DNA base oxidation in relation to TNM stages and chemotherapy treatment in colorectal cancer patients 2–9 months post-surgery

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The Nordic Nutrition Recommendations 2022-prioritisation of topics for de novo systematic reviews

Background: As part of the process of updating national dietary reference values (DRVs) and food-based dietary guidelines (FBDGs), the Nordic Nutrition Recommendations 2022 project (NNR2022) will select a limited number of topics for systematic reviews (SRs). Objective: To develop and transparently describe the results of a procedure for prioritisation of topics that may be submitted for SRs in the NNR2022 project. Design: In an open call, scientists, health professionals, national food and health authorities, food manufacturers, other stakeholders and the general population in the Nordic and Baltic countries were invited to suggest SR topics. The NNR2022 Committee developed scoping reviews (ScRs) for 51 nutrients and food groups aimed at identifying potential SR topics. These ScRs included the relevant nominations from the open call. SR topics were categorised, ranked and prioritised by the NNR2022 Committee in a modified Delphi process. Existing qualified SRs were identified to omit duplication. Results: A total of 45 nominations with suggestion for more than 200 exposure-outcome pairs were received in the public call. A number of additional topics were identified in ScRs. In order to omit duplication with recently qualified SRs, we defined criteria and identified 76 qualified SRs. The NNR2022 Committee subsequently shortlisted 52 PI/ECOTSS statements, none of which overlapped with the qualified SRs. The PI/ ECOTSS statements were then graded 'High' (n = 21), 'Medium' (n = 9) or 'Low' (n = 22) importance, and the PI/ECOTSS statements with 'High' were ranked in a Delphi process. The nine top prioritised PI/ECOTSS included the following exposure-outcome pairs: 1) plant protein intake in children and body growth, 2) pulses/ legumes intake, and cardiovascular disease and type 2 diabetes, 3) plant protein intake in adults, and atherosclerotic/cardiovascular disease and type 2 diabetes, 4) fat quality and mental health, 5) vitamin B12 and vitamin B12 status, 6) intake of white meat (no consumption vs. high consumption and white meat replaced with red meat), and all-cause mortality, type 2 diabetes and risk factors, 7) intake of n-3 LPUFAs from supplements during pregnancy, and asthma and allergies in the offspring, 8) nuts intake and cardiovascular disease (CVD) and type 2 diabetes in adults, 9) dietary fibre intake (high vs. low) in children and bowel function. Discussion: The selection of topics for de novo SRs is central in the NNR2022 project, as the results of these SRs may cause adjustment of existing DRVs and FBDGs. That is why we have developed this extensive process for the prioritisation of SR topics. For transparency, the results of the process are reported in this publication. Conclusion: The principles and methodologies developed in the NNR2022 project may serve as a framework for national health authorities or organisations when developing national DRVs and FBDGs. This collaboration between the food and health authorities in Denmark, Estonia, Finland, Iceland, Latvia, Lithuania, Norway and Sweden represents an international effort for harmonisation and sharing of resources and competence when developing national DRVs and FBDGs.Peer reviewe

Associations of the 2018 World Cancer Research Fund/American Institute of Cancer Research (WCRF/AICR) cancer prevention recommendations with stages of colorectal carcinogenesis

Background: While adherence to cancer prevention recommendations is linked to lower risk of colorectal cancer (CRC), few have studied associations across the entire spectrum of colorectal carcinogenesis. Here, we studied the relationship of the standardized 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) Score for cancer prevention recommendations with detection of colorectal lesions in a screening setting. As a secondary objective, we examined to what extent the recommendations were being followed in an external cohort of CRC patients. Methods: Adherence to the seven-point 2018 WCRF/AICR Score was measured in screening participants receiving a positive fecal immunochemical test and in CRC patients participating in an intervention study. Dietary intake, body fatness and physical activity were assessed using self-administered questionnaires. Multinomial logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for screen-detected lesions. Results: Of 1486 screening participants, 548 were free from adenomas, 524 had non-advanced adenomas, 349 had advanced lesions and 65 had CRC. Adherence to the 2018 WCRF/AICR Score was inversely associated with advanced lesions; OR 0.82 (95% CI 0.71, 0.94) per score point, but not with CRC. Of the seven individual components included in the score, alcohol, and BMI seemed to be the most influential. Of the 430 CRC patients included in the external cohort, the greatest potential for lifestyle improvement was seen for the recommendations concerning alcohol and red and processed meat, where 10% and 2% fully adhered, respectively. Conclusions: Adherence to the 2018 WCRF/AICR Score was associated with lower probability of screen-detected advanced precancerous lesions, but not CRC. Although some components of the score seemed to be more influential than others (i.e., alcohol and BMI), taking a holistic approach to cancer prevention is likely the best way to prevent the occurrence of precancerous colorectal lesions

