Volume 1 (2010)
Page 1 - 5
Stephan von Haehling, Stefan D. Anker
Cachexia as a major underestimated and unmet medical need: facts and numbersCachexia is a serious, however underestimated and underrecognised medical consequence of malignant cancer, chronic heart failure (CHF), chronic kidney disease (CKD), chronic obstructive pulmonary disease (COPD), cystic fibrosis, rheumatoid arthritis, Alzheimer's disease, infectious diseases, and many other chronic illnesses. The prevalence of cachexia is high, ranging from 5% to 15% in CHF or COPD to 60% to 80% in advanced cancer. By population prevalence, the most frequent cachexia subtypes are in order: COPD cachexia, cardiac cachexia (in CHF), cancer cachexia, and CKD cachexia. In industrialized countries (North America, Europe, Japan), the overall prevalence of cachexia (due to any disease) is growing and currently about 1%, i.e., about nine million patients. The relative prevalence of cachexia is somewhat less in Asia, but is a growing problem there as well. In absolute terms, cachexia is, in Asia (due to the larger population), as least as big a problem as in the Western world. Cachexia is also a big medical problem in South America and Africa, but data are scarce. A consensus statement recently proposed to diagnose cachexia in chronic diseases when there is weight loss exceeding 5% within the previous 3–12 months combined with symptoms characteristic for cachexia (e.g., fatigue), loss of skeletal muscle and biochemical abnormalities (e.g., anemia or inflammation). Treatment approaches using anabolics, anti-catabolic therapies, appetite stimulants, and nutritional interventions are under development. A more thorough understanding of the pathophysiology of cachexia development and progression is needed that likely will lead to combination therapies being developed. These efforts are greatly needed as presence of cachexia is always associated with high-mortality and poor-symptom status and dismal quality of life. It is thought that in cancer, more than 30% of patients die due to cachexia and more than 50% of patients with cancer die with cachexia being present. In other chronic illnesses, one can estimate that up to 30% of patients die with some degree of cachexia being present. Mortality rates of patients with cachexia range from 10% to 15% per year (COPD), to 20% to 30% per year (CHF, CKD) to 80% in cancer.
von Haehling S, Anker SD. Cachexia as a major underestimated and unmet medical need: facts and numbers. J Cachexia Sarcopenia Muscle 2010;1:1–5.
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Stephan von Haehling, John E. Morley, Andrew J. S. Coats, Stefan D. Anker
Ethical guidelines for authorship and publishing in the Journal of Cachexia, Sarcopenia and MuscleThe principles of ethical authorship and publishing in the Journal of Cachexia, Sarcopenia and Muscle (JCSM) are:
1. all authors listed on the manuscript have approved its submission and publication as provided to JCSM;
2. no person who has a right to be recognized as author has been omitted from the list of authors;
3. each author has made an independent material contribution to the work submitted for publication;
4. the submitted work is original and is neither under consideration elsewhere nor has it been published previously in whole or in part other than in abstract form;
5. all original research work is approved by the relevant bodies such as institutional review boards or ethics committees;
6. all conflicts of interest, financial or otherwise, that may affect the authors' ability to present data objectively have been duly declared in the manuscript;
7. the manuscript in its published form will be maintained on the servers of JCSM as a valid publication only as long as all statements in the guidelines on ethical publishing remain true;
8. if any of the aforementioned statements ceases to be true, the authors have a duty to notify the editors of JCSM as soon as possible so that the information available online can be updated and/or the manuscript can be withdrawn
von Haehling S, Morley JE, Coats AJ, Anker SD. Ethical guidelines for authorship and publishing in the Journal of Cachexia, Sarcopenia and Muscle. J Cachexia Sarcopenia Muscle 2010;1: 7-8.
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Karsten Lenk, Gerhard Schuler, Volker Adams
Skeletal muscle wasting in cachexia and sarcopenia: molecular pathophysiology and impact of exercise trainingSkeletal muscle is the most abundant tissue in the human body, and the maintenance of its mass is essential to ensure basic function as locomotion, strength and respiration. The decision to synthesize or to break down skeletal muscle proteins is regulated by a network of signaling pathways that transmit external stimuli to intracellular factors regulating gene transcription. The tightly regulated balance of muscle protein breakdown and synthesis is disturbed in several distinct myopathies, but also in two pathologies: sarcopenia and cachexia. In recent years, it became evident that in these two muscle wasting disorders specific regulating molecules are increased in expression (e.g. members of the ubiquitin–proteasome system, myostatin, apoptosis inducing factors), whereas other factors (e.g. insulin-like growth factor 1) are down-regulated. So far, not many treatment options to fight the muscle loss are available. One of the most promising approaches is exercise training that, due to its multifactorial effects, can act on several signaling pathways. Therefore, this review will concentrate on specific alterations discussed in the current literature that are present in the skeletal muscle of both muscle wasting disorders. In addition, we will focus on exercise training as an intervention strategy.
