Working to Answer the Effectiveness of Nutrition in IBD: Still a Ways to Go.

ABSTRACT: The Specific Carbohydrate diet (SCD) is an exclusion diet widely popular among patients with IBD, which restricts carbohydrates and processed foods. Two recently concluded controlled studies PRODUCE (Personalized Research on Diet in Ulcerative Colitis (UC) and Crohn's Disease) and DINE-CD (The Diet to Induce Remission in Crohn's disease) confirm efficacy of SCD on symptom control but fail to demonstrate a sustained anti-inflammatory response. These dietary studies are a welcome addition to a poorly understood field of dietary management of IBD, we explore some practical challenges including trial designs, recruitment, and retention in long term dietary intervention studies. Future dietary intervention studies should, therefore, incorporate endoscopic end points to establish a true anti-inflammatory response to elimination diets, preferably with detailed multi-omics analysis to understand mechanism of action.

Medical Disimpaction for Children With Organic Esophageal Foreign Body in the Era of Eosinophilic Esophagitis.

OBJECTIVE: Esophageal foreign body impaction (EFBI) is a common presentation in pediatric emergency medicine. Interventions (medical or endoscopic) are often required because of the severity of symptoms and risk of complications. Use of medical disimpaction (MD) such as glucagon injections and effervescent agents (eg, carbonated beverages) has been well described in adults; however, there are limited data in the pediatric literature. Eosinophilic esophagitis (EoE) is a relatively "new" clinicopathological entity that may present with EFBI mostly due to food with histological findings of EoE. Our study aim was to determine the efficacy of MD for organic EFBI in the pediatric population especially in children with EoE. METHODS: A retrospective chart review was performed using the International Classification of Diseases codes and the emergency department database of patients presenting with EFBI from January 2010 to December 2014. Response to MD was defined as symptomatic relief of obstruction. Age, object ingested, medical agent used, EoE status, complications, and outcome were recorded. RESULTS: A total of 317 presentations of EFBI were identified during the study period, of which organic EFBI accounted for 101 impactions (31.9%). Medical disimpaction was attempted for 42 (41.6%) with organic EFBI, resulting in resolution of symptoms for 16 (38.1%). One child with EoE responded to MD compared with 15 without EoE (4.8% vs 71.4%, P < 0.0001). CONCLUSIONS: Medical disimpaction was ineffective in children with EoE but may be of help with symptom resolution in approximately 70% of children without EoE.

Management of inflammatory bowel disease in children: It is time for an individualised approach.

Paediatric-onset inflammatory bowel disease (PO-IBD) is associated with greater morbidity compared to adult-onset IBD. However, as not all children with PO-IBD will have poor outcome and the best management decisions involve weighing risks versus benefit and wishes of patient's and family, we review risk factors of IBD progression in children and summarise rapidly expanding treatment choices, potential drug-related adverse events and risk minimisation strategies, ending with new treatment paradigms focusing on long-term goal of intestinal healing. For the purpose of this article, we have outlined the conventional approach, including medications currently licenced and available for use in Australia for paediatric IBD through the Pharmaceutical Benefit Scheme and briefly discuss other promising therapies that are shown to be effective in adults but are undergoing paediatric clinical trials.

Early Response to Corticosteroid and Baseline C-Reactive Protein Predicts Outcomes in Children with Moderate to Severe Ulcerative Colitis.

