Performance of empirical and model-based classifiers for detecting sucrase-isomaltase inhibition using the 13 C-sucrose breath test.

Background: Environmental enteric dysfunction (EED) is a syndrome characterized by epithelial damage including blunting of the small intestinal villi and altered digestive and absorptive capacity which may negatively impact linear growth in children. The 13 C-sucrose breath test ( 13 C-SBT) has been proposed to estimate sucrase-isomaltase (SIM) activity, which is thought to be reduced in EED. We previously showed how various summary measures of the 13 C-SBT breath curve reflect SIM inhibition. However, it is uncertain how the performance of these classifiers is affected by test duration. Methods: We leveraged SBT data from a cross-over study in 16 adults who received 0, 100, and 750 mg of Reducose, a natural SIM inhibitor. We evaluated the performance of a pharmacokinetic-model-based classifier, ρ , and three empirical classifiers (cumulative percent dose recovered at 90 minutes (cPDR90), time to 50% dose recovered, and time to peak dose recovery rate), as a function of test duration using receiver operating characteristic curves. We also assessed the sensitivity, specificity, and accuracy of consensus classifiers. Results: Test durations of less than 2 hours generally failed to accurately predict later breath curve dynamics. The cPDR90 classifier had the highest area-under-the-curve and, by design, was robust to shorter test durations. For detecting mild SIM inhibition, ρ had a higher sensitivity. Conclusions: We recommend SBT tests run for at least a 2-hour duration. Although cPDR90 was the classifier with highest accuracy and robustness to test duration in this application, concerns remain about its sensitivity to misspecification of CO 2 production rate. More research is needed to assess these classifiers in target populations.

A Model-Based 13C-Sucrose Breath Test Diagnostic for Gut Function Disorders Characterized by a Loss of Sucrase-Isomaltase Enzymatic Activity.

BACKGROUND: Environmental enteric dysfunction (EED) causes malnutrition in children in low-resource settings. Stable-isotope breath tests have been proposed as noninvasive tests of altered nutrient metabolism and absorption in EED, but uncertainty over interpreting the breath curves has limited their use. The activity of sucrose-isomaltase, the glucosidase enzyme responsible for sucrose hydrolysis, may be reduced in EED. We previously developed a mechanistic model describing the dynamics of the 13C-sucrose breath test (13C-SBT) as a function of underlying metabolic processes. OBJECTIVES: This study aimed to determine which breath test curve dynamics are associated with sucrose hydrolysis and with the transport and metabolism of the fructose and glucose moieties and to propose and evaluate a model-based diagnostic for the loss of activity of sucrase-isomaltase. METHODS: We applied the mechanistic model to 2 sets of exploratory 13C-SBT experiments in healthy adult participants. First, 19 participants received differently labeled sucrose tracers (U-13C fructose, U-13C glucose, and U-13C sucrose) in a crossover study. Second, 16 participants received a sucrose tracer accompanied by 0, 100, and 750 mg of Reducose, a sucrase-isomaltase inhibitor. We evaluated a model-based diagnostic distinguishing between inhibitor concentrations using receiver operator curves, comparing with conventional statistics. RESULTS: Sucrose hydrolysis and the transport and metabolism of the fructose and glucose moieties were reflected in the same mechanistic process. The model distinguishes these processes from the fraction of tracer exhaled and an exponential metabolic process. The model-based diagnostic performed as well as the conventional summary statistics in distinguishing between no and low inhibition [area under the curve (AUC): 0.77 vs. 0.66-0.79] and for low vs. high inhibition (AUC 0.92 vs. 0.91-0.99). CONCLUSIONS: Current summary approaches to interpreting 13C breath test curves may be limited to identifying only gross gut dysfunction. A mechanistic model-based approach improved interpretation of breath test curves characterizing sucrose metabolism.

Mechanistic inference of the metabolic rates underlying [Formula: see text]C breath test curves.

