Complications and Utility of Gastrointestinal Endoscopy Post Hematopoietic Stem Cell Transplantation: An 11 Year Experience.

OBJECTIVES: Diagnostic gastrointestinal (GI) endoscopy is used to differentiate GI graft versus host disease (GI-GvHD), which requires escalation of immunosuppressive treatment (IST), from other conditions such as viral infection, which may require reduction of IST. The aim of this study was to establish the clinical utility of GI endoscopy post hematopoietic stem cell transplant (HSCT) and the complication rate of these procedures. METHODS: This was a single-center observational retrospective cohort study. Hospital pediatric endoscopy and HSCT databases identified patients between January 2010 and December 2020. GI-GvHD was diagnosed if there were positive histological findings and clinical context. Data collected included demographics, timing of endoscopy post-HSCT, clinical utility, and complications of endoscopy. The endoscopy was deemed to be "clinically useful" if it resulted in a change of clinical management or helped to narrow down the differential diagnosis for the clinical team. RESULTS: Three hundred thirty-nine HSCT occurred in 320 children during the study period. Sixty-six of 339 (19%) HSCT needed an "endoscopy episode." One hundred nineteen endoscopies were performed (53 concurrent upper and lower GI endoscopies, 11 upper GI endoscopies, and 2 lower GI endoscopies). Four of 119 (3%) endoscopies had complications: septic shock (1), duodenal hematoma (1), GI bleeding (1), and colonic perforation (1). Four patients had incomplete records to assess utility of endoscopy. Fifty-seven of 62 (92%) endoscopy episodes were "clinically useful," and 41 of 62 (66%) had a change in IST. CONCLUSIONS: The clinical utility of endoscopy is high and in the majority of cases is associated with a change in patient management. Children post-HSCT are at high risk of complications from endoscopy; this should be made clear in the process of obtaining consent for procedures.

[ESPEN guideline: Clinical nutrition in inflammatory bowel disease]. / Guía ESPEN: Nutrición clínica en la enfermedad inflamatoria intestinal.

Introduction: Introduction: the ESPEN guideline offers a multidisciplinary focus on clinical nutrition in inflammatory bowel disease (IBD). Methodology: the guideline is based on a extensive systematic review of the literature, but relies on expert opinion when objective data are lacking or inconclusive. The conclusions and 64 recommendations have been subject to full peer review and a Delphi process, in which uniformly positive responses (agree or strongly agree) were required. Results: IBD is increasingly common and potential dietary factors in its etiology are briefly reviewed. Malnutrition is highly prevalent in IBD - especially in Crohn's disease. Increased energy and protein requirements are observed in some patients. The management of malnutrition in IBD is considered within the general context of support for malnourished patients. Treatment of iron deficiency (parenterally, if necessary) is strongly recommended. Routine provision of a special diet in IBD is not, however, supported. Parenteral nutrition is indicated only when enteral nutrition has failed or is impossible. The recommended perioperative management of patients with IBD undergoing surgery accords with general ESPEN guidance for patients having abdominal surgery. Probiotics may be helpful in UC but not in Crohn's disease. Primary therapy using nutrition to treat IBD is not supported in ulcerative colitis but is moderately well supported in Crohn's disease, especially in children, where the adverse consequences of steroid therapy are proportionally greater. However, exclusion diets are generally not recommended and there is little evidence to support any particular formula feed when nutritional regimens are constructed. Conclusions: available objective data to guide nutritional support and primary nutritional therapy in IBD are presented as 64 recommendations, of which 9 are very strong recommendations (grade A), 22 are strong recommendations (grade B), and 12 are based only on sparse evidence (grade 0); 21 recommendations are good practice points (GPP).

