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Abstract Background The amino acid-producing Gram-positive Corynebacterium glutamicum is auxotrophic for biotin although biotin ring assembly starting from the precursor pimeloyl-CoA is still functional. It possesses AccBC, the α-subunit of the acyl-carboxylases involved in fatty acid and mycolic acid synthesis, and pyruvate carboxylase as the only biotin-containing proteins. Comparative genome analyses suggested that the putative transport system BioYMN encoded by cg2147, cg2148 and cg2149 might be involved in biotin uptake by C. glutamicum. Results By comparison of global gene expression patterns of cells grown with limiting or excess supply of biotin or with dethiobiotin as supplement replacing biotin revealed that expression of genes coding for enzymes of biotin ring assembly and for the putative uptake system was regulated according to biotin availability. RT-PCR and 5'-RACE experiments demonstrated that the genes bioY, bioM, and bioN are transcribed from one promoter as a single transcript. Biochemical analyses revealed that BioYMN catalyzes the effective uptake of biotin with a concentration of 60 nM biotin supporting a half-maximal transport rate. Maximal biotin uptake rates were at least five fold higher in biotin-limited cells as compared to cells grown with excess biotin. Overexpression of bioYMN led to an at least 50 fold higher biotin uptake rate as compared to the empty vector control. Overproduction of BioYMN alleviated biotin limitation and interfered with triggering L-glutamate production by biotin limitation. Conclusions The operon bioYMN from C. glutamicum was shown to be induced by biotin limitation. Transport assays with radio-labeled biotin revealed that BioYMN functions as a biotin uptake system. Overexpression of bioYMN affected L-glutamate production triggered by biotin limitation.

Abstract Background The maintenance of internal pH in bacterial cells is challenged by natural stress conditions, during host infection or in biotechnological production processes. Comprehensive transcriptomic and proteomic analyses has been conducted in several bacterial model systems, yet questions remain as to the mechanisms of pH homeostasis. Results Here we present the comprehensive analysis of pH homeostasis in C. glutamicum, a bacterium of industrial importance. At pH values between 6 and 9 effective maintenance of the internal pH at 7.5 ± 0.5 pH units was found. By DNA microarray analyses differential mRNA patterns were identified. The expression profiles were validated and extended by 1D-LC-ESI-MS/MS based quantification of soluble and membrane proteins. Regulators involved were identified and thereby participation of numerous signaling modules in pH response was found. The functional analysis revealed for the first time the occurrence of oxidative stress in C. glutamicum cells at neutral and low pH conditions accompanied by activation of the iron starvation response. Intracellular metabolite pool analysis unraveled inhibition of the TCA and other pathways at low pH. Methionine and cysteine synthesis were found to be activated via the McbR regulator, cysteine accumulation was observed and addition of cysteine was shown to be toxic under acidic conditions. Conclusions Novel limitations for C. glutamicum at non-optimal pH values were identified by a comprehensive analysis on the level of the transcriptome, proteome, and metabolome indicating a functional link between pH acclimatization, oxidative stress, iron homeostasis, and metabolic alterations. The results offer new insights into bacterial stress physiology and new starting points for bacterial strain design or pathogen defense.

Abstract Background The influence of the membrane-bound AAA+ protease FtsH on membrane and cytoplasmic proteins of Corynebacterium glutamicum was investigated in this study. For the analysis of the membrane fraction, anion exchange chromatography was combined with SDS-PAGE, while the cytoplasmic protein fraction was studied by conventional two-dimensional gel electrophoresis. Results In contrast to the situation in other bacteria, deletion of C. glutamicum ftsH has no significant effect on growth in standard minimal medium or response to heat or osmotic stress. On the proteome level, deletion of the ftsH gene resulted in a strong increase of ten cytoplasmic and membrane proteins, namely biotin carboxylase/biotin carboxyl carrier protein (accBC), glyceraldehyde-3-phosphate dehydrogenase (gap), homocysteine methyltransferase (metE), malate synthase (aceB), isocitrate lyase (aceA), a conserved hypothetical protein (NCgl1985), succinate dehydrogenase A (sdhA), succinate dehydrogenase B (sdhB), succinate dehydrogenase CD (sdhCD), and glutamate binding protein (gluB), while 38 cytoplasmic and membrane-associated proteins showed a decreased abundance. The decreasing amount of succinate dehydrogenase A (sdhA) in the cytoplasmic fraction of the ftsH mutant compared to the wild type and its increasing abundance in the membrane fraction indicates that FtsH might be involved in the cleavage of a membrane anchor of this membrane-associated protein and by this changes its localization. Conclusion The data obtained hint to an involvement of C. glutamicum FtsH protease mainly in regulation of energy and carbon metabolism, while the protease is not involved in stress response, as found in other bacteria.

