Clinical course of inflammatory bowel disease and impact on liver disease outcomes in patients with autoimmune sclerosing cholangitis.

BACKGROUND & AIMS: Autoimmune sclerosing cholangitis (ASC) is a childhood sclerosing cholangitis frequently associated with inflammatory bowel disease (IBD). We describe the IBD phenotype in ASC patients and associated liver disease outcomes. METHODS: Single center retrospective observational review of ASC patients, with a control population of pediatric IBD. Demographic and clinical parameters were obtained. Clinical endpoints were escalation of IBD therapy (biologic or colectomy) and transplant-free survival. RESULTS: In 93 ASC patients (53.8% female) and median follow up of 172 months: 70% had IBD, 25.8% underwent liver transplant. Median age at liver transplant was 21.7 years, at 131 months from ASC diagnosis. There was no association between presence of IBD and transplant-free survival, whilst those requiring second-line immunomodulators for ASC had poorer long-term liver prognosis. During follow-up 22 (33.8%) ASC-IBD required biologic or colectomy. On multivariate analysis ASC was associated with a lower risk of escalation of IBD therapy (HR 0.14, 95% CI 0.05-0.42; P=.001), including biologic therapy (HR 0.21, 95% CI 0.08-0.55, P=.002), but not colectomy on univariate analysis (HR 1.54, 95% CI 0.43-5.44, P=.51). CONCLUSIONS: IBD is common in ASC and during longterm follow up a third of ASC-IBD required escalation of IBD therapy; however ASC-IBD was lower risk compared to IBD alone. IBD does not appear to impact on transplant-free survival in patients with ASC, however second-line immunomodulators for ASC are associated with poorer IBD and liver outcomes.

Safety, Tolerability, and Pharmacokinetics of Oral Ferric Maltol in Children With Iron Deficiency: Phase 1 Study.

Iron deficiency is common in children and can have negative effects on behavior and function. Standard oral ferrous iron replacement is poorly absorbed and can cause treatment-limiting gastrointestinal adverse events (AEs). Ferric maltol is formulated to improve gastrointestinal absorption and tolerability versus oral ferrous compounds. In adult phase 3 trials, it increased hemoglobin and iron stores versus placebo, with a gastrointestinal AE profile similar to placebo. Here, we assess different doses of ferric maltol in children with iron deficiency. Methods: This phase 1 trial involved children of age 10 to 17 years with ferritin <30 µg/L (or <50 µg/L with transferrin saturation [TSAT] <20%). Children were randomized 1:1:1 to oral ferric maltol 7.8 mg, 16.6 mg, or 30 mg twice daily for 9 days and once on day 10. The primary outcomes were iron uptake measures (serum iron and TSAT) and population pharmacokinetic analyses. Results: The trial included 37 children (mean age 14.0 years; baseline mean ± standard deviation ferritin 16.3 ± 8.02 µg/L). Ferric maltol increased iron uptake nondose-proportionally: serum iron and TSAT plateaued between the 2 higher doses on day 1 and were comparable across all doses on day 10. Twenty children (54%) experienced AEs (all mild/moderate, gastrointestinal 32%), with similar frequencies in each group. Conclusions: All 3 ferric maltol doses increased iron uptake in children with iron deficiency, even over the short study duration, and were well tolerated. Nondose-dependent changes in serum iron and TSAT indicate physiologic regulation of iron uptake to meet the body's needs.

Sub-10-minute High-quality Diagnostic Colonoscopy With Terminal Ileum Intubation in Children Is Feasible and Safe.

