire, should be utilized with a formal diagnosis being made by measuring grip strength or chair stand together with DXA estimation of appendicular muscle mass (indexed for height2). Assessments of the utility of ultrasound and creatine dilution techniques are ongoing. Use of ultrasound may not be easily reproducible. Primary sarcopenia is aging associated (mediated) loss of muscle mass. Secondary sarcopenia (or disease‐related sarcopenia) has predominantly focused on loss of muscle mass without the emphasis on muscle function. Diseases that can cause muscle wasting (i.e. secondary sarcopenia) include malignant cancer, COPD, heart failure, and renal failure and others. Management of sarcopenia should consist of resistance exercise in combination with a protein intake of 1 to 1.5 g/kg/day. There is insufficient evidence that vitamin D and anabolic steroids are beneficial. These recommendations apply to both primary (age‐related) sarcopenia and secondary (disease related) sarcopenia. Secondary sarcopenia also needs appropriate treatment of the underlying disease. It is important that primary care health professionals become aware of and make the diagnosis of age‐related and disease‐related sarcopenia. It is important to address the risk factors for sarcopenia, particularly low physical activity and sedentary behavior in the general population, using a life‐long approach. There is a need for more clinical research into the appropriate measurement for muscle mass and the management of sarcopenia. Accordingly, this position statement provides recommendations on the management of sarcopenia and how to progress the knowledge and recognition of sarcopenia.

Bauer, J., Morley, J. E., Schols, A. M. W. J., Ferrucci, L., Cruz‐Jentoft, A. J., Dent, E., Baracos, V. E., Crawford, J. A., Doehner, W., Heymsfield, S. B., Jatoi, A., Kalantar‐Zadeh, K., Lainscak, M., Landi, F., Laviano, A., Mancuso, M., Muscaritoli, M., Prado, C. M., Strasser, F., Coats, A. J. S., and Anker, S. D. ( 2019) Sarcopenia: A Time for Action. An SCWD Position Paper, Journal of Cachexia, Sarcopenia and Muscle, 10: 956– 961. https://doi.org/10.1002/jcsm.12483.

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     Article first published online:  24 May 2019

Ronaldo D. Piovezan. Camila Hirotsu, Renato Moizinho, Helton de Sá Souza, Vania D'Almeida, Sergio Tufik, Dalva Poyares

Associations between sleep conditions and body composition states: results of the EPISONO study
Background
Evidence suggests anthropometric indicators of obesity are associated with changes in sleep quality and quantity, and the presence of obstructive sleep apnoea (OSA). Investigations including diverse and objective evaluations of sleep and body composition are scarce. We aimed to evaluate the associations between indicators of sleep impairment and body composition states in a sample from a population‐based study.
Methods
Participants of the first follow‐up of the EPISONO (São Paulo, Brazil) >50 years were cross‐sectionally evaluated. Sleep was assessed through questionnaires, actigraphy, and polysomnography. Body composition was evaluated by bioelectrical impedance analysis. Appendicular skeletal muscle mass adjusted for body mass index defined sarcopenia (men <0.789 and women <0.512). Total body fat defined obesity (men >30% and women >40%). The overlap between both conditions defined sarcopenic obesity (SO). Final results were obtained by multinomial logistic regression analysis.
Results
Three hundred fifty‐nine adults [mean (standard deviation) age, 61 (8.8) years; 212 (59.1%) female] were enrolled. Obesity was detected in 22.6% of the sample, sarcopenia in 5.6%, and SO in 16.2%. After controlling for covariates, OSA was associated with SO [odds ratio = 3.14, 95% confidence interval (CI) = 1.49–6.61]. Additionally, nocturnal hypoxaemia was associated with both obesity (adjusted odds ratio = 2.59, 95% CI = 1.49–4.49) and SO (odds ratio = 2.92, 95% CI = 1.39–6.13). Other indicators of poor sleep/sleep disorders were not associated with body composition states.
Conclusions
Sarcopenic obesity but not obesity alone was associated with OSA. Both obesity and SO but not sarcopenia were associated with nocturnal hypoxaemia. The findings suggest a complex pathophysiologic relationship between adverse body composition states and OSA. Upcoming research on risk factors and therapeutic interventions for OSA should target synchronically the lean and adipose body tissues.

Piovezan, R. D., Hirotsu, C., Moizinho, R., de Sá Souza, H., D'Almeida, V., Tufik, S., and Poyares, D. ( 2019) Associations between sleep conditions and body composition states: results of the EPISONO study, Journal of Cachexia, Sarcopenia and Muscle, 10: 962– 973. https://doi.org/10.1002/jcsm.12445.

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     Article first published online:  29 May 2019

Itziar Abete, Jadwiga Konieczna, M. Angeles Zulet, Aina M. Galmés‐Panades, Idoia Ibero‐Baraibar, Nancy Babio, Ramón Estruch, Josep Vidal, Estefanía Toledo, Cristina Razquin, Rafael Bartolomé, Andrés Díaz‐Lopez, Miquel Fiol, Rosa Casas, Josep Vera, Pilar Buil‐Cosiales, Xavier Pintó, Emili Corbella, Maria Puy Portillo, Jose Antonio de Paz, Vicente Martín, Lidia Daimiel, Albert Goday, Nuria Rosique‐Esteban, Jordi Salas‐Salvadó, Dora Romaguera, J. Alfredo Martínez on behalf of PREDIMED‐PLUS Investigators