Objectives: Both superior mesenteric artery syndrome (SMAS) and cannabinoid hyperemesis syndrome (CHS) may present with abdominal pain, nausea, and emesis - making them difficult to differentiate or determine when they co-occur in adolescents who regularly use cannabis. Here, we present nine cases of CHS co-occurring with SMAS and characterize their clinical courses., Methods: Patients admitted at Children's Hospital of Colorado between January 1, 2015, and March 23, 2023, who had both cannabis use (F12.1-F12.99) and chronic vascular disorders of the intestine (K55.1) on their problem lists were identified from the electronic medical record using ICD 10 codes. Nine met criteria for SMAS and chronic cannabis use., Results: Six of nine patients were female. The most common presenting symptoms were nausea (9), vomiting (9), and weight loss (9). Four patients received cannabis cessation support. Patients lost a mean of 6.0 kg, had an average body mass index (BMI) of 15.61 percentile (17.7 kg/m 2 ) and BMI Z-scores of -1.5. Symptoms were present for a mean of 19.6 weeks before diagnosis., Conclusions: Adolescents who experience nausea, vomiting, abdominal pain, and weight loss in association with chronic cannabis use and/or SMAS can present with confusing and overlapping symptoms. Our cohort was described as having CHS with co-occurring SMAS on imaging. Although the etiology of weight loss cannot be definitively ascertained, we postulate that the recurring emetic attacks from CHS led to weight loss resulting in SMAS. Improvement in diagnostic criteria for this population as well as cannabis cessation programming may aid in deceasing morbidity from these co-occurring conditions., (© 2024 European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Purpose of Review: The prevalence of childhood and adolescent obesity in the United States has reached alarming levels, necessitating effective interventions such as bariatric surgery. This article reviews the current state of bariatric surgery in the adolescent population, highlighting the common complications encountered in post-bariatric patients. Furthermore, it outlines the pivotal role of endoscopy in both the prevention and management of these bariatric complications., Recent Findings: Though only a minority of eligible adolescent patients undergo bariatric surgery the number of cases continues to increase. Sleeve gastrectomy has emerged as the preferred type of surgery, with the best balance of safety and efficacy. However, only a small number of pediatric surgeons have additional bariatric training and a number of technical aspects of the surgery itself impact the risk for post-surgical complications. Gastric sleeve stenosis, anastomotic leaks and gastroesophageal reflux are the most common of these complications. Ability to perform dilation of sleeve stenosis, closure of anastomotic leaks and evaluation of reflux are critical tools in the endoscopic toolbox necessary for the management of these complicated patients. Bariatric surgery remains the most effective treatment available for management of morbid obesity in adolescents but has significant associated complications. Pediatric gastroenterologists must be familiar in the endoscopic management of these complications and are crucial in creating a high functioning adolescent bariatric program., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Aims: Pediatric advanced endoscopy consists primarily of endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound (EUS) and is becoming more common in pediatrics. This study aims to characterize the current landscape of pediatric advanced endoscopy training and practice by directly surveying independently practicing pediatric advanced endoscopists (PAEs). We also aim to ascertain expert opinion on competency in pediatric ERCP and EUS., Methods: A 66-question REDCap survey and a 73-question Qualtrics survey were distributed to members of the ERCP Special Interest Group of North American Society of Pediatric Gastroenterology, Hepatology, and Nutrition. Respondents currently performing ERCP or EUS independently in children were included. Statistical analysis was performed using Mann-Whitney U test., Results: Of 41 PAEs surveyed, 38 (92.7%) responded and 27 independent practitioners were included. Thirteen respondents performed EUS. PAEs who completed an advanced endoscopy fellowship (AEF) were more comfortable performing American Society for Gastrointestinal Endoscopy grade 3 or grade 4 ERCPs ( P < 0.0008) and felt more prepared to practice EUS independently than other trainees. Expert opinion of PAEs felt a threshold of 200 procedures was needed to attain competency in either ERCP or EUS. Pediatric duodenoscope exposure improved