Agreement between GLIM and PG-SGA for diagnosis of malnutrition depends on the screening tool used in GLIM.

BACKGROUND & AIM: The Global Leadership Initiative on Malnutrition (GLIM) has suggested a process for the diagnosis of malnutrition. The process consists of applying an existing screening tool for malnutrition screening, followed by malnutrition diagnostics, and finally categorization of malnutrition severity (moderate or severe) according to specific GLIM criteria. However, it is not known how well the GLIM process agrees with other diagnostic tools used in the current clinical practice. The aim of this study was to validate the GLIM process against the Patient Generated-Subjective Global Assessment (PG-SGA) when different screening tools were applied in the screening step of the GLIM process. METHODS: Colorectal cancer (CRC) patients from the ongoing CRC-NORDIET study were included. For the GLIM process, the patients were first screened for malnutrition using either 1) Nutritional risk screening, first 4 questions (NRS-2002-4Q), 2) Malnutrition Screening Tool (MST), 3) Malnutrition Universal Screening Tool (MUST) or 4) the PG-SGA short form (PG-SGA-SF). The GLIM malnutrition diagnosis was then based on combining the result from each of the screening methods with the etiological and phenotypic GLIM-criteria including weight loss, BMI and fat free mass. In parallel, the patients were diagnosed using the PG-SGA methodology categorizing the patients into either A: well nourished, B: moderately malnourished or C: severely malnourished. The four different GLIM based diagnoses were then validated against the diagnosis obtained by the PG-SGA tool. Sensitivity, specificity and positive predictive value (PPV) were calculated to evaluate validity. RESULTS: In total, 426 patients were included (mean age: 66, ±8 years) at a mean time of 166 (±56) days after surgery. The GLIM diagnosis based on the four different screening tools identified 10-24% of the patients to be malnourished, of which 3-8% were severely malnourished. The PG-SGA method categorized 15% as moderately malnourished (PG-SGA: category B) and no patients as severely malnourished (PG-SGA: category C). The agreement between the PG-SGA and GLIM process was in general low, but differed according to the tools: PG-SGA SF (sensitivity 47%, PPV 71%), MST (sensitivity 56%, PPV 47%), NRS-2002-4Q (sensitivity 63%, PPV 53%) and MUST (sensitivity 53%, PPV 34%). CONCLUSION: In this cross-sectional study of patients with CRC, the concordance between the GLIM-criteria and PG-SGA depended on the screening tool used in the GLIM process. Malnutrition frequency based on the GLIM process schould be reported with and without the use of a screening tool.

Use of bioelectrical impedance analysis to monitor changes in fat-free mass during recovery from colorectal cancer- a validation study.

BACKGROUND & AIMS: Although previous research show high correlation between fat-free mass (FFM) measured by bioelectrical impedance analysis (BIA) and dual-energy X-ray absorptiometry (DXA), the validity of BIA to track longitudinal changes in FFM is uncertain. Thus, the aim of this study was to validate the ability of BIA to assess changes in FFM during 6 months of recovery from non-metastatic colorectal cancer (CRC). METHODS: A total of 136 women and men (50-80 years) with stage I-III CRC and a wide range of baseline FFM (35.7-73.5 kg) were included in the study. Body composition was measured at study baseline within 2-9 months of surgery and again 6 months later. Whole-body BIA FFM estimates (FFMBIA) were calculated using three different equations (manufacturer's, Schols' and Gray's) before comparison to FFM estimates obtained by DXA (FFMDXA). RESULTS: Correlation between changes in FFMBIA and FFMDXA was intermediate regardless of equation (r ≈ 0.6). The difference in change of FFMBIA was significant compared to FFMDXA, using all three equations and BIA overestimated both loss and gain. However, BIA showed 100% sensitivity and about 90% specificity to identify individuals with ≥5% loss in FFM, using all three equations. Sensitivity of FFMBIA to detect a smaller loss of FFM (60-76%) or a gain in FFM of ≥5% (33-62%) was poor. CONCLUSION: In a well-nourished population of non-metastatic CRC patients, a single-frequency whole-body BIA device yielded imprecise data on changes in FFM, regardless of equation. BIA is thus not a valid option for quantifying changes in FFM in individuals. However, BIA could be used to identify patients with loss in FFM ≥5% in this population. The validity of BIA to monitor changes in FFM warrants further investigation before implementation in clinical praxis.

Agreement between PG-SGA category and fat-free mass in colorectal cancer patients.