Carbon stable isotope breath tests offer new opportunities to better understand gastrointestinal function in health and disease. However, it is often not clear how to isolate information about a gastrointestinal or metabolic process of interest from a breath test curve, and it is generally unknown how well summary statistics from empirical curve fitting correlate with underlying biological rates. We developed a framework that can be used to make mechanistic inference about the metabolic rates underlying a 13C breath test curve, and we applied it to a pilot study of 13C-sucrose breath test in 20 healthy adults. Starting from a standard conceptual model of sucrose metabolism, we determined the structural and practical identifiability of the model, using algebra and profile likelihoods, respectively, and we used these results to develop a reduced, identifiable model as a function of a gamma-distributed process; a slower, rate-limiting process; and a scaling term related to the fraction of the substrate that is exhaled as opposed to sequestered or excreted through urine. We demonstrated how the identifiable model parameters impacted curve dynamics and how these parameters correlated with commonly used breath test summary measures. Our work develops a better understanding of how the underlying biological processes impact different aspect of 13C breath test curves, enhancing the clinical and research potential of these 13C breath tests.

Association between Early Feeding Patterns and Neonatal Outcomes in Very Preterm Infants: A Retrospective Cohort Study.

OBJECTIVE: Mother's own milk (MOM) is the optimal feed for premature infants but may not always be sufficiently available. Alternative feeding includes donor human milk (DONOR), with or without fortification and preterm formula. This study evaluated the association between early feeding with exclusively and predominantly MOM (MAINLY-MOM) versus MOM supplemented with fortified DONOR (MOM + DONOR) or preterm formula (MOM + FORMULA) and in-hospital growth and neonatal morbidities. METHOD: This was a multicentre (n = 13 units) cohort study of infants born at <32 weeks' gestation. Data captured at the point of care were extracted from the UK National Neonatal Research Database. The study groups were defined based on feeding patterns within the first 2 weeks of life using predefined cut-offs. The primary outcome was the in-hospital growth rate. RESULTS: Data from 1,272 infants were analysed. Infants fell into two groups: extremely preterm (EPT) infants and very preterm (VPT) infants, born after <28 weeks and 28 to <32 weeks of gestation, respectively. Only 11 of 365 EPT infants received formula supplements, precluding a useful comparison of MOM + DONOR and MOM + FORMULA. There was no difference in median (25th-75th centile) growth velocity over the first 30 days of life between the MAINLY-MOM (n = 248) and MOM + DONOR (n = 106) groups: 10 (8-13) versus 10 (7-13) g/kg/day. Similarly, for VPT infants, there was no difference in growth velocities between MAINLY-MOM (n = 407), MOM + DONOR (N = 196), and MOM + FORMULA (N = 304): 11 (8-14) versus 11 (8-14) versus 11 (8-14) g/kg/day. Head growth did not differ (p value = 0.670). Cox regression analysis showed no difference in time to discharge between feeding types or any difference in major neonatal morbidities. In both EPT and VPT infants, growth velocity from the time of regaining birth weight to discharge was significantly lower in the MAINLY-MOM group compared to the MOM-DONOR group (EPT: 12.5 [11-14.2] vs. 14 [12.3-15.9] p = 0.45, VPT 13.5 [11-15.7] vs. 14.5 [12.6-16.8] p = 0.015). CONCLUSION: Early feeding with fortified DONOR, in comparison to formula, to supplement MOM was not associated with any differences in short-term growth, length of stay, and neonatal morbidities. However, early feeding with mainly maternal milk, compared to maternal milk supplemented with DONOR, was associated with significantly lower overall weight gain.

Effects of exercise training programmes on fasting gastrointestinal appetite hormones in adults with overweight and obesity: A systematic review and meta-analysis.

