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Objectives: To assess the clinical complications reported after the ingestion of magnetic foreign bodies (FBs) in pediatric age, along with their incidence among all FB ingestions and clinical presentation., Study Design: We've consecutively recruited all children aged 0-14 years who were admitted for single or multiple magnet ingestion from May 2015 to December 2022. Patient demographics, admission sources and discharge status were accurately recorded, along with their clinical management and outcomes., Results: Sixty-one children were enrolled, of whom 49/61 (80.3%) had ingested a single magnet and 12/61 (19.7%) multiple magnets. Only 1/49 children with single magnet required endoscopic removal due to esophageal retention. Among children having ingested multiple magnets, 5/12 (41.7%) undergo endoscopic removal since magnets were amenable to endoscopic retrieval whereas in 7/12 (58.3%) magnets could not be promptly removed. Among these, 4/12 (33.3%) later developed intestinal ischemia/necrosis or perforation and required FB surgical intervention whereas 3/12 (25%) uneventfully evacuated magnets., Conclusions: Our data confirm that multiple magnet ingestion, unlike single magnet ingestion, pose a serious health hazard. Parents and caregivers should remove them from the reach of children. Medical providers should maintain a high index of suspicion of their ingestion since prompt evaluation and likely removal may be lifesaving and intestine saving., Competing Interests: Conflict of interest The authors Paolo Quitadamo, Piergiorgio Gragnaniello, Sara Isoldi, Cristina Bucci, Francesco Esposito, Silvana Russo, Giovanna Grella, Mariano Caldore have no conflicts of interest to declare related to the manuscript., (Copyright © 2023 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Constipation is a common problem in children, accounting for about 3% of all primary care visits and up to 25% of referrals to paediatric gastroenterologists. Although polyethylene glycol often proves effective, most children require prolonged treatment and about 50% of them have at least one relapse within the first 5 years after initial recovery. When conventional treatment fails, children are considered to have refractory constipation. Children with refractory constipation deserve specialist management and guidance. Over the last decades, there has been a remarkable increase in our knowledge of normal and abnormal colonic and anorectal motility in children, and a number of different techniques to measure transit and motility have been developed. The present review analyses the possible diagnostic investigations for children with refractory constipation, focusing on their actual indications and their utility in clinical practice. Moreover, we have also analytically reviewed medical and surgical therapeutic options, which should be considered in selected patients in order to achieve the best clinical outcome., Competing Interests: Conflict of interest The authors Paolo Quitadamo, Renato Tambucci, Valentina Mancini, Angelo Campanozzi, Tamara Caldaro, Valentina Giorgio, Licia Pensabene, Sara Isoldi, Saverio Mallardo, Fabio Fusaro, Annamaria Staiano, Silvia Salvatore and Osvaldo Borrelli have no conflicts of interest to declare related to the manuscript., (Copyright © 2023 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

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., Competing Interests: Conflict of interest None., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Gastrointestinal endoscopy has grown dramatically over the past century, and with subsequent improvements in technology and anaesthesia, it has become a safe and useful tool for evaluation of GI pathology in children. There are substantial differences between paediatric and adult endoscopy beyond size, including: age-related patho-physiology and the different spectrum of diseases in children. Literature on endoscopic procedures in children is sparse but significant. The present review aims at describing the current knowledges on paediatric endoscopy practice and highlights the main areas of differences between paediatric and adult practice., Competing Interests: Declaration of Competing Interest None., (Copyright © 2021 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Foreign body and caustic ingestions in children are usually the most common clinical challenges for emergency physicians, general pediatricians and pediatric gastroenterologists. Management of these conditions often requires different levels of expertise and competence. Endoscopy is often necessary but there is a high risk of misusing this tool with incorrect timing and indications. The imprecise clinical history frequently leaves clinicians uncertain about timing and nature of the ingestion. Few clinical guidelines regarding management of these ingestions in children have been published, none of which from the Italian Society of Pediatric Gastroenterology, Hepatology and Nutrition (SIGENP). An expert panel of Italian endoscopists was convened by the SIGENP Endoscopy Working Group to produce the present article that outlines practical clinical approaches to