Association of lifestyle factors and inflammation with sarcopenic obesity: data from the PREDIMED‐Plus trial
Background
Sarcopenia is a progressive age‐related skeletal muscle disorder associated with increased likelihood of adverse outcomes. Muscle wasting is often accompanied by an increase in body fat, leading to ‘sarcopenic obesity’. The aim of the present study was to analyse the association of lifestyle variables such as diet, dietary components, physical activity (PA), body composition, and inflammatory markers, with the risk of sarcopenic obesity.
Methods
A cross‐sectional analysis based on baseline data from the PREDIMED‐Plus study was performed. A total of 1535 participants (48% women) with overweight/obesity (body mass index: 32.5 ± 3.3 kg/m2; age: 65.2 ± 4.9 years old) and metabolic syndrome were categorized according to sex‐specific tertiles (T) of the sarcopenic index (SI) as assessed by dual‐energy X‐ray absorptiometry scanning. Anthropometrical measurements, biochemical markers, dietary intake, and PA information were collected. Linear regression analyses were carried out to evaluate the association between variables.
Results
Subjects in the first SI tertile were older, less physically active, showed higher frequency of abdominal obesity and diabetes, and consumed higher saturated fat and less vitamin C than subjects from the other two tertiles (all P < 0.05). Multiple adjusted linear regression models evidenced significant positive associations across tertiles of SI with adherence to the Mediterranean dietary score (P‐trend < 0.05), PA (P‐trend < 0.0001), and the 30 s chair stand test (P‐trend < 0.0001), whereas significant negative associations were found with an inadequate vitamin C consumption (P‐trend < 0.05), visceral fat and leucocyte count (all P‐trend < 0.0001), and some white cell subtypes (neutrophils and monocytes), neutrophil‐to‐lymphocyte ratio, and platelet count (all P‐trend < 0.05). When models were additionally adjusted by potential mediators (inflammatory markers, diabetes, and waist circumference), no relevant changes were observed, only dietary variables lost significance.
Conclusions
Diet and PA are important regulatory mediators of systemic inflammation, which is directly involved in the sarcopenic process. A healthy dietary pattern combined with exercise is a promising strategy to limit age‐related sarcopenia.

Abete, I., Konieczna, J., Zulet, M. A., Galmés‐Panades, A. M., Ibero‐Baraibar, I., Babio, N., Estruch, R., Vidal, J., Toledo, E., Razquin, C., Bartolomé, R., Díaz‐Lopez, A., Fiol, M., Casas, R., Vera, J., Buil‐Cosiales, P., Pintó, X., Corbella, E., Portillo, M. P., de Paz, J. A., Martín, V., Daimiel, L., Goday, A., Rosique‐Esteban, N., Salas‐Salvadó, J., Romaguera, D., Martínez, J. A., and on behalf of PREDIMED‐PLUS Investigators ( 2019) Association of lifestyle factors and inflammation with sarcopenic obesity: data from the PREDIMED‐Plus trial, Journal of Cachexia, Sarcopenia and Muscle, 10: 974– 984. https://doi.org/10.1002/jcsm.12442.

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     Article first published online:  15 July 2019

Anne‐Julie Tessier, Simon S. Wing, Elham Rahme, José A. Morais, Stéphanie Chevalier

Physical function‐derived cut‐points for the diagnosis of sarcopenia and dynapenia from the Canadian longitudinal study on aging
Background
Aging is associated with sarcopenia (low muscle mass) and dynapenia (low muscle strength) leading to disability and mortality. Widely used previous cut‐points for sarcopenia were established from dated, small, or pooled cohorts. We aimed to identify cut‐points of low strength as a determinant of impaired physical performance and cut‐points of low appendicular lean mass (ALM) as a predictor of low strength in a single, large, and contemporary cohort of community‐dwelling older adults and compare these criteria with others.
Methods
Cross‐sectional analyses were conducted on baseline data from 4725 and 4363 community‐dwelling men and women (65–86 years, 96.8% Caucasian) of the Canadian longitudinal study on aging comprehensive cohort. Physical performance was evaluated from gait speed, timed up‐and‐go, chair rise, and balance tests; a weighted‐sum score was computed using factor analysis. Strength was measured by handgrip dynamometry; ALM, by dual‐energy X‐ray absorptiometry and ALM index (ALMI; kg/m2), was calculated. Classification and regression tree analyses determined optimal sex‐specific cut‐points of ALMI predicting low strength and of strength predicting impaired physical performance (score < 1.5 SD below the sex‐specific mean).
Results
Modest associations were found between ALMI and strength and between strength and physical performance score in both sexes. ALMI was not an independent predictor of physical performance score. Cut‐points of <33.1 and <20.4 kg were found to define dynapenia in men and in women, respectively, corresponding to 21.5% and 24.0% prevalence rates. Sarcopenia cut‐points were <7.76 kg/m2 in men and <5.72 kg/m2 in women; prevalence rates of 21.7% and 13.7%. Overall, 8.3% of men and 5.5% of women had sarco‐dynapenia. Sarcopenic were older and had lower fat mass and body mass index (BMI) than non‐sarcopenic participants. While the agreement between current criteria and the updated European Working Group for Sarcopenia in Older Persons recommendations was fair, we found only slight agreement with the Foundation for the National Institute of Health sarcopenia project. Older persons identified with sarcopenia as per the Foundation for the National Institute of Health criteria (using ALM/BMI as the index) have higher BMI and fat mass compared with non‐sarcopenic and have normal ALMI as per our criteria.
Conclusions
The proposed function‐derived cut‐points established from this single, large, and contemporary Canadian cohort should be used for the identification of sarcopenia and dynapenia in Caucasian older adults. We advise on using criteria based on ALMI in the diagnosis of sarcopenia. The modest agreement between sarcopenia and dynapenia denotes potential distinct health implications justifying to study both components separately.

Tessier, A.‐J., Wing, S. S., Rahme, E., Morais, J. A., and Chevalier, S. ( 2019) Physical function‐derived cut‐points for the diagnosis of sarcopenia and dynapenia from the Canadian longitudinal study on aging, Journal of Cachexia, Sarcopenia and Muscle, 10: 985– 999. https://doi.org/10.1002/jcsm.12462.

