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Reviewed articles

Explore our in-depth reviewed articles on sarcopenia, cachexia, and wasting disorders - conditions associated with muscle loss and functional decline.

2022: A year of research in JCSM

The Journal of Cachexia, Sarcopenia and Muscle mainly publishes research on cachexia, sarcopenia and muscle wasting disorders, but also includes papers on cancer, heart failure, ageing and many other conditions. Before November 2022, there were seen to be 775,000 downloads of the articles within the journal, with the top three countries downloading articles being China, the US and Japan. The most downloaded and cited article is entitled, Cachexia as a major underestimated and unmet medical need: facts and numbers. This review by Frohlich A et al. aimed to review the successes of the Journal of Cachexia, Sarcopenia and Muscle in 2022.

Frailty as a predictive metric for pre- and post-transplant outcomes

Frailty is a known risk factor for negative surgical outcomes, and the Liver Frailty Index (LFI) has been shown to predict mortality in patients awaiting liver transplants. Despite this, neither a diagnosis of frailty nor a patient’s LFI holds any weight when determining their position on liver transplant waitlists. The aim of this article was to assess frailty and the LFI’s ability to predict pre- and post-transplant outcomes.

Explaining and combatting the knowledge gaps surrounding sarcopenia

Sarcopenia is characterised by an age-related decline in muscle mass and strength combined with impairments in physical function. The risk of falls, fractures, and death is doubled in individuals with sarcopenia compared to those without. This patient population also frequently possesses comorbid diseases, including diabetes, cardiovascular disease, dementia, and chronic obstructive pulmonary disease. This may significantly increase their risk of suffering adverse outcomes post-surgery. The aim of this editorial was to expose the serious nature of sarcopenia and underscore associated knowledge gaps in clinical practice.

The inflammatory response in muscle homeostasis and plasticity: a review

Around half of a healthy person’s body weight is made up of skeletal muscle. This type of muscle is able to demonstrate high levels of plasticity. In muscle homeostasis, as well as repair processes, there are satellite cells and inflammatory cells which play key roles. However, if the recruitment of inflammatory cells is not carefully controlled, muscle atrophy and fibrosis may occur, leading to muscle function impairment. Hence, the inflammation occurring in muscle repair as a double-edged sword. This is because inflammatory mediators play a role in fighting pathogens as well as in the formation of mature myofibres, but may also cause damage to the muscle. For example, inflammation is also associated with cachexia - specifically, there is a correlation between cachexia and high levels of circulating cytokines. This paper also ends with a summary of approaches to treating muscle wasting disorders, such as cachexia, discussing exercise, nutritional interventions and targeting inflammatory pathways. This review by Bouredji Z et al. aimed to discuss inflammation in muscle homeostasis and repair, as well as some management approaches to muscle wasting disorders such as cachexia.

Review of the endocrine organ-like tumour hypothesis of cancer cachexia in pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma, PDAC, is one of the most fatal types of solid tumours. It is also linked to a high prevalence of cachexia, with around 80% of PDAC patients exhibiting cachexia. There is one hypothesis, the endocrine organ–like tumour hypothesis, which aims to explain the reasons behind cancer cachexia occurring during pancreatic ductal adenocarcinoma. Some of the reasons include metabolites, epigenetic changes, hormonal disturbance and genetic instability may be behind the development of cancer cachexia. Generally, the belief is held that metabolic disruption is the process behind cachexia development, but it is also believed there is not one single factor that triggers it. This review by Yu Y et al aimed to synthesise an understanding of cancer cachexia development and the response of cachexia to current available treatments.

Malnutrition risk and frailty in head and neck cancer patients: a review

For patients with head and neck cancer, malnutrition and frailty are linked with adverse treatment outcomes, higher mortality rates, complications post-surgery and generally lower quality of life. However, the relationship between malnutrition and frailty is not fully known. It is, however, clear that these two conditions often coexist, suggesting they may share similar risk factors. In this study on 197 patients, it was found that the risk of malnutrition is strongly positively associated with frailty. However, some other interesting factors were discovered. Alcohol consumption was shown to present a greater risk of developing malnutrition, but on the other hand, alcohol consumption seems protective for being frail. Overall, these conditions often coexist but do not always fully overlap: screening for both conditions is therefore recommended. This review by Dewansingh P et al aimed to understand the relationship between the risk of malnutrition and frailty in patients with head and neck cancer.

