Estimating Total Energy Expenditure to Determine Energy Requirements in Free-Living Children With Stage 3 Chronic Kidney Disease: Can a Structured Approach Help Improve Clinical Care?

OBJECTIVE: Malnutrition and obesity are complex burdensome challenges in pediatric chronic kidney disease (CKD) management that can adversely affect growth, disease progression, wellbeing, and response to treatment. Total energy expenditure (TEE) and energy requirements in children are essential for growth outcomes but are poorly defined, leaving clinical practice varied and insecure. The aims of this study were to explore a practical approach to guide prescribed nutritional interventions, using measurements of TEE, physical activity energy expenditure (PAEE), and their relationship to kidney function. DESIGN AND METHODS: In a cross-sectional prospective age-matched and sex-matched controlled study, 18 children with CKD (6-17 years, mean stage 3) and 20 healthy, age-matched, and gender-matched controls were studied. TEE and PAEE were measured using basal metabolic rate (BMR), activity diaries and doubly labeled water (healthy subjects). Results were related to estimated glomerular filtration rate (eGFR). The main outcome measure was TEE measured by different methods (factorial, doubly labeled water, and a novel device). RESULTS: Total energy expenditure and PAEE with or without adjustments for age, gender, weight, and height did not differ between the groups and was not related to eGFR. TEE ranged from 1927 ± 91 to 2330 ± 73 kcal/d; 95 ± 5 to 109 ± 5% estimated average requirement (EAR), physical activity level (PAL) 1.52 ± 0.01 to 1.71 ± 0.17, and PAEE 24 to 34% EAR. Comparisons between DLW and alternative methods in healthy children did not differ significantly, except for 2 (factorial methods and a fixed PAL; and the novel device). CONCLUSION: In clinical practice, structured approaches using supportive evidence (weight, height, BMI sds), predictive BMR or TEE values and simple questions on activity, are sufficient for most children with CKD as a starting energy prescription.

Evaluation of a COVID-19 fundamental nursing care guideline versus usual care: The COVID-NURSE cluster randomized controlled trial.

AIM: To evaluate the impact of usual care plus a fundamental nursing care guideline compared to usual care only for patients in hospital with COVID-19 on patient experience, care quality, functional ability, treatment outcomes, nurses' moral distress, patient health-related quality of life and cost-effectiveness. DESIGN: Parallel two-arm, cluster-level randomized controlled trial. METHODS: Between 18th January and 20th December 2021, we recruited (i) adults aged 18 years and over with COVID-19, excluding those invasively ventilated, admitted for at least three days or nights in UK Hospital Trusts; (ii) nurses caring for them. We randomly assigned hospitals to use a fundamental nursing care guideline and usual care or usual care only. Our patient-reported co-primary outcomes were the Relational Aspects of Care Questionnaire and four scales from the Quality from the Patient Perspective Questionnaire. We undertook intention-to-treat analyses. RESULTS: We randomized 15 clusters and recruited 581 patient and 418 nurse participants. Primary outcome data were available for 570-572 (98.1%-98.5%) patient participants in 14 clusters. We found no evidence of between-group differences on any patient, nurse or economic outcomes. We found between-group differences over time, in favour of the intervention, for three of our five co-primary outcomes, and a significant interaction on one primary patient outcome for ethnicity (white British vs. other) and allocated group in favour of the intervention for the 'other' ethnicity subgroup. CONCLUSION: We did not detect an overall difference in patient experience for a fundamental nursing care guideline compared to usual care. We have indications the guideline may have aided sustaining good practice over time and had a more positive impact on non-white British patients' experience of care. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: We cannot recommend the wholescale implementation of our guideline into routine nursing practice. Further intervention development, feasibility, pilot and evaluation studies are required. IMPACT: Fundamental nursing care drives patient experience but is severely impacted in pandemics. Our guideline was not superior to usual care, albeit it may sustain good practice and have a positive impact on non-white British patients' experience of care. REPORTING METHOD: CONSORT and CONSERVE. PATIENT OR PUBLIC CONTRIBUTION: Patients with experience of hospitalization with COVID-19 were involved in guideline development and writing, trial management and interpretation of findings.

