Plasma Ghrelin Levels Are Associated with Anorexia but Not Cachexia in Patients with NSCLC

Background and Aims: The ghrelin receptor is one of the new therapeutic targets in the cancer anorexia-cachexia syndrome. Previous studies revealed that plasma ghrelin levels were high in patients with anorexia nervosa and low in obese subjects. We studied to what extent ghrelin levels are related with anorexia and cachexia in patients with cancer. Materials and Methods: Fasted ghrelin levels were determined as well as anorexia and cachexia in patients with stage III/IV non-small cell lung cancer before chemotherapy. Total plasma ghrelin was measured by radioimmunoassay. Anorexia was measured with the FAACT-A/CS questionnaire (cut-off value ≤ 37). Cachexia was determined as > 5% weight loss (WL) in 6 months or > 2% WL in 6 months in combination with low BMI or low muscle mass. The Kruskal-Wallis test was performed to assess differences in plasma ghrelin levels between four groups: patients with (+) or without (-) anorexia (A) or cachexia (C). Multiple regression analyses were performed to assess differences in plasma ghrelin levels between patients C+ and C- and patients with A+ and A- (adjusted for age and sex). Results: Forty patients with stage III (33%) or stage IV (68%) were recruited, of which 50% was male. Mean age was 59.6 ± 10.3 years. Sixteen patients had no anorexia or cachexia (A-C-), seven patients had both anorexia and cachexia (A+C+), ten patients had anorexia without cachexia (A+C-) and seven patients had cachexia without anorexia (A-C+). The levels of total plasma ghrelin were significantly different between the four groups of patients with or without anorexia or cachexia (p = 0.032): the A+C- patients had significantly higher ghrelin levels [median (IQR): 1,754 (1,404-2,142) compared to the A-C+ patients 1,026 (952-1,357), p = 0.003]. A+ patients had significantly higher ghrelin levels compared A- patients (C+ and C- combined, β: 304, p = 0.020). Plasma ghrelin levels were not significantly different in C+ patients compared to C- patients (A+ and A- combined, β: -99, p = 0.450). Conclusions: Patients with anorexia had significantly higher ghrelin levels compared to patients without anorexia. We therefore hypothesize that patients with cancer anorexia might benefit from treatment with a ghrelin receptor agonist to prevent WL and deterioration in physical functioning

Associations Between Nutrient Intake and Corresponding Nutritional Biomarker Levels in Blood in a Memory Clinic Cohort:The NUDAD Project

Diet is a promising intervention target to prevent or slow Alzheimer's disease (AD). Early (predementia) stages of AD offer a unique opportunity for dietary interventions. Nutritional assessment methods to estimate nutrient intake have, however, not been validated in clinical populations. Hence, we assessed the association between nutrient intake assessed by food frequency questionnaire (FFQ) and nutrient status measured by nutritional biomarkers in blood in a clinical sample of controls, mild cognitive impairment (MCI), and patients with AD

Global Leadership Initiative on Malnutrition (GLIM):Guidance on Validation of the Operational Criteria for the Diagnosis of Protein-Energy Malnutrition in Adults

Background The Global Leadership Initiative on Malnutrition (GLIM) created a consensus-based framework consisting of phenotypic and etiologic criteria to record the occurrence of malnutrition in adults. This is a minimum set of practicable indicators for use in characterizing a patient/client as malnourished, considering the global variations in screening and nutrition assessment, and to be used across different healthcare settings. As with other consensus-based frameworks for diagnosing disease states, these operational criteria require validation and reliability testing, as they are currently based solely on expert opinion. Methods Several forms of validation and reliability are reviewed in the context of GLIM, providing guidance on how to conduct retrospective and prospective studies for criterion and construct validity. Results There are some aspects of GLIM that require refinement; research using large databases can be employed to reach this goal. Machine learning is also introduced as a potential method to support identification of the best cut points and combinations of indicators for use with the different forms of malnutrition, which the GLIM criteria were created to denote. It is noted as well that validation and reliability testing need to occur in a variety of sectors and populations and with diverse persons using GLIM criteria. Conclusion The guidance presented supports the conduct and publication of quality validation and reliability studies for GLIM

Study protocol: Cost-effectiveness of transmural nutritional support in malnourished elderly patients in comparison with usual care