OBJECTIVES: To critically appraise ileocolonoscopy (IC) practice in a large tertiary center, where IC is exclusively performed by experienced pediatric colonoscopists, particularly focusing on indications for the procedure; bowel preparation efficacy; IC completion rates and timings; diagnostic yield; and complications. PATIENTS AND METHODS: We prospectively evaluated all patients referred to our clinic between July 2015 and June 2016. Data on age, height and weight, sex, surgical history, indications for colonoscopy, bowel preparation given, and bowel cleansing efficacy were collected. The following were calculated: percentage of terminal ileal (TI) intubation; time to terminal ileum; total duration of each procedure. In addition, we evaluated the number and the type of complications encountered and the number of patients readmitted within 30 days from the elective procedure. Endoscopic diagnostic yield, stratified for indication, was calculated. RESULTS: A total of 1392 patients were referred; 181 required an endoscopic evaluation of the lower gastrointestinal (GI) tract (Outpatient Department conversion rate: 13%). Main indications for IC were: recurrent abdominal pain 38.1%; unexplained chronic diarrhea 16%; suspected inflammatory bowel disease (IBD) 24.9%; isolated rectal bleeding 13.2%; occult GI bleeding 1.6%; unexplained faltering growth 1.6%; IBD restaging 2.6%; and miscellaneous 1.6%. Terminal ileum was reached in all the patients (TI intubation rate = 100%). Median time to TI was 9.8 minutes (1-50 minutes). Time to TI was lower in younger patients compared to older ones (P = 0.005). Bowel cleansing was judged as grade 1 in 49.2%; grade 2 in 33.7%; grade 3 in 13.3%; and grade 4 in 3.9%. A significant statistical correlation was recorded between bowel cleansing and time to TI. The positive diagnostic yield was: 11.6% in patients with abdominal pain; 37.9% in patients with chronic diarrhea; 51.1% in patients with suspected IBD; 29.2% in patients with isolated rectal bleeding; 33.3% in patients with occult GI bleeding; 0% in patients with faltering growth; and 33% in the miscellaneous group. CONCLUSIONS: In conclusion, appropriately targeted IC in the management of children with GI symptoms is a safe, fast, and useful investigation. TI intubation rates of 100% are achievable and desirable and can be conducted quickly. Poor bowel preparation impacts negatively on this and IC duration may be faster in younger children. High diagnostic yields have been recorded in patients with a clinical suspicion of IBD. Diagnostic yield in isolated recurrent abdominal pain is low. Training to excellence in pediatric IC should be a persistent goal.

Improved Medical Treatment and Surgical Surveillance of Children and Adolescents with Ulcerative Colitis in the United Kingdom.

Background: Pediatric ulcerative colitis (UC) presents at an earlier age and increasing prevalence. Our aim was to examine morbidity, steroid sparing strategies, and surgical outcome in children with active UC. Methods: A national prospective audit was conducted for the inpatient period of all children with UC for medical or surgical treatment in the United Kingdom (UK) over 1 year. Thirty-two participating centers recruited 224 children in 298 admissions, comparisons over 6 years were made with previous audits. Results: Over 6 years, recording of Paediatric Ulcerative Colitis Activity Index (PUCAI) score (median 65)(23% to 55%, P < 0.001), guidelines for acute severe colitis (43% to 77%, P < 0.04), and ileal pouch surgery registration (4% to 56%, P < 0.001) have increased. Corticosteroids were given in 183/298 episodes (61%) with 61/183 (33%) not responding and requiring second line therapy or surgery. Of those treated with anti-TNFalpha (16/61, 26%), 3/16 (18.8%) failed to respond and required colectomy. Prescription of rescue therapy (26% to 49%, P = 0.04) and proportion of anti-TNFalpha (20% to 53%, P = 0.03) had increased, colectomy rate (23.7% to 15%) was not significantly reduced (P = 0.5). Subtotal colectomy was the most common surgery performed (n = 40), and surgical complications from all procedures occurred in 33%. In 215/224 (96%) iron deficiency anemia was detected and in 51% treated, orally (50.2%) or intravenously (49.8%). Conclusions: A third of children were not responsive to steroids, and a quarter of these were treated with anti-TNFalpha. Colectomy was required in 41/298 (13.7%) of all admissions. Our national audit program indicates effectiveness of actions taken to reduce steroid dependency, surgery, and iron deficiency. 10.1093/ibd/izy042_video1izy042.video15769503407001.

Real-life Anti-tumor Necrosis Factor Experience in More Than 500 Patients: High Co-immunosuppression Rates But Low Rates of Quantifying Treatment Response.