A systematic review and meta-analysis was performed to determine the effect of exercise training on fasting gastrointestinal appetite hormones in adults living with overweight and obesity. For eligibility, only randomised controlled trials (duration ≥ four weeks) examining the effect of exercise training interventions were considered. This review was registered in the International Prospective Register of Systematic Reviews (CRD42020218976). The searches were performed on five databases: MEDLINE, EMBASE, Cochrane Library, Web of Science, and Scopus. The initial search identified 13204 records. Nine studies, which include sixteen exercise interventions, met the criteria for inclusion. Meta-analysis was calculated as the standardised mean difference (Cohen's d). Exercise training had no effect on fasting concentrations of total ghrelin (d: 1.06, 95% CI -0.38 to 2.50, P = 0.15), acylated ghrelin (d: 0.08, 95% CI: -0.31 to 0.47, P = 0.68) and peptide YY (PYY) (d = -0.16, 95% CI: -0.62 to 0.31, P = 0.51) compared to the control group. Analysis of body mass index (BMI) (d: -0.31, 95% CI: -0.50 to -0.12, P < 0.01) and body mass (d: -0.22, 95% CI: -0.42 to -0.03, P = 0.03) found a significant reduction after exercise compared to controls. Overall, exercise interventions did not modify fasting concentrations of total ghrelin, acylated ghrelin, and PYY in individuals with overweight or obesity, although they reduced body mass and BMI. Thus, any upregulation of appetite and energy intake in individuals with overweight and obesity participating in exercise programmes is unlikely to be related to fasting concentrations of gastrointestinal appetite hormones.

13C-sucrose breath test for the non-invasive assessment of environmental enteropathy in Zambian adults.

Objectives: Environmental enteropathy (EE) is a subclinical disorder highly prevalent in tropical and disadvantaged populations and is thought to play a role in growth faltering in children, poor responses to oral vaccines, and micronutrient deficiencies. This study aims to evaluate the potential of a non-invasive breath test based on stable isotopes for evaluation of impaired digestion and absorption of sucrose in EE. Methods: We optimized a 13C-sucrose breath test (13C-SBT) in 19 young adults in Glasgow, United Kingdom. In a further experiment (in 18 adults) we validated the 13C-SBT using Reducose, an intestinal glucosidase inhibitor. We then compared the 13C-SBT to intestinal mucosal morphometry, immunostaining for sucrose-isomaltase (SI) expression, and SI activity in 24 Zambian adults with EE. Results: Fully labeled sucrose (0.3 mg/kg) provided clear breath enrichment signals over 2-3 h in both British and Zambian adults, more than fivefold higher than naturally enriched sucrose. Reducose dramatically impaired 13C-sucrose digestion, reducing 4 h 13CO2 breath recovery by > 50%. Duodenal biopsies in Zambian adults confirmed the presence of EE, and SI immunostaining was present in 16/24 adults. The kinetics of 13CO2 evolution were consistently faster in participants with detectable SI immunostaining. Although sucrase activity was strongly correlated with villus height (r = 0.72; P < 0.05) after adjustment for age, sex and body mass index, there were no correlations between 13C-SBT and villus height or measured sucrase activity in pinch biopsies. Conclusion: A 13C-SBT was developed which was easy to perform, generated clear enrichment of 13CO2 in breath samples, and clearly reports sucrase activity. Further work is needed to validate it and understand its applications in evaluating EE.

Interactions between dietary fibre and the gut microbiota.

Research characterising the gut microbiota in different populations and diseases has mushroomed since the advent of next-generation sequencing techniques. However, there has been less emphasis on the impact of dietary fibres and other dietary components that influence gut microbial metabolic activities. Dietary fibres are the main energy source for gut bacteria. However, fibres differ in their physicochemical properties, their effects on the gut and their fermentation characteristics. The diversity of carbohydrates and associated molecules in fibre-rich foods can have a major influence on microbiota composition and production of bioactive molecules, for example SCFAs and phenolic acids. Several of these microbial metabolites may influence the functions of body systems including the gut, liver, adipose tissues and brain. Dietary fibre intake recommendations have recently been increased (to 30 g daily) in response to growing obesity and other health concerns. Increasing intakes of specific fibre and plant food sources may differentially influence the bacteria and their metabolism. However, in vitro studies show great individual variability in the response of the gut microbiota to different fibres and fibre combinations, making it difficult to predict which foods or food components will have the greatest impact on levels of bioactive molecules produced in the colon of individuals. Greater understanding of individual responses to manipulation of the diet, in relation to microbiome composition and production of metabolites with proven beneficial impact on body systems, would allow the personalised approach needed to best promote good health.

DeepNavNet: Automated Landmark Localization for Neuronavigation.

