Sarcopenia is an age‐related progressive muscle disease characterized by loss of muscle mass, muscle strength and physical performance with high prevalence in chronic kidney disease (CKD). CKD is associated with decreased muscle protein synthesis and muscle breakdown due to a number of factors including, the uremic inflammatory environment of the disease. CKD patients are highly sedentary and at risk of malnutrition which may exacerbate sarcopenia outcomes even further. Short and long‐term exercise and nutritional interventions have been studied and found to have some positive effects on sarcopenia measures in CKD. This narrative review summarized evidence between 2010 and 2020 of resistance exercise (RE) alone or combined with nutritional interventions for improving sarcopenia outcomes in CKD. Due to lack of CKD‐specific sarcopenia measures, the second European Working Group on Sarcopenia in Older People (EWGSOP2) definition has been used to guide the selection of the studies. The literature search identified 14 resistance exercise‐based studies and 5 nutrition plus RE interventional studies. Muscle strength outcomes were increased with longer intervention duration, intervention supervision, and high participant adherence. Data also suggested that CKD patients may require increased RE intensity and progressive loading to obtain detectable results in muscle mass. Unlike muscle strength and muscle mass, physical performance was readily improved by all types of exercise in long or short‐term interventions. Four studies used RE with high‐protein nutritional supplementation. These showed significant benefits on muscle strength and physical performance in dialysis patients while non‐significant results were found in muscle mass. More research is needed to confirm if a combination of RE and vitamin D supplementation could act synergistically to improve muscle strength in CKD. The current evidence on progressive RE for sarcopenia in CKD is encouraging; however, real‐life applications in clinical settings are still very limited. A multidisciplinary patient‐centred approach with regular follow‐up may be most beneficial due to the complexity of sarcopenia in CKD. Long‐term randomized control trials are needed to verify optimal RE prescription and explore safety and efficacy of other nutritional interventions in CKD.

Cancer‐associated cachexia (CAC) is a wasting syndrome characterized by involuntary weight loss and anorexia. Clear definition and diagnostic criteria for CAC are lacking, which makes it difficult to estimate its prevalence, to interpret research and to compare studies. There is no standard treatment to manage CAC, but previous studies support the use of cannabinoids for cachexia in other chronic diseases including HIV and multiple sclerosis. However, only a few randomized controlled trials (RCTs) and one meta‐analysis of this intervention in cancer populations are available. Non‐randomized studies of interventions (NRSIs) are often excluded from reviews due to variable methodology and potential for biases. This review aimed to consider NRSIs alongside RCTs to provide a complete summary of the available evidence that clinical decision makers could use in future investigations. Literature searches were conducted using three databases for relevant RCTs or NRSIs according to Cochrane methodology. Abstract and full texts of retrieved manuscripts were selected and retrieved by two investigators based on the PRISMA‐A guidelines, and risk of bias and quality of evidence assessments were performed. Outcome data on weight, appetite, quality of life, performance status, adverse effects, and mortality were combined by narrative synthesis and meta‐analysis where possible. Ten studies were included, four of which were RCTs and six NRSIs matching the eligibility criteria. Very low‐quality evidence from meta‐analysis suggested no significant benefits of cannabinoids for appetite compared with control (standardized mean difference: −0.02; 95% confidence interval: −0.51, 0.46; P = 0.93). Patient‐reported observations from NRSIs suggested improvements in appetite. Another meta‐analysis of moderate quality evidence showed that cannabinoids were significantly less efficient than active or inactive control on quality of life (standardized mean difference: −0.25; 95% confidence interval: −0.43, −0.07; P = 0.007). The effectiveness of cannabinoids alone to improve outcomes of CAC remains unclear. Low‐quality evidence from both RCTs and NRSIs shows no significant benefits of cannabinoids for weight gain, appetite stimulation, and better quality of life, three important outcomes of cachexia. Higher quality research integrating cannabinoids into multi‐modal therapies may offer better opportunities for developing CAC‐specific treatments. This review also highlights that findings from non‐randomized studies of interventions (NRSIs) can provide evidence of the effects of an intervention and advocate for the feasibility of larger RCTs.

