Recent advances in the treatment of gastrointestinal motility disorders in children.

INTRODUCTION: Pediatric gastrointestinal motility disorders represent some of the most challenging clinical conditions with largely undefined pathogenetic pathways and therefore limited therapeutic options. Herein, we provide an overview of the recent advances in treatment options for these disorders and their clinical impact. AREAS COVERED: PubMed and Medline databases were searched for relevant articles related to the treatment of achalasia, esophageal atresia, gastroparesis, PIPO and constipation published between 2017 and 2022. In this article, we review and summarize recent advances in management of gastrointestinal motility disorders in children with a particular focus on emerging therapies as well as novel diagnostic modalities that help guide their application or develop new, more targeted treatments. EXPERT OPINION: Gastrointestinal motility disorders represent one of the most challenging conundrums in pediatric age and despite significant advances in investigative tools, the palette of treatment options remain limited. Overall, while pharmacological options have failed to bring a curative solution, recent advances in minimal invasive therapeutic and diagnostic techniques have emerged as potential keys to symptom and quality of life improvement, such as ENDOFLIP, POEM, cine-MRI, fecal microbiota transplantation.

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.

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.

Pancreatic family history does not predict disease progression but connotes alcohol consumption in adolescents and young adults with acute pancreatitis: Analysis of an international cohort of 2,335 patients.

Background: In pediatric acute pancreatitis (AP), a family history of pancreatic diseases is prognostic for earlier onset of recurrent AP (ARP) and chronic pancreatitis (CP). No evidence supports the same association in adult-onset pancreatitis. Age-specific reasons for familial aggregation are also unclear. We aimed to examine the prognostic role of pancreatic family history for ARP/CP and observe possible underlying mechanisms. Methods: We conducted a secondary analysis of the Hungarian Pancreatic Study Group's (HPSG) multicenter, international, prospective registry of patients with AP, both children and adults. We compared the positive family history and the negative family history of pancreatic diseases, in different age groups, and analyzed trends of accompanying factors. Chi-square and Fisher exact tests were used. Results: We found a higher rate of ARP/CP in the positive pancreatic family history group (33.7 vs. 25.9%, p = 0.018), peaking at 6-17 years. Idiopathic AP peaked in childhood in the positive family history group (75% 0-5 years) and was consistently 20-35% in the negative group. A higher rate of alcohol consumption/smoking was found in the positive groups at 12-17 years (62.5 vs. 15.8%, p = 0.013) and 18-29 years (90.9 vs. 58.1%, p = 0.049). The prevalence of diabetes and hyperlipidemia steadily rose with age in both groups. Conclusion: Positive family history most likely signifies genetic background in early childhood. During adolescence and early adulthood, alcohol consumption and smoking emerge-clinicians should be aware and turn to intervention in such cases. Contrary to current viewpoints, positive pancreatic family history is not a prognostic factor for ARP and CP in adults, so it should not be regarded that way.

Understanding and Responding to the Impact of COVID-19 on Paediatric Gastroenterology Training & Practice of Young ESPGHAN Members.

OBJECTIVES: Limited data exist about the impact of the coronavirus disease 2019 (COVID-19) pandemic on the training and clinical practice of young doctors. The aim of this study was to evaluate the impact on paediatric gastroenterologists in training posts during the first wave of the European COVID pandemic. METHODS: All Young members of European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) (YE) members received a multiple-choice questionnaire concerning the impact (if any) on their clinical practice, mental health, quality of care provided and fellowship/training experience. The survey was conducted between May 22, 2020 and June 10, 2020. RESULTS: Of the 144 responders (40% of YE members), 85% (n = 123) reported an impact of COVID-19. Ninety-six percent reported an impact on their clinical practice, including more virtual patient consultation (n = 91), underutilization of ambulatory care (n = 113) and reduced or lack of planned admissions (n = 75). Endoscopy restrictions to semi-urgent or emergency cases were reported in 82 and lack of medical equipment/drugs (n = 47) were also reported.Reported adverse mental health issues included poor concentration, increased stress levels, an impact on family life in 62% and a reduced quality of care in 45%; this was more often reported in doctors from Southern Europe (54%) than in those from other geographical areas.Seventy-seven percent reported an impact on the content of their fellowship, including lack of participation in national/international meetings, withdrawn research time and limited mentoring. CONCLUSIONS: The impact of the COVID-19 pandemic has been shown to affect the clinical practice, training and mental health of YE members. Adaptations of training programmes and targeted strategies to improve the clinical practice of young practitioners are needed and proposed in this manuscript.