Detecting low-intake dehydration using bioelectrical impedance analysis in older adults in acute care settings: a systematic review.

BACKGROUND: Dehydration is a frequent cause of excess morbidity and poor health outcomes, particularly in older adults who have an increased risk of fluid loss due to renal senescence, comorbidities, and polypharmacy. Detecting dehydration is key to instigating treatment to resolve the problem and prevent further adverse consequences; however, current approaches to diagnosis are unreliable and, as a result, under-detection remains a widespread problem. This systematic review sought to explore the value of bioelectrical impedance in detecting low-intake dehydration among older adults admitted to acute care settings. METHODS: A literature search using MEDLINE, EMBASE, CINAHL, Web of Science, and the Cochrane Library was undertaken from inception till May 2022 and led to the eventual evaluation of four studies. Risk of bias was assessed using the Cochrane tool for observational studies; three studies had a high risk of bias, and one had a low risk. Data were extracted using systematic proofs. Due to insufficient reporting, the data were analysed using narrative synthesis. RESULTS: One study showed that the sensitivity and specificity of bioelectrical impedance in detecting low-intake dehydration varied considerably depending on the total body water percentage threshold used to ascertain dehydration status. Other included studies supported the technique's utility when compared to conventional measures of hydration status. CONCLUSIONS: Given the scarcity of literature and inconsistency between findings, it is not possible to ascertain the value of bioelectrical impedance for detecting low-intake dehydration in older inpatients.

Association of nutritional status and health-related quality of life in children with chronic kidney disease.

PURPOSE: Health-related quality of life (HRQoL) is an important, patient-centred measure. Although nutritional status is altered in children with CKD, the impact of nutritional status on HRQoL in this population has not been explored. The aims of this study are to report the HRQoL scores as assessed by the validated PedsQL™ questionnaire and to explore the relationship of HRQoL scores to markers of nutritional status. It will also examine the concordance between the scores of the child and their parent/carer. METHODS: A single-centre, cross-sectional, observational study was performed exploring the markers of nutritional status (anthropometry-including presence of obesity, micronutrient status and appetite) and HRQoL and assessed by the PedsQL™ questionnaire in children aged 3-18 years with pre-dialysis, conservatively managed CKD. RESULTS: A total of 46 children were recruited, with a mean age of 10.5 years. HRQoL scores were lower than in healthy controls throughout all domains. Lower scores were associated with short stature and poor appetite. Markers of obesity or micronutrient status were not associated with HRQoL scores. DISCUSSION: Nutritional status impacts upon HRQoL. Further study is needed to evaluate how changing nutritional status may affect HRQoL in children with CKD, and this may be used to facilitate the development of patient-centred treatment goals and plans.

Environmental interventions to promote healthier eating and physical activity behaviours in institutions: a systematic review.

OBJECTIVE: The present review evaluated the effectiveness of environmental-based interventions aimed at improving the dietary and physical activity behaviours and body composition indices of adults in institutions. DESIGN: A systematic review was conducted. Electronic databases (MEDLINE, Embase, PsycINFO, CINAHL, The Cochrane Library, Web of Science, ProQuest Dissertation and Theses, Scopus and Athena) were searched for relevant articles published between database inception and October 2017. Searching, selecting and reporting were undertaken according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. SETTING: Military establishments and maritime workplaces.ParticipantsAdults in institutions, aged 18-45 years. RESULTS: A total of 27842 articles were screened for eligibility, nine studies (reported in eleven articles) were included in the review. Five studies used multilevel strategies and four used environmental strategies only. Duration of follow-up ranged from 3 weeks to 10 years. Eight of the studies reported significant positive effects on dietary behaviours, but effect sizes varied. The study that targeted physical activity had no effect on activity levels but did have a significant positive effect on physical fitness. No evidence was identified that the studies resulted in improvements in body composition indices. CONCLUSIONS: The evidence base appears to be in favour of implementing environmental interventions in institutions to improve the dietary behaviours of adults. However, due to the small number of studies included in the review, and the variable methodological quality of the studies and intervention reporting, further well-designed evaluation studies are required.