BACKGROUND: Malnutrition is a common consequence of disease in older patients. Both in hospital setting and in community setting oral nutritional support has proven to be effective. However, cost-effectiveness studies are scarce. Therefore, the aim of our study is to investigate the effectiveness and cost-effectiveness of transmural nutritional support in malnourished elderly patients, starting at hospital admission until three months after discharge. METHODS: This study is a randomized controlled trial. Patients are included at hospital admission and followed until three months after discharge. Patients are eligible to be included when they are > or = 60 years old and malnourished according to the following objective standards: Body Mass Index (BMI in kg/m2) < 20 and/or > or = 5% unintentional weight loss in the previous month and/or > or = 10% unintentional weight loss in the previous six months. We will compare usual nutritional care with transmural nutritional support (energy and protein enriched diet, two additional servings of an oral nutritional supplement, vitamin D and calcium supplementation, and consultations by a dietitian). Each study arm will consist of 100 patients. The primary outcome parameters will be changes in activities of daily living (determined as functional limitations and physical activity) between intervention and control group. Secondary outcomes will be changes in body weight, body composition, quality of life, and muscle strength. An economic evaluation from a societal perspective will be conducted alongside the randomised trial to evaluate the cost-effectiveness of the intervention in comparison with usual care. CONCLUSION: In this randomized controlled trial we will evaluate the effect of transmural nutritional support in malnourished elderly patients after hospital discharge, compared to usual care. Primary endpoints of the study are changes in activities of daily living, body weight, body composition, quality of life, and muscle strength. An economic evaluation will be performed to evaluate the cost-effectiveness of the intervention in comparison with usual care. TRIAL REGISTRATION: Netherlands Trial Register (ISRCTN29617677, registered 14-Sep-2005)

Prevalence and Determinants of Undernutrition in A Sample of Dutch Community-Dwelling Older Adults: Results from Two Online Screening Tools

To stimulate undernutrition screening among Dutch community-dwelling adults, a website was developed with general information on healthy eating for healthy aging and self-tests. Based on cross-sectional data obtained from the self-tests, we studied nutritional risk factors (early determinants) as well as risk of undernutrition (late symptoms). SCREEN II (n = 2470) was used to asses nutritional risk factors. This tool consists of 16 items regarding nutritional intake, perception of body weight, appetite, oral health and meal preparation. An adjusted SNAQ65+ (n = 687) was used to assess risk of undernutrition. This four-item tool contains questions on weight loss, appetite, walking stairs and body mass index. Differences between age-groups (65&#8722;74, 75&#8722;84, &#8805;85) were tested by logistic regression. Overall prevalence of nutritional risk factors was 84.1%, and increased risk of undernutrition was 56.8%. Participants aged &#8805;85 scored worst on almost all items of the SCREEN II and the SNAQ65+. In conclusion: A large proportion of older adults reported early determinants for increased nutrition risk, while a smaller, yet remarkable proportion scored positive on undernutrition risk. Internet screening may be a useful, contemporary, and easy, accessible way to reach older adults who are at nutritional risk and may thus contribute to early identification and prevention of undernutrition

Dietary advice with or without oral nutritional supplements for disease-related malnutrition in adults

