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.

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.

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.

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.

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.

The Role of Endoscopy in the Diagnosis and Management of Small Bowel Pathology in Children.

Small bowel evaluation has been transformed by capsule endoscopy and advances in small bowel imaging, which provide reliable and noninvasive means for assessing the mucosal surface. Device-assisted enteroscopy has been critical for histopathological confirmation and endoscopic therapy for a wide range of small bowel pathology that conventional endoscopy cannot reach. The purpose of this review is to provide a comprehensive overview of the indications, techniques, and clinical applications of capsule endoscopy; device-assisted enteroscopy; and imaging studies for small bowel evaluation in children.

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.

Role of age in dynamics of autoantibodies in pediatric Celiac disease.

BACKGROUND: Celiac disease (CD) is characterized by elevated serum titers of autoantibodies IgA anti-tissue transglutaminase 2 (TGA-IgA) and IgA anti-endomysial (EMA), with small bowel mucosa atrophy. We evaluated age differences between CD children exhibiting variable antibody titers at diagnosis. METHODS: CD children diagnosed between January 2014 and June 2019, according to 2012 ESPGHAN guidelines were studied. All had EMA and TGA-IgA measurements, while a proportion of them underwent esophagogastroduodenoscopy (EGD). Patients were grouped based on serum TGA-IgA titers normalized to the upper limit of normal (ULN) and differences in median age (years) assessed by analysis of variance (ANOVA) and creation of orthogonal contrasts. RESULTS: CD was diagnosed in 295 subjects (median age: 4.4 [IQR: 2.60-8.52]) with a biopsy sparing protocol (high titer: ≥ 10xULN) and in 204 by EGD biopsy. Of the latter, 142 (median age: 8.5 [IQR: 5.81-11.06]) and 62 (median age: 9.5 [IQR: 6.26-12.76]) had a low (< 5xULN) and a moderate (≥ 5 < 10xULN) TGA-IgA titer, respectively. Potential CD was diagnosed in 20 patients (median age: 3.6 [IQR: 2.47-6.91]). The median age was significantly lower in the no-biopsy group (ANOVA: F(3, 516) = 25.98, p < .001) than in low- and moderate titer groups (p < 0.0001), while there was no statistical difference between biopsy-sparing and potential CD groups. CONCLUSION: CD patients with greatly elevated antibody titers (≥ 10xULN) were diagnosed at an earlier age than those with lower titers. This may indicate that an increase in TGA-IgA is independent of age and suggests a polarization of autoimmunity in younger individuals with higher serum antibody levels.

Monitoring Patients With Eosinophilic Esophagitis in Routine Clinical Practice - International Expert Recommendations.

BACKGROUND & AIMS: There are no studies or recommendations on optimal monitoring strategies for patients with eosinophilic esophagitis (EoE). Our objective was to develop guidance on how to monitor patients with EoE in routine clinical practice, on the basis of available clinical evidence and expert opinion. METHODS: A multidisciplinary, international group of EoE experts identified the following important 3 questions during several consensus meetings: why, by what means, and when to monitor patients with EoE. A steering committee was named, and 3 teams were formed to review literature and to formulate statements for each topic. In a Delphi survey, a level of agreement of ≥75% was defined as threshold value for acceptance. In a final conference, results were presented, critical points and comments on the statements were discussed, and statements were rephrased/rewritten if necessary. RESULTS: Eighteen EoE experts (14 adult and pediatric gastroenterologists, 2 pathologists and 2 allergists) with a median of 21.7 years in clinical practice, mostly academic or university-based, completed the Delphi survey, which included 11 statements and a proposed algorithm for monitoring patients with EoE. Each statement attained ≥75% agreement. Participants discussed and debated mostly about the statement concerning surveillance intervals for EoE patients with stable disease. CONCLUSIONS: It was concluded that effective maintenance treatment probably reduces the development of EoE complications, and regular, structured, and, under certain conditions, individualized clinical follow-up is recommended to assess disease activity while opening a window to monitoring side effects, adjusting therapy, and encouraging adherence to treatment. Follow-up should comprise symptom assessment and periodic or repeated endoscopy with histological assessment in specific EoE settings.

Enteroscopy in diagnosis and treatment of small bowel bleeding: A Delphi expert consensus.

