Associations of Eosinophilic Gastrointestinal Disorders with Other Gastrointestinal and Allergic Diseases.

Eosinophilic gastrointestinal disorders (EGIDs) are becoming more common causing significant suffering and reduced quality of life. These conditions can affect different parts of the digestive system, either individually or in combination. Recognition of their link to allergic disorders or other gastrointestinal (GI) diseases has raised questions about their shared underlying mechanisms, which has had implications for diagnosis and management. The authors critically examine the current understanding of the connection between EGIDs and allergic conditions (ie, atopic dermatitis, allergic rhinitis, asthma, and food allergy) and GI diseases (ie, inflammatory bowel disease, celiac disease, gastroesophageal reflux disease, and motility disorders).

Efficacy and safety of a new low-volume PEG with citrate and simethicone bowel preparation for pediatric elective colonoscopy: Phase 3 RCT.

Background and study aims Currently available polyethylene glycol (PEG)-based preparations continue to represent a challenge in children. The aim of this study was to compare the efficacy and safety of a new low-volume PEG preparation with a conventional PEG-electrolyte solution (PEG-ES) in children and adolescents. Patients and methods This was a multicenter, randomized, observer-blind, parallel-group, phase 3 clinical trial, where patients were randomized between PMF104 (Clensia) and a conventional PEG-ES (Klean-Prep), and stratified by age stratum (2 to <6; 6 to < 12;12 to <18 years). The primary endpoint was to test the non-inferiority of PMF104 versus PEG-ES, in terms of colon cleansing. Safety, tolerability, acceptability, palatability, and compliance were also assessed. Efficacy endpoints were analyzed in the per protocol set (PPS) and full analysis set (FAS) and safety and tolerability endpoints in the safety set (SAF). Results Of the 356 patients enrolled, 258 were included in the PPS, 346 in the FAS, and 351 in the SAF. Non-inferiority of PMF104 was confirmed for children aged > 6 years and for all age groups in PPS and FAS, respectively. Optimal compliance was reported more frequently in the PMF104 than in the PEG-ES group, in both PPS (86.1% vs. 68.4%) and FAS (82.9% vs. 65.3%). Both preparations were equally safe and tolerable. Palatability and acceptability were considered better in the PMF104 group than in the PEG-ES group (27.1% vs. 15.3% and 15.3% vs. 3.5%, respectively). Conclusions In children aged 6 to 17 years, the new low-volume product PMF104 is non-inferior to the reference PEG-ES in terms of bowel cleansing, safety, and tolerability, with slightly better results in compliance, palatability, and acceptability.

Pan-enteric Capsule Endoscopy to Characterize Crohn's Disease Phenotypes and Predict Clinical Outcomes in Children and Adults: The Bomiro Study.

BACKGROUND: Pan-enteric capsule endoscopy (PCE) provides useful information for the management of Crohn's disease (CD), especially in children. No study has evaluated the ability of PCE to characterize CD phenotypes and outcomes in children and adults. METHODS: In a prospective multicenter observational study, we recruited patients with CD >6 years from 4 centers in Italy. Patients underwent clinical, biomarker assessment and PCE. Lesions were graded using the PCE system. For each segment, the most common lesion (MCL), the most severe lesion (MSL), and the extent of involvement were defined. Disease severity, extent, and clinical outcomes were compared between children and adults. A logistic regression analysis was used to identify predictive factors for negative outcomes in both age groups. RESULTS: One hundred ninety-four consecutive patients (adults/children: 144/50) were evaluated for a total of 249 procedures. Children were more likely to have extensive disease, particularly in the colon. Higher MCL scores were independently associated with treatment escalation (odds ratio [OR], 4.09; 95% CI, 1.80-9.25; P = .001), while >30% disease extent was more indicative of clinical and endoscopic relapse (OR, 2.98; 1.26-7.08; P = .013). Disease extent was the only factor associated with endoscopic recurrence in children (OR, 4.50; 95% CI, 1.47-13.77; P = .008), while severe lesions in adults provided a better predictor of treatment escalation (OR, 4.31; 95% CI, 1.52-12.1; P = .006). Postexamination, PCE contributed to a change of therapy in 196/249 (79%) of the procedures. CONCLUSIONS: PCE allowed the characterization of CD phenotypes in children and adults by assessing disease severity and extent, which are of different importance in predicting clinical outcomes in these age groups.