the pediatric patient with a variety of foreign body and caustic ingestions. The Italian Association of Hospital Gastroenterologists and Endoscopists (AIGO) has also endorsed the project since many adult endoscopists usually manage children with these conditions. Differently from the other published guidelines, the proposed one focuses on the role of the endoscopists (regardless of whether they are adult or pediatric gastroenterologists) in the diagnostic process of children with foreign body and caustic ingestions., Competing Interests: Conflict of Interest The authors have no conflicts of interest to disclose., (Copyright © 2020 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Objective: to investigate the reliability of laryngeal reflux finding score (RFS) and symptom index (RSI) in assessing gastroesophageal reflux (GER) in children and infants., Methods: patients with laryngeal or respiratory symptoms, who underwent laryngoscopy and esophageal pH-impedance (MII-pH) were recruited. RSI and RFS were correlated to MII-pH results. A RSI>13, RFS>7, acid exposure index>7%, total reflux episodes>100/24 h in infants or>70/24 h in children, or a positive symptom index or association probability, were considered pathological. Analysis considering age (12 months) was performed. Sensitivity, specificity, positive (PPV) and negative predictive values (NPV) of the laryngeal scores were calculated., Results: 197 children (median 53 months, 61 infants) were enrolled. MII-pH was pathological in 5/10 patients with RFS>7, and in 17/31 with RSI>13. RFS>7 had 3.9% sensitivity, 93% specificity, a PPV of 50 and a NPV of 34 in predicting GER disease. RFS was inversely associated to weakly acidic and proximal GER. RSI>13 had 13% sensitivity, 83% specificity, and a PPV and NPV similar to RFS. RSI was significantly associated with the number of acid reflux episodes, and, in infants, with bolus exposure index., Conclusions: RSI and RFS aren't accurate in predicting GER in infants and children. Acid reflux relates to laryngeal symptoms, but neither acid, nor proximal and weakly acidic GER relate to laryngeal alterations., Competing Interests: Declaration of Competing Interest Authors declare no conflict of interest related to this paper., (Copyright © 2020 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: Topical steroids are effective in eosinophilic esophagitis (EoE), but patients often show different tendencies to relapse. We assessed whether gene expression is associated with a sort of steroid dependency in EoE children., Methods: Biopsy samples were prospectively collected on EoE children responding to topical steroids. Patients treated with viscous budesonide for 24 weeks were subsequently classified as early (6 months) or late (>6 months) relapsing. RNA was isolated from esophageal biopsies at the time of the relapse and analyzed by NGS for transcriptome profiling., Results: Of 40 patients, 22 patients were considered for mRNA expression profile. Thirteen were included in the early-relapse group, and 9 were in the late-relapse. No significant difference was observed in the two groups for clinical, endoscopic or histological features. Using the mRNA expression profile we performed supervised clustering using the 10 top differentially expressed genes between early and late relapsing patients. The heatmap and PCA show a proper segregation among patients. SERPINB12 is the only gene attaining a significant differential expression between the two groups (FDR < 0.05)., Conclusions: Different tendencies to relapse in EoE children responding to topical steroids might be related to altered mRNA expressions. SERPINB12 presented a significantly higher expression in the late relapse group and it deserves further investigations., (Copyright © 2019. Published by Elsevier Ltd.)

De-regulated T-cell activation and functions are pivotal in the orchestration of immune-mediated tissue damage in IBD. We investigated the role of DNAM-1 (co-activating)/TIGIT (co-inhibitory)/ligand axis in the regulation of T-cell functions and its involvement in IBD pathogenesis. We show that DNAM-1 and TIGIT display a peculiar expression pattern on gut mucosa T-cell populations, in a microenvironment where their shared ligands (PVR and Nectin-2) are physiologically present. Moreover, DNAM-1 family receptor/ligand system is perturbed in IBD lesions, in a disease activity-dependent manner. The expression profile of CCR6 and CD103 mucosa addressins suggests that microenvironment-associated factors, rather than skewed recruitment of circulating T-cell populations, play a more relevant role in supporting the establishment of DNAM-1 and TIGIT expression pattern in mucosal T-cell populations, and may explain its alteration in IBD. Although both co-receptors mark functionally competent T cells, DNAM-1 and TIGIT segregate on T cells endowed with different proliferative potential. Moreover, their opposing role in regulating T-cell proliferation exquisitely depends on ligand availability. All together, our data propose a role for DNAM-1 and TIGIT in regulating mucosal T-cell activation and immune homeostasis, and highlight the involvement of an imbalance of this system in IBD.