Introducción: Introducción: la guía ESPEN ofrece un enfoque multidisciplinar de la nutrición clínica en la enfermedad inflamatoria intestinal (EII). Metodología: la guía se basa en una extensa revisión sistemática de la literatura y en la opinión de expertos cuando faltan datos objetivos o estos no son concluyentes. Las conclusiones y las 64 recomendaciones han sido objeto de una revisión completa por pares y de un proceso Delphi en el que se requerían respuestas fuertemente positivas (de acuerdo o totalmente de acuerdo). Resultados: la EII es cada vez más común y se revisan brevemente los posibles factores dietéticos en su etiología. La desnutrición es muy prevalente en la EII, especialmente en la enfermedad de Crohn. En algunos pacientes se observan mayores requerimientos de energía y proteínas. El manejo de la desnutrición en la EII se considera dentro del contexto general de apoyo a los pacientes desnutridos. Se recomienda fuertemente el tratamiento de la deficiencia de hierro (por vía parenteral, si es necesario). Sin embargo, no se aconseja la prescripción de rutina de una dieta especial en la EII. La nutrición parenteral está indicada solo cuando la nutrición enteral ha fallado o es imposible. El manejo perioperatorio recomendado de los pacientes con EII sometidos a cirugía se hace de acuerdo con la guía general de la ESPEN para pacientes sometidos a cirugía abdominal. Los probióticos pueden ser útiles en la CU pero no en la enfermedad de Crohn. El tratamiento primario con nutrición para tratar la EII no está respaldado en la colitis ulcerosa, aunque está moderadamente bien soportado en la enfermedad de Crohn, especialmente en los niños, donde las consecuencias adversas de la terapia con esteroides son proporcionalmente mayores. Sin embargo, las dietas de exclusión generalmente no se recomiendan y hay poca evidencia que respalde cualquier fórmula de nutrición en particular cuando se realizan regímenes nutricionales. Conclusiones: los datos objetivos disponibles para guiar el apoyo nutricional y la terapia nutricional primaria en la EII se presentan como 64 recomendaciones, de las cuales 9 son recomendaciones muy fuertes (grado A), 22 son recomendaciones fuertes (grado B) y 12 se basan solo en evidencia escasa (grado 0); 21 recomendaciones son recomendaciones de buenas prácticas (GPP).

Management of Enteritis Associated With Tricohepatoenteric Syndrome due to SKIV2L Mutation Using the Combination of JAK1/2 Inhibition and Azathioprine.

Tricohepatoenteric syndrome is a rare genetic disorder caused by mutations in SKIV2L or TTC37. An upregulation of type 1 interferon signaling is associated with the SKIV2L variation. Introduction of Baricitinib as a JAK1/ 2 kinase inhibitor alongside traditional immunosuppressive agents successfully reduced the symptoms of enteritis by blocking the inflammogenic effects of type 1 interferonopathy in a case of tricohepatoenteric syndrome diagnosed in a 5-year-old boy.

Fifteen-minute consultation: Childhood rumination syndrome.

Rumination syndrome is a functional bowel disorder where stomach contents effortlessly regurgitate into the mouth. It is an entirely separate entity to gastro-oesophageal reflux disease and requires behavioural rather than pharmaceutical management. Symptoms usually respond well to treatment, though in extreme cases, patients may experience significant weight loss and require inpatient admission.

Change in Incidence and Epidemiology of Inflammatory Bowel Disease in 2- to 9-Year-olds in Southwest England.

OBJECTIVES: The aim of the study was to characterize epidemiology, phenotype, and clinical outcome of Inflammatory Bowel Disease (IBD) diagnosed ages 2 to 9 years, and compare age groups 2 to 5 and 6 to 9 years. METHODS: A population-based retrospective cohort study of all <10-year-olds diagnosed with IBD between 2004 and 2017 in Southwest England was performed. Patients were divided into age groups at diagnosis. Demographics, investigations, and phenotype at diagnosis were collected. Treatments and outcomes were analysed at 1, 2, 5, and 10 years follow-up. Poisson regression was used for IBD incidence rate ratios; Wald test for variation by age group; parametric/nonparametric tests for phenotype. RESULTS: There were 666 new paediatric IBD (pIBD) patients ages ≤16 years, from which 136 were 2 to 9 (2-5 years: 32; 6-9 years: 104). Incidence of pIBD increased from 4 to 6 cases per 100,000 whereas in A1a group was stable around 2 cases per 100,000. Crohn Disease (CD) children were majority boys, 2- to 5-year-olds were more likely to have ileal sparing than 6 to 9-year group but had similar rates of surgery and anti-TNF therapy. Two- to 5-year-olds with ulcerative colitis were more likely to have surgery but rates for anti-TNF therapy were similar. Sixteen percent of 2- to 5-year-olds and 10% of 6- to 9-year-olds had IBD-unclassified. No significant differences in symptoms or time to diagnosis were found. CONCLUSIONS: Twenty percent of pIBD in Southwest England are 2 to 9 years old. pIBD incidence has increased but is stable in that group. In terms of phenotypic differences, ileal sparing in CD and pancolitis and surgery in UC, are more likely in 2- to 5-year-olds.

Prevalence of home parenteral nutrition in children.