The study introduces the pan-enteric capsule (PCE) as an efficient tool for assessing Crohn's disease in pediatric and adult patients, providing valuable insights into disease extent and severity, influencing treatment decisions, and improving patient care.

The 1st EoETALY Consensus on the Diagnosis and Management of Eosinophilic Esophagitis-Current Treatment and Monitoring.

The present document constitutes Part 2 of the EoETALY Consensus Statements guideline on the diagnosis and management of eosinophilic esophagitis (EoE) developed by experts in the field of EoE across Italy (i.e., EoETALY Consensus Group). Part 1 was published as a different document, and included three chapters discussing 1) definition, epidemiology, and pathogenesis; 2) clinical presentation and natural history and 3) diagnosis of EoE. The present work provides guidelines on the management of EoE in two final chapters: 4) treatment and 5) monitoring and follow-up, and also includes considerations on knowledge gaps and a proposed research agenda for the coming years. The guideline was developed through a Delphi process, with grading of the strength and quality of the evidence of the recommendations performed according to accepted GRADE criteria.This document has received the endorsement of three Italian national societies including the Italian Society of Gastroenterology (SIGE), the Italian Society of Neurogastroenterology and Motility (SINGEM), and the Italian Society of Allergology, Asthma, and Clinical Immunology (SIAAIC). The guidelines also involved the contribution of members of ESEO Italia, the Italian Association of Families Against EoE.

Mobile Health technology in pediatric esophagogastroduodenoscopy quality indicators assessment: results from a national program of the Italian Society of Pediatric Gastroenterology, Hepatology and Nutrition.

BACKGROUND AND AIMS: Upper endoscopy procedures (UEP, esophagogastroduodenoscopy [EGDS] and retrograde endoscopic retrograde cholangiography [ERCP]) are an established standard of care in pediatric gastroenterology. The Pediatric endoscopy quality improvement network (PEnQuIN) recently published its pediatric-specific endoscopy quality guidelines. This study, initiated by the Italian Society of Pediatric Gastroenterology, Hepatology and Nutrition (SIGENP), aims to evaluate the adherence of Italian Pediatric Endoscopy Centers to these established quality standards. METHODS: Conducted between April 2019 and March 2021, this nationwide study utilized a smartphone app-based approach. Data encompassing pediatric endoscopy facilities, patient profiles, endoscopy indications, 17 procedure-related PEnQuIN indicators, and a GHAA-9m patient satisfaction questionnaire were systematically collected. RESULTS: A comprehensive analysis of 3582 procedures from 24 PECs revealed that 2654 (76%) were UEP. The majority of centers (75%) involved more than one operator, with 9 PEC incorporating adult endoscopists, responsible for 5% of UEPs. Overall, adherence to quality standards was good; however, areas of improvement include sub-optimal reporting of sedation details, adherence to disease-specific guidelines, and patient satisfaction questionnaire completeness (56%). The complication rate aligned with literature standards (1%), and patient satisfaction was generally high. A noteworthy observation was a 30% decrease monthly reporting rate and a shift in disease-specific patterns following the COVID-19 outbreak. CONCLUSIONS: Pediatric UEP practices in Italy adhere well to established quality standards. Emphasizing the adoption of disease-specific guidelines is crucial for optimizing resources, enhancing diagnostic accuracy, and minimizing unnecessary procedures. Prioritizing patient satisfaction is important for immediate enhancements in practice as well as for future research endeavors.

The 1st EoETALY Consensus on the Diagnosis and Management of Eosinophilic Esophagitis - Definition, Clinical Presentation and Diagnosis.

Eosinophilic esophagitis (EoE) is a chronic type 2-mediated inflammatory disease of the esophagus that represents the most common eosinophilic gastrointestinal disease. Experts in the field of EoE across Italy (i.e., EoETALY Consensus Group) including gastroenterologists, endoscopists, allergologists/immunologists, and paediatricians conducted a Delphi process to develop updated consensus statements for the management of patients with EoE and update the previous position paper of the Italian Society of Gastroenterology (SIGE) in light of recent evidence. Grading of the strength and quality of the evidence of the recommendations was performed using accepted GRADE criteria. The guideline is divided in two documents: Part 1 includes three chapters, namely 1) definition, epidemiology, and pathogenesis; 2) clinical presentation and natural history, and 3) diagnosis, while Part 2 includes two chapters: 4) treatment and 5) monitoring and follow-up. This document has received the endorsement of three Italian national societies including the SIGE, the Italian Society of Neurogastroenterology and Motility (SINGEM), and the Italian Society of Allergology, Asthma, and Clinical Immunology (SIAAIC). With regards to patients' involvement, these guidelines involved the contribution of members of ESEO Italia, the Italian Association of Families Against EoE.