BACKGROUND AND AIMS: Low fat-free mass (FFM) is associated with adverse outcomes in colorectal cancer (CRC) patients. Patient-Generated Subjective Global Assessment (PG-SGA) is a widely used tool developed to detect patients with malnutrition or at risk of malnutrition. The aim of this study was to investigate the agreement between PG-SGA category and FFM in patients with non-metastatic CRC. METHODS: Ninety-seven patients were included and categorized as well nourished (PG-SGA:A, n = 67) or malnourished (PG-SGA:B, n = 30). No patients were severely malnourished (PG-SGA: C). Bioelectrical impedance analysis (BIA) was used to assess FFM. Low FFM was defined as low fat-free mass index (FFMI) according to cut-off values recently proposed by The European Society for Clinical Nutrition and Metabolism (ESPEN). RESULTS: Twenty-nine percent of the patients were identified with low FFMI. The proportion with low FFMI was significantly higher among patients classified as malnourished by PG-SGA compared to well nourished (p = 0.015). The sensitivity was however low, as the PG-SGA categorization classified only 50.0% of the patients with low FFMI as malnourished (PG-SGA B). Using the PG-SGA scores (cut-off point > 4), the sensitivity increased to 60.7%. Physical examination in the PG-SGA identified only 64.3% of the patients with low FFMI as muscle depleted. CONCLUSION: Our results indicate a low agreement between PG-SGA category and low FFMI among patients with non-metastatic CRC. In clinical practice, PG-SGA should be supplemented by muscle mass assessments by BIA or other methods in order to detect low FFM in this patient group.

DNA damage in blood cells in relation to chemotherapy and nutritional status in colorectal cancer patients-A pilot study.

DNA damage can be considered as a biomarker for toxicity and response to chemotherapy. It is not known whether the chemotherapy-induced genotoxicity is associated with malnutrition. In this pilot study, we assess genotoxicity by means of DNA damage in patients with lymph-node positive colorectal cancer (CRC) and explore associations with chemotherapy treatment and nutritional status. DNA damage was compared between patients receiving chemotherapy (n = 24) and those not receiving chemotherapy (n = 20). DNA damage was measured in frozen whole blood by the comet assay. Associations between DNA damage and various indicators of malnutrition were also explored, including Patient-Generated Subjective Global Assessment (PG-SGA), bioelectrical impedance analysis (BIA) and anthropometric measurements, using multiple linear regression models. Patients on chemotherapy have higher levels of DNA damage in blood cells than patients not receiving chemotherapy (median of 16.9 and 7.9% tail DNA respectively, p = 0.001). The moderately malnourished patients (PG-SGA category B), representing 41% of the patients, have higher levels of cellular DNA damage than patients with good nutritional status (mean difference of 7.5% tail DNA, p = 0.033). In conclusion, adjuvant chemotherapy and malnutrition are both associated with increased levels of DNA damage in blood cells of CRC patients. Carefully controlled longitudinal studies or randomized controlled trials should be performed to determine whether good nutritional status may protect against chemotherapy-induced genotoxicity and enhance compliance to therapy in CRC patients.

Validity of bioelectrical impedance analysis in estimation of fat-free mass in colorectal cancer patients.

BACKGROUND & AIMS: Bioelectrical impedance analysis (BIA) is an accessible and cheap method to measure fat-free mass (FFM). However, BIA estimates are subject to uncertainty in patient populations with altered body composition and hydration. The aim of the current study was to validate a whole-body and a segmental BIA device against dual-energy X-ray absorptiometry (DXA) in colorectal cancer (CRC) patients, and to investigate the ability of different empiric equations for BIA to predict DXA FFM (FFMDXA). METHODS: Forty-three non-metastatic CRC patients (aged 50-80 years) were enrolled in this study. Whole-body and segmental BIA FFM estimates (FFMwhole-bodyBIA, FFMsegmentalBIA) were calculated using 14 empiric equations, including the equations from the manufacturers, before comparison to FFMDXA estimates. RESULTS: Strong linear relationships were observed between FFMBIA and FFMDXA estimates for all equations (R2 = 0.94-0.98 for both devices). However, there were large discrepancies in FFM estimates depending on the equations used with mean differences in the ranges -6.5-6.8 kg and -11.0-3.4 kg for whole-body and segmental BIA, respectively. For whole-body BIA, 77% of BIA derived FFM estimates were significantly different from FFMDXA, whereas for segmental BIA, 85% were significantly different. For whole-body BIA, the Schols* equation gave the highest agreement with FFMDXA with mean difference ±SD of -0.16 ± 1.94 kg (p = 0.582). The manufacturer's equation gave a small overestimation of FFM with 1.46 ± 2.16 kg (p < 0.001) with a tendency towards proportional bias (r = 0.28, p = 0.066). For segmental BIA, the Heitmann* equation gave the highest agreement with FFMDXA (0.17 ± 1.83 kg (p = 0.546)). Using the manufacturer's equation, no difference in FFM estimates was observed (-0.34 ± 2.06 kg (p = 0.292)), however, a clear proportional bias was detected (r = 0.69, p < 0.001). Both devices demonstrated acceptable ability to detect low FFM compared to DXA using the optimal equation. CONCLUSION: In a population of non-metastatic CRC patients, mostly consisting of Caucasian adults and with a wide range of body composition measures, both the whole-body BIA and segmental BIA device provide FFM estimates that are comparable to FFMDXA on a group level when the appropriate equations are applied. At the individual level (i.e. in clinical practice) BIA may be a valuable tool to identify patients with low FFM as part of a malnutrition diagnosis.