Vitamin B6 in Pediatric Renal Transplant Recipients.

OBJECTIVES: Our aim was to assess the vitamin B6 intake and biochemical status in a sample of children who have undergone renal transplantation. METHODS: A prospective observational study was performed in 10 pediatric renal transplant recipients to determine their vitamin B6 status through dietary assessment and serum Pyridoxal 5'-phosphate (PLP) measurement. RESULTS: Ten children (mean age of 11.9 years) had median serum PLP concentrations of 62.45 nmol/L (interquartile range ±83.40). Two children (20%) had values above the reference range, and none below. Mean vitamin B6 intake was 138.7% of reference nutrient intake (standard deviation ±35.2%). No children were in receipt of vitamin B6 supplementation. CONCLUSION: There is no previous literature on vitamin B6 status in children who have undergone renal transplantation. In adult transplant recipients, elevated serum PLP concentrations have been described and ascribed to possible excessive intakes. In this sample, no children appeared biochemically deficient, but 20% had elevated concentrations. Dietary intakes were not excessive, and no children reported oral Vitamin B6 supplementation. Exploration of vitamin B6 metabolism in this population is required.

Impact of radiologically stratified exacerbations: insights into pneumonia aetiology in COPD.

BACKGROUND: COPD patients have increased risk of developing pneumonia, which is associated with poor outcomes. It can be symptomatically indistinguishable from exacerbations, making diagnosis challenging. Studies of pneumonia in COPD have focused on hospitalised patients and are not representative of the ambulant COPD population. Therefore, we sought to determine the incidence and aetiology of acute exacerbation events with evidence of pneumonic radiographic infiltrates in an outpatient COPD cohort. METHODS: One hundred twenty-seven patients with moderate to very severe COPD aged 42-85 years underwent blood and sputum sampling over one year, at monthly stable visits and within 72 h of exacerbation symptom onset. 343 exacerbations with chest radiographs were included. RESULTS: 20.1% of exacerbations had pneumonic infiltrates. Presence of infiltrate was highly seasonal (Winter vs summer OR 3.056, p = 0.027). In paired analyses these exacerbation events had greater increases in systemic inflammation. Bacterial detection rate was higher in the pneumonic group, with Haemophilus influenzae the most common bacteria in both radiological groups. Viral detection and sputum microbiota did not differ with chest radiograph appearance. CONCLUSIONS: In an outpatient COPD cohort, pneumonic infiltrates at exacerbation were common, and associated with more intense inflammation. Bacterial pathogen detection and lung microbiota were not distinct, suggesting that exacerbations and pneumonia in COPD share common infectious triggers and represent a continuum of severity rather than distinct aetiological events. TRIAL REGISTRATION: Trial registration Number: NCT01360398 .

Relationship of CT-quantified emphysema, small airways disease and bronchial wall dimensions with physiological, inflammatory and infective measures in COPD.

BACKGROUND: COPD is a complex, heterogeneous disease characterised by progressive development of airflow limitation. Spirometry provides little information about key aspects of pathology and is poorly related to clinical outcome, so other tools are required to investigate the disease. We sought to explore the relationships between quantitative CT analysis with functional, inflammatory and infective assessments of disease to identify the utility of imaging to stratify disease to better predict outcomes and disease response. METHODS: Patients from the AERIS study with moderate-very severe COPD underwent HRCT, with image analysis determining the quantity of emphysema (%LAA<- 950), small airways disease (E/I MLD) and bronchial wall thickening (Pi10). At enrolment subjects underwent lung function testing, six-minute walk testing (6MWT), blood sampling for inflammatory markers and sputum sampling for white cell differential and microbiological culture and PCR. RESULTS: 122 subjects were included in this analysis. Emphysema and small airways disease had independent associations with airflow obstruction (ß = - 0.34, p < 0.001 and ß = - 0.56, p < 0.001). %LAA<- 950 had independent associations with gas transfer (ß = - 0.37, p < 0.001) and E/I MLD with RV/TLC (ß = 0.30, p =0.003). The distance walked during the 6MWT was not associated with CT parameters, but exertional desaturation was independently associated with emphysema (ß = 0.73, p < 0.001). Pi10 did not show any independent associations with lung function or functional parameters. No CT parameters had any associations with sputum inflammatory cells. Greater emphysema was associated with lower levels of systemic inflammation (CRP ß = - 0.34, p < 0.001 and fibrinogen ß = - 0.28, p =0.003). There was no significant difference in any of the CT parameters between subjects where potentially pathogenic bacteria were detected in sputum and those where it was not. CONCLUSIONS: This study provides further validation for the use of quantitative CT measures of emphysema and small airways disease in COPD as they showed strong associations with pulmonary physiology and functional status. In contrast to this quantitative CT measures showed few convincing associations with biological measures of disease, suggesting it is not an effective tool at measuring disease activity.