Sarcopenia and frailty assessments’ predictive value in elderly patients with COVID-19

Dynapenia is characterised by an age-related loss of muscle strength. When coupled with low muscle mass, it is instead diagnosed as sarcopenia according to the European Working Group on Sarcopenia in Older People revised guidelines (EWGSOP2). The SARS-CoV-2 infection is accompanied by severe inflammation and increased catabolism, which may significantly impact infected patients’ skeletal muscle structure and function. These impacts may be detrimental to elderly patients, who are disproportionately affected and already highly burdened by the disease. Recent studies have suggested that sarcopenia at the time of hospital admission may shape older patients’ length of stay and increase mortality in those with moderate to severe COVID-19. The aim of this study was to examine the association between simple clinical biomarkers, including those for the assessment of muscle function and frailty, and the risk of poor survival as well as increased length of hospital stay in older patients with COVID-19. Sarcopenia was screened using SARC-F, while frailty was assessed in accordance with the Rockwood Clinical Frailty Scale.

Sarcopenia and its metabolic basis in CKD: the key to treating physical frailty?

Patients with chronic kidney disease (CKD) possess an increased risk of developing physical or phenotypic frailty. The skeletal muscle dysfunction underpinning physical frailty has been associated with increased mortality. CKD-related phenotypic frailty shares features with ageing-related frailty, and CKD has thus been touted as a clinically relevant model of premature ageing. The aim of this review was to examine the metabolic basis and pathogenesis of the skeletal muscle dysfunction responsible for phenotypic frailty in patients with CKD.

Sarcopenic obesity: prevalence and related outcomes

Ageing is associated with increased fat accumulation and weight gain due to altered energy metabolism. Sarcopenia, defined as a loss of muscle mass and function associated with increased mortality risk, is also linked to ageing. Sarcopenia obesity (SO) refers to the combination of age-related sarcopenia and obesity, and stems from the negative correlation between intermuscular adipose tissue accumulation and muscle performance. While elderly patients with obesity possess lower death rates than those with lower body mass indexes, patients with SO have higher mortality rates than these same peers. This, as well as obesity’s protective role against sarcopenia in the elderly, is the basis of the commonly known ‘obesity paradox’. The aim of this review was to assess the current clinical evidence relating to SO.

Frailty, non-cirrhotic NAFLD, and exercise: a new model of care?

It is known that advanced liver disease and frailty are heavily interlinked, and frailty’s association with an increased risk of progression to cirrhosis and death has been widely documented. Patients with advanced liver disease who are on waiting lists for liver transplants are urged to increase their physical activity prior to surgery. However, this patient population only represents a minority of liver disease patients. This article aims to examine the prevalence of frailty in patients with non-cirrhotic non-alcoholic fatty liver disease (NAFLD), and exposes the faults of current models of care for this patient population.

Cachexia staging score and cancer survival: a review

Cancer cachexia has no simple criteria to distinguish its severity in patients. Diagnostic criteria generally includes observing factors such as weight loss, fatigue, abnormal levels of albumin, reduced food intake and others. However, this study explored the cachexia staging score, a method of diagnosing cancer cachexia severity. This score explores strength, walking, rising from a chair, climbing up stairs and how often the patients fall. This allows clinicians to understand the patient’s muscle function. In this study, the cachexia staging score was testing in patients with advanced cancer who are receiving palliative care, to assess its usefulness in these patients. Here, the cachexia staging score was excellent at predicting life expectancy in the patients with advancing cancer receiving palliative care, and was able to classify patients according to their different stages of cachexia. This review by Ueshima J et al. aimed to assess whether the cachexia staging score could be applied to patients with advanced cancer under palliative care.