BACKGROUND: Initial response to corticosteroids (CS) is recognized as a strong predictor of outcomes in ulcerative colitis (UC). AIM: To compare outcomes of early poor responders (PR) versus good responders (GR) to initial CS at 1, 2, and 3 years from diagnosis. METHODS: In this retrospective study, we report longitudinal outcomes of children with moderate-severe UC, initiating oral/IV CS < 1 month of diagnosis and a minimum follow-up (FU) of 1 year. CS resistance (CSR) and CS dependency (CSD) were combined as PR, and those with CS-free remission (CSFR) at 6 months were GR. RESULTS: Of 116 children with UC, 76 (33 males) fulfilled study criteria. Median age at diagnosis was 12 years (IQR 12-14), and a median FU was 48 months (IQR 27-65). Thirty-five (46%, CSR = 10, CSD = 25) were PR, and 41 (54%) were GR. Mean relapse (2.39 vs. 1.1, p = 0.0009), acute severe UC flare-up (40% vs. 9.7%, p = 0.002), and colectomy rates (34.2% vs. 2.4%) were greater in PR versus GR, despite frequent early (< 6 months) use of azathioprine (74% vs. 27%, p = 0.004) and anti-TNFs (43% vs. 2.4%, p = 0.0001). Cumulative colectomy at 3 years was lowest in those with GR versus CSD and CSR (2.4% vs. 28% and 50% p = 0.001). On univariate analysis, CRP > 20 mg/L at diagnosis, Mayo Clinical Score > 1 at 3 months, and PR predicted colectomy. On multivariate regression, only baseline CRP > 20 mg/L predicted colectomy (HR 4.9, p = 0.03). CONCLUSIONS: Baseline CRP and poor response to initial CS are associated with unfavorable outcomes in children with UC.

Inflammatory bowel disease in adolescents.

BACKGROUND: Nearly 20% of all inflammatory bowel disease (IBD) is diagnosed in children and adolescents, where it follows a more compli-cated and aggressive course than adult-onset IBD. General practitioners (GPs) have a pivotal role in early diagnosis, and monitoring and supporting children and families with IBD. OBJECTIVE: This article will focus on recognising key differences between paediatric-onset IBD and adult-onset IBD, proposed treatment targets, and practical issues in the management of adolescents with IBD. DISCUSSION: IBD in children is more aggressive in nature, with additional issues of growth failure, delayed puberty and the consequences of a chronic disease commencing at a vulnerable period of psychosocial development. Traditional treatment targets focus on symptom control, but this is insufficient as long-term, end-organ (bowel) damage results from insufficiently controlled inflammation. In this article, we provide a brief overview of IBD in adolescents and cover key management issues, particularly focusing on newer treatment end-points by aiming for high rates of intestinal mucosal healing and evidence to support this approach.

Two-Year Outcomes After Exclusive Enteral Nutrition Induction Are Superior to Corticosteroids in Pediatric Crohn's Disease Treated Early with Thiopurines.

BACKGROUND: Impact of first-line induction therapy on medium-term outcomes in the setting of early thiopurine (TP) use in children with Crohn's disease has not been evaluated, in particular whether choice of exclusive enteral nutrition (EEN) over corticosteroids (CS) for induction impacts clinical outcomes at 12 and 24 months. AIMS AND METHODS: In this retrospective study, 89 children from our database with new diagnosis CD and follow-up of at least 2 years following induction with exclusive course of CS or EEN and early, dose-optimized TP (within 6 months from diagnosis) were evaluated. We compared steroid dependency (relapse <3 months of tapering first course CS or inability to wean <10 mg prednisolone), need for IFX, linear growth, and surgical resections over the first 2 years. RESULTS: Choice of EEN over CS induction was associated with reduced linear growth failure (7 vs. 26%, p = 0.02), CS dependency (7 vs. 43%, p = 0.002), and improved primary sustained response to IFX (86 vs. 68%, p = 0.02). Combined CS/IFX-free remission and surgical resection rates were similar. CONCLUSION: In the setting of early TP commencement, EEN induction is superior to CS induction for reducing growth failure, CS dependency, and loss of response to IFX over the first 2 years.

Synbiotic in the management of infantile colic: a randomised controlled trial.

