Konstantinos Gerasimidis

A four-stage evaluation of the Paediatric Yorkhill Malnutrition Score in a tertiary paediatric hospital and a district general hospital

Paediatric in-patients are at high risk of malnutrition but validated paediatric screening tools suitable for use by nursing staff are scarce. The present study aimed to assess the diagnostic accuracy of the new Paediatric Yorkhill Malnutrition Score (PYMS). During a pilot introduction in a tertiary referral hospital and a district general hospital, two research dietitians assessed the validity of the PYMS by comparing the nursing screening outcome with a full dietetic assessment, anthropometry and body composition measurements. An additional PYMS form was completed by the research dietitians to assess its inter-rater reliability with the nursing staff and for comparison with the Screening Tool for the Assessment of Malnutrition in Paediatrics (STAMP) and the Paediatric Subjective Global Nutritional Assessment (SGNA). Of the 247 children studied, the nurse-rated PYMS identified 59% of those rated at high risk by full dietetic assessment. Of those rated at high risk by the nursing PYMS, 47% were confirmed as high risk on full assessment. The PYMS showed moderate agreement with the full assessment (kappa = 0.46) and inter-rater reliability (kappa = 0.53) with the research dietitians. Children who screened as high risk for malnutrition had significantly lower lean mass index than those at moderate or low risk, but no difference in fat. When completed by the research dietitians, the PYMS showed similar sensitivity to the STAMP, but a higher positive predictive value. The SGNA had higher specificity than the PYMS but much lower sensitivity. The PYMS screening tool is an acceptable screening tool for identifying children at risk of malnutrition without producing unmanageable numbers of false-positive cases.

Decline in Presumptively Protective Gut Bacterial Species and Metabolites Are Paradoxically Associated with Disease Improvement in Pediatric Crohn’s Disease During Enteral Nutrition

Background:The gut microbiota is implicated in the pathogenesis of Crohn’s disease (CD). Exclusive enteral nutrition (EEN) is a successful treatment, but its mode of action remains unknown. This study assessed serial changes in the fecal microbiota milieu during EEN. Methods:Five fecal samples were collected from CD children: 4 during EEN (start, 15, 30, end EEN approximately 60 days) and the fifth on habitual diet. Two samples were collected from healthy control subjects. Fecal pH, bacterial metabolites, global microbial diversity abundance, composition stability, and quantitative changes of total and 7 major bacterial groups previously implicated in CD were measured. Results:Overall, 68 samples were from 15 CD children and 40 from 21 control subjects. Fecal pH and total sulfide increased and butyric acid decreased during EEN (all P < 0.05). Global bacterial diversity abundance decreased (P < 0.05); a higher degree of microbiota composition stability was seen in control subjects than in CD children during EEN (at P ⩽ 0.008). Faecalibacterium prausnitzii spp concentration significantly decreased after 30 days on EEN (P < 0.05). In patients who responded to EEN, the magnitude of the observed changes was greater and the concentration of Bacteroides/Prevotella group decreased (P < 0.05). All these changes reverted to pretreatment levels on free diet, and EEN microbiota diversity increased when the children returned to their free diet. Conclusions:EEN impacts on gut microbiota composition and changes fecal metabolic activity. It is difficult to infer a causative association between such changes and disease improvement, but the results do challenge the current perception of a protective role for F. prausnitzii in CD.

Extensive modulation of the fecal metagenome in children With Crohn’s disease during exclusive enteral nutrition

OBJECTIVES:Exploring associations between the gut microbiota and colonic inflammation and assessing sequential changes during exclusive enteral nutrition (EEN) may offer clues into the microbial origins of Crohn’s disease (CD).METHODS:Fecal samples (n=117) were collected from 23 CD and 21 healthy children. From CD children fecal samples were collected before, during EEN, and when patients returned to their habitual diets. Microbiota composition and functional capacity were characterized using sequencing of the 16S rRNA gene and shotgun metagenomics.RESULTS:Microbial diversity was lower in CD than controls before EEN (P=0.006); differences were observed in 36 genera, 141 operational taxonomic units (OTUs), and 44 oligotypes. During EEN, the microbial diversity of CD children further decreased, and the community structure became even more dissimilar than that of controls. Every 10 days on EEN, 0.6 genus diversity equivalents were lost; 34 genera decreased and one increased during EEN. Fecal calprotectin correlated with 35 OTUs, 14 of which accounted for 78% of its variation. OTUs that correlated positively or negatively with calprotectin decreased during EEN. The microbiota of CD patients had a broader functional capacity than healthy controls, but diversity decreased with EEN. Genes involved in membrane transport, sulfur reduction, and nutrient biosynthesis differed between patients and controls. The abundance of genes involved in biotin (P=0.005) and thiamine biosynthesis decreased (P=0.017), whereas those involved in spermidine/putrescine biosynthesis (P=0.031), or the shikimate pathway (P=0.058), increased during EEN.CONCLUSIONS:Disease improvement following treatment with EEN is associated with extensive modulation of the gut microbiome.

