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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.

Sarcopenia and Type 2 Diabetes: A Bidirectional Relationship

Sarcopenia is characterised by age-related reductions in skeletal muscle strength, mass, and functional ability. Importantly, sarcopenia is a multifactorial condition associated with metabolic alterations, including poor glucose disposal, insulin resistance, decreased metabolic rate and, thus, type 2 diabetes (T2D). Developing non-pharmaceutical guidelines for the prevention and treatment of both diseases when they coexist is essential to optimise patient health and reduce premature mortality within this patient population. This review aimed to examine 1) the pathophysiological link between sarcopenia and T2D, and 2) lifestyle interventions with the potential to mitigate both sarcopenia and T2D.

Leucine-enriched Protein Supplementation for the Pre-frail: What Are the Benefits?

It is known that one in five adults with pre-frailty progresses to frailty over a 3-year period. Low protein and energy intake, increased prevalence of multimorbidity, and a sedentary lifestyle are well-characterised drivers of sarcopenia. Consequently, they act as catalysts of older adults’ transition to frailty. In this vein, stimulating increased muscle protein synthesis through regular physical exercise and protein-enriched diet consumption is pivotal for pre-frail older adults. Current U.S. Food and Nutrition Board guidelines recommend a dietary allowance of 0.8 g/kg of protein per day for older adults. However, this amount may be insufficient for those with pre-frailty due to their low-grade inflammation, multimorbidity, and increased susceptibility to anabolic resistance. This study aimed to examine the impact of leucine-enriched protein supplementation with or without exercise on 1) physical function, 2) body composition, and 3) systemic inflammation in pre-frail older adults with a daily protein consumption of ≤1 g/kg.

Evaluating health-related quality of life in patients with sarcopenia

The normal ageing process is accompanied by progressive declines in muscle mass and strength. Abnormal and excessive losses of skeletal muscle mass and quality emerge as a consequence of age-related musculoskeletal disorders, e.g. sarcopenia. The latter confers affected patients with increased risks of adverse outcomes, including falls, fractures, and mortality. Moreover, sarcopenic patients often exhibit higher levels of dependency and disability, both of which impact their health-related quality of life (HRQoL). HRQoL measures are well-characterised predictors of hard clinical outcomes, including hospitalisation and mortality. Accordingly, the use of sarcopenia-specific HRQoL tools in clinical practice and interventional trials is recommended by recent European Working Group on Sarcopenia in Older People (EWGSOP2) guidelines. This meta-analysis aimed to characterise the relationship between sarcopenia and patient-reported HRQoL.

GDF-15: a mediator of exercise’s link with late-life weight loss?

Ageing is often associated with appetite reduction and ensuing weight loss. Although it is known that physical activity (PA) can prevent these ageing-related processes, the exact molecular mechanisms underpinning this ability remain unknown. Recent research has highlighted the role of exerkines, i.e. proteins released during and after PA, in controlling energy metabolism. Growth differentiation factor 15 (GDF-15), a stress-signalling cytokine secreted during PA and involved in ageing, exercise, and appetite control, has emerged as a potential mediator of late-life, ageing-related weight loss. This study aimed to explore the associations between PA, GDF-15, and body weight changes in older adults enrolled in the Multidomain Alzheimer Preventive Trial over a 3-year period.

Cancer cachexia risk score for digestive tract cancer: a review

Cancer cachexia, a form of malnutrition, can be viewed as a determinant of prognosis. However, there are no effective therapies or treatments for this condition. Hence, the identification of high-risk patients remains crucial for the assessment and management of cancer cachexia. The cancer cachexia risk score was validated to show good performance; it successfully identified at-risk digestive tract cancer patients before abdominal surgery. This risk score can provide vital help to clinicians in their cancer cachexia screening process, allowing them to understand a patient’s prognosis and build better-informed decisions for abdominal surgery. This review by Tan S et al. aimed to discuss the cancer cachexia risk score in relation to digestive tract cancer patients, to understand whether survival risks can be identified prior to surgery.

Nutrition in nasopharyngeal carcinoma: a review

Locoregionally advanced nasopharyngeal carcinoma is a type of head and neck cancer. Induction chemotherapy and concurrent chemoradiotherapy is the most common standard of care. However, due to the toxicity and intensity of these treatments, patients’ nutritional statuses are often negatively impacted. Weight loss and malnutrition are often overlooked in head and neck cancer patients, despite the fact that around half of all head and neck cancer patients suffer from malnutrition. This negatively affects their quality of life, affecting physical functioning, nausea and vomiting and can even affect emotional and cognitive functioning. This study supports the need to monitor patients’ nutritional statuses during the later phase of treatments and work on nutritional interventions. This review by Miao J et al. aimed to explore the need for nutritional interventions in nasopharyngeal carcinoma.