Haploinsufficiency of two histone modifier genes on 6p22.3, ATXN1 and JARID2, is associated with intellectual disability

BACKGROUND: Nineteen patients with deletions in chromosome 6p22-p24 have been published so far. The syndromic phenotype is varied, and includes intellectual disability, behavioural abnormalities, dysmorphic features and structural organ defects. Heterogeneous deletion breakpoints and sizes (1–17 Mb) and overlapping phenotypes have made the identification of the disease causing genes challenging. We suggest JARID2 and ATXN1, both harbored in 6p22.3, as disease causing genes. METHODS AND RESULTS: We describe five unrelated patients with de novo deletions (0.1-4.8 Mb in size) in chromosome 6p22.3-p24.1 detected by aCGH in a cohort of approximately 3600 patients ascertained for neurodevelopmental disorders. Two patients (Patients 4 and 5) carried non-overlapping deletions that were encompassed by the deletions of the remaining three patients (Patients 1–3), indicating the existence of two distinct dosage sensitive genes responsible for impaired cognitive function in 6p22.3 deletion-patients. The smallest region of overlap (SRO I) in Patients 1–4 (189 kb) included the genes JARID2 and DTNBP1, while SRO II in Patients 1–3 and 5 (116 kb) contained GMPR and ATXN1. Patients with deletion of SRO I manifested variable degrees of cognitive impairment, gait disturbance and distinct, similar facial dysmorphic features (prominent supraorbital ridges, deep set eyes, dark infraorbital circles and midface hypoplasia) that might be ascribed to the haploinsufficiency of JARID2. Patients with deletion of SRO II showed intellectual disability and behavioural abnormalities, likely to be caused by the deletion of ATXN1. Patients 1–3 presented with lower cognitive function than Patients 4 and 5, possibly due to the concomitant haploinsufficiency of both ATXN1 and JARID2. The chromatin modifier genes ATXN1 and JARID2 are likely candidates contributing to the clinical phenotype in 6p22-p24 deletion-patients. Both genes exert their effect on the Notch signalling pathway, which plays an important role in several developmental processes. CONCLUSIONS: Patients carrying JARID2 deletion manifested with cognitive impairment, gait disturbance and a characteristic facial appearance, whereas patients with deletion of ATXN1 seemed to be characterized by intellectual disability and behavioural abnormalities. Due to the characteristic facial appearance, JARID2 haploinsufficiency might represent a clinically recognizable neurodevelopmental syndrome

An overview of approaches for assessing the environmental sustainability of diets – a scoping review for Nordic Nutrition Recommendations 2023

Assessing the environmental impacts of food, food systems and diets is highly complex due to the multitude of processes involved, the uncertainty in assessment models, the variability in production systems and the large range of products available. No single assessment method alone can provide a complete evidence base. The increasing number of Life Cycle Assessment and food system analyses, and more recently the integration of planetary boundaries offer insights from which we can draw some robust high-level conclusions, whilst recognising there is a need for more detailed analysis to capture the inherent nuances of more location and context-specific situations. Despite the complexity of assessing the environmental sustainability of food, diets and food systems, there are a number of key considerations that could be used to guide this process, and in doing so, they help to increase utility of the outcomes and limit unintended adverse consequences. We identified five key considerations that can be applied (consider the thresholds, consider the system, consider the variables, consider the context and consider the spillover) to ensure assessments are comprehensive.</p

The Nordic Nutrition Recommendations 2022 – structure and rationale of qualified systematic reviews