Functional neurosurgery requires neuroimaging technologies that enable precise navigation to targeted structures. Insufficient image resolution of deep brain structures necessitates alignment to a brain atlas to indirectly locate targets within preoperative magnetic resonance imaging (MRI) scans. Indirect targeting through atlas-image registration is innately imprecise, increases preoperative planning time, and requires manual identification of anterior and posterior commissure (AC and PC) reference landmarks which is subject to human error. As such, we created a deep learning-based pipeline that consistently and automatically locates, with submillimeter accuracy, the AC and PC anatomical landmarks within MRI volumes without the need for an atlas. Our novel deep learning pipeline (DeepNavNet) regresses from MRI scans to heatmap volumes centered on AC and PC anatomical landmarks to extract their three-dimensional coordinates with submillimeter accuracy. We collated and manually labeled the location of AC and PC points in 1128 publicly available MRI volumes used for training, validation, and inference experiments. Instantiations of our DeepNavNet architecture, as well as a baseline model for reference, were evaluated based on the average 3D localization errors for the AC and PC points across 311 MRI volumes. Our DeepNavNet model significantly outperformed a baseline and achieved a mean 3D localization error of 0.79 ± 0.33 mm and 0.78 ± 0.33 mm between the ground truth and the detected AC and PC points, respectively. In conclusion, the DeepNavNet model pipeline provides submillimeter accuracy for localizing AC and PC anatomical landmarks in MRI volumes, enabling improved surgical efficiency and accuracy.

Understanding the role of the gut in undernutrition: what can technology tell us?

Gut function remains largely underinvestigated in undernutrition, despite its critical role in essential nutrient digestion, absorption and assimilation. In areas of high enteropathogen burden, alterations in gut barrier function and subsequent inflammatory effects are observable but remain poorly characterised. Environmental enteropathy (EE)-a condition that affects both gut morphology and function and is characterised by blunted villi, inflammation and increased permeability-is thought to play a role in impaired linear growth (stunting) and severe acute malnutrition. However, the lack of tools to quantitatively characterise gut functional capacity has hampered both our understanding of gut pathogenesis in undernutrition and evaluation of gut-targeted therapies to accelerate nutritional recovery. Here we survey the technology landscape for potential solutions to improve assessment of gut function, focussing on devices that could be deployed at point-of-care in low-income and middle-income countries (LMICs). We assess the potential for technological innovation to assess gut morphology, function, barrier integrity and immune response in undernutrition, and highlight the approaches that are currently most suitable for deployment and development. This article focuses on EE and undernutrition in LMICs, but many of these technologies may also become useful in monitoring of other gut pathologies.

Micronutrient deficiencies in children with coeliac disease; a double-edged sword of both untreated disease and treatment with gluten-free diet.

INTRODUCTION: In coeliac disease (CD) micronutrient deficiencies may occur due to malabsorption in active disease and diminished intake during treatment with a gluten-free diet (GFD). This study assessed the micronutrient status in children with CD at diagnosis and follow-up. METHODS: Fifteen micronutrients were analysed in 106 blood samples from newly diagnosed CD and from patients on a GFD for <6 months, 6-12 months and with longstanding disease (>12 months). Predictors of micronutrient status included: demographics, disease duration, anthropometry, gastrointestinal symptoms, raised tissue transglutaminase antibodies (TGA), multivitamin use and faecal gluten immunogenic peptide (GIP). Micronutrient levels were compared against laboratory reference values. RESULTS: At CD diagnosis (n = 25), low levels in ≥10% of patients were observed for: vitamins E (88%), B1 (71%), D (24%), K (21%), A (20%) and B6 (12%), ferritin (79%), and zinc (33%). One year post-diagnosis, repletion of vitamins E, K, B6 and B1 was observed (<10% patients). In contrast, deficiencies for vitamins D, A and zinc did not change significantly post-diagnosis. Copper, selenium and magnesium did not differ significantly between diagnosis and follow-up. All samples for B2, folate, vitamin C (except for one sample) and B12 were normal. A raised TGA at follow-up was associated with low vitamins A and B1 (raised vs normal TGA; vitamin A: 40% vs 17%, p = 0.044, vitamin B1: 37% vs 13%, p = 0.028). Low vitamin A (p = 0.009) and vitamin D (p = 0.001) were more common in samples collected during winter. There were no associations between micronutrient status with GIP, body mass index, height, socioeconomic status, or gastrointestinal symptom. Multivitamin use was less common in patients with low vitamin D. CONCLUSIONS: Several micronutrient deficiencies in CD respond to a GFD but others need to be monitored long-term and supplemented where indicated.