Diagnostic accuracy of multimodal noninvasive follow-up for pediatric ulcerative colitis: A single-center prospective study.

OBJECTIVES: Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) often requiring endoscopic evaluations, which can be uncomfortable and costly, especially for children. This study aimed to evaluate the diagnostic accuracy of a noninvasive approach combining fecal calprotectin (FCP), colonic ultrasonography (US), and colon capsule endoscopy (CCE) compared with standard ileocolonoscopy in pediatric UC. METHODS: UC children were enrolled and underwent FCP and US on Day 0, followed by CCE on Day 1 and ileocolonoscopy on Day 2. All procedures were performed by operators who were blinded to the patient's clinical history and all test results. The accuracy for disease activity and extension of each technique and their combination was assessed and compared. Tolerability and safety were also evaluated. RESULTS: Thirty-two patients were enrolled (15 males, mean age 13.2 ± 3.2 years). CCE showed a sensitivity of 95% and specificity of 100% in detecting colonic inflammation, with positive predictive value (PPV) and negative predictive value (NPV) of 100% and 92%, respectively. US demonstrated a sensitivity of 85% and specificity of 92%, with PPV and NPV of 94% and 79%. The combination of FCP, US, and CCE achieved 95% sensitivity and 100% specificity, with PPV of 100% and NPV of 92%. The noninvasive approach was better tolerated than colonoscopy (p < 0.05), and no serious adverse events were reported. CONCLUSION: The noninvasive approach combining fecal calprotectin (FCP), ultrasonography, and colon capsule endoscopy demonstrated high diagnostic accuracy and better tolerability compared with standard ileocolonoscopy in pediatric ulcerative colitis follow-up. Further multicenter studies are needed to confirm these findings and evaluate the reproducibility of this noninvasive approach.

Joint ESPGHAN/NASPGHAN Guidelines on Childhood Eosinophilic Gastrointestinal Disorders Beyond Eosinophilic Esophagitis.

INTRODUCTION: Eosinophilic gastrointestinal disorders beyond eosinophilic esophagitis (non-EoE EGIDs) are rare chronic inflammatory disorders of the gastrointestinal (GI) tract. Diagnosis is based on clinical symptoms and histologic findings of eosinophilic inflammation after exclusion of a secondary cause or systemic disease. Currently, no guidelines exist for the evaluation of non-EoE EGIDs. Therefore, the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) formed a task force group to provide consensus guidelines for childhood non-EoE EGIDs. METHODS: The working group was composed of pediatric gastroenterologists, adult gastroenterologists, allergists/immunologists, and pathologists. An extensive electronic literature search of the MEDLINE, EMBASE, and Cochrane databases was conducted up to February 2022. General methodology was used in the formulation of recommendations according to the Appraisal of Guidelines for Research and Evaluation (AGREE) II and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to meet current standards of evidence assessment. RESULTS: The guidelines provide information on the current concept of non-EoE EGIDs, disease pathogenesis, epidemiology, clinical manifestations, diagnostic and disease surveillance procedures, and current treatment options. Thirty-four statements based on available evidence and 41 recommendations based on expert opinion and best clinical practices were developed. CONCLUSION: Non-EoE EGIDs literature is limited in scope and depth, making clear recommendations difficult. These consensus-based clinical practice guidelines are intended to assist clinicians caring for children affected by non-EoE EGIDs and to facilitate high-quality randomized controlled trials of various treatment modalities using standardized, uniform disease definitions.

Swallowed topical corticosteroids for eosinophilic esophagitis: Utilization and real-world efficacy from the EoE CONNECT registry.