The Norwegian dietary guidelines and colorectal cancer survival (CRC-NORDIET) study: a food-based multicentre randomized controlled trial.

BACKGROUND: Colorectal cancer survivors are not only at risk for recurrent disease but also at increased risk of comorbidities such as other cancers, cardiovascular disease, diabetes, hypertension and functional decline. In this trial, we aim at investigating whether a diet in accordance with the Norwegian food-based dietary guidelines and focusing at dampening inflammation and oxidative stress will improve long-term disease outcomes and survival in colorectal cancer patients. METHODS/DESIGN: This paper presents the study protocol of the Norwegian Dietary Guidelines and Colorectal Cancer Survival study. Men and women aged 50-80 years diagnosed with primary invasive colorectal cancer (Stage I-III) are invited to this randomized controlled, parallel two-arm trial 2-9 months after curative surgery. The intervention group (n = 250) receives an intensive dietary intervention lasting for 12 months and a subsequent maintenance intervention for 14 years. The control group (n = 250) receives no dietary intervention other than standard clinical care. Both groups are offered equal general advice of physical activity. Patients are followed-up at 6 months and 1, 3, 5, 7, 10 and 15 years after baseline. The study center is located at the Department of Nutrition, University of Oslo, and patients are recruited from two hospitals within the South-Eastern Norway Regional Health Authority. Primary outcomes are disease-free survival and overall survival. Secondary outcomes are time to recurrence, cardiovascular disease-free survival, compliance to the dietary recommendations and the effects of the intervention on new comorbidities, intermediate biomarkers, nutrition status, physical activity, physical function and quality of life. DISCUSSION: The current study is designed to gain a better understanding of the role of a healthy diet aimed at dampening inflammation and oxidative stress on long-term disease outcomes and survival in colorectal cancer patients. Since previous research on the role of diet for colorectal cancer survivors is limited, the study may be of great importance for this cancer population. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01570010 .

Expression of N-methyl-d-aspartate (NMDA) receptor subunits and splice variants in an animal model of long-term voluntary alcohol self-administration.

Long-term, free-choice, alcohol self-administration with repeated alcohol deprivation phases is known to enhance N-methyl-d-aspartate (NMDA) receptor activity. We hypothesized that this might not only reflect an increase in NMDA receptor density, but that differential transcriptional regulation and alternative splicing of the various subunits comprising the NMDA receptor may lead to changes in receptor composition and subsequent function. We, therefore, aimed to further investigate this effect in various brain regions. The relative mRNA expression of exon 5 inclusion/exclusion variants of the NR1 subunit, and the relative expression of NR2A, NR2B and NR2C subunits was examined in rats subjected to long-term free-choice, alcohol self-administration with repeated alcohol deprivation phases. We observed a relative decrease of the NR2C/NR2A mRNA ratio and an increase of NR1 splice variants including exon 5 (NR1+E5) in the striatum but not in the cortex, hippocampus or cerebellum in the experimental group. Our results demonstrate that long-term voluntary alcohol self-administration, affects the regulation of genes encoding the various subunits and splice variants of the NMDA receptor in a brain regional-specific manner.

A pharmacological model for psychosis based on N-methyl-D-aspartate receptor hypofunction: molecular, cellular, functional and behavioral abnormalities.

BACKGROUND: The psychotomimetic effects of N-methyl-D-aspartate (NMDA) receptor antagonists such as phencyclidine (PCP) in healthy humans and their ability to exacerbate psychotic symptoms in schizophrenic patients have promoted a view of schizophrenia as being related to altered glutamatergic neurotransmission. METHODS: This prompted us and others to develop animal models for psychosis based on a glutamatergic approach. Pharmacological induction of a state of impaired glutamatergic neurotransmission based on chronic, low-dose application of MK-801, a highly selective noncompetitive NMDA antagonist, revealed marked parallels between schizophrenia and our animal model. RESULTS: MK-801 altered the expression of NR1 splice variants and NR2 subunits of the NMDA receptor in a pattern partially resembling the alterations detected in schizophrenia. Ultrastructurally, the number of gamma-aminobutyric-acid (GABA)ergic parvalbumin-positive interneurons was relatively decreased, a finding which again parallels observations in post mortem brain from schizophrenic patients. As a functional consequence, local inhibition of pyramidal cells which is largely mediated by recurrent axon collaterals, originating from GABAergic interneurons, was altered. Not unexpectedly, these animals showed cognitive deficits resembling findings in schizophrenic humans. CONCLUSIONS: These convergent lines of evidence suggest that our approach has a significant potential of serving as a model of the pathobiology of several aspects of psychosis and consequently could contribute to the development of new therapeutic strategies.