STEP-CD study: ustekinumab use in paediatric Crohn's disease-a multicentre retrospective study from paediatric IBD Porto group of ESPGHAN.

Ustekinumab is an effective therapy for adult Crohn's disease (CD), but data in paediatric CD patients are scarce. The aim of the study was to describe the real-life effectiveness and safety of ustekinumab in paediatric CD. This is a multicentre review of children with Crohn's disease treated with ustekinumab. The aim of our study was to describe the effectiveness and safety of ustekinumab in paediatric real-life practice. This is a study of the Paediatric IBD (inflammatory bowel disease) Porto group of ESPGHAN. Corticosteroid (CS)- and exclusive enteral nutrition (EEN)-free remission, defined as weighted Paediatric Crohn's Disease Activity Index (wPCDAI) < 12.5, and physician global assessment (PGA) were determined at weeks 12 and 52. A total of 101 children were included at a median age of 15.4 years (IQR 12.7-17.2) with a median follow-up of 7.4 months (IQR 5.6-11.8). Ninety-nine percent had received prior anti-TNF, 63% ≥ 2 anti-TNFα therapies and 22% vedolizumab. Baseline median wPCDAI was 39 (IQR 25-57.5) (71 (70%) patients with moderate-severe activity). Weeks 12 and 52 CS- and EEN-free remission were both 40.5%. Clinical response at week 6, iv induction route and older age at onset of ustekinumab treatment were predictive factors associated with clinical remission at week 12. Seven minor adverse events probably related to ustekinumab were reported. One patient died from an unrelated cause.  Conclusion: Our results suggest that ustekinumab is effective and safe in children with chronically active or refractory CD. What is Known: • Ustekinumab is an effective therapy for adult moderate to severe Crohn's disease (CD). • Off-label use of ustekinumab in children is increasing especially in anti-TNF refractory CD. What is New: • Is the largest cohort of real-world use of ustekinumab in paediatric CD to date. • Clinical response at week 6, iv induction and older age at onset of ustekinumab were predictive factors associated with clinical response at week 12.

Endoscopy in Pediatric Inflammatory Bowel Disease: A Position Paper on Behalf of the Porto IBD Group of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition.

Endoscopy is a central tool for the evaluation and management of inflammatory bowel disease (IBD). In the last few decades, gastrointestinal (GI) endoscopy has undergone significant technological developments including availability of pediatric-size equipment, enabling comprehensive investigation of the GI tract in children. Simultaneously, professional organization of GI experts have developed guidelines and training programs in pediatric GI endoscopy. This prompted the Porto Group on Pediatric IBD of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition to develop updated guidelines on the role of GI endoscopy in pediatric IBD, specifically taking into considerations of recent advances in the diagnosis, disease stratification, and novel therapeutic targets in these patients.

Therapeutic Upper Gastrointestinal Endoscopy in Pediatric Gastroenterology.

This paper seeks to give a broad overview of pediatric upper gastrointestinal (GI) pathologies that we are now able to treat endoscopically, acquired or congenital, and we hope this delivers the reader an impression of what is increasingly available to pediatric endoscopists and their patients.

Genes implicated in thiopurine-induced toxicity: Comparing TPMT enzyme activity with clinical phenotype and exome data in a paediatric IBD cohort.

The aim of our study was to assess the utility of next generation sequencing (NGS) for predicting toxicity and clinical response to thiopurine drugs in paediatric patients with inflammatory bowel disease. Exome data for 100 patients were assessed against biochemically measured TPMT enzyme activity, clinical response and adverse effects. The TPMT gene and a panel of 15 other genes implicated in thiopurine toxicity were analysed using a gene based statistical test (SKAT-O test). Nine patients out of 100 (Crohn's disease- 67, ulcerative colitis- 23 and IBDU-10) had known TPMT mutations associated with deficient enzyme activity. A novel and a highly pathogenic TPMT variant not detectable through standard genotyping, was identified through NGS in an individual intolerant to thiopurines. Of the 14 patients intolerant to thiopurines, NGS identified deleterious TPMT variants in 5 individuals whereas the biochemical test identified 8 individuals as intolerant (sensitivity 35.7% and 57.14%; specificity 93.75% and 50% respectively). SKAT-O test identified a significant association between MOCOS gene and TPMT activity (p = 0.0015), not previously reported. Although NGS has the ability to detect rare or novel variants not otherwise identified through standard genotyping, it demonstrates no clear advantage over the biochemical test in predicting toxicity in our modest cohort.

pANCA and ASCA in Children with IBD-Unclassified, Crohn's Colitis, and Ulcerative Colitis-A Longitudinal Report from the IBD Porto Group of ESPGHAN.