BACKGROUND: Swallowed topical corticosteroids (tC) are common therapy for patients with eosinophilic esophagitis (EoE). Widely heterogeneous results have occurred due to their active ingredients, formulations and doses. OBJECTIVE: To assess the effectiveness of topical corticosteroid therapy for EoE in real-world practice. METHODS: Cross-sectional study analysis of the multicentre EoE CONNECT registry. Clinical remission was defined as a decrease of ≥50% in dysphagia symptom scores; histological remission was defined as a peak eosinophil count below 15 per high-power field. The effectiveness in achieving clinico-histological remission (CHR) was compared for the main tC formulations. RESULTS: Overall, data on 1456 prescriptions of tC in monotherapy used in 866 individual patients were assessed. Of those, 904 prescriptions with data on formulation were employed for the induction of remission; 234 reduced a previously effective dose for maintenance. Fluticasone propionate formulations dominated the first-line treatment, while budesonide was more common in later therapies. A swallowed nasal drop suspension was the most common formulation of fluticasone propionate. Doses ≥0.8 mg/day provided a 65% CHR rate and were superior to lower doses. Oral viscous solution prepared by a pharmacist was the most common prescription of budesonide; 4 mg/day provided no benefit over 2 mg/day (CHR rated being 72% and 80%, respectively). A multivariate analysis revealed budesonide orodispersible tablets as the most effective therapy (OR 18.9, p < 0.001); use of higher doses (OR 4.3, p = 0.03) and lower symptom scores (OR 0.9, p = 0.01) were also determinants of effectiveness. CONCLUSION: Reduced symptom severity, use of high doses, and use of budesonide orodispersible tablets particularly were all independent predictors of tC effectiveness.

Foreign body ingestion in children: Definition of a nomogram to predict surgical or endoscopic intervention.

BACKGROUND AND AIMS: Foreign body ingestion (FBI) in children requires early identification to prevent adverse outcomes and may necessitate endoscopic or surgical intervention. This study aims to develop a nomogram that identifies children who require urgent surgical or endoscopic intervention by using the patient's medical history and clinical parameters collected at admission. METHODS: This study is a retrospective review (01/2015-12/2020) of a multicenter case series of children admitted for FBI. Data from 5864 records from 24 hospitals in Italy were analyzed. Logistic regression models were used to establish the probability of requiring surgical or endoscopic intervention based on patient history and clinical characteristics. The nomogram representing the results from the multivariable model was reported to examine the propensity for surgery/endoscopy. RESULTS: The study identified a significant association between intervention and various factors, including type of foreign body (blunt: reference category, disk battery (odds ratio OR:4.89), food bolus (OR:1.88), magnets (OR:2.61), sharp-pointed (OR:1.65), unknown (OR:1.02)), pre-existing diseases or conditions (OR 3.42), drooling (OR 10.91), dysphagia (OR 5.58), vomiting (OR 3.30), retrosternal pain (OR 5.59), abdominal pain (OR 1.58), hematemesis (OR 2.82), food refusal/poor feeding (OR 2.99), and unexplained crying (OR 2.01). The multivariable regression model showed good calibration and discrimination ability, with an area under the ROC curve of 0.77. CONCLUSIONS: This study developed the first nomogram to predict the probability of the need for surgical or endoscopic intervention in children with FBI, based on the information collected at admission. The nomogram will aid clinicians in identifying children who require early intervention to prevent adverse outcomes.

Histologic findings at diagnosis as predictive markers of clinical outcome in pediatric ulcerative colitis.

BACKGROUND: The role of histological inflammation at diagnosis as a possible prognostic factor for disease course has not been investigated. AIMS: To assess whether histologic findings at diagnosis could predict clinical outcomes and evaluate the association between clinical, biochemical, endoscopic, and histological findings. METHODS: Prospective single-center study including pediatric UC patients with a minimum follow-up of 12 months. The association between histological activity (Nancy Index, Robarts Histopathology Index, and Geboes Score) and 12-month clinical outcomes was evaluated. Secondarily, we assessed the correlation between histological scores and endoscopic and inflammatory markers at the diagnosis. Inter-observer agreement for histologic and endoscopic scores was also evaluated. RESULTS: Forty-nine UC patients were included. No association was found between 1-year clinical relapse and the three histological indices at diagnosis (p > 0.05). Good concordance was found among the three histological scores (p < 0.001), and between all histological and endoscopic indices (p < 0.05). No correlation was found between histologic scores and serum inflammatory markers. Inter-observer agreement was good for eMayo, Nancy and Robarts score (k = 0.71, k = 0.74 and k = 0.68, respectively) and moderate for Geboes (k = 0.46). CONCLUSIONS: Histological findings at diagnosis cannot be used as a predictor of the disease course. The three histological scores used in routine clinical practice show an overall good correlation and reliability.