comfort in performing ERCP in children <10 kg ( P = 0.009)., Conclusions: Training of pediatric gastroenterologists in ERCP and EUS are highly variable, though the skills attained are similar. AEF-trained specialists reported greater training volumes and felt more prepared to practice independently than those who did not. Competency thresholds determined by expert PAEs for ERCP and EUS agree with American Society for Gastrointestinal Endoscopy guidelines for adult advanced endoscopy trainees., Competing Interests: Dr Mark received a one-time consulting fee from EvoEndo; however this company does not produce any products for endoscopic retrograde cholangiopancreatography or endoscopic ultrasound. No other authors have any conflicts of interest to report., (Copyright © 2023 by European Society for European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

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., Competing Interests: Conflicts of interest: P.B. has served on the advisory boards of Biocodex, Nutricia, and Avanos. P.B. has received honoraria for speaking engagements from AbbVie, Nutricia, and Avanos. N.M.C.'s institution received speaker fees, advisory board fees, and research funding on his behalf from AbbVie, Eli Lilly, Takeda, Shire, Pfizer, and 4D Pharma. D.S.F. has received royalties from UpToDate (“Pediatric Caustic Ingestions”). I.H. has received honoraria for speaking engagements from BioGaia, Oktal Pharma, Nutricia, Abela Pharm, and Nestle. H.Q.H. has received research support from Janssen, AbbVie, Takeda, and Allergan. H.Q.H. has served on the advisory boards of AbbVie and Jansen. K.J. has received research support from Janssen, AbbVie, and the Center for Drug Research and Development (CDRD). K.J. has served on the advisory boards of Janssen, AbbVie, and Merck and participates in the speaker's bureau for AbbVie and Janssen. D.G.L. has received consultant fees from EvoEndo. J.R.L. has received research support from AbbVie and an honorarium from Mead Johnson. A.R.O. has received research support from Janssen, AbbVie, Pfizer, and Eli Lilly. A.R.O. has served on the advisory boards of Janssen, AbbVie, and Eli Lilly and participates in the speaker's bureau for AbbVie and Janssen. J.R.R. has received research support from AbbVie and Janssen. J.R.R. has served on the advisory boards of Janssen, BMS, Eli Lilly, and Pfizer. C.M.W. has received research support from AbbVie., (Copyright © 2021 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

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., Competing Interests: Conflicts of interest: P.B. has served on the advisory boards of Biocodex, Nutricia, and Avanos. P.B. has received honoraria for speaking engagements from AbbVie, Nutricia, and Avanos. N.M.C.'s institution received speaker fees, advisory board fees, and research funding on his behalf from AbbVie, Eli Lilly, Takeda, Shire, Pfizer, and 4D Pharma. D.S.F. has received royalties from UpToDate (“Pediatric Caustic Ingestions”). I.H. has received honoraria for speaking engagements from BioGaia, Oktal Pharma, Nutricia, Abela Pharm, and Nestle. H.Q.H. has received research support from Janssen, AbbVie, Takeda, and Allergan. H.Q.H. has served on the advisory boards of AbbVie and Jansen. K.J. has received research support from Janssen, AbbVie, and the Center for Drug Research and Development (CDRD). K.J. has served on the advisory boards of Janssen, AbbVie, and Merck and participates in the speaker's bureau for AbbVie and Janssen. D.G.L. has received consultant fees from EvoEndo. J.R.L. has received research support from AbbVie and an honorarium from Mead Johnson. A.R.O. has received research support from Janssen, AbbVie, Pfizer, and Eli Lilly. A.R.O. has served on the advisory boards of Janssen, AbbVie, and Eli Lilly and participates in the speaker's bureau for AbbVie and Janssen. J.R.R. has received research support from AbbVie and Janssen. J.R.R. has served on the advisory boards of Janssen, BMS, Eli Lilly, and Pfizer. C.M.W. has received research support from AbbVie., (Copyright © 2021 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Introduction: High-quality procedure reports are a cornerstone of high-quality pediatric endoscopy as they ensure the clear communication of procedural events and outcomes, guide patient care and facilitate continuous quality improvement. The aim of this document is to outline standardized reporting elements that achieved international consensus as requirements for high-quality pediatric endoscopy procedure reports., 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 Delphi methodology to identify key elements that should be found in all pediatric endoscopy reports. Item reduction was attained through iterative