Embedding electronic growth charts into clinical practice at a children's hospital.

Embedding electronic growth charts (EGCs) into clinical practice in a children's hospital. We employed initial implementation in the outpatient setting and subsequently extended this across inpatients with the growth chart following the child's records through both settings and significantly increasing growth data documentation.

A prospective, observational cohort study of the seasonal dynamics of airway pathogens in the aetiology of exacerbations in COPD.

BACKGROUND: The aetiology of acute exacerbations of COPD (AECOPD) is incompletely understood. Understanding the relationship between chronic bacterial airway infection and viral exposure may explain the incidence and seasonality of these events. METHODS: In this prospective, observational cohort study (NCT01360398), patients with COPD aged 40-85 years underwent sputum sampling monthly and at exacerbation for detection of bacteria and viruses. Results are presented for subjects in the full cohort, followed for 1 year. Interactions between exacerbation occurrence and pathogens were investigated by generalised estimating equation and stratified conditional logistic regression analyses. FINDINGS: The mean exacerbation rate per patient-year was 3.04 (95% CI 2.63 to 3.50). At AECOPD, the most common bacterial species were non-typeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis, and the most common virus was rhinovirus. Logistic regression analyses (culture bacterial detection) showed significant OR for AECOPD occurrence when M. catarrhalis was detected regardless of season (5.09 (95% CI 2.76 to 9.41)). When NTHi was detected, the increased risk of exacerbation was greater in high season (October-March, OR 3.04 (1.80 to 5.13)) than low season (OR 1.22 (0.68 to 2.22)). Bacterial and viral coinfection was more frequent at exacerbation (24.9%) than stable state (8.6%). A significant interaction was detected between NTHi and rhinovirus presence and AECOPD risk (OR 5.18 (1.92 to 13.99); p=0.031). CONCLUSIONS: AECOPD aetiology varies with season. Rises in incidence in winter may be driven by increased pathogen presence as well as an interaction between NTHi airway infection and effects of viral infection. TRIAL REGISTRATION NUMBER: Results, NCT01360398.

Impact and associations of eosinophilic inflammation in COPD: analysis of the AERIS cohort.

Eosinophilic inflammation in chronic obstructive pulmonary disease (COPD) predicts response to treatment, especially corticosteroids. We studied the nature of eosinophilic inflammation in COPD prospectively to examine the stability of this phenotype and its dynamics across exacerbations, and its associations with clinical phenotype, exacerbations and infection.127 patients aged 40-85 years with moderate to very severe COPD underwent repeated blood and sputum sampling at stable visits and within 72 h of exacerbation for 1 year.Blood eosinophils ≥2% was prevalent at baseline, and predicted both predominantly raised stable-state eosinophils across the year (area under the curve 0.841, 95% CI 0.755-0.928) and increased risk of eosinophilic inflammation at exacerbation (OR 9.16; p<0.001). Eosinophils ≥2% at exacerbation and eosinophil predominance at stable visits were associated with a lower risk of bacterial presence at exacerbation (OR 0.49; p=0.049 and OR 0.25; p=0.065, respectively). Bacterial infection at exacerbation was highly seasonal (winter versus summer OR 4.74; p=0.011) in predominantly eosinophilic patients.Eosinophilic inflammation is a common and stable phenotype in COPD. Blood eosinophil counts in the stable state can predict the nature of inflammation at future exacerbations, which when combined with an understanding of seasonal variation provides the basis for the development of new treatment paradigms for this important condition.