OBJECTIVE: The aim of this study was to measure the effectiveness, safety, and use of anti-tumor necrosis Factor (TNF) therapy in pediatric inflammatory bowel disease in the United Kingdom (UK). METHODS: Prospective UK audit of patients newly starting anti-TNF therapy. Disease severity was assessed using Physician Global Assessment +/or the Paediatric Crohn Disease Activity Index. RESULTS: A total of 37 centers participated (23/25 specialist pediatric inflammatory bowel disease sites). A total of 524 patients were included: 429 with Crohn disease (CD), 76 with ulcerative colitis (UC), and 19 with IBD unclassified (IBDU). Eighty-seven percent (488/562) of anti-TNF was infliximab; commonest indication was active luminal CD 77% (330/429) or chronic refractory UC/IBDU 56% (53/95); 79% (445/562) had concomitant co-immunosuppression. In CD (267/429 male), median time from diagnosis to treatment was 1.42 years (interquartile range 0.63-2.97). Disease (at initiation) was moderate or severe in 91% (156/171) by Physician Global Assessment compared to 41% (88/217) by Paediatric Crohn Disease Activity Index (Kappa (κ) 0.28 = only "fair agreement"; P < 0.001.Where documented, 77% (53/69) of patients with CD responded to induction; and 65% (46/71) entered remission. A total of 2287 infusions and 301.96 years of patient' follow-up (n = 385) are represented; adverse events affected 3% (49/1587) infliximab and 2% (2/98) adalimumab infusions (no deaths or malignancies). Peri-anal abscess drainage was less common after anti-TNF initiation (CD), that is 26% (27/102) before, 7% (3/42) after (P = 0.01); however, pre and post anti-TNF data collection was not over equal time periods. CONCLUSIONS: Anti-TNFs are effective treatments, usually given with thiopurine co-immunosuppression. This study highlights deficiencies in formal documentation of effect and disparity between disease severity scoring tools, which need to be addressed to improve ongoing patient care.

Anti-TNFα Treatment in Children and Adolescents With Combined Inflammatory Bowel Disease and Autoimmune Liver Disease.

OBJECTIVES: Inflammatory bowel disease (IBD) and autoimmune liver disease (AILD) are closely associated, the former often dictating progression of the latter. Antibodies to tumor necrosis factor alpha (anti-TNFα) are effective in the management of IBD, but may cause liver injury. METHODS: Retrospective review of medical records of patients with juvenile AILD who received anti-TNFα for IBD to evaluate the safety and efficacy of anti-TNFα. RESULTS: Eleven patients (6 boys), ages 9 to 15 years (median 13 years) were identified. Ten had ulcerative colitis and 1 Crohn disease; 2 had autoimmune hepatitis type 1 and 9 autoimmune hepatitis-sclerosing cholangitis variant. All patients were started on infliximab (IFX, 5 mg/kg) and 2 required dose increase (10 mg/kg); 3 of 11 switched to adalimumab due to allergic reaction or nonresponse. Three received adalimumab after losing response or developing antibodies to IFX. Liver function tests (LFTs) improved in 5, 1 continued to have stably abnormal LFTs and 2 maintained normal LFTs. Patients on adalimumab showed stable or improved liver function compared to pretreatment status. Six of 8 treated with a full course of IFX maintained clinical remission of IBD for 6 months to 2.5 years; of the 6 patients treated with adalimumab, 1 sustained IBD clinical remission for 24 months, 2 achieved remission only after tacrolimus addition and 3 did not respond. CONCLUSIONS: IBD in patients with AILD can be aggressive, requiring escalation to anti-TNFα or switching to other biologics. In this series, anti-TNFα did not impair liver function and improved gut disease in most of the patients, indicating that it can be beneficial and safe.

Feasibility of small bowel capsule endoscopy in children under the age of 4†years: a single centre experience.

