Time to grow up: readiness associated with improved clinical outcomes in pediatric inflammatory bowel disease patients undergoing transition.

Background: The transition from pediatric to adult healthcare in individuals with inflammatory bowel disease (IBD) poses significant challenges mainly due to the high burden of IBD during adolescence, a critical period of psychosocial development. So far, there are few longitudinal data linking transition readiness to long-term disease outcomes. Objective: We aimed to assess patients' readiness to transition and its impact on clinical outcomes, quality of life, and adherence to therapy. Design: An observational, prospective study was conducted in a tertiary adult and pediatric center, including adolescents aged ⩾17 years with a diagnosis of IBD, who underwent a 'structured transition' program including two joint adult-pediatric visits. Methods: Transition readiness skills were assessed with the Transition Readiness Assessment Questionnaire (TRAQ). All patients completed the TRAQ at the time of recruitment, which occurred during the initial joint adult-pediatric visit, to determine those deemed ready for transition versus those not ready. The Morisky Medication Adherence Scale and the 36-Item Short Form Health Survey Questionnaire (SF-36) were also completed at baseline and after 12 months. Clinical outcomes were collected at the 12-month follow-up. Results: In all, 80 patients were enrolled who had transitioned through a structured transition clinic and completed 12 months of follow-up. In total, 54 patients were ready for the transition, with a mean TRAQ = 3.2 ± 0.5. The number of clinical relapses and hospitalizations at 12 months was lower in ready compared to not-ready patients (p = 0.004 and p = 0.04, respectively). SF-36 did not differ between ready and not-ready patients and pre- and post-transition clinics (p > 0.05). Based on the receiver operating characteristic curve, a TRAQ cutoff ⩾3.16 could predict medication adherence with a sensibility of 77%, a specificity of 82%, and an AUC of 0.81 (0.71-0.91; p < 0.001). Conclusion: Patients ready for transition had better outcomes at 12 months compared to those who were not ready. Therefore, readiness assessment tools should be integrated into transition management to ensure that interventions are targeted, patient-centered, and responsive to individuals' changing needs.

Transition readiness associated with improved clinical outcomes The transition for individuals with inflammatory bowel disease (IBD) is a dynamic and complex process that must be planned and cannot simply be performed once the patient is 18 years old. Since it does not depend solely on the patient's age but also on developmental readiness, it requires preparation and education starting from early adolescence. In the current study, a 'joint-visit' including both pediatric and adult providers yields positive clinical outcomes over 12 months. Patients ready for transition reported fewer relapses, hospitalizations, and improved therapy adherence compared to those not ready. Readiness assessment tools should be integrated into transition clinics to facilitate targeted interventions for IBD patients based on the changing needs of individuals.

Patient-derived organoid biobank identifies epigenetic dysregulation of intestinal epithelial MHC-I as a novel mechanism in severe Crohn's Disease.

OBJECTIVE: Epigenetic mechanisms, including DNA methylation (DNAm), have been proposed to play a key role in Crohn's disease (CD) pathogenesis. However, the specific cell types and pathways affected as well as their potential impact on disease phenotype and outcome remain unknown. We set out to investigate the role of intestinal epithelial DNAm in CD pathogenesis. DESIGN: We generated 312 intestinal epithelial organoids (IEOs) from mucosal biopsies of 168 patients with CD (n=72), UC (n=23) and healthy controls (n=73). We performed genome-wide molecular profiling including DNAm, bulk as well as single-cell RNA sequencing. Organoids were subjected to gene editing and the functional consequences of DNAm changes evaluated using an organoid-lymphocyte coculture and a nucleotide-binding oligomerisation domain, leucine-rich repeat and CARD domain containing 5 (NLRC5) dextran sulphate sodium (DSS) colitis knock-out mouse model. RESULTS: We identified highly stable, CD-associated loss of DNAm at major histocompatibility complex (MHC) class 1 loci including NLRC5 and cognate gene upregulation. Single-cell RNA sequencing of primary mucosal tissue and IEOs confirmed the role of NLRC5 as transcriptional transactivator in the intestinal epithelium. Increased mucosal MHC-I and NLRC5 expression in adult and paediatric patients with CD was validated in additional cohorts and the functional role of MHC-I highlighted by demonstrating a relative protection from DSS-mediated mucosal inflammation in NLRC5-deficient mice. MHC-I DNAm in IEOs showed a significant correlation with CD disease phenotype and outcomes. Application of machine learning approaches enabled the development of a disease prognostic epigenetic molecular signature. CONCLUSIONS: Our study has identified epigenetically regulated intestinal epithelial MHC-I as a novel mechanism in CD pathogenesis.