Quality control issues related to assessment of body composition.

There are no internationally agreed quality standards for the measurement of stature, weight, and body composition. This lack of agreement constrains the quality of work in nutrition and must be addressed in order to build systemic capacity within the Scaling Up Nutrition agenda. There is a need to reach agreement and define standards of performance and the required training to be able to demonstrate the competency of those responsible for making the measurements. This, together with the adoption of standardized protocols, traceable reference materials, quality assurance frameworks, and publication guidance, would mark an important first step in improving the conduct and interpretation of measurements of growth and body composition.

Assessment of body composition in breast cancer patients: concordance between transverse computed tomography analysis at the fourth thoracic and third lumbar vertebrae.

Introduction: Specific body composition markers derived from L3 axial computed tomography (CT) images predict clinical cancer outcomes, including chemotherapy toxicity and survival. However, this method is only applicable to those undergoing lumbar (L3) CT scanning, which is not universally conducted in early breast cancer cases. This study aimed to evaluate CT analysis at T4 as a feasible alternative marker of body composition in breast cancer. Method: All patients participated in the Investigating Outcomes from Breast Cancer: Correlating Genetic, Immunological, and Nutritional (BeGIN) Predictors observational cohort study (REC reference number: 14/EE/1297). Staging chest-abdomen-pelvic CT scan images from 24 women diagnosed with early breast cancer at University Hospital Southampton were analysed. Adipose tissue, skeletal muscle, and muscle attenuation were measured from the transverse CT slices' cross-sectional area (CSA) at T4 and L3. Adipose tissue and skeletal muscle area measurements were adjusted for height. Spearman's rank correlation coefficient analysis was used to determine concordance between body composition measurements using CT analysis at L3 and T4 regions. Results: Derived estimates for total adipose tissue, subcutaneous adipose tissue, and intramuscular adipose tissue mass following adjustment for height were highly concordant when determined from CSAs of CT slices at T4 and L3 (Rs = 0.821, p < 0.001; Rs = 0.816, p < 0.001; and Rs = 0.830, p < 0.001). In this cohort, visceral adipose tissue (VAT) and skeletal muscle estimates following height adjustment were less concordant when measured by CT at T4 and L3 (Rs = 0.477, p = 0.039 and Rs = 0.578, p = 0.003). The assessment of muscle attenuation was also highly concordant when measured by CT at T4 and L3 (Rs = 0.840, p < 0.001). Discussion: These results suggest that the CT analysis at T4 and L3 provides highly concordant markers for total adipose, subcutaneous adipose, and intramuscular adipose estimation, but not VAT, in this breast cancer population. High concordance between T4 and L3 was also found when assessing skeletal muscle attenuation. Lower concordance was observed for the estimates of skeletal muscle area, potentially explained by differences in the quantity and proportions of axial and appendicular muscle between the thorax and abdomen. Future studies will determine the value of T4 metrics as predictive tools for clinical outcomes in breast cancer.

Micronutrient Status in Adult Crohn's Disease during Clinical Remission: A Systematic Review.

Adults with Crohn's disease (CD) may be at risk of micronutrient insufficiency in clinical remission through restrictive eating, malabsorption, abnormal losses or inflammation. This systematic review synthesises the literature on micronutrient insufficiency in CD in clinical remission in terms of the prevalence of low circulating micronutrient concentrations and as a comparison against a healthy control (HC). Studies were included if the population was predominantly in remission. A total of 42 studies met the inclusion criteria; 12 were rated as low quality, leaving 30 studies covering 21 micronutrients of medium/high quality that were included in the synthesis. Vitamins D and B12 were the most frequently reported nutrients (8 and 11); there were few eligible studies for the remaining micronutrients. The prevalence studies were consistent in reporting individuals with low Vitamins A, B6, B12 and C, ß-carotene, D, Magnesium, Selenium and Zinc. The comparator studies were inconsistent in finding differences with CD populations; Vitamin D, the most reported nutrient, was only lower than the HC in one-quarter of the studies. Adult CD populations are likely to contain individuals with low levels of one or more micronutrients, with the most substantial evidence for Vitamins D and B12. The studies on other micronutrients are of insufficient number, standardisation and quality to inform practice.