BACKGROUND: Enteroscopy plays an important role in the management of small bowel bleeding. However, current guidelines are not specifically designed for small bowel bleeding and recommendations from different international societies do not always align. Consequently, there is heterogeneity in the definitions of clinical entities, clinical practice policies, and adherence to guidelines among clinicians. This represents an obstacle to providing the best patient care and to obtain homogeneous data for clinical research. AIMS: The aims of the study were to establish a consensus on the definitions of bleeding entities and on the role of enteroscopy in the management of small bowel bleeding using a Delphi process. METHODS: A core group of eight experts in enteroscopy identified five main topics of small bowel bleeding management and drafted statements on each topic. An expert panel of nine gastroenterologists participated in three rounds of the Delphi process, together with the core group. RESULTS: A total of 33 statements were approved after three rounds of Delphi voting. CONCLUSION: This Delphi consensus proposes clear definitions and a unifying strategy to standardize the management of small bowel bleeding. Furthermore, it provides a useful guide in daily practice for both clinical and technical issues of enteroscopy.

Occurrence and Clinical Impact of Eosinophilic Esophagitis in a Large Cohort of Children With Inflammatory Bowel Disease.

BACKGROUND: Scarce data have investigated the association between pediatric inflammatory bowel disease (IBD) and eosinophilic esophagitis (EoE). We, therefore, aimed to describe the epidemiology and the possible peculiar phenotype and natural history of such an association. METHODS: Case-control study is based on the Italian Society for Pediatric Gastroenterology (SIGENP) national registry. All children with a combined diagnosis of IBD and EoE were included. The overall prevalence and incidence in 2 periods, 2009 to 2015, and 2016 to 2021, were calculated. Cases were matched with IBD only and EoE only patients in a 1:3:3 ratio. Phenotype and outcomes (courses of steroids, risk of complications, surgery, treatment escalation, and hospitalization) were compared between groups. RESULTS: Eleven patients (age 11.2 ±â€…2.8 years, Males 91%) with EoE-IBD out of 3090 patients with IBD were identified, resulting in an overall prevalence of 0.35% and an incidence of 0.18% for 2009 to 2015 and 0.45% for 2016 to 2021. Treatment escalation rates for IBD were significantly higher in patients with IBD compared with EoE-IBD at 12- and 24-month follow-up (0% vs 30%, P = .04; and 9% vs 45.5%, P = .03, respectively). Furthermore, patients with IBD were at a significantly higher risk of hospitalization than both EoE-IBD and EoE patients (log rank P < .001). We found no significant differences in major outcomes related to the EoE course in EoE-IBD patients compared with EoE ones. CONCLUSIONS: The incidence and prevalence of EoE in children with IBD are low, although the incidence seems to be rising in recent years. Having EoE appears to be associated with a milder IBD disease course, whereas having IBD does not seem to affect the natural history of EoE. More data are needed to better define the phenotype of such association.

We investigated the association between pediatric inflammatory bowel disease (IBD) and eosinophilic esophagitis (EoE). Our results showed that having an EoE might be associated with a milder IBD disease course, but larger cohort analyses are needed to confirm such result.

Characterization of Eosinophilic Esophagitis From the European Pediatric Eosinophilic Esophagitis Registry (pEEr) of ESPGHAN.

OBJECTIVES: Few pediatric data on phenotypic aspects of eosinophilic esophagitis (EoE) are available. The pEEr registry was developed to prospectively characterize children with EoE from Europe and Israel. METHODS: pEEr is an ongoing prospective registry enrolling children with esophageal eosinophilia (≥15 eos/HPF). Anonymized data were collected from 19 pediatric centers. Data regarding demographics, clinical manifestations, endoscopy, histology, and therapies were collected. RESULTS: A total of 582 subjects (61% male) were analyzed. The median age at diagnosis was 10.5 years [interquartile range (IQR): 5.7-17.7], whereas the age at symptom onset was 9.2 years (IQR: 4.3-16.4), resulting in a median diagnostic delay of 1.2 years (IQR: 0.7-2.3). The diagnostic delay was longer below age <6 years. Shorter diagnostic delays were associated with the presence of food allergy or a family history for EoE. Symptoms varied by age with dysphagia and food impaction more common in adolescents, while vomiting and failure to thrive more common in younger children ( P < 0.001). Among endoscopic findings, esophageal rings were more common in adolescents, whereas exudates were more frequent in younger children( P < 0.001). Patients who responded to proton pump inhibitors (PPIs) were more likely to be older, males, and less often presented severe endoscopic findings. Patients unresponsive to PPIs received topical steroids (40%), elimination diet (41%), or a combined therapy (19%). CONCLUSIONS: EoE findings vary according to age in pediatric EoE. Young children are commonly characterized by non-specific symptoms, atopic dermatitis, food allergy, and inflammatory endoscopic lesions. Adolescents usually have dysphagia or food impaction, fibrostenotic lesions, and a better PPI response.

Impact of COVID-19 pandemic on pediatric endoscopy: A multicenter study on behalf of the SIGENP Endoscopy Working Group.