Investigating the Relationship Between COVID-19 and Celiac Disease. A Dual Research Approach.

Background: Most evidence on the coronavirus disease 2019 (COVID-19) pandemic, has been obtained from web- or telephone-based surveys. In particular, few laboratory data, often incomplete, have been reported on the frequency of COVID-19-related serology at celiac disease (CD) diagnosis or on the effects of COVID-19 on the development of CD-specific autoimmunity. Objectives: The objective of this retrospective cross-sectional case/control study was to: (1) evaluate the frequency of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in 78 children and adolescents at CD diagnosis (CD, 44 females, median age 7.4 years); (2) evaluate the frequency of IgA-anti-transglutaminase antibodies (IgA-tTGAbs) in 97 nonceliac patients (50 females, median age 9.0 years) who contracted SARS-CoV-2 infection during the pandemic (February-April 2021). As a control (CTRL) group, we analyzed 141 healthy subjects (79 females, median age 9.8 years) enrolled during the pandemic. Methods: SARS-CoV-2 IgM- and IgG-antibodies were detected by chemiluminescent microparticle immunoassays. IgA-tTGAbs were detected by a fluid-phase radioimmunoassay. Results: Six out of 78 (7.7%) CD patients tested positive for SARS-CoV-2Abs, with a frequency not significantly different from CTRL subjects (9.2%). None of the 97 nonceliac COVID-19 patients tested positive for IgA-tTG antibodies. Conclusion: These 2 distinct research approaches showed (1) similar frequencies of SARS-CoV-2 immunoreactivities in CD patients and CTRL subjects and, (2) no ability of SARS-CoV-2 to induce a CD-specific immune response, at least in the 3-4 months following SARS-CoV-2 infection.

A journey towards pediatric gastrointestinal endoscopy and its training: a narrative review.

Background and aims: Gastrointestinal (GI) endoscopy in pediatric setting has unique features and, therefore, requires an approach that is tailored to pediatric practice. There is still heterogeneity between training programs worldwide in terms of duration, number of procedures and assessment during and at the end of the training process. Methods: We conducted a narrative review aiming to describe and summarize the existing literature on the various training methods for pediatric GI endoscopy to highlight the significance of specific pediatric endoscopy training. Results: Simulation-based tools have been implemented in several training programs, providing a safer learning environment for trainees, especially in their earlier stages of training. Assessment of competence is gradually shifting from the sole evaluation of procedural numbers towards the development of more reliable and valid tools that can accurately measure technical competence. Despite such seismic shift, there is still a need for a standardized and comprehensive pediatric-oriented endoscopy curriculum that incorporates acquisition of procedural skills education and is built on the current competency-based model of training. All the above must sink their roots in trainees and to ensure that the endoscopists of tomorrow are capable of delivering high quality of care for children undergoing endoscopy. Conclusion: It is crucial to parallelly focus on the way trainers teach trainees. In this context, the implementation of "train the trainers" courses has improved important quality meters in GI endoscopy. Future research should put the focus on the potential subsequent favorable benefits of these changes on child health.

A Treat-to-Target Strategy Guided by Pan-Enteric Evaluation in Children With Crohn's Disease Improves Outcomes at 2 Years.

BACKGROUND AND AIMS: It is uncertain whether a treat-to-target approach could be an effective strategy for improving outcomes in children with Crohn's disease (CD). Previously, we reported mucosal healing (MH) and deep remission rates throughout the intestinal tract by performing 3 pan-enteric capsule assessments and using a treat-to-target strategy over 52 weeks in children with CD. This report describes the outcomes of this approach at 104 weeks. METHODS: Children with known CD who completed the 52-week protocol repeated pan-enteric capsule endoscopy (PCE) at 104 weeks. Results at weeks 52 and 104 were compared, and long-term outcomes between patients, with and without MH, were calculated using an intention-to-treat analysis of clinical relapse, need for steroids, treatment escalation, hospitalization, and surgery. RESULTS: Of the previous study cohort of 48 patients, 46 (96%) were available for this extension study (28 [61%] of 46 with MH and 18 [39%] of 46 without MH at 52 weeks). When evaluated at 104 weeks, MH was maintained in 93% of patients with MH at 52 weeks. In the intention-to-treat analysis, complete MH at 52 weeks was associated with reduced risk of steroid use (log-rank P < .0001), treatment escalation (log-rank P < .0001), hospitalization (log-rank P < .0001), and clinical relapse (log-rank P < .0001). CONCLUSIONS: When a PCE-based, treat-to-target strategy is employed, MH is sustainable (93%) over a 1-year period and is correlated with improved patient outcomes, including reduced need for steroids, treatment escalation, hospitalization, and clinical relapses at 104 weeks.ClinicalTrials.gov number: NCT03161886.