A critical view of the use of predictive energy equations for the identification of hypermetabolism in motor neuron disease: A pilot study.

BACKGROUND AND AIMS: People living with motor neuron disease (MND) frequently struggle to consume an optimal caloric intake. Often compounded by hypermetabolism, this can lead to dysregulated energy homeostasis, prompting the onset of malnutrition and associated weight loss. This is associated with a poorer prognosis and reduced survival. It is therefore important to establish appropriate nutritional goals to ensure adequate energy intake. This is best done by measuring resting energy expenditure (mREE) using indirect calorimetry. However, indirect calorimetry is not widely available in clinical practice, thus dietitians caring for people living with MND frequently use energy equations to predict resting energy expenditure (pREE) and estimate caloric requirements. Energy prediction equations have previously been shown to underestimate resting energy expenditure in over two-thirds of people living with MND. Hypermetabolism has previously been identified using the metabolic index. The metabolic index is a ratio of mREE to pREE, whereby an increase of mREE by ≥110% indicates hypermetabolism. We aim to critically reflect on the use of the Harris-Benedict (1919) and Henry (2005) energy prediction equations to inform a metabolic index to indicate hypermetabolism in people living with MND. METHODS: mREE was derived using VO2 and VCO2 measurements from a GEMNutrition indirect calorimeter. pREE was estimated by Harris-Benedict (HB) (1919), Henry (2005) and kcal/kg/day predictive energy equations. The REE variation, described as the percentage difference between mREE and pREE, determined the accuracy of pREE ([pREE-mREE]/mREE) x 100), with accuracy defined as ≤ ± 10%. A metabolic index threshold of ≥110% was used to classify hypermetabolism. All resting energy expenditure data are presented as kcal/24hr. RESULTS: Sixteen people living with MND were included in the analysis. The mean mREE was 1642 kcal/24hr ranging between 1110 and 2015 kcal/24hr. When REE variation was analysed for the entire cohort, the HB, Henry and kcal/kg/day equations all overestimated REE, but remained within the accuracy threshold (mean values were 2.81% for HB, 4.51% for Henry and 8.00% for kcal/kg/day). Conversely, inter-individual REE variation within the cohort revealed HB and Henry equations both inaccurately reflected mREE for 68.7% of participants, with kcal/kg/day inaccurately reflecting 41.7% of participants. Whilst the overall cohort was not classified as hypermetabolic (mean values were 101.04% for HB, 98.62% for Henry and 95.64% for kcal/kg/day), the metabolic index ranges within the cohort were 70.75%-141.58% for HB, 72.82%-127.69% for Henry and 66.09%-131.58% for kcal/kg/day, indicating both over- and under-estimation of REE by these equations. We have shown that pREE correlates with body weight (kg), whereby the lighter the individual, the greater the underprediction of REE. When applied to the metabolic index, this underprediction biases towards the classification of hypermetabolism in lighter individuals. CONCLUSION: Whilst predicting resting energy expenditure using the HB, Henry or kcal/kg/day equations accurately reflects derived mREE at group level, these equations are not suitable for informing resting energy expenditure and classification of hypermetabolism when applied to individuals in clinical practice.

Individualised Exercise Training Enhances Antioxidant Buffering Capacity in Idiopathic Pulmonary Fibrosis.