Helicobacter pylori infection found during upper endoscopy performed for the diagnosis of celiac, inflammatory bowel diseases, and eosinophilic esophagitis: A multicenter pediatric European study.

BACKGROUND: Helicobacter pylori may be found during upper gastrointestinal endoscopy (UGE) performed to diagnose celiac disease (CeD), inflammatory bowel disease (IBD), and eosinophilic esophagitis (EoE). We aimed to describe the frequency of H. pylori in children undergoing UGE for CeD, IBD, and EoE and the number of children receiving eradication treatment. MATERIALS AND METHODS: A retrospective multicenter study from 14 countries included pediatric patients diagnosed with CeD, IBD, and EoE between January 2019 and December 2021. DATA COLLECTED: age, gender, hematologic parameters, endoscopic, histologic, and H. pylori culture results, and information on eradication treatment. RESULTS: H. pylori was identified in 349/3890 (9%) children [167 (48%) male, median 12 years (interquartile range 8.1-14.6)]. H. pylori was present in 10% (173/1733) CeD, 8.5% (110/1292) IBD and 7.6% (66/865) EoE patients (p = NS). The prevalence differed significantly between Europe (Eastern 5.2% (28/536), Southern 3.8% (78/2032), Western 5.6% (28/513)) and the Middle East 26.6% (215/809) [odds ratio (OR) 7.96 95% confidence interval (CI) (6.31-10.1) p < 0.0001]. Eradication treatment was prescribed in 131/349 (37.5%) patients, 34.6% CeD, 35.8% IBD, and 56.1% EoE. Predictors for recommending treatment included erosions/ulcers [OR 6.45 95% CI 3.62-11.47, p < 0.0001] and nodular gastritis [OR 2.25 95% CI 1.33-3.81, p 0.003]. Treatment rates were higher in centers with a low H. pylori prevalence (<20%) [OR 3.36 95% CI 1.47-7.66 p 0.004]. CONCLUSIONS: Identifying H. pylori incidentally during UGE performed for the most common gastrointestinal diseases varies significantly among regions but not among diseases. The indications for recommending treatment are not well defined, and less than 40% of children received treatment.

The ten "hard" questions in pediatric functional constipation.

Functional constipation is a common problem in childhood and has a great impact on social, physical, and emotional functioning of affected children and their caregivers. No organic cause of the constipation can be found in approximately 95% of children, defining the "so-called" chronic functional constipation. Its prevalence has been reported to range from 0.7 to 29.6%, with a median of 12%. The diagnosis of functional constipation is exclusively clinical based on the pediatric diagnostic Rome criteria for functional gastrointestinal disorders and does not routinely require laboratory and/or radiological investigations. In case of alarm signs and symptoms that may suggest organic diseases, further investigations can be required. The therapeutic management is based on non-pharmacological and pharmacological approaches. Education, demystification of constipation and reward-based toilet training represent the cornerstones of nonpharmacological management. Disimpaction, maintenance treatment and weaning of medication are all elements of pharmacological treatment. Osmotic laxatives, mainly polyethylene glycol (PEG), are considered the first-choice laxative for both disimpaction and maintenance treatment. The aim of this review is to provide pediatric gastroenterologists with a practical tool to support the clinical and therapeutic management of children and adolescents affected by chronic functional constipation.

Diagnosis and management of anemia in pediatric inflammatory bowel diseases: Clinical practice guidelines on behalf of the SIGENP IBD Working group.

Anemia is one of the most frequent extra-intestinal manifestations of inflammatory bowel disease. Insidious onset, variability of symptoms and lack of standardized screening practices may increase the risk of underestimating its burden in children with IBD. Despite its relevance and peculiarity in everyday clinical practice, this topic is only dealt with in a few documents specifically for the pediatric field. The aim of the current guidelines is therefore to provide pediatric gastroenterologists with a practical update to support the clinical and therapeutic management of children with IBD and anemia. A panel of 19 pediatric gastroenterologists and 1 pediatric hematologist with experience in the field of pediatric IBD was agreed by IBD Working group of the Italian Society of Gastroenterology, Hepatology and Nutrition (SIGENP) to produce the present article outlining practical clinical approaches to the pediatric patient with IBD and anemia. The levels of evidence and recommendations have been defined for each part of the statement according to the GRADE system.