Human and Doll's Hair in a Gastric Trichobezoar, Endoscopic Retrieval Hazards.

Trichobezoars are masses of ingested hair, usually the individual's own hair, that accumulate in the gastrointestinal tract, most commonly in the stomach. When extending into the small intestine, this is termed "Rapunzel syndrome." Removal has traditionally been by laparotomy; however, successful endoscopic removal has also been described. We report the case of a 9-year-old-girl with undiagnosed coeliac disease and Rapunzel syndrome who underwent endoscopic removal of a large trichobezoar, which was followed by unexpected multiple perforations of the small bowel and stomach. Argon plasma coagulation (APC) and snare electrocautery were employed during endoscopy to remove the trichobezoar piecemeal, and approximately 70% was removed without any clear signs of damage to the mucosa. It was discovered subsequently that about 20 of her dolls were found without hair. On investigating the composition of a specific doll hair from the manufacturer, it was discovered that it could be hazardous if burned. It was, therefore, hypothesized that a constellation of factors had conspired to lead to perforation, that is, the potentially hazardous gas produced from the electrical energy applied to the synthetic hair and possible mucosal damage by the physical abrasion of this hair. A review of the literature on endoscopic attempts to remove trichobezoars irrespective of the result reveals a success rate of 30.7%.

Adequacy of scoring systems in diagnosing paediatric autoimmune hepatitis: retrospective study using a control group children with Hepatitis B infection.

AIM: To evaluate how correct is made the diagnosis of autoimmune hepatitis (AIH) in children, comparing the adults scoring systems - the 1999 revised scoring system by International Autoimmune Hepatitis Group and the 2007 Simplified Scoring System. The inaccuracies in diagnosis have been analysed. METHODS: The two scoring systems have been applied for 28 children with AIH pre-treatment and 28 with Hepatitis B infection - matched by sex and age, all diagnosed between 2010 and 2017 in an emergency children's hospital in Bucharest, Romania. They were retrospectively followed throughout the period assessed. RESULTS: Autoimmune hepatitis was present in 85.7% cases according to the 1999 revised score, respectively, 57.0% as per the 2007 simplified score. The 2007 simplified score led to false negative results when AIH was associated with another autoimmune disease (p = 0.009). Patients who did not undergo liver biopsy were associated with a downgraded diagnosis by the 2007 simplified score (p = 0.001). CONCLUSION: There is a need for a scoring system tailored to children's characteristics. Two compulsory components of the future score might be liver biopsy and associated autoimmune disorders. The existing scores could be used in children with consideration, preferably both at once and together with liver biopsy for increased accuracy.

TLR activation regulates damage-associated molecular pattern isoforms released during pyroptosis.

Infection of macrophages by bacterial pathogens can trigger Toll-like receptor (TLR) activation as well as Nod-like receptors (NLRs) leading to inflammasome formation and cell death dependent on caspase-1 (pyroptosis). Complicating the study of inflammasome activation is priming. Here, we develop a priming-free NLRC4 inflammasome activation system to address the necessity and role of priming in pyroptotic cell death and damage-associated molecular pattern (DAMP) release. We find pyroptosis is not dependent on priming and when priming is re-introduced pyroptosis is unaffected. Cells undergoing unprimed pyroptosis appear to be independent of mitochondrial involvement and do not produce inflammatory cytokines, nitrous oxide (NO), or reactive oxygen species (ROS). Nevertheless, they undergo an explosive cell death releasing a chemotactic isoform of the DAMP high mobility group protein box 1 (HMGB1). Importantly, priming through surface TLRs but not endosomal TLRs during pyroptosis leads to the release of a new TLR4-agonist cysteine redox isoform of HMGB1. These results show that pyroptosis is dominant to priming signals and indicates that metabolic changes triggered by priming can affect how cell death is perceived by the immune system.