Background: Qualified systematic reviews (SRs) will form the main basis for evaluating causal effects of nutrients or food groups on health outcomes in the sixth edition of Nordic Nutrition Recommendations to be published in 2022 (NNR2022). Objective: To describe rationale and structure of SRs used in NNR2022. Design: The SR methodologies of the previous edition of NNR were used as a starting point. Methodologies of recent SRs commissioned by leading national food and health authorities or international food and health organizations were examined and scrutinized. Methodologies for developing SRs were agreed by the NNR2022 Committee in a consensus-driven process. Results: Qualified SRs will be developed by a cross-disciplinary group of experts and reported according to the requirements of the EQUATOR network. A number of additional requirements must also be fulfilled, including 1) a clearly stated set of objectives and research questions with pre-defined eligibility criteria for the studies, 2) an explicit, reproducible methodology, 3) a systematic search that attempts to identify all studies that would meet the eligibility criteria, 4) an assessment of the validity of the findings of the included studies through an assessment of 'risk of bias' of the studies, 5) a systematic presentation and synthesis of the characteristics and findings of the included studies, and 6) a grading of the overall evidence. The complete definition and requirements of a qualified SR are described. Discussion: Most SRs published in scientific journals do not fulfill all criteria of the qualified SRs in the NNR2022 project. This article discusses the structure and rationale for requirements of qualified SRs in NNR2022. National food and health authorities have only recently begun to use qualified SRs as a basis for nutrition recommendations. Conclusion: Qualified SRs will be used to inform dietary reference values (DRVs) and food-based dietary guidelines (FBDGs) in the NNR2022 project.Peer reviewe

The Nordic Nutrition Recommendations 2022 – handbook for qualified systematic reviews

Background: Systematic reviews (SRs) constitute a major part of the Nordic Nutrition Recommendations (NNRs). The step-by-step procedure used to develop SRs has evolved considerably over time and is often tailored to fit the exposure and outcomes in focus. Objective: To describe a detailed procedure for developing qualified SRs commissioned by the NNR2022 project. Design: Scrutinizing procedures of recent SRs commissioned by leading national food and health authorities or international food and health organizations. Results: The following eight steps must be included when developing qualified SRs for the NNR2022 project: 1) define research question, 2) protocol development, 3) literature search, 4) screening and selection of studies, 5) data extraction, 6) assessing risk of bias, 7) synthesis and grading of total strength of evidence, and 8) reporting according to certain standards. Discussion: This guide is based on the guidelines developed for the fifth edition of NNR but includes some important new domains in order to adhere to more recent, authoritative standards. Conclusion: All qualified SRs in the NNR2022 project will follow the protocol described here.Peer reviewe

The Nordic Nutrition Recommendations 2022 – principles and methodologies

Background: The Nordic Nutrition Recommendations (NNRs) constitute the scientific basis for national dietary reference values (DRVs) and food-based dietary guidelines (FBDGs) in the Nordic and Baltic countries. Objective: To define principles and methodologies for the sixth edition of NNR to be published in 2022 (NNR2022). Design: The principles and methodologies of the previous edition of NNR were used as a starting point. Recent nutrition recommendations commissioned by other national food and health authorities or international food and health organizations were examined and dissected. Updated principles and methodologies were agreed by the NNR2022 Committee in a consensus-driven process. Results: An organizational model with 'checks and balances' was developed to minimize the influence of subjective biases of the committee members and experts. Individual chapters on all included nutrients and food groups will be updated as scoping reviews. Systematic reviews (SRs), which are the main basis for evaluating causal effects of nutrients or food groups on health outcomes, will be embedded in each chapter. A NNR SR Centre will be established for performing de novo SRs on prioritized topics. To avoid duplication and optimize the use of resources, qualified SRs commissioned by other national and international organizations and health authorities will also inform DRVs and FBDGs in NNR2022. Discussion: The evidence-based methods defined in the NNR2022 project are compatible with most contemporary methods used by leading national food and health authorities. Global harmonization of methodological approaches to nutrition recommendations is strongly encouraged. Conclusion: Evidence-informed principles and methodologies underpinned by SRs will ensure that DRVs and FBDGs defined in the NNR2022 project are based on the best available evidence and as far as possible free from overt bias.Peer reviewe

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