Background: Blue Rubber Bleb Nevus Syndrome (BRBNS) is a rare, severe, sporadically occurring disorder characterized by multiple venous malformations., Aims: To present and analyze a case series of pediatric patients with BRBNS and to describe diagnostic approaches and management options applied., Patients and Methods: Multicenter, retrospective study, evaluating the diagnosis and management of children with BRBNS., Results: Eighteen patients diagnosed with BRBNS were included. Cutaneous venous malformations were observed in 78% and gastrointestinal venous malformations in 89%. Lesions were also found in other organs including muscles, joints, central nervous system, eyes, parotid gland, spine, kidneys and lungs. Gastrointestinal lesions were more common in the small intestine than in stomach or colon. The management varied significantly among centers. Endoscopic therapy and surgical therapy alone failed to prevent recurrence of lesions. In younger children and in patients with musculoskeletal or other organ involvement, sirolimus was used with 100% success rate in our series (5 patients treated) although poor compliance with subtherapeutic sirolimus trough levels led to recurrence in a minority., Conclusions: Considering the multi-organ involvement in BRBNS, diagnosis and management requires a multidisciplinary approach. The treatment includes conservative, medical, endoscopic and surgical options. Prospective multicenter studies are needed to identify the optimal management of this rare condition., (Copyright © 2019 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background and Aims: Recent evidence implicates gut microbiota (GM) and immune alterations in autism spectrum disorders (ASD). We assess GM profile and peripheral levels of immunological, neuronal and bacterial molecules in ASD children and controls. Alarmin HMGB1 was explored as a non-invasive biomarker to monitor gastrointestinal (GI) symptoms., Methods: Thirty ASD children and 14 controls entered into the study. GM metagenomic analysis was performed for 16 ASD patients and 7 controls. GM functional profile was assessed by GO term analysis. Blood levels of IL-1β, TNFα, TGFβ, IL-10, INFγ, IL-8, lipopolysaccharide, Neurotensin, Sortilin1 and GSSG/GSH ratio were analyzed in all subjects by ELISA. Fecal HMGB1 was analyzed by Western blot., Results: We observed a significant decrease in bacterial diversity. Furthermore, 82 GO terms underrepresented in ASD. Four of them pointed at 3,3 phenylpropionate catabolism and were imputable to Escherichia coli (E. coli) group. Serum levels of TNFα, TGFβ, NT, and SORT-1 increased in ASD patients. Fecal levels of HMGB1 correlated with GI sign severity in ASD children., Conclusions: We suggest that a decrease of E. coli might affect the propionate catabolism in ASD. We report occurrence of peripheral inflammation in ASD children. We propose fecal HMGB1 as a non-invasive biomarker to detect GI symptoms., (Copyright © 2019 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: Gastro-oesophageal reflux is very common in the paediatric age group. There is no single and reliable test to distinguish between physiologic and pathological gastro-oesophageal reflux, and this lack of clear distinction between disease and normal can have a negative impact on the management of children., Aims: To evaluate the usefulness of 24-h oesophageal pH-impedance study in infants and children with suspected gastro-oesophageal reflux disease., Methods: Patients were classified by age groups (A-C) and reflux-related symptoms (typical and atypical). All underwent pH-impedance study. If the latter suggested an abnormal reflux, patients received therapy in accordance with NASPGHAN/ESPGHAN recommendations, while those with normal study had an additional diagnostic work-up. The efficacy of therapy was evaluated with a specific standardized questionnaire for different ages., Results: The study was abnormal in 203/428 patients (47%) while normal in 225/428 (53%). Of those with abnormal study, 109 exhibited typical symptoms (54%), and 94 atypical (46%). The great majority of the patients with abnormal study were responsive to medical anti-reflux therapy., Conclusions: We confirm the utility of prolonged oesophageal pH-impedance study in detecting gastro-oesophageal reflux disease in children and in guiding therapy. Performing oesophageal pH-impedance monitoring in children with suspected gastro-oesophageal reflux disease is helpful to establish the diagnosis and avoid unnecessary therapy., (Copyright © 2018 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)