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

Assessment of Nutritional Status, Digestion and Absorption, and Quality of Life in Patients with Locally Advanced Pancreatic Cancer

Background and Aim. To provide a comprehensive quantitative assessment of nutritional status, digestion and absorption, and quality of life (QoL) in patients with locally advanced pancreatic cancer (LAPC). Methods. Sixteen patients with LAPC were prospectively assessed for weight loss (WL), body mass index (BMI), fat-free mass index (FFMI), handgrip strength (HGS), dietary macronutrient intake, serum vitamin levels, resting and total energy expenditure (REE and TEE, indirect calorimetry), intestinal absorption capacity and fecal losses (bomb calorimetry), exocrine pancreatic function (fecal elastase-1 (FE1)), and gastrointestinal quality of life (GIQLI). Results. Two patients had a low BMI, 10 patients had WL > 10%/6 months, 8 patients had a FFMI < P10, and 8 patients had a HGS < P10. Measured REE was 33% higher (P=0.002) than predicted REE. TEE was significantly higher than daily energy intake (P=0.047). Malabsorption (<85%) of energy, fat, protein, and carbohydrates was observed in, respectively, 9, 8, 12, and 10 patients. FE1 levels were low (<200 μg/g) in 13 patients. Total QoL scored 71% (ample satisfactory). Conclusion. Patients with LAPC have a severely impaired nutritional status, most likely as a result of an increased REE and malabsorption due to exocrine pancreatic insufficiency. The trial is registered with PANFIRE clinicaltrials.gov NCT01939665

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

ESPEN guidelines on definitions and terminology of clinical nutrition

BACKGROUND: A lack of agreement on definitions and terminology used for nutrition-related concepts and procedures limits the development of clinical nutrition practice and research. OBJECTIVE: This initiative aimed to reach a consensus for terminology for core nutritional concepts and procedures. METHODS: The European Society of Clinical Nutrition and Metabolism (ESPEN) appointed a consensus group of clinical scientists to perform a modified Delphi process that encompassed e-mail communication, face-to-face meetings, in-group ballots and an electronic ESPEN membership Delphi round. RESULTS: Five key areas related to clinical nutrition were identified: concepts; procedures; organisation; delivery; and products. One core concept of clinical nutrition is malnutrition/undernutrition, which includes disease-related malnutrition (DRM) with (eq. cachexia) and without inflammation, and malnutrition/undernutrition without disease, e.g. hunger-related malnutrition. Over-nutrition (overweight and obesity) is another core concept. Sarcopenia and frailty were agreed to be separate conditions often associated with malnutrition. Examples of nutritional procedures identified include screening for subjects at nutritional risk followed by a complete nutritional assessment. Hospital and care facility catering are the basic organizational forms for providing nutrition. Oral nutritional supplementation is the preferred way of nutrition therapy but if inadequate then other forms of medical nutrition therapy, i.e. enteral tube feeding and parenteral (intravenous) nutrition, becomes the major way of nutrient delivery. CONCLUSION: An agreement of basic nutritional terminology to be used in clinical practice, research, and the ESPEN guideline developments has been established. This terminology consensus may help to support future global consensus efforts and updates of classification systems such as the International Classification of Disease (ICD). The continuous growth of knowledge in all areas addressed in this statement will provide the foundation for future revisions

Low Mid-Upper Arm Circumference, Calf Circumference, and Body Mass Index and Mortality in Older Persons

Background.Low body mass index is a general measure of thinness. However, its measurement can be cumbersome in older persons and other simple anthropometric measures may be more strongly associated with mortality. Therefore, associations of low mid-upper arm circumference, calf circumference, and body mass index with mortality were examined in older persons.Methods.Data of the Longitudinal Aging Study Amsterdam, a population-based cohort study in the Netherlands, were used. The present study included community-dwelling persons 65 years and older in 1992-1993 (n = 1,667), who were followed until 2007 for their vital status. Associations between anthropometric measures and 15-year mortality were examined by spline regression models and, below the nadir, Cox regression models, transforming all measures to sex-specific Z scores.Results.Mortality rates were 599 of 826 (73%) in men and 479 of 841 (57%) in women. Below the nadir, the hazard ratio of mortality per 1 standard deviation lower mid-upper arm circumference was 1.79 (95% confidence interval, 1.48-2.16) in men and 2.26 (1.71-3.00) in women. For calf circumference, the hazard ratio was 1.45 (1.22-1.71) in men and 1.30 (1.15-1.48) in women and for body mass index 1.38 (1.17-1.61) in men and 1.56 (1.10-2.21) in women. Excluding deaths within the first 3 years after baseline did not change these associations. Excluding those with a smoking history, obstructive lung disease, or cancer attenuated the associations of calf circumference (men) and body mass index (women).Conclusions.Based on the stronger association with mortality and given a more easy assessment in older persons, mid-upper arm circumference seems a more feasible and valid anthropometric measure of thinness than body mass index in older men and women. © 2010 The Author. Published by Oxford University Press on behalf of The Gerontological Society of America

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)

A prospective investigation of swallowing, nutrition, and patient-rated functional impact following altered fractionation radiotherapy with concomitant boost for oropharyngeal cancer

Altered fractionation radiotherapy for head and neck cancer has been associated with improved locoregional control, overall survival, and heightened toxicity compared with conventional treatment. Swallowing, nutrition, and patient-perceived function for altered fractionation radiotherapy with concomitant boost (AFRT-CB) for T1–T3 oropharyngeal squamous cell carcinoma (SCC) have not been previously reported. Fourteen consecutive patients treated with AFRT-CB for oropharyngeal SCC were recruited from November 2006 to August 2009 in a tertiary hospital in Brisbane, Australia. Swallowing, nutrition, and patient-perceived functional impact assessments were conducted pretreatment, at 4–6 weeks post-treatment, and at 6 months post-treatment. Deterioration from pretreatment to 4–6 weeks post-treatment in swallowing, nutrition, and functional impact was evident, likely due to the heightened toxicity associated with AFRT-CB. There was significant improvement at 6 months post-treatment in functional swallowing, nutritional status, patient-perceived swallowing, and overall function, consistent with recovery from acute toxicity. However, weight and patient perception of physical function and side effects remained significantly worse than pretreatment scores. The ongoing deficits related to weight and patient-perceived outcomes at 6 months revealed that this treatment has a long-term impact on function possibly related to the chronic effects of AFRT-CB

Beneficial immune modulatory effects of a specific nutritional combination in a murine model for cancer cachexia

The majority of patients with advanced cancer are recognised by impaired immune competence influenced by several factors, including the type and stage of the tumour and the presence of cachexia. Recently, a specific nutritional combination containing fish oil, specific oligosaccharide mixture, high protein content and leucine has been developed aimed to support the immune system of cancer patients in order to reduce the frequency and severity of (infectious) complications. In a recently modified animal model cachexia is induced by inoculation of C26 tumour cells in mice. In a pre-cachectic state, no effect was observed on contact hypersensitivity, a validated in vivo method to measure Th1-mediated immune function, after adding the individual nutritional ingredients to the diet of tumour-bearing mice. However, the complete mixture resulted in significantly improved Th1 immunity. Moreover, in a cachectic state, the complete mixture reduced plasma levels of pro-inflammatory cytokines and beneficially affected ex vivo immune function. Accordingly, the combination of the nutritional ingredients is required to obtain a synergistic effect, leading to a reduced inflammatory state and improved immune competence. From this, it can be concluded that the specific nutritional combination has potential as immune-supporting nutritional intervention to reduce the risk of (infectious) complications in cancer patients