Impact of the source of fermentable carbohydrate on SCFA production by human gut microbiota in vitro - a systematic scoping review and secondary analysis.

Short chain fatty acids (SCFA) are produced by bacterial fermentation of non-digestible carbohydrates (NDC) and have many potential tissue and SCFA specific actions, from providing fuel for colonic cells to appetite regulation. Many studies have described the fermentation of different carbohydrates, often using in vitro batch culture. As evidence-based critical evaluation of substrates selectively promoting production of individual SCFA is lacking, we performed a systematic scoping literature review. Databases were searched to identify relevant papers published between 1900 and 12/06/2016. Search terms included In vitro batch fermentation and In vitro short chain fatty acid production. Articles were considered for essential criteria allowing equivalent comparison of SCFA between NDC. Seventy seven articles were included in the final analysis examining 29 different carbohydrates. After 24-hour fermentation, galacto-oligosaccharide ranked highest for butyrate and total SCFA production and second for acetate production. Rhamnose ranked highest for propionate production. The lowest SCFA production was observed for kiwi fiber, polydextrose, and cellulose. This review demonstrates that choosing a substrate to selectively enhance a specific SCFA is difficult, and the molar proportion of each SCFA produced by individual substrates may be misleading. Instead the rate and ratio of SCFA production should be evaluated in parallel.

Alterations in Intestinal Microbiota of Children With Celiac Disease at the Time of Diagnosis and on a Gluten-free Diet.

BACKGROUND AND AIMS: It is not clear whether alterations in the intestinal microbiota of children with celiac disease (CD) cause the disease or are a result of disease and/or its treatment with a gluten-free diet (GFD). METHODS: We obtained 167 fecal samples from 141 children (20 with new-onset CD, 45 treated with a GFD, 57 healthy children, and 19 unaffected siblings of children with CD) in Glasgow, Scotland. Samples were analyzed by 16S ribosomal RNA sequencing, and diet-related metabolites were measured by gas chromatography. We obtained fecal samples from 13 children with new-onset CD after 6 and 12 months on a GFD. Relationships between microbiota with diet composition, gastrointestinal function, and biomarkers of GFD compliance were explored. RESULTS: Microbiota α diversity did not differ among groups. Microbial dysbiosis was not observed in children with new-onset CD. In contrast, 2.8% (Bray-Curtis dissimilarity index, P = .025) and 2.5% (UniFrac distances, P = .027) of the variation in microbiota composition could be explained by the GFD. Between 3% and 5% of all taxa differed among all group comparisons. Eleven distinctive operational taxonomic units composed a microbe signature specific to CD with high diagnostic probability. Most operational taxonomic units that differed between patients on a GFD with new-onset CD vs healthy children were associated with nutrient and food group intake (from 75% to 94%) and with biomarkers of gluten ingestion. Fecal levels of butyrate and ammonia decreased during the GFD. CONCLUSIONS: Although several alterations in the intestinal microbiota of children with established CD appear to be effects of a GFD, specific bacteria were found to be distinct biomarkers of CD. Studies are needed to determine whether these bacteria contribute to pathogenesis of CD.

Is there evidence for bacterial transfer via the placenta and any role in the colonization of the infant gut? - a systematic review.

With the important role of the gut microbiome in health and disease, it is crucial to understand key factors that establish the microbial community, including gut colonization during infancy. It has been suggested that the first bacterial exposure is via a placental microbiome. However, despite many publications, the robustness of the evidence for the placental microbiome and transfer of bacteria from the placenta to the infant gut is unclear and hence the concept disputed. Therefore, we conducted a systematic review of the evidence for the role of the placental, amniotic fluid and cord blood microbiome in healthy mothers in the colonization of the infant gut. Most of the papers which were fully assessed considered placental tissue, but some studied amniotic fluid or cord blood. Great variability in methodology was observed especially regarding sample storage conditions, DNA/RNA extraction, and microbiome characterization. No study clearly considered transfer of the normal placental microbiome to the infant gut. Moreover, some studies in the review and others published subsequently reported little evidence for a placental microbiome in comparison to negative controls. In conclusion, current data are limited and provide no conclusive evidence that there is a normal placental microbiome which has any role in colonization of infant gut.