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     Article first published online:  04 July 2019

Yusuke Osawa, Nancy Chiles Shaffer, Michelle D. Shardell, Stephanie A. Studenski, Luigi Ferrucci

Changes in knee extension peak torque and body composition and their relationship with change in gait speed
Background
Slow gait speed is a powerful predictor of disability in activities of daily living and mortality. Muscle strength and body composition change over time, but their changes differ by sex. How these parameters jointly affect gait speed decline is unknown. Understanding this association could help develop and evaluate the sex‐specific effects of lifestyle interventions to delay gait speed decline in older adults. We assessed whether changes in strength (Δstrength), appendicular lean mass (ΔALM), and fat mass (Δfat) jointly relate to change in gait speed and whether the association differs by sex.
Methods
The analytic sample comprised 575 women and 539 men aged 22–95 years enrolled in the Baltimore Longitudinal Study of Aging. Mean follow‐up was 4.0 years. Measures included isometric knee extension strength, dual‐energy X‐ray absorptiometry‐assessed ALM and fat mass, and gait speed from the 400 m fast pace walk. Sex‐specific linear mixed models were adjusted for follow‐up time and baseline age, race, height, ALM, fat mass, peak torque, and gait speed. We also included second‐order interaction terms of the key predictive variables (e.g. Δstrength × ΔALM). To interpret the interactions, we estimated average gait declines using the 25th or 75th percentile of the two significant predictive variables and then assessed which condition relates to larger decline in gait speed.
Results
In both sexes, independent of ΔALM and Δfat, larger decline in strength significantly related to larger decline in gait speed (P = 0.01 for both sexes). In men, interactions between Δstrength × ΔALM and Δfat by ΔALM were associated with change in gait speed; men with greater declines in both muscle strength and ALM or greater declines in both ALM and fat have steeper gait speed decline. In contrast, in women, the interaction between Δfat and ΔALM was associated with change in gait speed; women with an increase in fat mass combined with less decline in ALM have steeper gait speed decline.
Conclusions
While change in strength affects change in gait speed in both sexes, the effects of body composition change differ by sex. Dual‐energy X‐ray absorptiometry‐based estimates of lean mass may be confounded by intramuscular fat. Future studies should examine sex‐specific combined effects of change in strength and body composition on mobility using multiple techniques to measure body composition. Intervention studies should consider testing sex‐specific interventions on body composition.

Osawa, Y., Chiles Shaffer, N., Shardell, M. D., Studenski, S. A., and Ferrucci, L. ( 2019) Changes in knee extension peak torque and body composition and their relationship with change in gait speed, Journal of Cachexia, Sarcopenia and Muscle, 10: 1000– 1008. https://doi.org/10.1002/jcsm.12458.

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     Article first published online:  08 May 2019

Miguel A. Perez-Sousa, Luis Carlos Venegas-Sanabria, Diego Andrés Chavarro-Carvajal, Carlos Alberto Cano-Gutierrez, Mikel Izquierdo, Jorge Enrique Correa-Bautista, Robinson Ramírez-Vélez

Gait speed as a mediator of the effect of sarcopenia on dependency in activities of daily living
Background
Sarcopenia in older adults is strongly associated with an increase in dependency in activities of daily living (ADL) and with a decline in gait speed. Interestingly, gait speed has been shown to independently predict mortality. In this context, our study aimed to explore the mediator role of gait speed on the relationship between sarcopenia and dependency in ADL.
Methods
A cross-sectional study was conducted in Colombia, 19 705 older adults with a mean age of 70 years, 55.6% women, 16.1% with sarcopenia, and 14.7% mild, moderate, or severe dependency in ADL, according to ‘SABE Survey 2015’. Sarcopenia was assessed by calf circumference and ADL dependence through the Barthel Index. Gait speed was measured over a distance of 3 m. The association between sarcopenia condition and gait speed and dependency level was analysed by linear regression adjusted by covariates. To examine whether gait speed mediated the association between sarcopenia and dependence components of physical function, simple mediation models were generated using ordinary least squares with the macro PROCESS version 3.2, adjusted for age, sex, and body mass index (BMI).
Results
Significant differences (P < 0.05) were found in gait speed and dependency in ADL between the sarcopenia and non-sarcopenia groups after adjusting for age, sex, and BMI. BMI was significantly higher in the non-sarcopenia group whereas dependency was significantly higher in the sarcopenia group (19.6% vs. 13.8%). Results from mediation model regression analysis indicated a significant and direct detrimental effect of sarcopenia on dependency in ADL (ß = -0.05; P < 0.001), and a significant indirect effect of gait speed on the direct effect (-0.009 to -0.004).
Conclusions
The negative effect of sarcopenia on functional dependence was mediated by the gait speed. Therefore, gait speed may positively influence the detrimental effect of sarcopenia for dependency, after adjusting for age, gender, and BMI. Consequently, physical exercise should be promoted and focused to circumvent the gait speed decline associated with age in older people with sarcopenia.

Perez‐Sousa, M. A., Venegas‐Sanabria, L. C., Chavarro‐Carvajal, D. A., Cano‐Gutierrez, C. A., Izquierdo, M., Correa‐Bautista, J. E., and Ramírez‐Vélez, R. ( 2019) Gait speed as a mediator of the effect of sarcopenia on dependency in activities of daily living. Journal of Cachexia, Sarcopenia and Muscle, 10: 10091015. https://doi.org/10.1002/jcsm.12444.

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     Article first published online:  07 May 2019

Pradeep Harish, Alberto Malerba, Ngoc Lu-Nguyen, Leysa Forrest, Ornella Cappellari, Fanny Roth, Capucine Trollet, Linda Popplewell, George Dickson

Inhibition of myostatin improves muscle atrophy in oculopharyngeal muscular dystrophy (OPMD)
Background
Oculopharyngeal muscular dystrophy (OPMD) is a late-onset muscle disease affecting one per 80 000 of the general population characterized by profound dysphagia and ptosis, and limb weakness at later stages. Affected muscles are characterized by increased fibrosis and atrophy. Myostatin is a negative regulator of muscle mass, and inhibition of myostatin has been demonstrated to ameliorate symptoms in dystrophic muscles.
Methods
In this study, we performed a systemic delivery of a monoclonal antibody to immunologically block myostatin in the A17 mouse model of OPMD. The mice were administered a weekly dose of 10 mg/kg RK35 intraperitonially for 10 weeks, following which histological analyses were performed on the samples.
Results
This treatment significantly (P < 0.01) improved body mass (11%) and muscle mass (for the tibialis anterior and extensor digitorum longus by 19% and 41%) in the A17 mice treated with RK35 when compared to saline controls. Similarly, a significantly (P < 0.01) increased muscle strength (18% increase in maximal tetanic force) and myofibre diameter (17% and 44% for the tibialis anterior and extensor digitorum longus), and reduced expression of markers of muscle fibrosis (40% reduction in area of expression), was also observed. No change in the density of intranuclear inclusions (a hallmark of disease progression of OPMD) was however observed.
Conclusions
Our study supports the clinical translation of such antibody-mediated inhibition of myostatin as a treatment of OPMD. This strategy has implications to be used as adjuvant therapies with gene therapy based approaches, or to stabilize the muscle prior to myoblast transplantation.