BACKGROUND: Use of HPN in paediatrics in the UK has increased rapidly over the last 20 years but the prevalence of HPN has been challenging to define. Clinicians in the UK have noted an evolving complexity of cases and perceive improved outcomes and increased acceptability of long-term PN. These factors combined have the potential to increase the burden on existing paediatric gastroenterology services in the UK. METHODS: A national database was interrogated to define the prevalence of HPN in children in the UK and to explore outcomes for patients receiving HPN. RESULTS: Since 2015, 525 children were notified to the database; of these patients, mortality was <5% and intestinal transplant occurred in 1%. In 2019, 389 children received HPN in the UK; this is nearly double the number last reported in 2012 and is a prevalence of 30 per million children. Short bowel syndrome is the largest category of these patients. However, a poorly defined group including those with multisystem disease has increased 10 fold since 2012 and is now the second largest category. CONCLUSIONS: Long term HPN in childhood is safe and associated with good survival and low risk of the need for intestinal transplantation.

ESPEN practical guideline: Clinical Nutrition in inflammatory bowel disease.

The present guideline is the first of a new series of "practical guidelines" based on more detailed scientific guidelines produced by ESPEN during the last few years. The guidelines have been shortened and now include flow charts that connect the individual recommendations to logical care pathways and allow rapid navigation through the guideline. The purpose of the present practical guideline is to provide an easy-to-use tool to guide nutritional support and primary nutritional therapy in inflammatory bowel disease (IBD). The guideline is aimed at professionals working in clinical practice, either in hospitals or in outpatient medicine, and treating patients with IBD. In 40 recommendations, general aspects of care in patients with IBD, and specific aspects during active disease and in remission are addressed. All recommendations are equipped with evidence grades, consensus rates, short commentaries and links to cited literature.

ESPEN guideline: Clinical nutrition in inflammatory bowel disease.

INTRODUCTION: The ESPEN guideline presents a multidisciplinary focus on clinical nutrition in inflammatory bowel disease (IBD). METHODOLOGY: The guideline is based on extensive systematic review of the literature, but relies on expert opinion when objective data were lacking or inconclusive. The conclusions and 64 recommendations have been subject to full peer review and a Delphi process in which uniformly positive responses (agree or strongly agree) were required. RESULTS: IBD is increasingly common and potential dietary factors in its aetiology are briefly reviewed. Malnutrition is highly prevalent in IBD - especially in Crohn's disease. Increased energy and protein requirements are observed in some patients. The management of malnutrition in IBD is considered within the general context of support for malnourished patients. Treatment of iron deficiency (parenterally if necessary) is strongly recommended. Routine provision of a special diet in IBD is not however supported. Parenteral nutrition is indicated only when enteral nutrition has failed or is impossible. The recommended perioperative management of patients with IBD undergoing surgery accords with general ESPEN guidance for patients having abdominal surgery. Probiotics may be helpful in UC but not Crohn's disease. Primary therapy using nutrition to treat IBD is not supported in ulcerative colitis, but is moderately well supported in Crohn's disease, especially in children where the adverse consequences of steroid therapy are proportionally greater. However, exclusion diets are generally not recommended and there is little evidence to support any particular formula feed when nutritional regimens are constructed. CONCLUSIONS: Available objective data to guide nutritional support and primary nutritional therapy in IBD are presented as 64 recommendations, of which 9 are very strong recommendations (grade A), 22 are strong recommendations (grade B) and 12 are based only on sparse evidence (grade 0); 21 recommendations are good practice points (GPP).

How to use: nutritional assessment in neonates.

Adequate nutrition and growth during the neonatal period are important, especially for preterm infants, for whom there is evidence of poor nutrient intakes and growth, and this has important implications for their health in later life. Increased nutritional support while on the neonatal intensive care unit has been shown to improve growth, but such support is not universally available. Being able to carry out and interpret a nutritional assessment is therefore an important skill for paediatricians caring for neonates. This article aims to explain how to use nutritional assessment in neonates and provides some tools to make this process as straightforward as possible.

Next generation exome sequencing of paediatric inflammatory bowel disease patients identifies rare and novel variants in candidate genes.