Data on the use of wireless capsule endoscopy (WCE) in younger children remain limited. However, this single centre study suggests that it is a relatively complication-free procedure that may be considered in younger children below 4 years of age, when small bowel pathology is suspected. We retrospectively reviewed the King's College Hospital WCE database between August 2009 and August 2011. Patients aged 4 years or younger were included in the study. Six children fulfilled the inclusion criteria. The indications for WCE were unexplained gastrointestinal tract (GIT) bleeding (n=4), chronic diarrhoea with (n=1) and without (n=1) GIT bleeding (n=1). All had an oesophagogastroduodenoscopy and an ileocolonoscopy before WCE. The mean age at the time of WCE was 2 years 6 months (range 1 year 7 months to 3 years 7 months). The mean weight at WCE was 13.3 kg (range 9-17 kg). Four children had a complete study.

Gastrostomy feeding in cerebral palsy: enough and no more.

AIM: gastrostomy feeding children with spastic quadriplegic cerebral palsy (SQCP) improves weight gain but may cause excess deposition of body fat. This study was designed to investigate whether weight gain could be achieved without an adverse effect on body composition by using a low-energy feed in gastrostomy-fed children with SQCP. METHOD: ourteen children (seven male; seven female; median age 2y; range 10mo-11y) with SQCP were studied, 13 of whom were classified as Gross Motor Function Classification Score (GMFCS) level V and one as GMFCS level IV. Children were eligible for the study if they weighed between 8 and 30kg with a diagnosis of severe SQCP and significant feeding difficulties in whom a clinical decision had been made to insert a gastrostomy feeding tube. The feed used in the study had an energy concentration of 0.75kcal/mL (Nutrini Low Energy Multi Fibre). Assessments were performed before gastrostomy insertion (baseline) and after 6months, and included body composition, growth, nutritional intake, and gastrointestinal symptoms. RESULTS: there was a significant increase in weight (median difference 1.9kg; 95% confidence interval [CI] 0.85-3.03kg; p=0.012), mid-upper arm circumference (median difference 1.45cm; 95% CI -0.36cm to 3.47cm; p=0.043), and lower leg length (median difference 1.62cm; 95% CI 0.44-3.95cm; p=0.012) over the 6 months. There was no significant increase in fat mass index (median diff 1.21, 95% CI -1.15 to 2.94, p=0.345) or fat free mass index (median diff -1.43, 95% CI -1.15 to 2.94, p=0.249). Micronutrient levels remained within reference ranges with the exception of elevated chromium. The median percentage intake of the estimated average requirements for energy (kcal) was 43% at the beginning of the study and 48.8% after 6 months on the low-energy feed. INTERPRETATION: children with SQCP who are fed a low-energy, micronutrient-complete, high-fibre feed continue to grow even with energy intakes below 75% of the estimated average requirements. This was not associated with a disproportionate rise in fat mass or fat percentage, and the majority of micronutrient levels remained within the reference range.

Diabetic ketoacidosis, hyperosmolarity and hypernatremia: are high-carbohydrate drinks worsening initial presentation?

The case of five pediatric patients who presented to the Royal Children's Hospital, Melbourne with newly diagnosed diabetes mellitus between January 2001 and September 2003 is reported. Each case was complicated by hyperosmolarity and hypernatremia and required intensive therapy. Fluid intake prior to admission in each case was documented and consisted of between 5 and 12 L of carbonated carbohydrate beverages and 'isotonic' sports drinks. At presentation, biochemical results of the four cases (four males and one female), mean age 13.6 yr (range 11.7-15.1 yr) included glucose (mean 1460 mg/dL; range 864-2106), adjusted sodium (mean 176.3 mmol/L; range 165-183), serum osmolarity (mean 399 mmol/kg; range 364-424), anion gap (mean 48 mEq/L; range 42-84), and pH (mean 7.15; range 7.01-7.27). All five cases had evidence of ketonuria on presentation. Treatment in all five cases consisted of replacement of fluids over a prolonged period of 72 h and careful monitoring of electrolyte response. Three of five cases required hemofiltration in the first 48 h postadmission. All five cases made a complete recovery without neurological sequelae. Carbonated carbohydrate fluid intake may precipitate a more severe presentation of type 1 diabetes mellitus (T1DM). Fluid composition and intake should be carefully estimated at admission to help identify and manage similar cases.