Lenk K, Schuler G, Adams V. Skeletal muscle wasting in cachexia and sarcopenia: molecular pathophysiology and impact of exercise training. J Cachexia Sarcopenia Muscle 2010;1:9-21.
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Pontus M. A. Siren, Matti J. Siren
Systemic zinc redistribution and dyshomeostasis in cancer cachexiaCachexia affects up to two thirds of all cancer patients and is a significant cause of morbidity and mortality. It is a complex metabolic syndrome associated with the underlying illness and characterized by loss of skeletal muscle tissue with or without loss of fat mass. Cachexia’s other prominent clinical symptoms include anorexia, systemic inflammation, pediatric growth failure, and hypogonadism. The relationship between the symptoms of cancer cachexia and the underlying illness is unclear, and there is an urgent need for a better understanding of the pathophysiology of this syndrome. Normal Zn metabolism is often disrupted in cancer patients, but the possible effects of systemic Zn dyshomeostasis in cachexia have not been investigated. We propose that the acute phase response can mediate Zn redistribution and accumulation in skeletal muscle tissue and contribute to the activation of the ubiquitin–proteasome pathway that regulates protein catabolism. This chronic redistribution deprives Zn from other tissues and organs and compromises critical physiological functions in the body. The cardinal symptoms of Zn deficiency are anorexia, systemic inflammation, growth failure in children, and hypogonadism. These symptoms also prominently characterize cancer cachexia suggesting that the role of systemic Zn dyshomeostasis in cachexia should be investigated.
Siren PM, Siren MJ. Systemic zinc redistribution and dyshomeostasis in cancer cachexia. J Cachexia Sarcopenia Muscle 2010;1:23-33.
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Piotr Rozentryt, Stephan von Haehling, Mitja Lainscak, Jolanta U. Nowak, Kamyar Kalantar-Zadeh, et al.
The effects of a high-caloric protein-rich oral nutritional supplement in patients with chronic heart failure and
cachexia on quality of life, body composition, and inflammation markers: a randomized, double-blind pilot studyThe prevalence of cardiac cachexia in chronic heart failure is approximately 5% to 15% and 18-month mortality rates can reach 50%. Treatment with angiotensin-converting enzyme inhibitors and beta-blockers may confer some benefit but no proven therapy exists. We tested the effects of an oral nutritional supplement in cachectic patients with heart failure. This was a prospective, randomized, double-blind, placebo-controlled pilot study which randomized 29 patients to a high-caloric (600 kcal) high-protein (20 g) oral nutritional supplement or placebo for a duration of 6 weeks in addition to the patients’ usual food intake. At baseline, 6 weeks, and 18 weeks, we measured body weight, quality of life, body composition, heart function, laboratory parameters, and exercise performance. Edema-free body weight increased in 19 of 20 patients receiving intervention at 6 weeks and in 17 of 19 patients at 18 weeks with an average weight gain of 2.0 ± 1.7 kg (3.1 ± 2.4%, p = 0.0001) and 2.3 ± 3.1 kg (3.6 ± 4.7%, p = 0.007) at 6 and 18 weeks, respectively. Most of the weight gain was fat tissue with an absolute gain of 1.5 ± 1.7 kg (p = 0.003) and 1.6 ± 2.7 kg (p = 0.008). A significant improvement in quality of life and decrease in serum levels of tumor necrosis factor-α were observed (p < 0.05 for both). We demonstrated the feasibility of oral nutritional supplement in cachectic patients with heart failure and significant clinical benefit in terms of body size and body composition, laboratory parameters, and quality of life (www.clinicaltrials.gov identifier NCT00654719). </p>
Rozentryt P, von Haehling S, Lainscak M, Nowak JU, Kalantar-Zadeh K, Polonski L, Anker SD. The effects of a high-caloric protein-rich oral nutritional supplement in patients with chronic heart failure and cachexia on quality of life, body composition, and inflammation markers: a randomized, double-blind pilot study. J Cachexia Sarcopenia Muscle 2010;1:35-42.
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