Major Abdominal Surgery for Pediatric Crohn's Disease in the Anti-TNF Era: 10-Year Analysis of Data From the IBD Registry of Italian Society of Pediatric Gastroenterology, Hepatology, and Nutrition.

BACKGROUND: The natural history of Crohn's disease (CD) can result in complications requiring surgery. Pediatric data are scarce about major abdominal surgery. The IBD Registry from the Italian Society of Pediatric Gastroenterology, Hepatology, and Nutrition has been active since 2008 and collects data from major pediatric IBD centers in Italy. The aim of the present report was to explore the prevalence of major abdominal surgery among children affected by CD in an era when antitumor necrosis factor (anti-TNF-α) agents were already used so that we might appraise the incidence of surgical-related complications and identify the factors associated with postoperative disease recurrence. METHODS: We retrospectively analyzed data from patients enrolled in the registry from January 2009 to December 2018. Patients with monogenic IBD and patients undergoing surgery for perianal disease were excluded. RESULTS: In total, 135 of 1245 patients were identified. We report the prevalence of major abdominal surgery of 10.8%. Pediatric surgeons performed the procedure in 54.1% of cases, and a laparoscopic approach was used in 47.4% of surgical procedures. Seventeen patients (12.6%) experienced a total of 21 early postoperative complications, none of which was severe. A laparoscopic approach was the only factor negatively associated with the occurrence of postoperative complications (odds ratio, 0.22; 95% confidence interval, 0.06-0.8; P = .02). Fifty-four (40%) patients experienced postoperative endoscopic recurrence, and 33 (24.4%) of them experienced postoperative clinical recurrence. The postoperative treatment with anti-TNF-α drugs was significantly associated with a reduced risk of endoscopic recurrence (odds ratio, 0.19; 95% confidence interval, 0.05-0.79; P = .02). CONCLUSION: In our cohort, the overall prevalence of major abdominal surgery was low, as well as the rate of surgical-related complications. Postoperative anti-TNF-α therapy seems be protective against endoscopic recurrence.

Data from the IBD SIGENP registry show that the prevalence of major abdominal surgery is 10.8%, with a relatively low occurrence of short-term postoperative complications. The administration of anti-TNF-α drugs after surgery seems to effectively prevent postoperative endoscopic recurrence of disease.

Disease course of ulcerative proctitis in children: A population-based study on behalf of the SIGENP IBD Group.

BACKGROUND: The natural history of ulcerative proctitis (UP) has been poorly investigated in children. AIMS: We aimed to compare the disease course of children with UP at diagnosis to the other locations and to identify extension predictors. METHODS: This was a multicenter, observational study carried out from data prospectively entered in the SIGENP-IBD-Registry. Children with ulcerative colitis (UC) diagnosis and at least 1-year follow-up were included. On the basis of Paris classification UP patients were identified and compared with the other locations. RESULTS: 872 children were enrolled (median age at diagnosis: 11.2 years; M/F: 426/446), of whom 78 (9%) with UP. Kaplan-Meier analysis demonstrated increased cumulative probabilities of disease extension in the E1 group [1 year: 20.3%; 5 years: 52.7%; 10 years: 72.4%] compared to E3 group [1 year: 8.5%; 5 years: 24.9% and 10 years: 60.1%, p=0.001]. No differences were observed comparing E1 and E2 groups [p=0.4]. Cumulative probabilities of surgery at 1, 5 and 10 years were 1.3, 2.8 and 2.8% in the E1 group and 2.5, 8 and 12.8% in the E2-E3-E4 group, respectively (p=0.1). Cox regression analysis demonstrated that PUCAI>35 at diagnosis was associated with endoscopic extension (HR=4.9; CI 95% 1.5-15.2, p=0.006). CONCLUSIONS: UP is associated with similar short and long-term outcomes compared to other locations.

How dietary advanced glycation end products could facilitate the occurrence of food allergy.