AIM: Infant colic is a frequent problem affecting up to 10-30% of infants in first 3 months of life. Results from previous trials have shown that manipulation of gut microbiota can lead to symptomatic improvements. In a randomised clinical trial, we aimed to determine efficacy of synbiotic in reducing average infant crying time at day 7 and day 30 after starting intervention. METHODS: Fifty breastfed infants aged 15-120 days with infantile colic randomly assigned to receive either the synbiotic sachet containing 1 billion CFU of: Lactobacillus casei, L. rhamnosus, Streptococcus thermophilus, Bifidobacterium breve, L. acidophilus, B. infantis, L. bulgaricus and fructooligosacharide (Protexin Healthcare, Somerset, UK), or placebo daily for 30 days. Parents were asked to record details of crying times in a symptoms diary. The primary outcome measure was the treatment success (reduction in the daily crying time >50%) and the secondary outcome measure was symptom resolution (reduction in the daily crying time >90%). RESULTS: The treatment success was significantly higher in synbiotic group (82.6%) compared with placebo (35.7%) at day 7 (P < 0.005). At day30, treatment success was 87% and 46% in synbiotic and placebo group, respectively (P < 0.01). Symptom resolution was also higher in synbiotic group (39%) compared with placebo (7%) at day 7 (P < 0.03) but not at day 30 (56% vs.36%, P = 0.24). We encountered no complication related to synbiotic use. CONCLUSION: This synbiotic (a mixture of seven probiotic strains plus FOS) significantly improved colic symptoms in comparison with placebo.

Glutamine supplementation for young infants with severe gastrointestinal disease.

BACKGROUND: Endogenous glutamine biosynthesis may be insufficient to meet the needs of people with severe gastrointestinal disease. Studies using experimental animal models and controlled trials in adult patients with severe gastrointestinal disease have suggested that glutamine supplementation improves clinical outcomes. This review examines evidence for the effect of glutamine supplementation in young infants with severe gastrointestinal disease. OBJECTIVES: To assess the evidence from randomised controlled trials that providing supplemental glutamine reduces mortality and morbidity in young infants with severe gastrointestinal disease. SEARCH METHODS: We used the standard search strategy of the Cochrane Neonatal Review Group. This included searches of the Cochrane Central Register of Controlled Trials (The Cochrane Library, 2012, Issue 1), MEDLINE, EMBASE, and CINAHL (to November 2011), conference proceedings, and previous reviews. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials that compared glutamine supplementation versus no glutamine supplementation in infants up to three months old (corrected for preterm birth if necessary) with severe gastrointestinal disease defined as a congenital or acquired gastrointestinal condition that is likely to necessitate providing parenteral nutrition for at least 24 hours. DATA COLLECTION AND ANALYSIS: We extracted data using the standard methods of the Cochrane Neonatal Review Group with separate evaluation of trial quality and data extraction by two review authors. We synthesised data using a fixed-effect model and reported typical risk ratio (RR), typical risk difference (RD), and weighted mean difference (WMD). MAIN RESULTS: We found two trials in which a total of 100 infants participated. The trials were of good methodological quality but were too small to detect clinically important effects of glutamine supplementation. Meta-analysis did not reveal a statistically significant difference in the risk of death before hospital discharge (typical RR 1.57; 95% confidence interval (95% CI) 0.25 to 9.66; RD 0.02; 95% CI -0.06 to 0.10) or in the rate of invasive infection [typical RR 1.22; 95% CI 0.55 to 2.70; RD 0.04; 95% CI -0.12 to 0.20). AUTHORS' CONCLUSIONS: The available data from randomised controlled trials are insufficient to determine whether glutamine supplementation has any important benefits for young infants with severe gastrointestinal disease.

Comparing quality of life improvement after antegrade continence enema (ACE) therapy for patients with organic and functional constipation / encopresis.