rounds of anonymized online voting using a 6-point scale. Responses were analyzed after each round and items were excluded from subsequent rounds if ≤50% of panelists rated them as 5 ("agree moderately") or 6 ("agree strongly"). Reporting elements that ≥70% of panelists rated as "agree moderately" or "agree strongly" were considered to have achieved consensus., Results: Twenty-six PEnQuIN group members from 25 centers internationally rated 63 potential reporting elements that were generated from a systematic literature review and the Delphi panelists. The response rates were 100% for all three survey rounds. Thirty reporting elements reached consensus as essential for inclusion within a pediatric endoscopy report., Discussion: It is recommended that the PEnQuIN Reporting Elements for pediatric endoscopy be universally employed across all endoscopists, procedures and facilities as a foundational means of ensuring high-quality endoscopy services, while facilitating quality improvement activities in pediatric endoscopy., Competing Interests: Conflicts of interest: P.B. has served on the advisory boards of Biocodex, Nutricia, and Avanos. P.B. has received honoraria for speaking engagements from AbbVie, Nutricia, and Avanos. N.M.C.'s institution received speaker fees, advisory board fees, and research funding on his behalf from AbbVie, Eli Lilly, Takeda, Shire, Pfizer, and 4D Pharma. D.S.F. has received royalties from UpToDate (“Pediatric Caustic Ingestions”). I.H. has received honoraria for speaking engagements from BioGaia, Oktal Pharma, Nutricia, Abela Pharm, and Nestle. H.Q.H. has received research support from Janssen, AbbVie, Takeda, and Allergan. H.Q.H. has served on the advisory boards of AbbVie and Jansen. K.J. has received research support from Janssen, AbbVie, and the Center for Drug Research and Development (CDRD). K.J. has served on the advisory boards of Janssen, AbbVie, and Merck and participates in the speaker's bureau for AbbVie and Janssen. D.G.L. has received consultant fees from EvoEndo. J.R.L. has received research support from AbbVie and an honorarium from Mead Johnson. A.R.O. has received research support from Janssen, AbbVie, Pfizer, and Eli Lilly. A.R.O. has served on the advisory boards of Janssen, AbbVie, and Eli Lilly and participates in the speaker's bureau for AbbVie and Janssen. J.R.R. has received research support from AbbVie and Janssen. J.R.R. has served on the advisory boards of Janssen, BMS, Eli Lilly, and Pfizer. C.M.W. has received research support from AbbVie., (Copyright © 2021 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

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., Competing Interests: Conflicts of interest: P.B. has served on the advisory boards of Biocodex, Nutricia, and Avanos. P.B. has received honoraria for speaking engagements from AbbVie, Nutricia, and Avanos. N.M.C.'s institution received speaker fees, advisory board fees, and research funding on his behalf from AbbVie, Eli Lilly, Takeda, Shire, Pfizer, and 4D Pharma. D.S.F. has received royalties from UpToDate (“Pediatric Caustic Ingestions”). I.H. has received honoraria for speaking engagements from BioGaia, Oktal Pharma, Nutricia, Abela Pharm, and Nestle. H.Q.H. has received research support from Janssen, AbbVie, Takeda, and Allergan. H.Q.H. has served on the advisory boards of AbbVie and Jansen. K.J. has received research support from Janssen, AbbVie, and the Center for Drug Research and Development (CDRD). K.J. has served on the advisory boards of Janssen, AbbVie, and Merck and participates in the speaker's bureau for AbbVie and Janssen. D.G.L. has received consultant fees from EvoEndo. J.R.L. has received research support from AbbVie and an honorarium from Mead Johnson. A.R.O. has received research support from Janssen, AbbVie, Pfizer and Eli Lilly. A.R.O. has served on the advisory boards of Janssen, AbbVie, and Eli Lilly and participates in the speaker's bureau for AbbVie and Janssen. J.R.R. has received research support from AbbVie and Janssen. J.R.R. has served on the advisory boards of Janssen, BMS, Eli Lilly, and Pfizer. C.M.W. has received research support from AbbVie., (Copyright © 2021 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Introduction: High-quality pediatric endoscopy requires reliable performance of procedures by competent individual providers who consistently uphold all standards determined to assure optimal patient outcomes. Establishing consensus expectations for ongoing monitoring and assessment of individual pediatric endoscopists is a method for confirming the highest possible quality of care for such procedures worldwide. We aim to provide guidance to define and measure quality of endoscopic care for children., 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 endoscopists. 