BACKGROUND: Food allergy (FA) is one of the most common chronic conditions in children with an increasing prevalence facilitated by the exposure to environmental factors in predisposed individuals. It has been hypothesized that the increased consumption of ultra-processed foods, containing high levels of dietary advanced glycation end products (AGEs), could facilitate the occurrence of FA. OBJECTIVE: We sought to provide preclinical and clinical evidence on the potential role of AGEs in facilitating the occurrence of FA. METHODS: Human enterocytes, human small intestine organ culture, and PBMCs from children at risk for allergy were used to investigate the direct effect of AGEs on gut barrier, inflammation, TH2 cytokine response, and mitochondrial function. Intake of the 3 most common glycation products in Western diet foods, Nε-(carboxymethyl) lysine, Nε-(1-carboxyethyl) lysin, and Nδ-(5-hydro-5- methyl-4-imidazolone-2-yl)-ornithine (MG-H1), and the accumulation of AGEs in the skin were comparatively investigated in children with FA and in age-matched healthy controls. RESULTS: Human enterocytes exposed to AGEs showed alteration in gut barrier, AGE receptor expression, reactive oxygen species production, and autophagy, with increased transepithelial passage of food antigens. Small intestine organ cultures exposed to AGEs showed an increase of CD25+ cells and proliferating crypt enterocytes. PBMCs exposed to AGEs showed alteration in proliferation rate, AGE receptor activation, release of inflammatory and TH2 cytokines, and mitochondrial metabolism. Significant higher dietary AGE intake and skin accumulation were observed children with FA (n = 42) compared with age-matched healthy controls (n = 66). CONCLUSIONS: These data, supporting a potential role for dietary AGEs in facilitating the occurrence of FA, suggest the importance of limiting exposure to AGEs children as a potential preventive strategy against this common condition.

Infliximab therapy decreases the expression of serum and faecal miR-126 and miR-20a in paediatric Crohn's disease: A pilot study.

AIM: We aimed to evaluate the serum and faecal expression of miR-126 and miR-20a in children with Crohn's disease (CD) during infliximab (IFX) therapy. METHODS: In this prospective observational study, serum and faeces from CD patients were collected before IFX therapy (T0), after induction (T1) and after 6 months from IFX (T2). IFX levels were determined by Enzyme-linked immunosorbent assay at T1 and T2. miRNAs were profiled through Real-Time RT-PCR. The activity of disease was evaluated through the Paediatric Crohn's disease activity index (PCDAI), serum C-reactive protein (CRP) and faecal calprotectin. RESULTS: Nine CD children were enrolled. Serum and faecal miR-126 and miR-20a levels were higher at T0 and showed a time-dependent decrease, being significantly down-regulated after IFX treatment at T2. Specifically, IFX levels recorded at T1 and T2 negatively correlated with the serum and faecal expression of miR-126 and miR-20a. Serum and faecal changes of miR-126 and miR20-a were positively associated with the decrease of the inflammatory marker CRP and PDCAI at all time points. CONCLUSION: In children with CD, IFX therapy decreases the expression of serum and faecal miR-126 and miR-20a, suggesting an involvement of these two miRNAs in the action of the drug.

Clusters of Disease Activity and Early Risk Factors of Clinical Course of Pediatric Crohn's Disease.

BACKGROUND: This study aimed to define clusters of disease activity and prognostic factors of disease course in a well-characterized cohort of children with Crohn's disease (CD). METHODS: All patients from the SIGENP IBD (Italian Society of Pediatric Gastroenterology Hepatology and Nutrition Inflammatory Bowel Disease) registry with a 5-year follow-up and 6-monthly evaluation were included. Active disease was defined for each semester as follows: clinical activity (weighted Pediatric Crohn's Disease Activity Index ≥12.5 or Mucosal Inflammation Noninvasive Index ≥8) and active disease on endoscopy (Simple Endoscopic Score for Crohn's Disease >3 or fecal calprotectin >250 µg/g) or imaging. Formula-based clusters were generated based on previously published patterns in adults. RESULTS: Data from 332 patients were analyzed. A total of 105 (32%) experienced a quiescent disease course; 49 (15%) and 31 (9%) a moderate-to-severe chronically active and chronic intermittent disease, respectively; 104 (31%) and 43 (13%) had active disease in the first 2 years after diagnosis and remission thereafter and vice versa, respectively. Surgery at diagnosis was significantly associated with a quiescent course (odds ratio [OR], 10.05; 95% confidence interval [CI], 3.05-25.22; P=.0005), while growth impairment at the diagnosis and active disease requiring corticosteroids at 6 months were inversely related to the quiescent group (OR, 0.48; 95% CI, 0.27-0.81; P= .007; and OR, 0.35; 95% CI, 0.16-0.71; P= .005, respectively). Perianal involvement at diagnosis and moderate-severe activity at 6 months correlated with disease progression (OR, 3.85; 95% CI, 1.20-12.85; P=.02). CONCLUSIONS: During the first 5 years of follow-up, one-third of children with CD experience a quiescent course. However, another one-third have a moderate-to-severe disease course. Surgery at the diagnosis is related to a quiescent course, while growth impairment and lack of response to induction therapy correlate with more severe disease activity during follow-up.