BACKGROUND: Aim of the present report was to investigate the repercussions of COVID-19 pandemic on the procedural volumes and on the main indications of pediatric digestive endoscopy in Italy. METHODS: An online survey was distributed at the beginning of December 2020 to Italian digestive endoscopy centers. Data were collected comparing two selected time intervals: the first from 1st of February 2019 to 30th June 2019 and the second from 1st February 2020 to 30th June 2020. RESULTS: Responses to the survey came from 24 pediatric endoscopy Units. Globally, a reduction of 37.2% was observed between 2019 and 2020 periods with a significant decrease in median number of procedures (111 vs 57, p < 0.001). Both the median number of procedures performed for new diagnoses and those for follow-up purposes significantly decreased in 2020 (63 vs 36, p < 0.001 and 42 vs 21, p< 0.001, respectively). We reported a drastic reduction of procedures performed for suspected Celiac Disease and Functional Gastrointestinal Disorders (55.1% and 58.0%, respectively). Diagnostic endoscopies for suspected IBD decreased of 15.5%, whereas procedures for Mucosal Healing (MH) assessment reduced of 48.3%. CONCLUSIONS: Our study provides real-world data outlining the meaningful impact of COVID-19 on pediatric endoscopy practice in Italy.

Epidemiological trends of pediatric IBD in Italy: A 10-year analysis of the Italian society of pediatric gastroenterology, hepatology and nutrition registry.

INTRODUCTION: The present study aimed at evaluating Italian epidemiological trends of pediatric inflammatory bowel diseases (IBD) over the period 2009-2018. MATERIALS AND METHODS: Data from 1969 patients enrolled in the Italian Society of Pediatric Gastroenterology, Hepatology and Nutrition Registry, by 49 pediatric IBD centers throughout the country, were analyzed, comparing three different time intervals (2009-2012, 2013-2015, 2016-2018). RESULTS: The number of new IBD diagnoses ranged from 175 to 219 per year, evenly distributed over the examined period of time. From 2009 to 2018, the minimal incidence ranged from 1.59 to 2.04 /105 inhabitants aged < 18 years, with an overall slight predominance of ulcerative colitis (UC) over Crohn's disease (CD) (ratio: 1.1). Mean diagnostic delay was 6.8 months for CD and 4.1 months for UC, with a significant reduction for CD when comparing the three-time intervals (p =0.008). The most frequent disease locations according to the Paris classification were ileocolonic for CD (41.3%) and pancolitis for UC (54.6%). CONCLUSIONS: The minimal incidence rate in Italy seems to have stabilized over the last two decades, even if it has increased when compared to previous reports. UC is still slightly more prevalent than CD in our country. Diagnostic delay significantly decreased for CD, reflecting an improved diagnostic capacity.

A new double immunohistochemistry method to detect mucosal anti-transglutaminase IgA deposits in coeliac children.

BACKGROUND: Intestinal transglutaminase (TG2) IgA deposits represent early marker of coeliac disease (CeD) and can predict the evolution towards intestinal atrophy. AIMS: To validate a double immunohistochemistry method for the determination of intestinal TG2 IgA deposits on formalin-fixed paraffin-embedded biopsies. METHODS: Immunohistochemistry was tested on: 1) children with overt CeD [persistently positive serum IgA anti-tissue transglutaminase type 2 (TGA-IgA) with moderate or low titer, and histological findings of CeD]; 2) potential CeD (persistently positive serum TGA-IgA and normal intestinal mucosa) and 3) controls (negative serum TGA-IgA and normal intestinal mucosa). RESULTS: Samples from 61 children were analyzed (32 overt CeD, 14 potential CeD, and 15 controls). Deposits appeared as focal, multifocal, or confluent extracellular foci of red and brown staining colocalization in the sub-epithelium and around mucosal vessels. Deposits were present in all 32 children with overt CeD and in 9/14 potential CeD. Deposits were never observed in the 15 controls. Patients with higher serum level of TGA-IgA and with mucosal atrophy showed mostly a multifocal/diffuse pattern of deposits distribution. The bulb appeared most severely involved. In potential CeD deposits showed mainly a focal distribution. CONCLUSION: Our results indicate double immunohistochemistry as promising diagnostic tool to improve diagnosis of CeD.

Overview of the Pediatric Endoscopy Quality Improvement Network Quality Standards and Indicators for Pediatric Endoscopy: A Joint NASPGHAN/ESPGHAN Guideline.