Hypoalbuminemia Reflects Nutritional Risk, Body Composition and Systemic Inflammation and Is Independently Associated with Survival in Patients with Colorectal Cancer.

It has long been recognized that albumin has prognostic value in patients with cancer. However, although the Global Leadership Initiative on Malnutrition GLIM criteria (based on five diagnostic criteria, three phenotypic criteria and two etiologic criteria) recognize inflammation as an important etiologic factor in malnutrition, there are limited data regarding the association between albumin, nutritional risk, body composition and systemic inflammation, and whether albumin is associated with mortality independent of these parameters. The aim of this study was to examine the relationship between albumin, nutritional risk, body composition, systemic inflammation, and outcomes in patients with colorectal cancer (CRC). A retrospective cohort study (n = 795) was carried out in which patients were divided into normal and hypoalbuminaemic groups (albumin < 35 g/L) in the presence and absence of a systemic inflammatory response C-reactive protein (CRP > 10 and <10 mg/L, respectively). Post-operative complications, severity of complications and mortality were considered as outcome measures. Categorical variables were analyzed using Chi-square test χ2 or linear-by-linear association. Survival data were analyzed using univariate and multivariate Cox regression. In the presence of a systemic inflammatory response, hypoalbuminemia was directly associated with Malnutrition Universal Screening Tool MUST (p < 0.001) and inversely associated with Body Mass Index BMI (p < 0.001), subcutaneous adiposity (p < 0.01), visceral obesity (p < 0.01), skeletal muscle index (p < 0.001) and skeletal muscle density (p < 0.001). There was no significant association between hypoalbuminemia and either the presence of complications or their severity. In the absence of a systemic inflammatory response (n = 589), hypoalbuminemia was directly associated with MUST (p < 0.05) and inversely associated with BMI (p < 0.01), subcutaneous adiposity (p < 0.05), visceral adiposity (p < 0.05), skeletal muscle index (p < 0.01) and skeletal muscle density (p < 0.001). Hypoalbuminemia was, independently of inflammatory markers, associated with poorer cancer-specific and overall survival (both p < 0.001). The results suggest that hypoalbuminemia in patients with CRC reflects both increased nutritional risk and greater systemic inflammatory response and was independently associated with poorer survival in patients with CRC.

Dietary Fibres Differentially Impact on the Production of Phenolic Acids from Rutin in an In Vitro Fermentation Model of the Human Gut Microbiota.

Polyphenols are often ingested alongside dietary fibres. They are both catabolised by, and may influence, the intestinal microbiota; yet, interactions between them and the impact on their resultant microbial products are poorly understood. Dietary fibres (inulin, pectin, psyllium, pyrodextrin, wheat bran, cellulose-three doses) were fermented in vitro with human faeces (n = 10) with and without rutin (20 µg/mL), a common dietary flavonol glycoside. Twenty-eight phenolic metabolites and short chain fatty acids (SCFA) were measured over 24 h. Several phenolic metabolites were produced during fibre fermentation, without rutin. With rutin, 3,4-dihydroxyphenylacetic acid (3,4diOHPAA), 3-hydroxyphenylacetic acid (3OHPAA), 3-(3 hydroxyphenyl)propionic acid (3OHPPA) and 3-(3,4-dihydroxyphenyl)propionic acid (3,4diOHPPA; DOPAC) were produced, with 3,4diOHPAA the most abundant, confirmed by fermentation of 13C labelled quercetin. The addition of inulin, wheat bran or pyrodextrin increased 3,4diOHPAA 2 2.5-fold over 24 h (p < 0.05). Rutin affected SCFA production, but this depended on fibre, fibre concentration and timepoint. With inulin, rutin increased pH at 6 h from 4.9 to 5.6 (p = 0.01) but increased propionic, butyric and isovaleric acid (1.9, 1.6 and 5-fold, p < 0.05 at 24 h). Interactions between fibre and phenolics modify production of phenolic acids and SCFA and may be key in enhancing health benefits.