Hand grip strength-based cachexia index: a review

Cancer cachexia can be mainly categorised with the occurrence of muscle loss, malnutrition and systemic inflammation. Its prognosis can be assessed through the cachexia index, but the use of this index is limited due to it being a complicated procedure with high testing costs. This study explored using a hand grip strength-based cachexia index, testing it with 14, 682 cancer patients. A low hand grip strength index score was found to be associated with high systemic inflammation, high levels of malnutrition and co-morbidities, implying that this index may be associated with disease progression. Overall, using the hand grip strength index for cachexia reflects the muscular and inflammatory conditions of cachexia in one assessment, rather than using multiple such as serum albumin testing, in a simple, non-invasive measure. Furthermore, there is a potential that hand grip strength can provide information about the prognosis of other malignancies. This review by Xie H et al. aimed to compare the hand grip strength-based cachexia index to the original cachexia index to understand its benefits.

Sarcopenia and cachexia prevalence in older patients with colorectal cancer

Colorectal cancer (CRC) incidence has been shown to increase with age, an association which is clinically significant in the context of global ageing populations. Frailty, defined as increased vulnerability to stressors like surgery, is a marker associated with poor outcomes in patients with CRC. Sarcopenia, characterised by an age- and disease-related loss in muscle function and mass, has been identified as a major contributor to frailty. Patients with cancer also commonly experience cancer cachexia, i.e., loss of fat and muscle mass. This syndrome has also been associated with poorer survival rates for cancer patients. As such, both sarcopenia and cachexia constitute potentially modifiable risk factors of negative surgical outcomes. This study aimed to examine the prevalence of preoperative sarcopenia and cachexia in a group of older (≥65 years) vulnerable patients undergoing resection for localized CRC.

Sarcopenia in kidney transplant recipients: prevalence, predictors, and prognosis

Patients with end-stage kidney disease (ESKD) are recommended to consider kidney transplantation (KT), a procedure known for improving survival and quality of life a smaller cost than dialysis. Current studies in kidney transplant recipients (KTRs) note heterogenous prevalence rates for sarcopenia, which ranges from 3.7% to 72.1%. This heterogeneity could be attributed to differences in diagnostic criteria and/or sample sizes. Ultimately, however, it contributes to the uncertainty surrounding sarcopenia’s clinical predictors and its impact on outcomes in KTRs. The aim of this study was to investigate the literature on KTRs to determine the most common reported diagnostic criteria of sarcopenia, its prevalence, clinical predictors, and its impact on KTRs’ outcomes.

Amino acids in cancer and cachexia: a review

Amino acid metabolism is hugely altered in tumours. Cancer cells use amino acids for energy production, which supports cell proliferation. In this sense, their amino acid dependency provides a metabolic vulnerability for treatment. Research has been aimed at starving cancerous cells of amino acids to improve cancer treatment outcomes. However, supplementing amino acids has also shown benefits both in vivo and in vitro. Further research into amino acid supplementation is needed, as deprivation exacerbates cancer cachexia, a risk best avoided in cancer treatment. Supplementing branched-chain amino acids has been proved as beneficial in hepatocellular carcinoma, and an essential amino acid rich diet has demonstrated decreased tumour growth in mice. Understanding more about amino acid metabolism in cancer may provide more efficient, personalised treatments for cancer patients. This review by Ragni M et al. aimed to discuss amino acid deprivation and supplementation in reducing tumour growth, underscoring the complexity of the metabolic pathways involved.

The bone-muscle connection in breast cancer: a review

Breast cancer treatments often lead to musculoskeletal morbidity; muscle loss in general is seen as a complication of breast cancer, affecting survival and quality of life. Emerging new research into the biochemical and molecular links between the skeletal and muscular systems is beginning to be taken into account, alongside the well-known anatomical relationship, to improve our understanding of these effects. This paper discussed treatments such as anti-oestrogen therapy, which deteriorates bone health and muscle mass, and the significance of these effects in lower survival rates and worse outcomes for patients. In this sense, exercise is concluded to be of aid for patients with breast cancer in improving their outcomes. This review by Ballinger T et al. aimed to understand the relevance of musculoskeletal health to breast cancer, and the strategies that could aid patients in this disease.

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