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 6 standards that all providers who perform pediatric endoscopy should uphold and 2 standards for pediatric endoscopists in training, with 7 corresponding indicators that can be used to identify high-quality endoscopists. Additionally, these can inform continuous quality improvement at the provider level. Minimum targets for defining high-quality pediatric ileocolonoscopy were set for 2 key indicators: cecal intubation rate (≥90%) and terminal ileal intubation rate (≥85%)., Discussion: It is recommended that all individual providers performing or training to perform pediatric endoscopy initiate and engage with these international endoscopist-related standards and indicators developed by PEnQuIN., Competing Interests: Conflicts of interest: P.B. has served on the advisory boards of Biocodex, Nutricia, and Avanos. P.B. has received honoraria for speaking engagements from AbbVie, Nutricia, and Avanos. N.M.C.'s institution received speaker fees, advisory board fees, and research funding on his behalf from AbbVie, Eli Lilly, Takeda, Shire, Pfizer, and 4D Pharma. D.S.F. has received royalties from UpToDate (“Pediatric Caustic Ingestions”). I.H. has received honoraria for speaking engagements from BioGaia, Oktal Pharma, Nutricia, Abela Pharm, and Nestle. H.Q.H. has received research support from Janssen, AbbVie, Takeda, and Allergan. H.Q.H. has served on the advisory boards of AbbVie and Jansen. K.J. has received research support from Janssen, AbbVie, and the Center for Drug Research and Development (CDRD). K.J. has served on the advisory boards of Janssen, AbbVie, and Merck and participates in the speaker's bureau for AbbVie and Janssen. D.G.L. has received consultant fees from EvoEndo. J.R.L. has received research support from AbbVie and an honorarium from Mead Johnson. A.R.O. has received research support from Janssen, AbbVie, Pfizer, and Eli Lilly. A.R.O. has served on the advisory boards of Janssen, AbbVie, and Eli Lilly and participates in the speaker's bureau for AbbVie and Janssen. J.R.R. has received research support from AbbVie and Janssen. J.R.R. has served on the advisory boards of Janssen, BMS, Eli Lilly, and Pfizer. C.M.W. has received research support from AbbVie., (Copyright © 2021 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Etiologically, 5% of all cancers worldwide are caused by the high-risk human papillomaviruses (hrHPVs). These viruses encode two oncoproteins (E6 and E7) whose expression is required for cancer initiation and maintenance. Among their cellular targets are the p53 and the retinoblastoma tumor suppressor proteins. Inhibition of the hrHPV E6-mediated ubiquitylation of p53 through the E6AP ubiquitin ligase results in the stabilization of p53, leading to cellular apoptosis. We utilized a live cell high-throughput screen to determine whether exogenous microRNA (miRNA) transfection had the ability to stabilize p53 in hrHPV-positive cervical cancer cells expressing a p53-fluorescent protein as an in vivo reporter of p53 stability. Among the miRNAs whose transfection resulted in the greatest p53 stabilization was 375-3p, which has previously been reported to stabilize p53 in HeLa cells, providing validation of the screen. The top 32 miRNAs, in addition to 375-3p, were further assessed using a second cell-based p53 stability reporter system, as well as in nonreporter HeLa cells to examine their effects on endogenous p53 protein levels, resulting in the identification of 23 miRNAs whose transfection increased p53 levels in HeLa cells. While a few miRNAs that stabilized p53 led to decreases in E6AP protein levels, all targeted HPV oncoprotein expression. We further examined subsets of these miRNAs for their abilities to induce apoptosis and determined whether it was p53-mediated. The introduction of specific miRNAs revealed surprisingly heterogeneous responses in different cell lines. Nonetheless, some of the miRNAs described here have potential as therapeutics for treating HPV-positive cancers. IMPORTANCE Human papillomaviruses cause approximately 5% of all cancers worldwide and encode genes that contribute to both the initiation and maintenance of these cancers. The viral oncoprotein E6 is expressed in all HPV-positive cancers and functions by targeting the degradation of p53 through the engagement of the cellular ubiquitin ligase E6AP. Inhibiting the degradation of p53 leads to apoptosis in HPV-positive cancer cells. Using a high-throughput live cell assay, we identified several miRNAs whose transfection stabilize p53 in HPV-positive cells. These miRNAs have the potential to be used in the treatment of HPV-positive cancers.