Early versus Delayed Fortification of Human Milk in Preterm Infants: A Systematic Review.

Expressed breast milk (EBM) is commonly supplemented with commercially prepared human milk fortifier to meet the additional nutritional needs of preterm infants. The optimal milk intake at which to introduce fortification is unknown. The objective of this systematic review was to compare the effect of early fortification (EF) versus that of delayed introduction of human milk fortifier (DF) on short-term outcomes including growth, feeding intolerance, length of hospital stay, and maturity at discharge in very-low-birth-weight infants. The search was carried out until March 2019 using 5 electronic databases (PubMed, Ovid Medline, Web of Science, Ovid Embase, and the Cochrane Library). The search was supplemented with a search of the clinical trial registry and reference lists. Eligible studies involved randomized controlled trials that had been designed to compare EF against DF using multi-nutrient fortifier for infants of a birth weight of <1,500 g who were fed exclusively or predominantly EBM. Four authors independently screened the studies for eligibility. A total of 1,972 articles were screened; 2 studies met the inclusion criteria and were included with a total number of participants of 171. The definition of EF and DF was not consistent between the 2 studies. There was no significant impact of EF versus DF on all outcomes. In conclusion, current data are limited and do not provide evidence on the optimal time to start fortification. The definition of EF and DF needs to be agreed upon and further larger randomized controlled trials are required.

The relation between Malnutrition Universal Screening Tool (MUST), computed tomography-derived body composition, systemic inflammation, and clinical outcomes in patients undergoing surgery for colorectal cancer.

BACKGROUND: Nutritional status is an important factor affecting a patient's clinical outcomes. Early identification of patients who are at risk of malnutrition is important to improve clinical outcomes and reduce health cost. The Malnutrition Universal Screening Tool (MUST) has been recommended as part of the routine nursing assessment for all patients at hospital admission. OBJECTIVE: The aim of this study was to examine the association between nutritional status (MUST), systemic inflammatory response (SIR), body composition, and clinical outcomes in patients undergoing surgery for colorectal cancer. METHODS: The malnutrition risk was examined using MUST in patients admitted for surgery for colorectal cancer between March 2013 and June 2016. Preoperative computed tomography scans were used to define the body composition. The presence of SIR was evidenced by the modified Glasgow prognostic score and the neutrophil to lymphocyte ratio. Postoperative complications, severity of complication, length of hospital stay, and mortality were considered as outcome measures. RESULTS: The study included 363 patients (199 males, 164 females); 21% of the patients presented with a medium or high nutritional risk. There were significant associations between MUST and subcutaneous adiposity (P < 0.001), visceral obesity (P < 0.001), and low skeletal muscle index (P < 0.001). No statistically significant association was identified between MUST score and presence of any complication or severity of complication. On multivariate analysis, MUST remained independently associated with the length of hospital stay (OR: 2.17; 95% CI: 1.45, 3.26; P < 0.001). Kaplan-Meier survival curves showed an increased number of deaths for patients at medium or high risk of malnutrition (P < 0.001). This association was found to be independent of other confounding factors (HR: 1.45; 95% CI: 1.06, 1.99; P = 0.020). CONCLUSIONS: MUST score is an independent marker of risk in those undergoing surgery for colorectal cancer and should remain a key part of preoperative assessment.

Donated human milk use and subsequent feeding pattern in neonatal units.