Harish, P., Malerba, A., Lu‐Nguyen, N., Forrest, L., Cappellari, O., Roth, F., Trollet, C., Popplewell, L., and Dickson, G. ( 2019) Inhibition of myostatin improves muscle atrophy in oculopharyngeal muscular dystrophy (OPMD). Journal of Cachexia, Sarcopenia and Muscle, 10: 10161026. https://doi.org/10.1002/jcsm.12438.

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     Article first published online:  09 May 2019

Robert A. Blum, Stuart Mair, Elizabeth M. Duus

Appetite and food intake results from phase I studies of anamorelin
Background
Loss of appetite and body weight are potentially devastating, highly prevalent cancer complications. The ghrelin receptor is a mediator of appetite and metabolism, and anamorelin is a novel, orally administered ghrelin receptor agonist. Effects on appetite and food intake may influence body‐weight gain but can be difficult to measure in multi‐site studies. Here, we summarize two single‐centre trials.
Methods
Both trials were phase I, randomized, double‐blind, placebo‐controlled, partly/wholly crossover studies of healthy young adults. Study 102 tested single anamorelin doses of 1–20 mg. Assessments included post‐dose self‐ratings on 100 mm visual analogue scales for hunger, anticipated eating pleasure, and anticipated quantity of food consumption. Study 101 tested single 10, 25, and 50 mg doses. Assessments included the same scales plus caloric intake beginning 4 h post‐dose.
Results
Study 102 treated 16 male subjects (mean age, 26.3 years). Mean hunger scores generally increased after all treatments, with significant differences from placebo (P < 0.05) in the 5 mg anamorelin group at 0.5 and 1 h post‐dose (+8.2 and +13.2 mm). Results for other scales were similar. Study 101 treated nine male subjects (mean age, 26.3 years). Pooled findings for anamorelin 25 and 50 mg vs. placebo showed significant mean increases in hunger scores at all but 1 pre‐prandial time point, including the first assessment, 0.5 h post‐dose (+10.9 vs. +0.7 mm, P = 0.0077), and the last assessment, 4 h post‐dose (+32.7 vs. +7.0 mm, P = 0.0170), with a significant mean 18.4% increase vs. placebo in caloric intake (P = 0.0148).
Conclusions
In single‐centre studies of healthy adults, single anamorelin doses of 1–20 mg elicited modest increases in hunger, and single doses of 25 and 50 mg achieved significant increases in hunger and caloric intake. The findings are consistent with dose‐related weight gain reported in a prior phase I study as well as multi‐centre findings in cachectic cancer patients and expand the evidence supporting anamorelin as a potential intervention.

Blum, R. A., Mair, S., and Duus, E. M. ( 2019) Appetite and food intake results from phase I studies of anamorelin, Journal of Cachexia, Sarcopenia and Muscle, 10: 1027– 1035. https://doi.org/10.1002/jcsm.12439.

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     Article first published online:  08 May 2019

Patrick J. Owen, Robin M. Daly, Jack Dalla Via, Niamh L. Mundell, Patricia M. Livingston, Timo Rantalainen, Steve F. Fraser

The clinical relevance of adiposity when assessing muscle health in men treated with androgen deprivation for prostate cancer
Background
Androgen deprivation therapy (ADT) for prostate cancer (PCa) may prospectively decrease absolute lean mass (LM) and increase absolute fat mass (FM). Given that estimates of LM by dual-energy X-ray absorptiometry may be overestimated in obese people, this study examined the influence of adiposity on muscle health in men treated with ADT for PCa.
Methods
This cross-sectional study examined the influence of adiposity on total and appendicular LM (ALM), muscle cross-sectional (CSA), and muscle strength in 70 men treated with ADT [mean (standard deviation) age, 71 (6) years] for PCa compared with age-matched PCa (n = 52) and healthy controls (n = 70). Total body LM, FM and ALM, and 66% tibia and radius muscle CSA were quantified by dual-energy X-ray absorptiometry and peripheral quantitative computed tomography, respectively. ALM was further divided by height (m2) or body mass index, with muscle CSA expressed as a per cent of total limb CSA. Upper and lower body and back (three-repetition maximum and dynamometry) muscle strength were expressed per kilogram of body weight.
Results
On average, ADT-treated men had 4.4–6.4 kg greater FM compared with controls (P = 0.014) and there were no differences in total body or ALM. Total body per cent LM and ALMBMI were 3.8–5.4% (P = 0.001) and 7.8–9.4% (P = 0.001) lower, respectively, in ADT-treated men compared with both controls. Percentage muscle CSA at both sites and muscle strength (except leg) were 3.0–6.0% (P = 0.031) and 15–17% (P = 0.010) lower, respectively, in ADT-treated men compared with both controls.
Conclusions
The findings from this study indicate muscle mass, size, and strength are compromised in men treated with ADT after accounting for their increased adiposity or body size.

Owen, P. J., Daly, R. M., Dalla Via, J., Mundell, N. L., Livingston, P. M., Rantalainen, T., and Fraser, S. F. ( 2019) The clinical relevance of adiposity when assessing muscle health in men treated with androgen deprivation for prostate cancer, Journal of Cachexia, Sarcopenia and Muscle, 10: 10361044. https://doi.org/10.1002/jcsm.12446.