Exercise training is recommended for patients with idiopathic pulmonary fibrosis (IPF); however, the mechanism(s) underlying its physiological benefits remain unclear. We investigated the effects of an individualised aerobic interval training programme on exercise capacity and redox status in IPF patients. IPF patients were recruited prospectively to an 8-week, twice-weekly cardiopulmonary exercise test (CPET)-derived structured responsive exercise training programme (SRETP). Systemic redox status was assessed pre- and post-CPET at baseline and following SRETP completion. An age- and sex-matched non-IPF control cohort was recruited for baseline comparison only. At baseline, IPF patients (n = 15) had evidence of increased oxidative stress compared with the controls as judged by; the plasma reduced/oxidised glutathione ratio (median, control 1856 vs. IPF 736 p = 0.046). Eleven IPF patients completed the SRETP (median adherence 88%). Following SRETP completion, there was a significant improvement in exercise capacity assessed via the constant work-rate endurance time (+82%, p = 0.003). This was accompanied by an improvement in post-exercise redox status (in favour of antioxidants) assessed via serum total free thiols (median increase, +0.26 µmol/g protein p = 0.005) and total glutathione concentration (+0.73 µM p = 0.03), as well as a decrease in post-exercise lipid peroxidation products (-1.20 µM p = 0.02). Following SRETP completion, post-exercise circulating nitrite concentrations were significantly lower compared with baseline (-0.39 µM p = 0.04), suggestive of exercise-induced nitrite utilisation. The SRETP increased both endurance time and systemic antioxidant capacity in IPF patients. The observed reduction in nitrite concentrations provides a mechanistic rationale to investigate nitrite/nitrate supplementation in IPF patients.

Faster rehabilitation weight gain during childhood is associated with risk of non-communicable disease in adult survivors of severe acute malnutrition.

Nutritional rehabilitation during severe acute malnutrition (SAM) aims to quickly restore body size and minimize poor short-term outcomes. We hypothesized that faster weight gain during treatment is associated with greater cardiometabolic risk in adult life. Anthropometry, body composition (DEXA), blood pressure, blood glucose, insulin and lipids were measured in a cohort of adults who were hospitalized as children for SAM between 1963 and 1993. Weight and height measured during hospitalization and at one year post-recovery were abstracted from hospital records. Childhood weight gain during nutritional rehabilitation and weight and height gain one year post-recovery were analysed as continuous variables, quintiles and latent classes in age, sex and minimum weight-for-age z-scores-adjusted regression models against adult measurements. Data for 278 adult SAM survivors who had childhood admission records were analysed. Of these adults, 85 also had data collected 1 year post-hospitalisation. Sixty percent of participants were male, mean (SD) age was 28.2 (7.7) years, mean (SD) BMI was 23.6 (5.2) kg/m2. Mean admission age for SAM was 10.9 months (range 0.3-36.3 months), 77% were wasted (weight-for-height z-scores<-2). Mean rehabilitation weight gain (SD) was 10.1 (3.8) g/kg/day and 61.6 (25.3) g/day. Rehabilitation weight gain > 12.9 g/kg/day was associated with higher adult BMI (difference = 0.5 kg/m2, 95% CI: 0.1-0.9, p = 0.02), waist circumference (difference = 1.4 cm, 95% CI: 0.4-2.4, p = 0.005), fat mass (difference = 1.1 kg, 95% CI: 0.2-2, p = 0.02), fat mass index (difference = 0.32kg/m2, 95% CI: -0.0001-0.6, p = 0.05), and android fat mass (difference = 0.09 kg, 95% CI: 0.01-0.2, p = 0.03). Post-recovery weight gain (g/kg/month) was associated with lean mass (difference = 1.3 kg, 95% CI: 0.3-2.4, p = 0.015) and inversely associated with android-gynoid fat ratio (difference = -0.03, 95% CI: -0.07to-0.001 p = 0.045). Rehabilitation weight gain exceeding 13g/kg/day was associated with adult adiposity in young, normal-weight adult SAM survivors. This challenges existing guidelines for treating malnutrition and warrants further studies aiming at optimising these targets.

No relation between disease activity measured by multiple methods and REE in childhood Crohn disease.