Joint ESPGHAN/NASPGHAN Guidelines on Childhood Eosinophilic Gastrointestinal Disorders beyond Eosinophilic Esophagitis.

INTRODUCTION: Eosinophilic Gastrointestinal Disorders beyond Eosinophilic Esophagitis (non-EoE EGIDs) are rare chronic inflammatory disorders of the gastrointestinal (GI) tract. Diagnosis is based on clinical symptoms and histologic findings of eosinophilic inflammation after exclusion of a secondary cause or systemic disease. Currently, no guidelines exist for the evaluation of non-EoE EGIDs. Therefore, the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) formed a task force group to provide consensus guidelines for childhood non-EoE EGIDs. METHODS: The working group was composed of pediatric gastroenterologists, adult gastroenterologists, allergists/immunologists, and pathologists. An extensive electronic literature search of the MEDLINE, EMBASE, and Cochrane databases was conducted up to February 2022. General methodology was used in the formulation of recommendations according to the Appraisal of Guidelines for Research and Evaluation (AGREE) II and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to meet current standards of evidence assessment. RESULTS: The guidelines provide information on the current concept of non-EoE EGIDs, disease pathogenesis, epidemiology, clinical manifestations, diagnostic and disease surveillance procedures, and current treatment options. Thirty-four statements based on available evidence and 41 recommendations based on expert opinion and best clinical practices were developed. CONCLUSION: Non-EoE EGIDs literature is limited in scope and depth, making clear recommendations difficult. These consensus-based clinical practice guidelines are intended to assist clinicians caring for children affected by non-EoE EGIDs and to facilitate high-quality randomized controlled trials of various treatment modalities using standardized, uniform disease definitions.

Identification of Iatrogenic Perforation in Pediatric Gastrointestinal Endoscopy.

OBJECTIVES: Iatrogenic viscus perforation in pediatric gastrointestinal endoscopy (GIE) is a very rare, yet potentially life-threatening event. There are no evidence-based recommendations relating to immediate post-procedure follow-up to identify perforations and allow for timely management. This study aims to characterize the presentation of children with post-GIE perforation to better rationalize post-procedure recommendations. METHODS: Retrospective study based on unrestricted pooled data from centers throughout Europe, North America, and the Middle East affiliated with the Endoscopy Special Interest Groups of European Society for Paediatric Gastroenterology Hepatology and Nutrition and North American Society for Pediatric Gastroenterology Hepatology and Nutrition. Procedural and patient data relating to clinical presentation of the perforation were recorded on standardized REDCap case-report forms. RESULTS: Fifty-nine cases of viscus perforation were recorded [median age 6 years (interquartile range 3-13)]; 29 of 59 (49%) occurred following esophagogastroduodenoscopy, 26 of 59 (44%) following ileocolonoscopy, with 2 of 59 (3%) cases each following balloon enteroscopy and endoscopic retrograde cholangiopancreatography; 28 of 59 (48%) of perforations were identified during the procedure [26/28 (93%) endoscopically, 2/28 (7%) by fluoroscopy], and a further 5 of 59 (9%) identified within 4 hours. Overall 80% of perforations were identified within 12 hours. Among perforations identified subsequent to the procedure 19 of 31 (61%) presented with pain, 16 of 31 (52%) presented with fever, and 10 of 31 (32%) presented with abdominal rigidity or dyspnea; 30 of 59 (51%) were managed surgically, 17 of 59 (29%) managed conservatively, and 9 of 59 (15%) endoscopically; 4 of 59 (7%) patients died, all following esophageal perforation. CONCLUSIONS: Iatrogenic perforation was identified immediately in over half of cases and in 80% of cases within 12 hours. This novel data can be utilized to generate guiding principles of post-procedural follow-up and monitoring. PLAIN LANGUAGE SUMMARY: Bowel perforation following pediatric gastrointestinal endoscopy is very rare with no evidence to base post-procedure follow-up for high-risk procedures. We found that half were identified immediately with the large majority identified within 12 hours, mostly due to pain and fever.