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     Article first published online:  04 July 2019

Joanna D.C.C. Lima, Estefania Simoes, Gabriela de Castro, Mychel Raony P.T. Morais, Emidio M. de Matos‐Neto, Michele J. Alves, Nelson I. Pinto, Raquel G. Figueredo, Telma M.T. Zorn, Aloísio S. Felipe‐Silva, Flavio Tokeshi, José P. Otoch, Paulo Alcantara, Fernanda J. Cabral, Emer S. Ferro, Alessandro Laviano, Marilia Seelaender

Tumour‐derived transforming growth factor‐β signalling contributes to fibrosis in patients with cancer cachexia
Background
Cachexia is a paraneoplastic syndrome related with poor prognosis. The tumour micro‐environment contributes to systemic inflammation and increased oxidative stress as well as to fibrosis. The aim of the present study was to characterise the inflammatory circulating factors and tumour micro‐environment profile, as potentially contributing to tumour fibrosis in cachectic cancer patients.
Methods
74 patients (weight stable cancer n = 31; cachectic cancer n = 43) diagnosed with colorectal cancer were recruited, and tumour biopsies were collected during surgery. Multiplex assay was performed to study inflammatory cytokines and growth factors. Immunohistochemistry analysis was carried out to study extracellular matrix components.
Results
Higher protein expression of inflammatory cytokines and growth factors such as epidermal growth factor, granulocyte–macrophage colony‐stimulating factor, interferon‐α, and interleukin (IL)‐8 was observed in the tumour and serum of cachectic cancer patients in comparison with weight‐stable counterparts. Also, IL‐8 was positively correlated with weight loss in cachectic patients (P = 0.04; r = 0.627). Immunohistochemistry staining showed intense collagen deposition (P = 0.0006) and increased presence of α‐smooth muscle actin (P < 0.0001) in tumours of cachectic cancer patients, characterizing fibrosis. In addition, higher transforming growth factor (TGF)‐β1, TGF‐β2, and TGF‐β3 expression (P = 0.003, P = 0.05, and P = 0.047, respectively) was found in the tumour of cachectic patients, parallel to p38 mitogen‐activated protein kinase alteration. Hypoxia‐inducible factor‐1α mRNA content was significantly increased in the tumour of cachectic patients, when compared with weight‐stable group (P = 0.005).
Conclusions
Our results demonstrate TGF‐β pathway activation in the tumour in cachexia, through the (non‐canonical) mitogen‐activated protein kinase pathway. The results show that during cachexia, intratumoural inflammatory response contributes to the onset of fibrosis. Tumour remodelling, probably by TGF‐β‐induced transdifferentiation of fibroblasts to myofibroblasts, induces unbalanced inflammatory cytokine profile, angiogenesis, and elevation of extracellular matrix components (EMC). We speculate that these changes may affect tumour aggressiveness and present consequences in peripheral organs.

Lima, J. D. C. C., Simoes, E., De Castro, G., Morais, M. R. P. T., de Matos‐Neto, E. M., Alves, M. J., Pinto, N. I., Figueredo, R. G., Zorn, T. M. T., Felipe‐Silva, A. S., Tokeshi, F., Otoch, J. P., Alcantara, P., Cabral, F. J., Ferro, E. S., Laviano, A., and Seelaender, M. ( 2019) Tumour‐derived transforming growth factor‐β signalling contributes to fibrosis in patients with cancer cachexia, Journal of Cachexia, Sarcopenia and Muscle, 10: 1045– 1059. https://doi.org/10.1002/jcsm.12441.

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     Article first published online:  27 May 2019

Aniek T. Zwart,Anouk van der Hoorn, Peter M.A. van Ooijen, Roel J.H.M. Steenbakkers, Geertruida H. de Bock, Gyorgy B. Halmos

CT‐measured skeletal muscle mass used to assess frailty in patients with head and neck cancer
Background
Skeletal muscle depletion or sarcopenia is related to multiple adverse clinical outcome. However, frailty questionnaires are currently applied in the daily practice to identify patients who are potentially (un)suitable for treatment but are time consuming and straining for patients and the clinician. Screening for sarcopenia in patients with head and neck cancer (HNC) could be a promising fast biomarker for frailty. Our objective was to quantify sarcopenia with pre‐treatment low skeletal muscle mass from routinely obtained neck computed tomography scans at level of third cervical vertebra in patients diagnosed with HNC and evaluate its association with frailty.
Methods
A total of 112 HNC patients with Stages III and IV disease were included from a prospective databiobank. The amount of skeletal muscle mass was retrospectively defined using the skeletal muscle index (SMI). Correlation analysis between SMI and continuous frailty data and the observer agreement were analysed with Pearson's r correlation coefficients. Sarcopenia was present when SMI felt below previously published non‐gender specific thresholds (<43.2 cm2/m2). Frailty was evaluated by Geriatrics 8 (G8), Groningen Frailty Indicator, Timed Up and Go test, and Malnutrition Universal Screening Tool. A univariate and multivariate logistic regression analysis was performed for all patients and men separately to obtain odds ratios (ORs) and 95% confidence intervals (95% CIs).
Results
The cohort included 82 men (73%) and 30 women (27%), with a total mean age of 63 (±9) years. The observer agreement for cross‐sectional measurements was excellent for both intra‐observer variability (r = 0.99, P < 0.001) and inter‐observer variability (r = 0.98, P < 0.001). SMI correlated best with G8 frailty score (r = 0.38, P < 0.001) and did not differ per gender. Sarcopenia was present in 54 (48%) patients, whereof 25 (46%) men and 29 (54%) women. Prevalence of frailty was between 5% and 54% depending on the used screening tool. The multivariate regression analysis for all patients and men separately isolated the G8 questionnaire as the only independent variable associated with sarcopenia (OR 0.76, 95% CI 0.66–0.89, P < 0.001 and OR 0.76, 95% CI 0.66–0.88, P < 0.001, respectively).
Conclusions
This is the first study that demonstrates that sarcopenia is independently associated with frailty based on the G8 questionnaire in HNC patients. These results suggest that in the future, screening for sarcopenia on routinely obtained neck computed tomography scans may replace time consuming frailty questionnaires and help to select the (un)suitable patients for therapy, which is highly clinically relevant.

Zwart, A. T., van der Hoorn, A., van Ooijen, P. M. A., Steenbakkers, R. J. H. M., de Bock, G. H., and Halmos, G. B. ( 2019) CT‐measured skeletal muscle mass used to assess frailty in patients with head and neck cancer, Journal of Cachexia, Sarcopenia and Muscle, 10: 1060– 1069. https://doi.org/10.1002/jcsm.12443.