Background: Donated human milk (DHM) is a safe alternative in the absence of mother's own milk (MOM); however, specific clinical indications for DHM use and its impact on subsequent feeding practice remain unclear. We aimed to audit local DHM use and explore the impact of the introduction of DHM as the first enteral feed on subsequent MOM availability. Methods: We retrospectively audited DHM recipients nursed in Royal Hospital for Children, Glasgow from 2014 to 2016 against local guidelines. Data were collected from an operational electronic database. Descriptive data analysis was performed to describe DHM use. To explore the association between the first human milk feed with subsequent MOM availability Kruskal Wallis test was used. Adjustments for confounding variables were performed using analysis of variance (ANOVA). Results: A total of 165 recipients of DHM (5.3% of all admission to RHC) were identified. The majority of recipients (69%) were born < 32 weeks of gestation. The main indication for DHM was prematurity, other indications included congenital anomalies of bowel and heart. The local guideline was adhered to in 87% of cases. The median interquartile range (IQR) at DHM introduction was 6 days (3, 17) and the duration of use was 12 days (6, 22). In those born < 32 weeks of gestation the type of human milk (DHM and/ or MOM) used as first feed did not influence the subsequent median IQR days of feeding with any MOM [DHM 40 (9, 51); MOM 28 (17, 49), MOM & DHM 17 (10, 26) p value = 0.465] after adjusting for birthweight and length of hospital stay. Conclusions: In our unit, DHM is mainly used in preterm neonates in accordance with existing local guidance. Using DHM as first milk feed did not affect subsequent MOM availability.

Short Chain Fatty Acid Production from Mycoprotein and Mycoprotein Fibre in an In Vitro Fermentation Model.

Dietary mycoprotein (marketed as QuornTM) has many health benefits, including reductions in energy intake. The majority of studies evaluating mycoprotein focus on the protein content and very few consider the fibre content. Fibre consumption is also associated with decreased energy intake, which is partly attributed to short chain fatty acids (SCFAs) from fibre fermentation by colonic bacteria. To study the SCFA-producing capability of mycoprotein, in vitro batch fermentations were conducted, and SCFA production compared with that from extracted mycoprotein fibre, oligofructose (OF), rhamnose, and laminarin. Mycoprotein and mycoprotein fibre were both fermentable, resulting in a total SCFA production of 24.9 (1.7) and 61.2 (15.7) mmol/L, respectively. OF led to a significantly higher proportion of acetate compared to all other substrates tested (92.6 (2.8)%, p < 0.01). Rhamnose generated the highest proportion of propionate (45.3 (2.0)%, p < 0.01), although mycoprotein and mycoprotein fibre yielded a higher proportion of propionate compared with OF and laminarin. Butyrate proportion was the highest with laminarin (28.0 (10.0)although mycoprotein fibre led to a significantly higher proportion than OF (p < 0.01). Mycoprotein is a valuable source of dietary protein, but its fibre content is also of interest. Further evaluation of the potential roles of the fibre content of mycoprotein is required.

The relationship between body mass index, sex, and postoperative outcomes in patients undergoing potentially curative surgery for colorectal cancer.

BACKGROUND: There is increasing evidence that an increased BMI is associated with increased complications after surgery for colorectal cancer (CRC). However, the basis of this relationship is not clear. Since men and women have different fat distribution, with men more likely to have excess visceral fat in BMI defined obesity, there may be a sex difference in the surgical site infection (SSIs) rate in the obese. Therefore, the aim of this study was to examine the relationship between sex, BMI, clinic-pathological characteristics and the development of postoperative infective complications after surgery for CRC and to establish whether there were gender differences in complication following surgery for CRC. DESIGN: Data were recorded prospectively for patients undergoing potentially curative surgery for CRC in a single centre between 1997 and 2016. Patient characteristics were recorded and complications were classified as either infective or non-infective. The relationship between sex, BMI, associated clinicopathological characteristics and presences of complications were examined by Chi-square test for linear association and multivariate binary logistic regression model. RESULTS: A total of 1039 patients were included. There were significant differences in the presence of complications between male and female (p ≤ 0.001), the rate of complication was higher in obese male (44%); in particular SSIs, wound infection and anastomotic leak (p ≤ 0.05). The rate of surgical site infection was 12% in male patients with normal BMI compared with 26% in those with a BMI ≥30 (p ≤ 0.001), while the rate of SSIs in female patients was 10% in those with normal BMI and those with a BMI ≥30. In males, BMI remained significantly associated with SSI on multivariate analysis [(OR = 1.42, 95% CI 1.13-1.78) P = 0,002]. CONCLUSIONS: Obesity prior to surgery for CRC increases the risk of infective complications in both male and female. Increased BMI in male patients was associated greater risk of SSIs and wound infection compared to female patients. Male obese patients should be considered at high risk of developing post-operative infective complications.