We aimed to define clusters of disease activity and prognostic factors of disease course in pediatric Crohn's disease. One-third of patients have a quiescent course; however, half of them have an active disease by the end of the 5-year follow-up.

De Novo Crohn's Disease in Children With Ulcerative Colitis Undergoing Ileal Pouch-Anal Anastomosis: A Multicenter, Retrospective Study From the Pediatric IBD Porto Group of the ESPGHAN.

BACKGROUND AND AIMS: We sought to define the prevalence and to characterize possible predictive factors of Crohn's disease (CD) occurring in children with ulcerative colitis (UC) after ileal pouch-anal anastomosis (IPAA). METHODS: This was a multicenter, retrospective study including 15 centers of the Porto IBD group of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition. Children with a confirmed diagnosis of UC undergoing colectomy with IPAA and a minimal follow up of 6 months were identified. The following data were collected: demographic data; endoscopic and histologic data; disease activity; laboratory exams; therapeutic history; indication for surgery, type, and timing; and IPAA functional outcomes and complications. In de novo CD cases, time of diagnosis, phenotype, location, and therapies were gathered. RESULTS: We identified 111 UC children undergoing IPAA from January 2008 to June 2018 (median age at colectomy: 13 years; age range: 1-18 years; female/male: 59/52). The median time from diagnosis to colectomy was 16 (range, 0-202) months. At the last follow-up, 40 (36%) of 111 children developed pouchitis. The criteria for de novo CD were met in 19(17.1%) of 111 children with a 25-month median (range, 3-61 months). At last follow-up, 12 (63.1%) of 19 were treated with biologics and in 5 (26.3%) of 19 children, the pouch was replaced with definitive ileostomy. In a multivariable logistic regression model, decreased preoperative body mass index z scores (odds ratio, 2.2; 95% confidence interval, 1.1-4.4; P = .01) resulted as the only variable associated with CD development. CONCLUSIONS: Children with UC undergoing IPAA carry a high risk of developing subsequent CD. De novo CD cases showed decreased preoperative body mass index z scores, identifying a poor nutritional status as a possible predictive factor.

This is the largest European study describing the prevalence of Crohn's disease (CD) development in children with ulcerative colitis undergoing subtotal colectomy with ileal pouch­anal anastomosis. Children affected by ulcerative colitis carry a higher risk when compared with adults to develop de novo CD after surgery. On the other hand, the multivariate analysis identified decreased values of preoperative body mass index z scores as a possible predictor of new-onset CD.

Clinical Features and Natural History of Paediatric Patients with Ulcerative Proctitis: A Multicentre Study from the Paediatric IBD Porto Group of ESPGHAN.

BACKGROUND AND AIMS: Ulcerative proctitis [UP] is an uncommon presentation in paediatric patients with ulcerative colitis. We aimed to characterize the clinical features and natural history of UP in children, and to identify predictors of poor outcomes. METHODS: This was a retrospective study involving 37 sites affiliated with the IBD Porto Group of ESPGHAN. Data were collected from patients aged <18 years diagnosed with UP between January 1, 2016 and December 31, 2020. RESULTS: We identified 196 patients with UP (median age at diagnosis 14.6 years [interquartile range, IQR 12.5-16.0]), with a median follow-up of 2.7 years [IQR 1.7-3.8]. The most common presenting symptoms were bloody stools [95%], abdominal pain [61%] and diarrhoea [47%]. At diagnosis, the median paediatric ulcerative colitis activity index [PUCAI] score was 25 [IQR 20-35], but most patients exhibited moderate-severe endoscopic inflammation. By the end of induction, 5-aminosalicylic acid administration orally, topically or both resulted in clinical remission rates of 48%, 48%, and 73%, respectively. The rates of treatment escalation to biologics at 1, 3, and 5 years were 10%, 22%, and 43%, respectively. In multivariate analysis, the PUCAI score at diagnosis was significantly associated with initiation of systemic steroids, or biologics, and subsequent acute severe colitis events and inflammatory bowel disease-associated admission, with a score ≥35 providing an increased risk for poor outcomes. By the end of follow-up, 3.1% of patients underwent colectomy. Patients with UP that experienced proximal disease progression during follow-up [48%] had significantly higher rates of a caecal patch at diagnosis and higher PUCAI score by the end of induction, compared to those without progression. CONCLUSION: Paediatric patients with UP exhibit high rates of treatment escalation and proximal disease extension.