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     Article first published online:  10 July 2019

Seyyed Mohammad Reza Kazemi‐Bajestani, Harald Becher, Charles Butts, Naveen S. Basappa, Michael Smylie, Anil Abraham Joy, Randeep Sangha,Andrea Gallivan, Peter Kavsak, Quincy Chu, Vickie E. Baracos

Rapid atrophy of cardiac left ventricular mass in patients with non‐small cell carcinoma of the lung
Background
Cancer is a systemic catabolic condition affecting skeletal muscle and fat. We aimed to determine whether cardiac atrophy occurs in this condition and assess its association with cardiac function, symptoms, and clinical outcomes.
Methods
Treatment naïve metastatic non‐small cell lung cancer patients (n = 50) were assessed prior to and 4 months after commencement of carboplatin‐based palliative chemotherapy. Methods included echocardiography for left ventricular mass (LVM) and LV function [LV ejection fraction, global longitudinal strain (GLS), diastolic function], computed tomography to quantify skeletal muscle and total adipose tissue, Eastern Cooperative Oncology Group Performance Status (ECOG‐PS), validated questionnaires for dyspnoea and fatigue, plasma biomarkers, tumour response to therapy, and overall survival.
Results
During 112 ± 6 days, the median change in LVM was −8.9% [95% confidence interval (95% CI) −10.8 to −4.8, P < 0.001]. Quartiles of LVM loss were −20.1%, −12.9%, −4.8%, and +5.5%. Losses of muscle, adipose tissue, and LVM were frequently concurrent; LVM loss > median value was associated with loss of skeletal muscle [odds ratio (OR) = 4.5, 95% CI: 1.4–14.8, P=0.01] and loss of total adipose tissue (OR = 10.0, 95% CI: 2.7–36.7, P < 0.001). LVM loss was associated with decreased GLS (OR = 6.6, 95% CI: 1.9–22.7, P=0.003) but not with LV ejection fraction or diastolic function. In the population overall, plasma levels of C‐reactive protein (P=0.008), high sensitivity troponin T (hs‐TnT) (P=0.03), and galectin‐3 (P=0.02) increased over time, while N‐terminal pro B‐type natriuretic peptide and hs‐cTnI did not change over time. C‐reactive protein was the only biomarker associated with LVM loss but at the univariate level only. Independent predictors of LVM loss were prior weight loss (adjusted OR = 10.2, 95% CI: 2.2–46.9, P=0.003) and tumour progression (adjusted OR = 14.6, 95% CI: 1.4–153.9, P=0.02). LVM loss was associated with exacerbations of fatigue (OR = 6.6, 95% CI: 1.9–22.7, P=0.003), dyspnoea (OR = 9.3, 95% CI: 2.4–35.8, P<0.001), and deterioration of performance status (OR = 4.8, 95% CI: 1.3–18.3,P=0.02). Patients with concurrent loss of LVM, skeletal muscle, and fat were more likely to deteriorate in all three symptom domains and to have reduced survival (P=0.05).
Conclusions
Intense LVM atrophy is associated with non‐small cell lung cancer‐induced cachexia. Loss of LVM was associated with emerging alterations of GLS, indicating subtle changes in left ventricular function. Longer term studies are needed to assess the full scope of cardiac atrophy and its impact. LVM atrophy arises in conjunction with losses of fat and skeletal muscle and is temporally associated with meaningful declines in performance status, worsening of fatigue, and dyspnoea, as well as poorer tumour response and decreased survival. The specific contribution of LVM atrophy to these outcomes requires further study.

Kazemi‐Bajestani, S. M. R., Becher, H., Butts, C., Basappa, N. S., Smylie, M., Joy, A. A., Sangha, R., Gallivan, A., Kavsak, P., Chu, Q., and Baracos, V. E. ( 2019) Rapid atrophy of cardiac left ventricular mass in patients with non‐small cell carcinoma of the lung, Journal of Cachexia, Sarcopenia and Muscle, 10: 1070– 1082. https://doi.org/10.1002/jcsm.12451.

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     Article first published online:  08 July 2019

Xiaoling Zhong, Marianne Pons, Christophe Poirier, Yanlin Jiang, Jianguo Liu, George E. Sandusky, Safi Shahda, Attila Nakeeb, C. Max Schmidt, Michael G. House, Eugene P. Ceppa. Nicholas J. Zyromski, Yunlong Liu, Guanglong Jiang, Marion E. Couch, Leonidas G. Koniaris, Teresa A. Zimmers

The systemic activin response to pancreatic cancer: implications for effective cancer cachexia therapy
Background
Pancreatic ductal adenocarcinoma (PDAC) is a particularly lethal malignancy partly due to frequent, severe cachexia. Serum activin correlates with cachexia and mortality, while exogenous activin causes cachexia in mice.
Methods
Isoform‐specific activin expression and activities were queried in human and murine tumours and PDAC models. Activin inhibition was by administration of soluble activin type IIB receptor (ACVR2B/Fc) and by use of skeletal muscle specific dominant negative ACVR2B expressing transgenic mice. Feed‐forward activin expression and muscle wasting activity were tested in vivo and in vitro on myotubes.
Results
Murine PDAC tumour‐derived cell lines expressed activin‐βA but not activin‐βB. Cachexia severity increased with activin expression. Orthotopic PDAC tumours expressed activins, induced activin expression by distant organs, and produced elevated serum activins. Soluble factors from PDAC elicited activin because conditioned medium from PDAC cells induced activin expression, activation of p38 MAP kinase, and atrophy of myotubes. The activin trap ACVR2B/Fc reduced tumour growth, prevented weight loss and muscle wasting, and prolonged survival in mice with orthotopic tumours made from activin‐low cell lines. ACVR2B/Fc also reduced cachexia in mice with activin‐high tumours. Activin inhibition did not affect activin expression in organs. Hypermuscular mice expressing dominant negative ACVR2B in muscle were protected for weight loss but not mortality when implanted with orthotopic tumours. Human tumours displayed staining for activin, and expression of the gene encoding activin‐βA (INHBA) correlated with mortality in patients with PDAC, while INHBB and other related factors did not.
Conclusions
Pancreatic adenocarcinoma tumours are a source of activin and elicit a systemic activin response in hosts. Human tumours express activins and related factors, while mortality correlates with tumour activin A expression. PDAC tumours also choreograph a systemic activin response that induces organ‐specific and gene‐specific expression of activin isoforms and muscle wasting. Systemic blockade of activin signalling could preserve muscle and prolong survival, while skeletal muscle‐specific activin blockade was only protective for weight loss. Our findings suggest the potential and need for gene‐specific and organ‐specific interventions. Finally, development of more effective cancer cachexia therapy might require identifying agents that effectively and/or selectively inhibit autocrine vs. paracrine activin signalling.