Disease associated malnutrition correlates with length of hospital stay in children

BACKGROUND & AIMS Previous studies reported a wide range of estimated malnutrition prevalence (6-30%) in paediatric inpatients based on various anthropometric criteria. We performed anthropometry in hospitalised children and assessed the relationship between malnutrition and length of hospital stay (LOS) and complication rates. METHODS In a prospective multi-centre European study, 2567 patients aged 1 month to 18 years were assessed in 14 centres in 12 countries by standardised anthropometry within the first 24 h after admission. Body mass index (BMI) and height/length <-2 standard deviation scores (SDS, WHO reference) were related to LOS (primary outcome), frequency of gastrointestinal (diarrhoea and vomiting) and infectious complications (antibiotic use), weight change during stay (secondary outcomes) and quality of life. RESULTS A BMI <-2 SDS was present in 7.0% of the patients at hospital admission (range 4.0-9.3% across countries) with a higher prevalence in infants (10.8%) and toddlers aged 1-2 years (8.3%). A BMI <-2 to ≥-3 SDS (moderate malnutrition) and a BMI <-3 SDS (severe malnutrition) was associated with a 1.3 (CI95: 1.01, 1.55) and 1.6 (CI95: 1.27, 2.10) days longer LOS, respectively (p = 0.04 and p < 0.001). Reduced BMI <-2 SDS was also associated to lower quality of life, and more frequent occurrence of diarrhoea (22% vs 12%, p < 0.001) and vomiting (26% vs 14%, p < 0.001). CONCLUSION Disease associated malnutrition in hospitalised children in Europe is common and is associated with significantly prolonged LOS and increased complications, with possible major cost implications, and reduced quality of life. This study was registered at clinicaltrials.gov as NCT01132742.

The aetiology and impact of malnutrition in paediatric inflammatory bowel disease

Disease-associated undernutrition of all types is very common in paediatric inflammatory bowel disease (IBD). Recent weight loss remains one of the triad of clinical manifestations and a cornerstone for the diagnosis of Crohns disease (CD), although significantly fewer patients now present as being underweight. Recent evidence suggests that the introduction of medical treatment will quickly restore body weight, although this does not reflect concomitant changes in body composition. CD children present with features of nutritional cachexia with normal fat stores but depleted lean mass. Poor bone health, delayed puberty and growth failure are additional features that further complicate clinical management. Suboptimal nutritional intake is a main determinant of undernutrition, although activation of the immune system and secretion of pro-inflammatory cytokines exert additional independent effects. Biochemically low concentrations of plasma micronutrients are commonly reported in IBD patients, although their interpretation is difficult in the presence of an acute phase response and other indices of body stores adequacy are needed. Anaemia is a common extraintestinal manifestation of the IBD child. Iron-deficient anaemia is the predominant type, with anaemia of chronic disease second. Decreased dietary intake, as a result of decreased appetite and food aversion, is the major cause of undernutrition in paediatric IBD. Altered energy and nutrient requirements, malabsorption and increased gastrointestinal losses are additional factors, although their contribution to undernutrition in paediatric CD needs to be studied further.

Clinical progress in the two years following a course of exclusive enteral nutrition in 109 paediatric patients with Crohn's disease

Exclusive enteral nutrition (EEN) is an effective first line treatment for active paediatric Crohns disease (CD).

Dietary modifications, nutritional supplements and alternative medicine in paediatric patients with inflammatory bowel disease.

Background  Data on use of complementary and alternative medicine in children with inflammatory bowel disease are scarce.