BACKGROUND: We compared patient- and family-reported overall and stool-related quality of life (QoL) before and after an antegrade continence enema (ACE) procedure (cecostomy tube insertion) for refractory chronic constipation or fecal incontinence (CCFI). We hypothesized that patients with functional diagnoses experience similar improvements in QoL compared to those with organic diagnoses. METHODS: This is a cross-sectional study of patients undergoing cecostomy tube insertion for CCFI at a tertiary pediatric hospital from 2012 to 2019. Patients and/or primary caregivers completed validated stooling and overall QoL surveys based on three time points: before surgery, three months after surgery, and at the time of survey / date of last follow-up. Repeated measures analyses compared scores over time between subjects and within the diagnostic groups. RESULTS: The response rate was 65% (22/34 patients, 12 organic and 10 functional diagnoses). Mean age was 8.3 years and 32% of the participants were female. Organic diagnoses were: spina bifida (6), anorectal malformation (5), and Hirschsprung Disease (1). There was substantial improvement in stool-related and overall QoL at three months post-ACE procedure (both p<0.001) for all patients; both scores continued to improve significantly until the date of last follow-up (median 4.1 years, IQR 2.3-5.6, p<0.001). There was no statistically significant difference in scores between patients with organic and functional diagnoses. CONCLUSIONS: Caregivers perceive a significant, sustainable improvement in stooling habits and QoL following ACE therapy. The improvement is comparable between patients with a functional diagnosis and those with an underlying organic reason for their CCFI.

A pilot study of disease related education and psychotherapeutic support for unresolved grief in parents of children with CF.

Diagnosis of chronic disease in a child can result in unresolved grief (UG) in parents. This study aimed to evaluate the efficacy of psychological insight-oriented therapy (IOT) as a treatment for UG compared to disease related education in parents of children with cystic fibrosis (CF). Sequence of delivery, first IOT then disease related education (or vice versa) was also examined, to let all participants experience both interventions. Parents were screened for UG. Parents with UG were randomised to either five 1-h sessions of IOT or five 1-h sessions of education. Measures were assessed pre-intervention, after the first intervention period (primary efficacy assessment), and after the second intervention period (swapping intervention). Forty-seven parents were screened of which 46.8% (22/47) had UG. Median duration of UG was 5 years (range: 6 months-14 years). Anxiety (50% vs. 20%, p = 0.03) and stress (59% vs. 28%, p = 0.03) were significantly more prevalent in parents with UG. There was no difference between arms in the odds of UG resolving either following the first intervention period (OR 0.88; 95% CI 0.5, 1.5) or the second intervention period (OR 0.91; 95% CI 0.5, 1.6). While not statistically significant, adjusted mean values for seven of the eight mental health measures were lower in the IOT (first) arm compared to the ED (first) arm, following the first intervention period. UG is a significant burden for families affected by CF. Provision of disease related education and psychological support, regardless of sequence, can result in resolution of grief.Trial registration number: ACTRN12621000796886, date of registration 24/06/2021, retrospectively registered.

Predictors of poor outcomes in children with tracheoesophageal fistula/oesophageal atresia: an Australian experience.

Objective: The aim of this study is to characterize long-term morbidities of oesophageal atresia (OA) with or without tracheoesophageal fistula (TOF). Methods: Infants born with OA/TOF from 2000 to 2016 in Western Australia were included for analysis. Infants were categorized into high-risk and low-risk groups based on the presence of one or more perioperative risk factors [low birth weight, vertebraldefects, anal atresia, cardiac defects, TOF, renalanomalies, limb abnormalities (VACTERL), anastomotic leak, long gap OA, and failure to establish oral feeds within the first month] identified by a previous Canadian study. Frequency of morbidities in infants with perioperative risk factors was compared. Results: Of 102 patients, 88 (86%) had OA with distal TOF (type C). The most common morbidities in our cohort were anastomotic oesophageal strictures (AS) (n=53, 52%), tracheomalacia (n=48, 47%), gastroesophageal reflux disease (GORD) (n=42, 41%) and recurrent respiratory tract infections (n=40, 39%). Presence of GORD (30/59 vs 12/43, p=0.04) and median frequency of AS dilatations (8 vs 3, n=59, p=0.03) were greater in the high-risk group. This study further confirmed that inability to be fed orally within the first month was associated with high morbidities. Conclusions: Gastrointestinal and respiratory morbidities remain high in OA/TOF regardless of perioperative risk factors. Inability to be fed orally within the first month is a predictor of poor outcomes with high frequency of gastrointestinal and respiratory comorbidities.