Zhong, X., Pons, M., Poirier, C., Jiang, Y., Liu, J., Sandusky, G. E., Shahda, S., Nakeeb, A., Schmidt, C. M., House, M. G., Ceppa, E. P., Zyromski, N. J., Liu, Y., Jiang, G., Couch, M., Koniaris, L. G., and Zimmers, T. A. ( 2019) The systemic activin response to pancreatic cancer: implications for effective cancer cachexia therapy, Journal of Cachexia, Sarcopenia and Muscle, 10: 1083– 1101. https://doi.org/10.1002/jcsm.12461.

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     Article first published online:  29 May 2019

Volker Adams, T. Scott Bowen, Sarah Werner, Peggy Barthel, Christina Amberger, Anne Konzer, Johannes Graumann, Peter Sehr, Joe Lewis, Jan Provaznik, Vladimir Benes, Petra Büttner, Alexander Gasch, Norman Mangner, Christian C. Witt, Dittmar Labeit, Axel Linke, Siegfried Labeit

Small‐molecule‐mediated chemical knock‐down of MuRF1/MuRF2 and attenuation of diaphragm dysfunction in chronic heart failure
Background
Chronic heart failure (CHF) leads to diaphragm myopathy that significantly impairs quality of life and worsens prognosis. In this study, we aimed to assess the efficacy of a recently discovered small‐molecule inhibitor of MuRF1 in treating CHF‐induced diaphragm myopathy and loss of contractile function.
Methods
Myocardial infarction was induced in mice by ligation of the left anterior descending coronary artery. Sham‐operated animals (sham) served as controls. One week post‐left anterior descending coronary artery ligation animals were randomized into two groups—one group was fed control rodent chow, whereas the other group was fed a diet containing 0.1% of the compound ID#704946—a recently described MuRF1‐interfering small molecule. Echocardiography confirmed development of CHF after 10 weeks. Functional and molecular analysis of the diaphragm was subsequently performed.
Results
Chronic heart failure induced diaphragm fibre atrophy and contractile dysfunction by ~20%, as well as decreased activity of enzymes involved in mitochondrial energy production (P < 0.05). Treatment with compound ID#704946 in CHF mice had beneficial effects on the diaphragm: contractile function was protected, while mitochondrial enzyme activity and up‐regulation of the MuRF1 and MuRF2 was attenuated after infarct.
Conclusions
Our murine CHF model presented with diaphragm fibre atrophy, impaired contractile function, and reduced mitochondrial enzyme activities. Compound ID#704946 rescued from this partially, possibly by targeting MuRF1/MuRF2. However, at this stage of our study, we refrain to claim specific mechanism(s) and targets of compound ID#704946, because the nature of changes after 12 weeks of feeding is likely to be complex and is not necessarily caused by direct mechanistic effects.

Adams, V., Bowen, T. S., Werner, S., Barthel, P., Amberger, C., Konzer, A., Graumann, J., Sehr, P., Lewis, J., Provaznik, J., Benes, V., Büttner, P., Gasch, A., Mangner, N., Witt, C. C., Labeit, D., Linke, A., and Labeit, S. ( 2019) Small‐molecule‐ mediated chemical knock‐down of MuRF1/MuRF2 and attenuation of diaphragm dysfunction in chronic heart failure, Journal of Cachexia, Sarcopenia and Muscle, 10: 1102– 1115. https://doi.org/10.1002/jcsm.12448.

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     Article first published online:  15 July 2019

Raquel G.F. Costa, Paula L. Caro, Emídio M. de Matos‐Neto, Joanna D.C.C. Lima, Katrin Radloff, Michele J. Alves, Rodolfo G. Camargo, Ana Flávia M. Pessoa, Estefania Simoes, Patrícia Gama, Denise C. Cara, Aloísio S.F. da Silva, Welbert O. Pereira, Linda F. Maximiano, Paulo S.M. de Alcântara, José P. Otoch, Giorgio Trinchieri, Alessandro Laviano, Maurizio Muscaritoli, Marília Seelaender

Cancer cachexia induces morphological and inflammatory changes in the intestinal mucosafailure
Background
Cachexia is a multifactorial and multiorgan syndrome associated with cancer and other chronic diseases and characterized by severe involuntary body weight loss, disrupted metabolism, inflammation, anorexia, fatigue, and diminished quality of life. This syndrome affects around 50% of patients with colon cancer and is directly responsible for the death of at least 20% of all cancer patients. Systemic inflammation has been recently proposed to underline most of cachexia‐related symptoms. Nevertheless, the exact mechanisms leading to the initiation of systemic inflammation have not yet been unveiled, as patients bearing the same tumour and disease stage may or may not present cachexia. We hypothesize a role for gut barrier disruption, which may elicit persistent immune activation in the host. To address this hypothesis, we analysed the healthy colon tissue, adjacent to the tumour.
Methods
Blood and rectosigmoid colon samples (20 cm distal to tumour margin) obtained during surgery, from cachectic (CC = 25) or weight stable (WSC = 20) colon cancer patients, who signed the informed consent form, were submitted to morphological (light microscopy), immunological (immunohistochemistry and flow cytometry), and molecular (quantification of inflammatory factors by Luminex® xMAP) analyses.
Results
There was no statistical difference in gender and age between groups. The content of plasma interleukin 6 (IL‐6) and IL‐8 was augmented in cachectic patients relative to those with stable weight (P = 0.047 and P = 0.009, respectively). The number of lymphocytic aggregates/field in the gut mucosa was higher in CC than in WSC (P = 0.019), in addition to those of the lamina propria (LP) eosinophils (P < 0.001) and fibroblasts (P < 0.001). The area occupied by goblet cells in the colon mucosa was decreased in CC (P = 0.016). The M1M2 macrophages percentage was increased in the colon of CC, in relation to WSC (P = 0.042). Protein expression of IL‐7, IL‐13, and transforming growth factor beta 3 in the colon was significantly increased in CC, compared with WSC (P = 0.02, P = 0.048, and P = 0.048, respectively), and a trend towards a higher content of granulocyte‐colony stimulating factor in CC was also observed (P = 0.061). The results suggest an increased recruitment of immune cells to the colonic mucosa in CC, as compared with WSC, in a fashion that resembles repair response following injury, with higher tissue content of IL‐13 and transforming growth factor beta 3.
Conclusions
The changes in the intestinal mucosa cellularity, along with modified cytokine expression in cachexia, indicate that gut barrier alterations are associated with the syndrome.