Impact of exclusive enteral nutrition on body composition and circulating micronutrients in plasma and erythrocytes of children with active Crohn's disease†

Background: Nutritional therapy is the primary treatment for active pediatric Crohns disease (CD) in the UK/Europe, improving disease activity and anthropometry. This study assessed changes in micronutrient status during exclusive enteral nutrition (EEN). Methods: Seventeen children (male/female: 8/9; median age: 12.7 years) with active CD were treated exclusively for 6–8 weeks on a polymeric feed (Modulen IBD; Nestle, UK). Body impedance was measured at baseline, during EEN, and posttreatment on normal diet and converted to z‐scores of fat and lean mass. Blood samples for nutrient analysis were collected from 13 children at baseline, end of EEN, and posttreatment. Results: Lean but not fat mass improved at the end of EEN (initiation vs. end of EEN; fat mass [z‐score]: −0.5 vs. −0.3; P = 0.141; lean mass [z‐score]: −2.1 vs. −0.8; P < 0.0001). At baseline several children presented with suboptimal concentrations of carotenoids, trace elements, vitamin C, B6, and folate in plasma but not in erythrocytes. EEN improved concentrations for several nutrients, but more than 90% of patients had depleted concentrations of all carotenoids. The latter improved on normal diet but other micronutrients, which improved during EEN, returned toward pretreatment concentrations. Conclusions: Lean but not fat mass improved at the end of EEN. Median concentrations for several plasma micronutrients improved on EEN but carotenoids were depleted. These findings may have implications for clinical practice and producers of enteral feeds. As plasma concentrations for many micronutrients can be affected by the acute phase response, measurements in erythrocytes may be a better marker of actual body stores. (Inflamm Bowel Dis 2012;)

Serial fecal calprotectin changes in children with Crohn's disease on treatment with exclusive enteral nutrition: associations with disease activity, treatment response, and prediction of a clinical relapse.

Background Exclusive enteral nutrition (EEN) induces clinical remission in pediatric Crohns disease (CD). Goals This study explored changes in fecal calprotectin concentration during treatment with EEN. Study Fecal calprotectin was measured in 4 serial stool samples from CD children during EEN. The Pediatric Crohns Disease Activity Index (PCDAI) and systemic markers of disease activity were measured at the beginning and end of treatment. Results Fifteen CD children (7 girls; 11.6±2.3 y) participated. PCDAI decreased in 14 children and 7 children achieved clinical remission (PCDAI ⩽10). Fecal calprotectin concentration decreased (30 d, P=0.014; 60 d, P<0.0001) only in those children who entered clinical remission (PCDAI ⩽10). In the whole group mean calprotectin concentration at baseline (2158±642 mg/kg) was reduced by 975 mg/kg (95% confidence interval −1783; −167) after 30 days and 1700 mg/kg (95% confidence interval −2508; −892) on EEN completion. Only one child reached normal levels by the end of EEN. Decrease of pretreatment calprotectin levels by more than 18% after 30 days on EEN predicted clinical response at the end of EEN. Calprotectin levels at the end of EEN treatment did not predict the length of time lapsed to a future relapse. Conclusions In this pilot study calprotectin decreased in patients who achieved clinical remission and may be useful to predict response to treatment.

Role of Gut Microbiota in the Aetiology of Obesity: Proposed Mechanisms and Review of the Literature

The aetiology of obesity has been attributed to several factors (environmental, dietary, lifestyle, host, and genetic factors); however none of these fully explain the increase in the prevalence of obesity worldwide. Gut microbiota located at the interface of host and environment in the gut are a new area of research being explored to explain the excess accumulation of energy in obese individuals and may be a potential target for therapeutic manipulation to reduce host energy storage. Several mechanisms have been suggested to explain the role of gut microbiota in the aetiology of obesity such as short chain fatty acid production, stimulation of hormones, chronic low-grade inflammation, lipoprotein and bile acid metabolism, and increased endocannabinoid receptor system tone. However, evidence from animal and human studies clearly indicates controversies in determining the cause or effect relationship between the gut microbiota and obesity. Metagenomics based studies indicate that functionality rather than the composition of gut microbiota may be important. Further mechanistic studies controlling for environmental and epigenetic factors are therefore required to help unravel obesity pathogenesis.