BACKGROUND: Multiple genes have been implicated by association studies in altering inflammatory bowel disease (IBD) predisposition. Paediatric patients often manifest more extensive disease and a particularly severe disease course. It is likely that genetic predisposition plays a more substantial role in this group. OBJECTIVE: To identify the spectrum of rare and novel variation in known IBD susceptibility genes using exome sequencing analysis in eight individual cases of childhood onset severe disease. DESIGN: DNA samples from the eight patients underwent targeted exome capture and sequencing. Data were processed through an analytical pipeline to align sequence reads, conduct quality checks, and identify and annotate variants where patient sequence differed from the reference sequence. For each patient, the entire complement of rare variation within strongly associated candidate genes was catalogued. RESULTS: Across the panel of 169 known IBD susceptibility genes, approximately 300 variants in 104 genes were found. Excluding splicing and HLA-class variants, 58 variants across 39 of these genes were classified as rare, with an alternative allele frequency of <5%, of which 17 were novel. Only two patients with early onset Crohn's disease exhibited rare deleterious variations within NOD2: the previously described R702W variant was the sole NOD2 variant in one patient, while the second patient also carried the L1007 frameshift insertion. Both patients harboured other potentially damaging mutations in the GSDMB, ERAP2 and SEC16A genes. The two patients severely affected with ulcerative colitis exhibited a distinct profile: both carried potentially detrimental variation in the BACH2 and IL10 genes not seen in other patients. CONCLUSION: For each of the eight individuals studied, all non-synonymous, truncating and frameshift mutations across all known IBD genes were identified. A unique profile of rare and potentially damaging variants was evident for each patient with this complex disease.

Anaemia and iron deficiency in children with inflammatory bowel disease.

BACKGROUND AND AIMS: Anaemia and iron deficiency are common in children with Inflammatory Bowel Disease (IBD) however it is not known if the prevalence of anaemia and iron deficiency alters following diagnosis. METHODS: Laboratory results from diagnosis, and at follow up one and two years later were recorded retrospectively in children with IBD recruited from a tertiary centre. Anaemia was defined using WHO standards and iron deficiency defined using published guidelines. RESULTS: 46 children (16 girls) with Crohn's disease and 34 children (18 girls) with UC were studied. 75% of children with IBD were anaemic at diagnosis, 30% were anaemic at follow up two years later. 90% of children with Crohn's and 95% of children with Ulcerative Colitis (UC) were iron deficient at diagnosis. At follow up two years later 70% of children with Crohn's and 65% of children with UC were iron deficient. CONCLUSIONS: Persistent anaemia and iron deficiency are common in childhood IBD, prevalence alters with duration of time from diagnosis.

Ten-year experience of home parenteral nutrition in a single centre.

AIM: Recent data are scarce on the provision of home parenteral nutrition (HPN) in children from the UK but would help to commission intestinal failure services. Our aim was to describe 10 years of HPN experience in our centre, which serves a population of 650,000 children. METHODS: Outcome and complication data were collected retrospectively from hospital records of children receiving HPN from April 2001. Data from other centres were used to compare complications and outcomes in the provision of HPN. RESULTS: Nineteen children (12 females) received 10,213 days (28 years) of HPN. In this group, incidence of blood culture positive sepsis was four episodes/1000 days PN. Two children had early intestinal failure-associated liver disease. Of the 19, seven still receive HPN at our centre, six survived PN, three were transferred to other services while still on HPN and three died. CONCLUSION: Outcome and complication data for HPN from a single UK regional paediatric centre are similar to larger centres. These data provide recent evidence of the disease burden of HPN, which are important for the commissioning of intestinal failure services.

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.

Body composition in childhood inflammatory bowel disease.

BACKGROUND & AIMS: Little is known about the impact of disease and treatment on the pattern of growth in children with Inflammatory Bowel Disease (IBD). Significant deficits in height and weight in children with Crohn's disease have been reported but changes in fat and fat free mass are less well defined. This study aims to describe the height, weight and body composition of a cohort of children with IBD. METHODS: Height, weight, skinfold thicknesses and bioelectrical impedance analysis was performed. Disease activity was assessed with clinical scoring systems. RESULTS: 55 children, median age 13.7 years (range 6.5-17.7) were studied. Median (25th, 75th percentile) Standard Deviation Score for BMI, Height and Weight were - 0.3 (- 0.97, 0.65), - 0.56 (- 1.42, 0.06), - 0.62 (- 1.43, 0.19). In Crohn's disease, using multiple regression analysis disease activity measured by PCDAI was significantly inversely related to fat free mass (ß - 0.2, 95% CI -0.17, -0.03, p 0.005). CONCLUSIONS: Children with IBD were both under and overweight. Nutritional deficits were more common in Crohn's disease. Fat free mass was related to disease activity in children with Crohn's disease regardless of changes in weight. Weight or BMI may mask deficits in lean tissue in the presence of normal or increased proportions of body fat.