Costa, R. G. F., Caro, P. L., de Matos‐Neto, E. M., Lima, J. D. C. C., Radloff, K., Alves, M. J., Camargo, R. G., Pessoa, A. F. M., Simoes, E., Gama, P., Cara, D. C., da Silva, A. S. F., Pereira, W. O., Maximiano, L. F., de Alcântara, P. S. M., Otoch, J. P., Trinchieri, G., Laviano, A., Muscaritoli, M., and Seelaender, M. ( 2019) Cancer cachexia induces morphological and inflammatory changes in the intestinal mucosa, Journal of Cachexia, Sarcopenia and Muscle, 10: 1116– 1127. https://doi.org/10.1002/jcsm.12449.

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     Article first published online:  18 July 2019

Merve Erdem, Diana Möckel, Sandra Jumpertz, Cathleen John, Athanassios Fragoulis, Ines Rudolph, Johanna Wulfmeier, Jochen Springer, Henrike Horn, Marco Koch, Georg Lurje, Twan Lammers, Steven Olde Damink, Gregory van der Kroft, Felix Gremse, Thorsten Cramer

Macrophages protect against loss of adipose tissue during cancer cachexia
Background
Cancer cachexia represents a central obstacle in medical oncology as it is associated with poor therapy response and reduced overall survival. Systemic inflammation is considered to be a key driver of cancer cachexia; however, clinical studies with anti‐inflammatory drugs failed to show distinct cachexia‐inhibiting effects. To address this contradiction, we investigated the functional importance of innate immune cells for hepatocellular carcinoma (HCC)‐associated cachexia.
Methods
A transgenic HCC mouse model was intercrossed with mice harbouring a defect in myeloid cell‐mediated inflammation. Body composition of mice was analysed via nuclear magnetic resonance spectroscopy and microcomputed tomography. Quantitative PCR was used to determine adipose tissue browning and polarization of adipose tissue macrophages. The activation state of distinct areas of the hypothalamus was analysed via immunofluorescence. Multispectral immunofluorescence imaging and immunoblot were applied to characterize sympathetic neurons and macrophages in visceral adipose tissue. Quantification of pro‐inflammatory cytokines in mouse serum was performed with a multiplex immunoassay. Visceral adipose tissue of HCC patients was quantified via the L3 index of computed tomography scans obtained during routine clinical care.
Results
We identified robust cachexia in the HCC mouse model as evidenced by a marked loss of visceral fat and lean mass. Computed tomography‐based analyses demonstrated that a subgroup of human HCC patients displays reduced visceral fat mass, complementing the murine data. While the myeloid cell‐mediated inflammation defect resulted in reduced expression of pro‐inflammatory cytokines in the serum of HCC‐bearing mice, this unexpectedly did not translate into diminished but rather enhanced cachexia‐associated fat loss. Defective myeloid cell‐mediated inflammation was associated with decreased macrophage abundance in visceral adipose tissue, suggesting a role for local macrophages in the regulation of cancer‐induced fat loss.
Conclusions
Myeloid cell‐mediated inflammation displays a rather unexpected beneficial function in a murine HCC model. These results demonstrate that immune cells are capable of protecting the host against cancer‐induced tissue wasting, adding a further layer of complexity to the pathogenesis of cachexia and providing a potential explanation for the contradictory results of clinical studies with anti‐inflammatory drugs.

Erdem, M., Möckel, D., Jumpertz, S., John, C., Fragoulis, A., Rudolph, I., Wulfmeier, J., Springer, J., Horn, H., Koch, M., Lurje, G., Lammers, T., Olde Damink, S., van der Kroft, G., Gremse, F., and Cramer, T. ( 2019) Macrophages protect against loss of adipose tissue during cancer cachexia, Journal of Cachexia, Sarcopenia and Muscle, 10: 1128– 1142. https://doi.org/10.1002/jcsm.12450.

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     Article first published online:  29 October 2019

Stephan von Haehling, John E. Morley, Andrew J. S. Coats, Stefan D. Anker

Ethical guidelines for publishing in the Journal of Cachexia, Sarcopenia and Muscle: update 2019update 2019
This article details an updated version of the principles of ethical authorship and publishing in the Journal of Cachexia, Sarcopenia and Muscle (JCSM) and its two daughter journals JCSM Rapid Communication and JCSM Clinical Reports. We request of all author sending to the journal a paper for consideration that at the time of submission to JCSM, the corresponding author, on behalf of all co‐authors, needs to certify adherence to these principles.

von Haehling, S., Morley, J. E., Coats, A. J. S., and Anker, S. D. ( 2019) Ethical guidelines for publishing in the Journal of Cachexia, Sarcopenia and Muscle: update 2019, Journal of Cachexia, Sarcopenia and Muscle, 10: 1143– 1145. https://doi.org/10.1002/jcsm.12501.

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     Article first published online:  21 May 2019

Charlotte Suetta, Andrea B. Maier

Is muscle failure a better term than sarcopenia?
no abstract

Suetta, C., and Maier, A. B. ( 2019) Is muscle failure a better term than sarcopenia?, Journal of Cachexia, Sarcopenia and Muscle, 10: 1146– 1147. https://doi.org/10.1002/jcsm.12447.

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     Article first published online:  21 May 2019

Corrigendum to: Mitochondrial oxidative stress impairs contractile function but paradoxically increases muscle mass via fibre branching
no abstract

( 2019) Corrigendum, Journal of Cachexia, Sarcopenia and Muscle, 10: 1148. https://doi.org/10.1002/jcsm.12493.

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