Prevalence of functional gastrointestinal disorders in Italian children living in different regions: analysis of the difference and the role of diet.

BACKGROUND: Functional Gastrointestinal Disorders (FGIDs) are common in pediatric age. AIMS: To estimate the prevalence of FGIDs in Italian children and evaluate the impact of diet. METHODS: Healthy children aged 4-18 years were recruited in a multicenter cross-sectional study. We evaluated their eating habits and the presence of FGIDs, using Rome IV criteria, 3-day food diaries and Mediterranean Diet Quality Index (KIDMED) questionnaires. RESULTS: Seven hundred forty subjects were enrolled:369 children aged 4-9 years (Group A), and 371 adolescents 10-18 years old (Group B). The overall prevalence of FGIDs was 26.4% in Group A and 26.2% in Group B, with a significant higher prevalence in females in both groups. The most frequent disorders were functional constipation, functional dyspepsia, and abdominal migraine. No significant difference in FGIDs prevalence was found between Northern and Southern Italy, despite significant variation in diet. In Group A there was a significant difference in KIDMED between North and South (5.3 ± 1 vs 6 ± 1.2, respectively; p = 0.001). A significant association between FGIDs and KIDMED was found in Group A (OR=0.83, p = 0.034), but not in Group B (OR=0.89, p = 0.166). CONCLUSIONS: FGIDs are common in Italian children, with a higher prevalence in females. Despite significant differences in dietary habits between North and South, FGIDs prevalence does not vary significantly.

Drugs in Focus: Domperidone.

Domperidone is a peripheral dopamine-2 receptor antagonist with prokinetic and antiemetic properties. Its prokinetic effects are mainly manifest in the upper gastrointestinal (GI) tract. Currently its use is restricted to relief of nausea and vomiting in children older than 12 years for a short period of time. However, among (pediatric) gastroenterologists, domperidone is also used outside its authorized indication ("off label") for treatment of symptoms associated with gastro-esophageal reflux disease, dyspepsia, and gastroparesis. Little is known about its efficacy in the treatment of GI motility disorders in children and controversial data have emerged in the pediatric literature. As its use is off label, appropriate knowledge of its efficacy is helpful to support an "off label/on evidence" prescription. Based on this, the purpose of this review is to summarize all evidence on the efficacy of domperidone for the treatment of GI disorders in infants and children and to report an overview of its pharmacological properties and safety profile.

Pediatric Magnet Ingestion, Diagnosis, Management, and Prevention: A European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) Position Paper.

Magnet ingestion is a special category of foreign body ingestion associated with high levels of morbidity and mortality worldwide, particularly if it is associated with staggered ingestion of multiple magnets or with simultaneous ingestion of other metallic foreign bodies, especially button batteries. A special category of magnet ingestion is the ingestion of earth magnets, which have higher levels of magnetism and therefore, potentially, carries a worse outcome. Legislative bodies, scientific Societies and community-led initiatives have been implemented worldwide with the aim of mitigating the effects of this growing, yet avoidable potential medical emergency. A scoping literature review summarized epidemiology, diagnosis, management, and prevention, including an algorithm for the diagnosis and management of magnet ingestion is presented and compared to previously published reviews and position papers (North American Society of Pediatric Gastroenterology, Hepatology and Nutrition, National Poison Center, Royal College of Emergency Medicine). The main emphasis of the algorithm is on identification of staggered/multiple magnet ingestion, and early joint gastroenterology and surgical consultation and management.

The use of calgranulin-C (S100A12) and fecal zonulin as possible non-invasive markers in children with inflammatory bowel disease: a clinical study.