Background: Disease-related malnutrition has been reported in 10% to 55% of people in hospital and the community and is associated with significant health and social-care costs. Dietary advice (DA) encouraging consumption of energy- and nutrient-rich foods rather than oral nutritional supplements (ONS) may be an initial treatment. Objectives: To examine evidence that DA with/without ONS in adults with disease-related malnutrition improves survival, weight, anthropometry and quality of life (QoL). Search methods: We identified relevant publications from comprehensive electronic database searches and handsearching. Last search: 01 March 2021. Selection criteria: Randomised controlled trials (RCTs) of DA with/without ONS in adults with disease-related malnutrition in any healthcare setting compared with no advice, ONS or DA alone. Data collection and analysis: Two authors independently assessed study eligibility, risk of bias, extracted data and graded evidence. Main results: We included 94, mostly parallel, RCTs (102 comparisons; 10,284 adults) across many conditions possibly explaining the high heterogeneity. Participants were mostly older people in hospital, residential care and the community, with limited reporting on their sex. Studies lasted from one month to 6.5 years. DA versus no advice - 24 RCTs (3523 participants). Most outcomes had low-certainty evidence. There may be little or no effect on mortality after three months, RR 0.87 (95% confidence interval (CI) 0.26 to 2.96), or at later time points. We had no three-month data, but advice may make little or no difference to hospitalisations, or days in hospital after four to six months and up to 12 months. A similar effect was seen for complications at up to three months, MD 0.00 (95% CI -0.32 to 0.32) and between four and six months. Advice may improve weight after three months, MD 0.97 kg (95% CI 0.06 to 1.87) continuing at four to six months and up to 12 months; and may result in a greater gain in fat-free mass (FFM) after 12 months, but not earlier. It may also improve global QoL at up to three months, MD 3.30 (95% CI 1.47 to 5.13), but not later. DA versus ONS - 12 RCTs (852 participants). All outcomes had low-certainty evidence. There may be little or no effect on mortality after three months, RR 0.66 (95% CI 0.34 to 1.26), or at later time points. Either intervention may make little or no difference to hospitalisations at three months, RR 0.36 (95% CI 0.04 to 3.24), but ONS may reduce hospitalisations up to six months. There was little or no difference between groups in weight change at three months, MD -0.14 kg (95% CI -2.01 to 1.74), or between four to six months. Advice (one study) may lead to better global QoL scores but only after 12 months. No study reported days in hospital, complications or FFM. DA versus DA plus ONS - 22 RCTs (1286 participants). Most outcomes had low-certainty evidence. There may be little or no effect on mortality after three months, RR 0.92 (95% CI 0.47 to 1.80) or at later time points. At three months advice may lead to fewer hospitalisations, RR 1.70 (95% CI 1.04 to 2.77), but not at up to six months. There may be little or no effect on length of hospital stay at up to three months, MD -1.07 (95% CI -4.10 to 1.97). At three months DA plus ONS may lead to fewer complications, RR 0.75 (95% CI o.56 to 0.99); greater weight gain, MD 1.15 kg (95% CI 0.42 to 1.87); and better global QoL scores, MD 0.33 (95% CI 0.09 to 0.57), but this was not seen at other time points. There was no effect on FFM at three months. DA plus ONS if required versus no advice or ONS - 31 RCTs (3308 participants). Evidence was moderate- to low-certainty. There may be little or no effect on mortality at three months, RR 0.82 (95% CI 0.58 to 1.16) or at later time points. Similarly, little or no effect on hospitalisations at three months, RR 0.83 (95% CI 0.59 to 1.15), at four to six months and up to 12 months; on days in hospital at three months, MD -0.12 (95% CI -2.48 to 2.25) or for complications at any time point. At three months, advice plus ONS probably improve weight, MD 1.25 kg (95% CI 0.73 to 1.76) and may improve FFM, 0.82 (95% CI 0.35 to 1.29), but these effects were not seen later. There may be little or no effect of either intervention on global QoL scores at three months, but advice plus ONS may improve scores at up to 12 months. DA plus ONS versus no advice or ONS - 13 RCTs (1315 participants). Evidence was low- to very low-certainty. There may be little or no effect on mortality after three months, RR 0.91 (95% CI 0.55 to 1.52) or at later time points. No study reported hospitalisations and there may be little or no effect on days in hospital after three months, MD -1.81 (95% CI -3.65 to 0.04) or six months. Advice plus ONS may lead to fewer complications up to three months, MD 0.42 (95% CI 0.20 to 0.89) (one study). Interventions may make little or no difference to weight at three months, MD 1.08 kg (95% CI -0.17 to 2.33); however, advice plus ONS may improve weight at four to six months and up to 12 months. Interventions may make little or no difference in FFM or global QoL scores at any time point. Authors' conclusions: We found no evidence of an effect of any intervention on mortality. There may be weight gain with DA and with DA plus ONS in the short term, but the benefits of DA when compared with ONS are uncertain. The size and direction of effect and the length of intervention and follow-up required for benefits to emerge were inconsistent for all other outcomes. There were too few data for many outcomes to allow meaningful conclusions. Studies focusing on both patient-centred and healthcare outcomes are needed to address the questions in this review

The effect of oral omega-3 polyunsaturated fatty acid supplementation on muscle maintenance and quality of life in patients with cancer: A systematic review and meta-analysis