INTRODUCTION: Pediatric-specific quality standards for endoscopy are needed to define best practices, while measurement of associated indicators is critical to guide quality improvement. The international Pediatric Endoscopy Quality Improvement Network (PEnQuIN) working group was assembled to develop and define quality standards and indicators for pediatric gastrointestinal endoscopic procedures through a rigorous guideline consensus process. METHODS: The Appraisal of Guidelines for REsearch and Evaluation (AGREE) II instrument guided PEnQuIN members, recruited from 31 centers of various practice types representing 11 countries, in generating and refining proposed quality standards and indicators. Consensus was sought via an iterative online Delphi process, and finalized at an in-person conference. Quality of evidence and strength of recommendations were rated according to the GRADE (Grading of Recommendation Assessment, Development, and Evaluation) approach. RESULTS: Forty-nine quality standards and 47 indicators reached consensus, encompassing pediatric endoscopy facilities, procedures, endoscopists, and the patient experience. The evidence base for PEnQuIN standards and indicators was largely adult-based and observational, and downgraded for indirectness, imprecision, and study limitations to "very low" quality, resulting in "conditional" recommendations for most standards (45/49). CONCLUSIONS: The PEnQuIN guideline development process establishes international agreement on clinically meaningful metrics that can be used to promote safety and quality in endoscopic care for children. Through PEnQuIN, pediatric endoscopists and endoscopy services now have a framework for auditing, providing feedback, and ultimately, benchmarking performance. Expansion of evidence and prospective validation of PEnQuIN standards and indicators as predictors of clinically relevant outcomes and high-quality pediatric endoscopic care is now a research priority.

Pediatric Endoscopy Quality Improvement Network Quality Standards and Indicators for Pediatric Endoscopy Facilities: A Joint NASPGHAN/ESPGHAN Guideline.

INTRODUCTION: There is increasing international recognition of the impact of variability in endoscopy facilities on procedural quality and outcomes. There is also growing precedent for assessing the quality of endoscopy facilities at regional and national levels by using standardized rating scales to identify opportunities for improvement. METHODS: With support from the North American and European Societies of Pediatric Gastroenterology Hepatology and Nutrition (NASPGHAN and ESPGHAN), an international working group of the Pediatric Endoscopy Quality Improvement Network (PEnQuIN) used the methodological strategy of the Appraisal of Guidelines for REsearch and Evaluation (AGREE) II instrument to develop standards and indicators relevant for assessing the quality of facilities where endoscopic care is provided to children. Consensus was reached via an iterative online Delphi process and subsequent in-person meeting. The quality of evidence and strength of recommendations were rated according to the GRADE (Grading of Recommendation Assessment, Development and Evaluation) approach. RESULTS: The PEnQuIN working group achieved consensus on 27 standards for facilities supporting pediatric endoscopy, as well 10 indicators that can be used to identify high-quality endoscopic care in children. These standards were subcategorized into three subdomains: Quality of Clinical Operations (15 standards, 5 indicators); Patient and Caregiver Experience (9 standards, 5 indicators); and Workforce (3 standards). DISCUSSION: The rigorous PEnQuIN process successfully yielded standards and indicators that can be used to universally guide and measure high-quality facilities for procedures around the world where endoscopy is performed in children. It also underscores the current paucity of evidence for pediatric endoscopic care processes, and the need for research into this clinical area.

Pediatric Endoscopy Quality Improvement Network Quality Standards and Indicators for Pediatric Endoscopic Procedures: A Joint NASPGHAN/ESPGHAN Guideline.

INTRODUCTION: High-quality pediatric gastrointestinal procedures are performed when clinically indicated and defined by their successful performance by skilled providers in a safe, comfortable, child-oriented, and expeditious manner. The process of pediatric endoscopy begins when a plan to perform the procedure is first made and ends when all appropriate patient follow-up has occurred. Procedure-related standards and indicators developed to date for endoscopy in adults emphasize cancer screening and are thus unsuitable for pediatric medicine. METHODS: With support from the North American and European Societies of Pediatric Gastroenterology Hepatology and Nutrition (NASPGHAN and ESPGHAN), an international working group of the Pediatric Endoscopy Quality Improvement Network (PEnQuIN) used the methodological strategy of the Appraisal of Guidelines for REsearch and Evaluation (AGREE) II instrument to develop standards and indicators relevant for assessing the quality of endoscopic procedures. Consensus was sought via an iterative online Delphi process and finalized at an in-person conference. The quality of evidence and strength of recommendations were rated according to the GRADE (Grading of Recommendation Assessment, Development, and Evaluation) approach. RESULTS: The PEnQuIN working group achieved consensus on 14 standards for pediatric endoscopic procedures, as well as 30 indicators that can be used to identify high-quality procedures. These were subcategorized into three subdomains: Preprocedural (3 standards, 7 indicators), Intraprocedural (8 standards, 18 indicators), and Postprocedural (3 standards, 5 indicators). A minimum target for the key indicator, "rate of adequate bowel preparation," was set at ≥80%. DISCUSSION: It is recommended that all facilities and individual providers performing pediatric endoscopy worldwide initiate and engage with the procedure-related standards and indicators developed by PEnQuIN to identify gaps in quality and drive improvement.