Cancer cachexia (CC) is a multifactorial syndrome driven by inflammation, defined by ongoing loss of skeletal muscle mass (with or without loss of fat mass) that cannot be fully reversed by conventional nutritional support. CC leads to progressive functional impairment, with its clinical management complicated and limited therapeutic options available. The objective of this review was to assess the efficacy and safety of non‐steroidal anti‐inflammatory drugs (NSAIDs) on patient‐centred outcomes in patients with CC. In 2013, two systematic reviews concluded that there was insufficient evidence to recommend NSAIDs for clinical management of CC outside of clinical trials. However, clinical trials of multi‐component CC interventions have included NSAIDs as an intervention component, so an up‐to‐date assessment of the evidence for NSAIDs in the treatment of CC is warranted. Four databases (MEDLINE, EMBASE, CENTRAL and CINAHL) and three trial registers (clinicaltrials.gov, WHO ICTRP and ISRCTN) were searched on 16 December 2022. Randomized controlled trials (RCTs) comparing any NSAID (any dose or duration) with a control arm, in adult patients with CC, reporting measures of body weight, body composition, nutrition impact symptoms, inflammation, physical function or fatigue, were eligible for inclusion. Primary outcomes (determined with patient involvement) were survival, changes in muscle strength, body composition, body weight and quality of life. Included studies were assessed for risk of bias using the Revised Cochrane risk‐of‐bias tool for randomized trials. Five studies were included, which investigated Indomethacin (n = 1), Ibuprofen (n = 1) and Celecoxib (n = 3). Four studies were judged to be at high risk of bias for all outcomes, with one study raising concerns for most outcomes. Considerable clinical and methodological heterogeneity amongst the studies meant that meta‐analysis was not appropriate. There was insufficient evidence to determine whether Indomethacin or Ibuprofen is effective or safe for use in patients with CC; RCTs with lower risk of bias are needed. Celecoxib studies indicated it was safe for use in this population at the doses tested (200–400 mg/day) but found contrasting results regarding efficacy, potentially reflecting heterogeneity amongst the studies. There is inadequate evidence to recommend any NSAID for CC. While current clinical trials for CC treatments are shifting towards multi‐component interventions, further research to determine the efficacy and safety of NSAIDs alone is necessary if they are to be included in such multi‐component interventions. Furthermore, the lack of data on patient‐determined primary outcomes in this review highlights the need for patient involvement in clinical trials for CC.

Chimeric Antigen Receptor (CAR) T-cell therapy has emerged as a revolutionary treatment for patients with refractory or relapsed B-cell malignancies. However, a significant proportion of patients experience negative outcomes, including severe inflammatory toxicities and relapse. Cachexia and malnutrition are known secondary syndromes in many cancer patients, attributed to the effects of active malignancy, systemic inflammation, and cumulative treatment burden; however, further research is required to accurately characterise these issues in CAR T-cell patients. The aims of this service evaluation were to explore the changes in nutritional status (malnutrition and cachexia) in CAR T-cell therapy patients and the potential impact on patient outcomes including survival. Additionally, we describe the utilisation of dietetic resources in this specific patient population in a London tertiary referral centre. Adult haematology patients receiving licensed CD19-targeting CAR T-cell therapy at University College London Hospital between 01/04/19 and 01/09/21 were included. Data were collected from the time of treatment consent, and throughout admission to day of discharge: body weight (BW), C-reactive protein, albumin, lactate dehydrogenase, nutrition-risk screening scores (hospital-specific) and dietetic input. Clinical outcomes such as 12-month all-cause mortality, intensive care unit (ICU) admission, high-grade toxicities, and length of hospital stay (LoS) were also recorded. Cachexia and malnutrition were defined using the modified Glasgow Prognostic Score (mGPS) and Global Leadership Initiative on Malnutrition (GLIM) consensus, respectively. 114 patients (55.6 ± 15.1 years; 57% males) with B-cell non-Hodgkin's lymphoma (n = 109) and B-cell acute lymphoblastic leukaemia (n = 5), receiving axicabtagene ciloleucel (n = 89) and tisagenlecleucel (n = 25) were included. Median LoS for treatment was 34 (27-38) days. Prior to treatment, 31.5% of patients developed malnutrition, with pre-cachexia/refractory cachexia (mGPS) identified in 43.6% of patients. This altered nutritional status pre-treatment was significantly associated with adverse patient outcomes post-infusion; mGPS was independently associated with inferior overall survival (HR = 3.158, CI = 1.36-7.323, p = 0.007), with malnutrition and mGPS associated with increased LoS (p = 0.037), sepsis (p = 0.022) and ICU admission (p = 0.039). During admission, patients experienced significant BW loss (-5.6% (-8.8 to -2.4); p=<0.001), with 68.4% developing malnutrition. Malnutrition screening during admission identified 57% patients at-risk, with 66.6% of patients referred to dietetics; however, there was a lack of malnutrition screening and dietetic referrals prior to treatment. Pre-treatment malnutrition and cachexia was significantly associated with adverse CAR T patient outcomes, including mGPS cachexia status independently associated with inferior overall survival. Further research in this novel space is essential to confirm the extent and impact of nutritional issues, to assist with implementing dietetic pathways, and to identify potential interventions with a view to optimising outcomes.