Background & aims: Omega-3 polyunsaturated fatty acid (PUFA) supplementation has been proposed as a potential therapy for cancer-related malnutrition, which affects up to 70% of patients with cancer. The aim of this systematic review and meta-analysis was to examine the effects of oral omega-3 PUFA supplementation on muscle maintenance, quality of life, body weight and treatment-related toxicities in patients with cancer. Methods: Randomised controlled trials in patients with cancer aged ≥18 years were retrieved from 5 electronic databases: MEDLINE (via PubMed), EMBASE, CENTRAL, CINAHL (via EBSCOhost), and Web of Science, from database inception until 31st of December 2019. The quality of included studies was assessed using the Cochrane risk of bias tool. Trials supplementing ≥600 mg/d omega-3 PUFA (oral capsules, pure fish oil or oral nutritional supplements) compared with a control intervention for ≥3 weeks were included. Meta-analyses were performed in RevMan to determine the mean differences (MD) in muscle mass, quality of life and body weight, and odds ratio (OR) for the incidence of treatment-related toxicities between omega-3 PUFA and control groups with 95% confidence intervals (CI) and I 2 for heterogeneity. Results: We included 31 publications in patients with various types of cancers and degrees of malnutrition. The Cochrane risk of bias tool graded most trials as ‘unclear’ or ‘high’ risk of bias. Meta-analyses showed no significant difference between omega-3 PUFA supplements and control intervention on muscle mass, quality of life and body weight. Oral omega-3 PUFA supplements reduced the likelihood of developing chemotherapy-induced peripheral neuropathy (OR: 0.20; 95% CI: 0.10–0.40; p < 0.001; I 2 = 0%). Conclusion: This systematic review and meta-analysis indicates that oral omega-3 PUFA supplementation does not improve muscle maintenance, quality of life or body weight in patients with cancer, but may reduce the incidence of chemotherapy-induced peripheral neuropathy. Well-designed large-scale randomised controlled trials in homogenous patient cohorts are required to confirm these findings

Cancer Cachexia: Identification by Clinical Assessment versus International Consensus Criteria in Patients with Metastatic Colorectal Cancer

Background: Cancer cachexia is associated with poorer outcomes and is often diagnosed by the Fearon criteria. Oncologists clinically identify cachexia based on a patient’s presentation. In this study agreement between these identification methods was evaluated and associations with outcomes were studied in patients with metastatic colorectal cancer. Methods: Fearon criteria comprised weight loss >5% OR weight loss >2% with either BMI <20 kg/m2 or sarcopenia (determined by CT-imaging). Clinical assessment by the oncologist was based on the patient’s clinical presentation. Agreement was tested with Kappa. Associations with treatment tolerance and progression free survival (PFS) were tested with logistic regressions and Cox proportional hazards, respectively. Results: Of 69 patients, 52% was identified as cachectic according to Fearon criteria and 9% according to clinical assessment. Agreement between both methods was slight (Kappa 0.049, P = 0.457). Clinically cachectic patients had a shorter PFS than clinically non-cachectic patients (HR 3.310, P = 0.016). No other differences in outcomes were found between cachectic vs. non-cachectic patients using both methods. Conclusions: The agreement between cancer cachexia identification by clinical assessment vs. Fearon criteria was slight. Further improvement of cachexia criteria is necessary to identify cachectic patients at risk of poorer outcomes, who may benefit from targeted cachexia interventions

Identifying the Barriers and Enablers to Nutrition Care in Head and Neck and Esophageal Cancers: An International Qualitative Study

Background: The goal of this work was to identify barriers and enablers to the implementation of nutrition care in head and neck and esophageal (HNE) cancers and to prioritize barriers to help improve the nutrition care process. Materials and Methods: This study used a multimethod qualitative study design (including semistructured interviews, focus group). Interviews (n = 29) were conducted at 5 European sites providing care and treatment to patients with HNE cancers. A focus group (n = 21) reviewed and corroborated interview findings and identified priorities for nutrition care. Participants were healthcare providers and researchers with direct experience in the field of HNE cancer. Results: Five themes with accompanying barriers and enablers were identified related to nutrition care: (1) evidence for the benefit of nutrition interventions, (2) implementation of nutrition care processes (assessment, intervention, and follow-up), (3) characteristics of healthcare providers, (4) site factors, and (5) patient characteristics. Focus group discussions identified 2 priorities that must be acted on to improve nutrition care: (1) improve the evidence base and (2) develop standardized nutrition care pathways. Conclusion: Themes related to nutrition care in HNE cancers were similar between sites, but barriers and enablers differed. Interview and focus group participants agreed the following actions will result in improvements in nutrition care: (1) enhance the evidence base to test the benefit of nutrition interventions, with a focus on resolving specific controversies regarding nutrition therapy, and (2) establish a minimum data set with a goal to create standardized nutrition care pathways where roles and responsibilities for care are clearly define