Appetite loss, malnutrition, and mortality: a significant association in need of urgent recognition?
Despite its high prevalence among older adults, appetite loss is underrecognized in clinical practice. Explanations for this underrecognition include the lack of uniform terminology for the condition paired with an absence of defined, standardised approaches to assessing it. Moreover, appetite loss is commonly misconstrued as a normal and irreversible part of the ageing process. Together, these reasons create heterogeneity across anorexia of ageing studies, thereby hindering the recognition and management of appetite loss among older adults. To overcome this gap, a better understanding of appetite loss’ effects on morbidity and mortality in older adults is needed. This systematic literature review aimed to investigate the relationship between appetite loss and negative outcomes in older adults aged ≥ 65 years.
Sarcopenia and its prognostic value in advanced gastroesophageal cancer
Esophageal, gastroesophageal, and gastric cancers make up a significant proportion of the global cancer burden. Associated with a poor prognosis and 5-year survival rate, up to half of patients present with an advanced stage of disease upon diagnosis, hindering the success of curative treatments. Fluorine-18-Fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) is a standard test with great diagnostic and prognostic value amongst patients with esophageal, gastroesophageal, and gastric cancers. Its inclusion of computed tomography facilitates the assessment of skeletal muscle, and thus, sarcopenia, in this patient population. Although sarcopenia has been shown to influence postoperative complications, its prognostic value for patients with advanced disease has not yet been characterised. The aim of this study was to ascertain the prognostic value sarcopenia measurements and metabolic activity parameters of primary gastroesophageal cancer in patients with advanced metastatic disease.
Metabolic dysfunction and candidate biomarkers: an overview of anorexia of ageing
Anorexia of ageing is characterised by an age-associated reduction in appetite and food intake. With a prevalence of 20% in older adults, this syndrome may engender malnutrition and metabolic impairments, both of which are associated with increased negative health outcomes. Indeed, elderly individuals with anorexia of ageing possess higher risks of sarcopenia, disability, hospitalisation, and mortality. Importantly, malnutrition has also been identified as a major risk factor for frailty. This article aims to summarise the state of research on anorexia of ageing in the context of age-related metabolic changes, with a focus on its candidate biomarkers.
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.
PIH and sarcopenia in COPD: a causal relationship?
Nocturnal hypoxia commonly occurs in patients with chronic obstructive pulmonary disease (COPD), and in this context may be referred to as prolonged intermittent hypoxia (PIH). It is estimated that 1 in 5 COPD patients also suffer from sarcopenia, which may affect both respiratory and non-respiratory skeletal muscles and be causally linked to PIH. The presentation of sarcopenia alongside COPD is known to reduce quality of life and increase both hospitalisation and mortality rates in affected patients. Despite this, the adaptive cellular responses to PIH in skeletal muscle have not yet been adequately investigated. The aim of this article was to discuss findings from a 2022 paper by Attaway and colleagues, which itself aimed to explore adaptive cellular responses to PIH.
Latest treatments for cancer cachexia: a review
Currently, there are many interventions and treatments for cancer cachexia. Early nutritional intervention and care are essential to ensure that sufficient nutritional requirements are met for the patients. This includes oral nutrition where possible, as well as nutrition and exercise therapy. Furthermore, preventive care to minimise loss of skeletal muscle mass is vital. Pharmacological options are also available. These include many options, such as non-steroidal anti-inflammatory drugs, anti-cytokine therapy and eicosapentaenoic acid. Furthermore, steroids are often used for cachexia. However, they have limited effects are limited, so recently, anamorelin hydrochloride, a ligand with a similar action to that of ghrelin, was developed. It is used to treat weight loss by increasing appetite and has been approved for use in cachexia. Anamorelin hydrochloride holds great promise to function as an effective therapeutic drug for cancer cachexia. This review by Watanabe H & Oshima T aimed to review the current treatments of cancer cachexia, as well as anamorelin hydrochloride, a new and promising treatment.
Body composition in colorectal cancer: a review
Personalised therapy is a challenge in advanced colorectal cancer care. Much research has been carried out on prognostic and predictive markers of this disease, and a strong correlation was found between sarcopenia and survival in such patients. Currently, selecting personalised strategies for patients is based on very few parameters, not making sufficient use of all available clinical information. Therefore, this paper suggests that it is possible to use body composition and liver tumour burden through automated extraction from CT images. Such automated segmentation would allow one to extract prognostic parameters from the routine imaging data which is collected from patients. This could provide personalised survival modelling for colorectal cancer patients. Specifically, the inclusion of body composition as a factor holds great promise in improving current strategy making for patient care. This review by Keyl J et al. aimed to explore automated assessment of body composition and liver metastases from CT images can improve personalised risk assessment.
Are immunosenescence and mitochondrial dysfunction hallmarks of frailty?
The development of frailty has been attributed to a number of biological mechanisms, including immunosenescence and mitochondrial dysfunction. Impairments in immune cell mitochondria have been proposed to both cause and interact with immunosenescence, hypothetically leading to ageing-related increases in sterile inflammation, commonly known as ‘inflammaging’. However, despite the convincing evidence supporting these suggestions, claims regarding the effects of immunosenescence on clinical outcomes such as frailty have recently been challenged. The aim of this article was to examine the association between immunosenescence, mitochondrial dysfunction, and frailty syndrome in community-dwelling frail and non-frail older adults.
GDF15 and muscle function in cancer cachexia: a review
In this study, TOV21G cancer cachexia mouse models were used to demonstrate impaired muscle function and performance which is seen in cachexia patients. With growth differentiation factor 15, GDF15, neutralization, the mice were seen to exhibit restored muscle function and performance. GDF15 is a stress-responsive cytokine which is secreted by many cells, including tumour cells and damaged cells. GDF15 functions by activating glial cell line-derived neurotrophic factor, GDNF, receptor GFRAL. This is expressed in the hindbrain and leads to reducing food intake and weight loss. This is relevant to cachexia patients, and patients with chronic diseases such as heart failure, as their GDF15 levels are significantly higher than that of healthy people. In this study, the mice were treated with mAB2, an anti-GDF15 antibody. They demonstrated weight gain in terms of fat mass and lean mass, improved muscle function and physical performance. Hence, it is thought that GDF15-related therapy may be effective for patients with cachexia. However, symptoms of cachexia such as fatigue do not appear to be related to GDF15 levels, so further exploration is necessary. This review by Kim-Muller JY et al. aimed to explore how GDF15 levels are related to weight loss and highlight how GDF15 neutralization could be an option for treating cachexia.