Assessment of European Society of Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) guidelines in an Australian paediatric population.

Coeliac disease (CD) diagnosis is based on clinical assessment, detection of specific autoantibodies and histological examination of small intestinal biopsies. The European Society of Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) guidelines have recently been updated and recommend CD may be diagnosed without a biopsy or HLA typing in symptomatic patients with high titre IgA tissue transglutaminase antibodies (aTTG) and positive endomysial antibodies (EMA). However, the need for EMA in patients with high level aTTG has been questioned. We aimed to determine the diagnostic benefit of HLA typing, EMA and IgG antibodies to deamidated gliadin (DGP) in children with high level aTTG. We prospectively evaluated children presenting for assessment of possible CD. All patients underwent small bowel biopsy, serological testing and HLA typing. Results were analysed and correlated with histopathological diagnosis. A total of 209 children were assessed; 61.5% were found to have CD and 29% could have avoided biopsy as per 2020 ESPGHAN guidelines. Titres of aTTG ≥60 U/mL or DGP ≥28 U/mL gave 100% specificity and 100% positive predictive value (PPV) for CD. HLA typing and EMA did not improve the PPV of patients with aTTG ≥60 U/mL, but addition of DGP ≥28 U/mL improved diagnostic sensitivity whilst retaining 100% specificity. Addition of HLA and EMA testing in patients with high titre aTTG antibodies does not improve diagnostic performance and may possibly be omitted from the serological workup in these patients. Our data support combining aTTG and DGP testing and optimising cut-offs to maximise specificity as an alternative biopsy-free diagnostic approach.

Predicting and preventing complications in children with inflammatory bowel disease.

Paediatric-onset inflammatory bowel disease (IBD) is associated with greater disease burden and morbidity compared to adult-onset IBD. Accurate risk prediction for a complicated disease course in childhood onset IBD is essential for making the best treatment choices. Complicating course in IBD is closely linked with choice of therapies and treatment targets. In this review article, we examine risk factors of complicated disease course in children with IBD in the era of increasing use of biologics and tighter treatment targets. We also discuss emerging paediatric data supporting an early intensive approach targeting deeper healing, aiming for remission beyond symptoms with repeat endoscopic examination to make treatment adjustments.

Probiotic for irritable bowel syndrome in pediatric patients: a randomized controlled clinical trial.

BACKGROUND: Irritable bowel syndrome (IBS) is a common gastrointestinal disorder in children. Recently, probiotics have been suggested as a treatment option for gastrointestinal disorders. The most effective species and the most appropriate doses are still unknown. OBJECTIVE: The aim of this study was to assess the effects of Lactobacillus GG (LGG) for treating IBS in pediatric patients. METHODS: In a controlled, double blind, randomized trial, patients with IBS diagnosed by Rome III criteria from August 2012 to September 2012 at Dr. Sheikh Hospital, Mashhad University of Medical Sciences, Iran, were assigned to one of two groups, i.e., intervention and control groups. For four weeks, the intervention group received a probiotic in capsule form that contained LGG at a concentration of 1×10(10) cfu/ml bacteria. For the same period, the control group received a placebo capsule that had the same shape and color but only contained inulin, which also was present in the LGG capsules. The primary outcome was any change in the severity of the patients' pain, and we used a five-point Likert scale to evaluate the severity of their pain. Secondary outcomes were ghanges of the functional scale, stool patterns, and associated problems. RESULTS: Fifty-two patients participated in the study, and 26 patients were assigned randomly to each of the two groups. The severity of the patients' pain decreased significantly in the intervention group after one, two, three, and four weeks of treatment, as indicated by P-values of 0.01, 0.00, 0.00, and 0.00, respectively. Also, there was significant improvement in the functional scale after two weeks of treatment (P-value ≤ 0.00). CONCLUSION: Lactobacillus GG at a concentration of 1×10(10) cfu/ml for a period of four weeks can lessen the severity of the patients' pain and improve the functional scale in patients with irritable bowel syndrome. Probiotics can have therapeutic effects for IBS patients.