INTRODUCTION: No study to date has evaluated perinuclear antineutrophil cytoplasmic antibody (pANCA) and anti-Saccharomyces cerevisiae antibody (ASCA) in pediatric inflammatory bowel disease-unclassified (IBDU) as compared with Crohn's colitis (CC) and ulcerative colitis (UC), which represent the diagnostic challenge. We aimed to explore the diagnostic utility of serology and to assess whether serology can predict disease severity in these subgroups. METHODS: This was a multicenter retrospective longitudinal study including 406 children with inflammatory bowel diseases (IBD) from 23 centers affiliated with the Porto group of European Society of Pediatric Gastroenterology, Hepatology and Nutrition (mean age 10.5 ± 3.9, 54% males); 117 (29%) with CC, 143 (35%) with UC, and 146 (36%) with IBDU. Median follow-up period was 2.8 years (interquartile range, 1.6-4.2). RESULTS: The most prevalent serologic profile in IBDU was pANCA-/ASCA- (41%), followed by pANCA+/ASCA- (34%) and pANCA-/ASCA+ (17%). pANCA-/ASCA+ differentiated well between CC versus IBDU (83% specificity, 96% positive predictive value [PPV]) and UC (97% specificity, 90% PPV) patients, albeit with a low negative predictive value (13% and 40%, respectively). pANCA+/ASCA- did not differentiate as well between IBD subgroups, but UC children with pANCA+/ASCA- had more often severe disease at diagnosis (36 [62%] versus 22 [38%], P = 0.033) and needed more often calcineurin inhibitors, biologics, or colectomy (25 [80%] versus 6 [20%], P = 0.026). In CC, double positivity for ASCA and not pANCA-/ASCA+ profile was associated with disease severity. CONCLUSIONS: Serology may have some role in predicting disease course and outcomes in colonic IBD, but its routine use needs to be supported by more studies. Serology cannot routinely be recommended for differentiating between IBDU versus CC or UC as a sole diagnostic criterion given its low diagnostic utility.

The role of magnetic assisted capsule endoscopy (MACE) to aid visualisation in the upper GI tract.

Examination of the upper gastrointestinal tract by a standard endoscope is often thought as a daunting experience to many who have undertaken or are about to undergo the procedure. The overall perceived size of the gastroscope, unpleasantness of stimulation of the gag reflex and the need often for sedation is discouraging to many. A method to visualise the upper gastrointestinal mucosa which negates the need for sedation, the associated expensive decontamination costs and the possibility of having a community based examination would be particularly welcoming to this endoscopy field. Since the first swallow of a capsule endoscope by a human volunteer in 1999, their usage for examining the small bowel has exponentially grown to that of over a million patients worldwide. More recently, innovation in this field have shown plausibility for its use to visualise the upper gastrointestinal tract, with the integration of magnets within the capsule the most promising method.

Utilisation of magnets to enhance gastrointestinal endoscopy.

Methods to assess, access and treat pathology within the gastrointestinal tract continue to evolve with video endoscopy replacing radiology as the gold standard. Whilst endoscope technology develops further with the advent of newer higher resolution chips, an array of adjuncts has been developed to enhance endoscopy in other ways; most notable is the use of magnets. Magnets are utilised in many areas, ranging from endoscopic training, lesion resection, aiding manoeuvrability of capsule endoscopes, to assisting in easy placement of tubes for nutritional feeding. Some of these are still at an experimental stage, whilst others are being increasingly incorporated in our everyday practice.

Therapeutic upper gastrointestinal tract endoscopy in Paediatric Gastroenterology.

Since the first report of use of endoscopy in children in the 1970s, there has seen an exponential growth in published experience and innovation in the field. In this review article we focus on modern age therapeutic endoscopy practice, explaining use of traditional as well as new and innovative techniques, for diagnosis and treatment of diseases in the paediatric upper gastrointestinal tract.

Parental knowledge of coeliac disease.

AIM: Little information exists regarding parental knowledge of CD at diagnosis. We aimed for assessment of parental information at disease diagnosis to help us develop a tailored coeliac information package. METHODS: Children and teenagers referred for endoscopy and duodenal biopsy, with the sole indication for the diagnosis of CD, were prospectively recruited to the study. Parents were asked information and concerns regarding use of GFD. RESULTS: Sixty-three children (median 6.9 yrs (IQR 3.71-10.94)) and families were prospectively recruited in the study. The parents were very knowledgeable with an impressive 98% of the parents understanding that GFD is the treatment of CD; 95% knowing that this treatment is for life. However, specific dietary information was lacking with one-third correctly identifying all the Gluten containing foods. Internet (70.6%) was the most common source of information. Knowing someone with CD (p = 0.038), particularly in the same household in the family (p = 0.013) and researching about the disease (p = 0.001) rather than level of parental education (p = ns) was predictive of better parental knowledge. CONCLUSION: Internet is a major influence to parental knowledge in today's age but there is a continued need for hospitals regarding provision of accurate information and alleviating anxieties regarding use of GFD.

Diverticular disease in adolescence.

Diverticular disease is rare in the adolescent. Acute diverticulitis is almost never considered as a diagnosis for a young patient presenting with abdominal pain. Unfortunately, unrecognized it may be associated with significant morbidity and mortality. Also, when present, diverticulitis in the young adult is considered to be more aggressive compared to diverticulitis in older adults. Therefore, it is important to recognize, diagnose and manage diverticular disease appropriately in this age group. In tis chapter we will review the available literature on diverticula disease in the adolescent and young adult, discuss epidemiology, aetiology and pathogenesis and suggest guidelines for diagnosis and management.

A very high amylase can be benign in paediatric Crohn's disease.

A 12.5-year-old boy with Crohn's disease with abdominal pain had a raised amylase of 1835 IU/l with normal lipase levels. Ultrasound showed no evidence of inflammation of pancreas. The amylase to creatinine clearance ratio, was 0.8% (reference interval 2%-5%; >6% consistent with acute pancreatitis; <1.6% with macroamylasemia), suggesting he had raised serum amylase with a corresponding reduced clearance of amylase in his urine, positively supporting the diagnosis of macroamylasemia. Macroamylasemia has no clinical significance other than misdiagnosis as acute pancreatitis. Awareness of this condition is important and a positive diagnosis should always be made to avoid unnecessary changes in treatments.