BACKGROUND AND AIMS: Increased resting energy expenditure (REE) unmatched by dietary intake is implicated as a cause of poor nutrition in childhood inflammatory conditions. Adequate description of disease activity and correction of REE data for body composition are important to reach reliable conclusions about changes in REE associated with disease. The present study aimed to determine the effect of disease activity measured by clinical status, systemic and stool inflammatory markers on REE in children with Crohn disease using appropriate correction for confounding factors. METHODS: Sixty children with Crohn disease were recruited from the regional paediatric gastroenterology unit and studied on 1 occasion. REE was measured by indirect calorimetry. Fat-free mass (FFM) was estimated by skinfold thickness. Disease activity was measured using systemic (C-reactive protein [CRP], erythrocyte sedimentation rate [ESR]) and faecal markers of inflammation (lactoferrin, calprotectin) and clinical scores (Paediatric Crohn Disease Activity Index). RESULTS: Using a multiple regression model, there was no significant change in REE from active or inactive disease (ß = 0.03, P = 0.7) nor from CRP (ß = -0.05, P = 0.52), ESR (ß = -0.07, P = 0.43), faecal calprotectin (ß = -0.07, P = 0.38), and faecal lactoferrin (ß = 0.01, P = 0.88). REE/kg FFM was not associated with the Paediatric Crohn Disease Activity Index (r = 0.1, P = 0.44), CRP (r = -0.3, P = 0.84) or ESR (r = 0.12, P = 0.4), faecal calprotectin (r = 0.04, P = 0.97), or faecal lactoferrin (r = 0.02, P = 0.87). CONCLUSIONS: REE corrected for physiologically relevant confounders is not associated with degree of disease activity using clinical tools or systemic and local inflammatory markers, and therefore is an unlikely mechanism for poor nutritional state.

Systems redox biology in health and disease.

Living organisms need to be able to cope with environmental challenges and other stressors and mount adequate responses that are as varied as the spectrum of those challenges. Understanding how the multi-layered biological stress responses become integrated across and between different levels of organization within an organism can provide a different perspective on the nature and inter-relationship of complex systems in health and disease. We here compare two concepts which have been very influential in stress research: Selye's 'General Adaptation Syndrome' and Sies's 'Oxidative Stress' paradigm. We show that both can be embraced within a more general framework of 'change and response'. The 'Reactive Species Interactome' allows each of these to be considered as distinct but complementary aspects of the same system, representative of roles at different levels of organization within a functional hierarchy. The versatile chemistry of sulfur - exemplified by hydrogen sulfide, glutathione and proteinous cysteine thiols - enriched by its interactions with reactive oxygen, nitrogen and sulfur species, would seem to sit at the heart of the 'Redox Code' and underpin the ability of complex organisms to cope with stress.

Body composition and chemotherapy toxicity in women with early breast cancer (CANDO-3): protocol for an observational cohort study.

INTRODUCTION: Systemic anticancer therapy is given to selected patients with early breast cancer (EBC) before or after surgery with the aim of eradicating micrometastatic spread and reducing the risk of cancer recurrence. Chemotherapy treatment is most effective when patients receive the optimum dose, on time and without delays or reductions in their treatment doses. Most chemotherapy drugs are dosed according to body surface area calculated from a patient's height and weight. These calculations were however designed based on data from normal weight patients. This has resulted in uncertainty as to the optimal dosing for patients with different amounts of blood, muscle and fatty tissue (body composition). This study uses segmental bioelectrical impedance analysis (using the Seca mBCA 515) to determine whether differences in the measures of resistance and reactance, and derived estimates of body composition, are predictive of chemotherapy toxicity in the treatment of EBC. METHODS AND ANALYSIS: A prospective observational cohort study of women with EBC in whom adjuvant or neoadjuvant chemotherapy is planned. A total of 300 participants will be recruited across nine UK hospital sites. The primary outcome is to determine if higher fat mass index is associated with increased National Cancer Institute Common Terminology Criteria for Adverse Events v5.0 grade 3 (or higher) chemotherapy toxicity. ETHICS AND DISSEMINATION: This study has received ethical approval from the South Central Hampshire B Research Ethics Committee, England (19/SC/0596: IRAS: 263666). The chief investigator and coinvestigators will be responsible for publication of the study findings in a peer-reviewed journal, on behalf of all collaborators. TRIAL REGISTRATION NUMBER: ISRCTN79577461.