Calgranulin-C (S100A12) and zonulin are considered markers of intestinal inflammation. Our aim was to evaluate fecal S100A12 (f-S100A12) and fecal zonulin (f-zonulin) in children with inflammatory bowel disease (IBD), compared to fecal calprotectin (FC) and serum inflammatory markers. We enrolled children with a previous diagnosis of Crohn's disease (CD) and ulcerative colitis (UC). F-S100A12, f-zonulin, and FC were determined by enzyme-linked immunosorbent assay (ELISA). Endoscopic examination was considered in the patients who underwent ileocolonoscopy within 2 weeks from the enrollment. One hundred seventeen children, 39.3% with CD and 60.7% with UC were enrolled. In both CD and UC, there was a significant direct correlation between FC and f-S100A12 levels. In children with CD and UC, both FC and f-S100A12 correlated with markers of serum inflammation. We found difference in FC and f-S100A12 levels between patients in clinical relapse and remission (FC: mean 1027 ± 818 mcg/ml vs 580 ± 695 mcg/ml respectively, p = 0.028; f-S100A12: mean 66.4 ± 48.2 mcg/ml vs 42.7 ± 40 mcg/ml, respectively p = 0.02). Moreover, we found difference in FC between children with endoscopic inflammation and remission (mean 825 ± 779 mcg/ml vs 473.3 ± 492 mcg/ml, respectively p = 0.048), as well as for f-S100A12 (53 ± 43 mcg/ml vs mean 31 ± 33 mcg/ml vs, respectively p = 0.019). No significant results were found for f-zonulin. CONCLUSION: Our data suggest that f-S100A12 and FC are both useful non-invasive biomarkers in the management of pediatric IBD in follow up and in monitoring endoscopic and clinical relapse. WHAT IS KNOWN: • Fecal calprotectin (FC), fecal S100A12 (f- S100A12), and fecal zonulin represent potential noninvasive markers of gut inflammation. • Since S100A12 is predominantly expressed by granulocytes, high levels of f-S100A12 should be more specific for inflammation than FC. WHAT IS NEW: • FC and f-S100A12 were correlated to each other and despite the lack of correlation with disease location, they were associated with endoscopic inflammation and clinical relapse in children with IBD. • No significant correlations were found between f-zonulin and the inflammatory parameters.

Increased expression of CB2 receptor in the intestinal biopsies of children with inflammatory bowel disease.

OBJECTIVES: The Cannabinoid Receptor type 2 (CB2) is involved in inflammation and immune cell modulation. In previous studies, we demonstrated the association between the CNR2 rs35761398 polymorphism and the risk for pediatric inflammatory bowel disease (IBD). In this study, we analyzed the intestinal biopsies from Crohn disease (CD) and ulcerative colitis (UC) pediatric patients at the diagnosis to evaluate the expression of CB2 and several factors associated with IBD inflammatory pathways. METHODS: We enrolled five patients with CD, five with UC, and five controls (CTR). We analyzed ileum and rectum biopsies from patients of each group evaluating the expression of CB2, Toll-like receptor 4, interleukin-6, and interleukin-1ß by western blot and immunofluorescence. RESULTS: Western blot analysis showed a significant increase of CB2 in the CD ileum and in the UC rectum biopsies and an increase of TLR4 in the UC rectum. We also observed a significant over-expression of the IL-6 in UC rectum. The immunofluorescence analysis confirmed western blot data, showing also a T-lymphocytes infiltration colocalized with CB2 expression in the CD ileum and UC rectum. CONCLUSIONS: Our results show an upregulation of CB2 in pediatric IBD, which might have implications for drug discovery. IMPACT: The Cannabinoid Receptor type 2 (CB2) is involved in the inflammation and modulation of the immune response in pediatric inflammatory bowel disease (IBD). CB2 receptor is more expressed in the inflamed intestine of pediatric IBD patients. CB2 could be used as a potential therapeutic target to reduce IBD-related inflammatory state in childhood.

Hypnotherapy in Pediatric Gastroenterology.

In several countries, gut-directed hypnotherapy is becoming an established and evidence-based treatment in pediatric gastroenterology. This article describes what hypnotherapy is, offers an overview of its effect in gut-brain disorders and explains its potential mode of action. Moreover, the use of hypnotherapy in other areas of pediatric gastroenterology, as a supportive tool to reduce pain, stress, depression, and anxiety and improve quality of life, will be also discussed. Guidance toward implementing hypnotherapy in clinical practice is provided, including examples of how you can explain hypnosis to patients with gastroenterological symptoms.