PARP1 Activation Induces HMGB1 Secretion Promoting Intestinal Inflammation in Mice and Human Intestinal Organoids.

Extracellular High-mobility group box 1 (HMGB1) contributes to the pathogenesis of inflammatory disorders, including inflammatory bowel diseases (IBD). Poly (ADP-ribose) polymerase 1 (PARP1) has been recently reported to promote HMGB1 acetylation and its secretion outside cells. In this study, the relationship between HMGB1 and PARP1 in controlling intestinal inflammation was explored. C57BL6/J wild type (WT) and PARP1-/- mice were treated with DSS to induce acute colitis, or with the DSS and PARP1 inhibitor, PJ34. Human intestinal organoids, which are originated from ulcerative colitis (UC) patients, were exposed to pro-inflammatory cytokines (INFγ + TNFα) to induce intestinal inflammation, or coexposed to cytokines and PJ34. Results show that PARP1-/- mice develop less severe colitis than WT mice, evidenced by a significant decrease in fecal and serum HMGB1, and, similarly, treating WT mice with PJ34 reduces the secreted HMGB1. The exposure of intestinal organoids to pro-inflammatory cytokines results in PARP1 activation and HMGB1 secretion; nevertheless, the co-exposure to PJ34, significantly reduces the release of HMGB1, improving inflammation and oxidative stress. Finally, HMGB1 release during inflammation is associated with its PARP1-induced PARylation in RAW264.7 cells. These findings offer novel evidence that PARP1 favors HMGB1 secretion in intestinal inflammation and suggest that impairing PARP1 might be a novel approach to manage IBD.

Approach to Endoscopic Balloon Dilatation in Pediatric Stricturing Crohn Disease: A Position Paper of the Endoscopy Special Interest Group of ESPGHAN.

Crohn disease (CD) is often complicated by bowel strictures that can lead to obstructive symptoms, resistant inflammation, and penetrating complications. Endoscopic balloon dilatation of CD strictures has emerged as a safe and effective technique for relieving these strictures, which may obviate the need for surgical intervention in the short and medium term. This technique appears to be underutilized in pediatric CD. This position paper of the Endoscopy Special Interest Group of European Society for Pediatric Gastroenterology, Hepatology and Nutrition describes the potential applications, appropriate evaluation, practical technique, and management of complications of this important procedure. The aim being to better integrate this therapeutic strategy in pediatric CD management.

Endoscopic Balloon Dilatation in Pediatric Crohn Disease: An IBD Porto Group Study.

OBJECTIVE/BACKGROUND: Endoscopic balloon dilatation (EBD) has been shown to be effective and safe in adults with stricturing Crohn disease (CD) yet pediatric data is sparse. We aimed to assess efficacy and safety of EBD in stricturing pediatric CD. METHODS: International collaboration included 11 centers from Europe, Canada, and Israel. Recorded data included patient demographics, stricture features, clinical outcomes, procedural adverse events, and need for surgery. Primary outcome was surgery-free over 12 months and secondary outcomes were clinical response and adverse events. RESULTS: Eighty-eight dilatations were performed over 64 dilatation series in 53 patients. Mean age at CD diagnosis was 11.1 (±4.0) years, stricture length 4 cm [interquartile range (IQR) 2.8-5], and bowel wall thickness 7 mm (IQR 5.3-8). Twelve of 64 (19%) patients underwent surgery in the year following the dilatation series, at a median of 89 days (IQR 24-120; range 0-264) following EBD. Seven of 64 (11%) had subsequent unplanned EBD over the year, of whom two eventually underwent surgical resection. Two of 88 (2%) perforations were recorded, 1 of whom was managed surgically, and 5 patients had minor adverse events managed conservatively. There was a significant improvement in all clinical measures following EBD with weighted pediatric CD activity index-defined remission increasing from 13% at baseline to 44%, 46%, and 61%, and absence of obstructive symptoms in 55%, 53%, and 64% of patients at week 2, 8, and 24 respectively. CONCLUSIONS: In this largest study of EBD in pediatric stricturing CD to date, we demonstrated that EBD is effective in relieving symptoms and avoiding surgery. Adverse events rates were low and consistent with adult data.