Exclusive enteral nutrition induces early clinical, mucosal and transmural remission in paediatric Crohn's disease.

BACKGROUND AND AIMS: Exclusive enteral nutrition (EEN) induces clinical and mucosal healing (MH) in Crohn's disease (CD), with MH the best determinant of future outcome. We investigated efficacy of EEN for inducing early clinical, biochemical, mucosal and transmural remission of CD and related early endoscopic response to outcomes at 1 year. METHODS: In a prospective, open label study 34 children (mean 13.1 years; 21 males) with new diagnosis CD were offered EEN, 26 completed a minimum 6 weeks EEN and underwent paired clinical, biochemical and endoscopic assessment at start and completion using PCDAI, BMI, CRP and Simple Endoscopic Score for CD (SES-CD). A subset, 16/26, had paired MR enterography scored. Early good endoscopic response (complete MH, or near complete, SES-CD 0-3) was related to outcome at 1 year. RESULTS: EEN improved mean PCDAI (37.88-7.01, p < 0.001; BMI Z scores (-1.54 to -0.54, p < 0.01); weight Z score (-0.79 to -0.08, p < 0.03); CRP (44.86-5.5, p < 0.001); endoscopy (SES-CD 14.28-3.88, p < 0.001) and MRE (5.14-2.79, p = 0.01). Of 26 children, 22 (84 %) achieved clinical remission; 20 (76 %) biochemical remission. Fifteen (58 %) had early good endoscopic response (11 complete, 4 near complete MH) and 3/14 (21 %) had complete transmural remission of ileal CD (MRE-CD: 0-1). Early good endoscopic response was associated with reduced endoscopic confirmed relapse (53 vs. 100 %, p = 0.02), anti-TNF use (33 vs. 88 %, p = 0.01) and hospitalisation (40 vs. 88 %) at 1 year. CONCLUSIONS: EEN is effective for inducing early clinical, biochemical, mucosal and transmural remission. Early endoscopic remission improves outcomes at 1 year.

Predictors of response to Infliximab in children with luminal Crohn's disease.

OBJECTIVE: A significant proportion of patients with initial response to Inflximab (IFX), subsequently lose response (LOR). Multicentre paediatric studies report LOR in 33% to 50% with 3-5year follow-up. Our retrospective study examined durability of response and predictors of LOR. METHODS: From our IBD database of 185 children with CD, 65 received IFX maintenance therapy for luminal or fistulising Crohn's disease between January, 2006 and April, 2013. 47 with luminal CD ≥1year follow-up after commencing IFX were included. We evaluated variables associated with response and describe outcomes on those remaining on IFX at four time points; before IFX, after induction, at 1year and at the last follow-up. Response was divided into sustained primary, recovered, durable (combined sustained primary and recovered) and complete LOR (discontinuation from LOR or intolerance). RESULTS: Overall, 28/47 (60%) children sustained primary response over a median duration of 2.83years (1.6-4.4, IQR). 19/47 (40%) developed LOR (including 2 intolerant) at a median of 11months (9-19, IQR). Of 17 with LOR, 7 were successfully re-induced giving durable response (35/47, 74%); 6 failed dose intensification needing surgery (n=2), second anti-TNF (n=2) or both (n=2). 4 had surgery without dose intensification. LOR was associated with low BMI at diagnosis, lower height Z scores prior to induction, elevated CRP following induction (p=0.007) and failure to use concomitant IM (p=0.02). CONCLUSION: The cumulative probability of durable response to IFX in luminal CD was 83%, 74% and 70% after 1, 2, and 3years on IFX maintenance therapy.