Inflammatory burden index for the prognosis of non-small cell lung cancer: a review

There is an urgent need to find predictive biomarkers for the prognosis of non-small cell lung cancer for survival assessment. Tumour-related factors, such as the pathological stage or histological subtype, are used widely but often vary in patient outcome. Hence, haematological inflammatory parameters, such as neutrophils, lymphocytes and platelets have been used to reflect the inflammation found in cancer. These biomarkers demonstrate prognostic value in cancers such as non-small cell lung cancer. However, it remains unclear which specific combination of biomarkers may help in assessing prognosis, so this study used the newly developed inflammatory burden index (IBI). It was found to be associated with survival, 90-day outcomes, length of hospitalisation and cachexia in non-small cell lung cancer patients. Hence, this may be an advantageous tool for prognosis prediction. This review by Xie H et al. aimed to compare the prognostic value of inflammation biomarkers in patients with non-small cell lung cancer.

Immunology and cachexia: a review

Many types of conditions and diseases are associated with wasting syndromes such as cachexia. However, despite its prevalence, there is limited knowledge regarding the diagnosis and treatment of cachexia due to our lack of understanding of the causative molecular mechanisms. Cachexia must be viewed through an immunological context to understand its full consequences on patient prognosis. For example, it is known that cytokines such as tumour necrosis factor, IL-1β, IL-6 and IFNγ are consistently upregulated in cases of cachexia in both immune and non-immune cells. This appears to lead to the changes in transcriptional regulation, inducing catabolic pathways in muscles and adipose tissue. Yet, despite this understanding, targeting such cytokines has not shown successful in clinical settings. Further research has also been done to identify the involvement of immune cells such as macrophages, neutrophils, myeloid-derived suppressor cells and T cells in cachexia. Yet, their full involvement in the condition is not yet understood. Hence, many questions remain about this interplay between cachexia and immune system. It is vital to discover the common and unique properties of cancer cachexia and infection-associated cachexia to develop effective therapeutic strategies for cachexia. This review by Baazim H et al. aimed to highlight the relationship between the immune system and cachexia, as well as our current lack of knowledge surrounding this syndrome.

Cachexia staging score predicts survival: a review

The guidelines most commonly used to diagnose cachexia are the European Palliative Care Research Collaborative (EPCRC) guidelines. Here, cachexia is classified according to weight loss. However, for patients in palliative care with advanced cancer, there are often cases of oedema and ascites. This hampers the ability to detect weight loss, affecting the likelihood to be diagnosed with cachexia. Therefore, this study wished to examine the validity of diagnosing cachexia based upon other items. Alongside weight loss, this includes factors such as fatigue, decreasing muscle mass in the mid-upper arm, abnormal levels of white blood cells, reduced food intake and others. This study validated the CSS, Cachexia Staging Score, which demonstrated that patients without cachexia had a higher survival rate, and that the risk of mortality was higher with more severe cachexia. They also validated that cachexia prevalence was not significantly different compared to previous studies. Hence, such a multidimensional assessment helps to evaluate disorders including cachexia. This review by Ueshima J et al. aimed to validate the Cachexia Staging Score for patients with advanced cancer who are under palliative care.

Tumour derived exosomes and cancer cachexia: a review

Exosomes are extracellular vesicles that contain cargo such as proteins, lipids, nucleic acids and more. Their function is to alter cell signalling in the cell it releases its cargo into. For example, exosomes have been seen to alter muscle and adipose tissue metabolism. This has led to the thought that they may be involved in cancer cachexia. Inhibiting tumour derived exosome release therefore may improve survival and cancer cachexia in patients. Specifically, tumour derived exosome micro-RNAs have been associated with muscle wasting and tumour presence. Furthermore, they may package inflammatory cytokines. This could play a causal role in cancer cachexia as increase cytokine circulation is thought to precede the loss of appetite in cachexia, holding a causal role in the disease progression. This review by Pitzer CR et al. aimed to summarise the potential involvement of tumour derived exosomes in cancer cachexia.

Sarcopenia, unpreparedness, and the developing world: an urgent concern?

Muscle strength has recently been defined as sarcopenia’s main component by the revised European Working Group in Sarcopenia for Older People (EWGSOP2). This shift from muscle mass to strength has had transformative implications within clinical practice and has greatly facilitated sarcopenia’s diagnostic process. Despite this trailblazing consensus, sarcopenia remains an issue of growing concern throughout high-income countries (HICs). Although low- and middle-income countries (LMICs) are disproportionately affected by the threat of sarcopenia, their care providers and healthcare systems seem to be the least prepared to tackle it. The aim of this article is to expose the state of sarcopenia awareness and management in LMICs. It further proposes solutions to prepare the developing world for this growing concern.

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