Objectives: Use of non-steroidal anti-inflammatory drugs (NSAIDs) for post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) prevention in pediatrics is not well studied. Because of difficulty in accurately dosing indomethacin suppositories in pediatric patients, our center has used intravenous ketorolac for PEP prevention and present data on its safety and associated PEP rates., Methods: Prospective monitoring of PEP for all patients who underwent ERCP at a pediatric tertiary care center from July 2010 to June 2018. Retrospective review of patient and procedural factors and severity of PEP. Routine use of ketorolac for PEP prevention began in 2014., Results: Two hundred and ninety-eight ERCPs were analyzed. One hundred and sixty-six patients received intraprocedural ketorolac and 132 did not. One patient had post-ERCP bleeding and bleeding rates were not significantly different between ketorolac and non-ketorolac groups (0.6% vs 0%, P = 1). Overall rates of PEP were not significantly different between the ketorolac and no ketorolac group (9% vs 13%, P = 0.29); however, for high-risk pediatric patients with injection of contrast into and/or cannulation of the pancreatic duct, the rates of PEP were significantly lower for patients who received ketorolac (11% vs 25%, P = 0.035)., Conclusions: Pediatric patients undergoing ERCP with manipulation of the pancreatic duct are high risk for PEP, and ketorolac was associated with a lower rate of PEP in these patients. Ketorolac was well tolerated without a higher rate of bleeding after ERCP. These results are the first to provide evidence showing an association with intraprocedural NSAID use and lower rates of PEP in select pediatric patients., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Background: Lithium button battery ingestions have been increasing in frequency since the early 2000s and can develop severe and sometimes fatal complications from caustic injury even after rapid battery removal. To aid in clinical decision-making, we began obtaining magnetic resonance imaging (MRI)/MR angiography in these patients., Objective: Our goal was to review MRI/MR angiography imaging in button battery ingestion cases and compare with other imaging, clinical data and outcomes in these patients., Materials and Methods: In this retrospective institutional-review-board-approved study, we reviewed all button battery ingestion cases with MRI from April 2012 to September 2018. Clinical data, endoscopic findings and all imaging studies were rereviewed. MRIs were evaluated for inflammation, blooming artifact and complications including vascular injury, tracheoesophageal fistula, esophageal perforation and spondylodiscitis, and compared to endoscopy, esophagram and bronchoscopy., Results: Twenty-three patients with button battery ingestions had a total of 51 MRI/MR angiograms. Seventy percent of the cohort was male with a median age of 2 years (range: 0.94-17 years). Severe complications were found in 48% of patients (11/23), including esophageal perforation (n=11), tracheoesophageal fistula (n=3) and spondylodiscitis (n=1). No patients had vascular injury. Cervical location of the battery was significantly associated with severe complications (10/11 cases). The length of the blooming artifact was greater than 2 cm in those with severe complications and, in most cases, <2 cm in those without severe complications. All complications were seen on initial screening MR exam with serial exams showing decreased inflammation., Conclusion: MRI/MR angiography can provide valuable information about complications, including esophageal perforation, tracheoesophageal fistula and spondylodiscitis. Decreasing inflammation surrounding the esophagus and vasculature is believed to be clinically reassuring and aids in managing button battery ingestion patients., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Endoscopy and mucosal biopsies are essential to the diagnosis of EoE. Together they either confirm or exclude mucosal eosinophilia and provide a visual inspection of the esophagus that may be consistent with EoE or suggest other underlying etiologies. Endoscopy also plays an important therapeutic role in the management of EoE including the assessment of treatment response and treatment of associated complications including esophageal stricture and food impaction. Assessment of treatment response largely depends on endoscopy and mucosal biopsies although less invasive strategies may eventually provide alternative means to assess mucosal inflammation. Herein we will review current use of endoscopy in EoE, including recently developed technologies and their role in the management of EoE., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Nguyen, Kramer and Menard-Katcher.)

Approximately 5% of cancers are caused by high-risk human papillomaviruses. Although very effective preventive vaccines will reduce this cancer burden significantly over the next several decades, they have no therapeutic effect for those already infected and remaining at risk for malignant progression of hrHPV lesions. HPV-associated cancers are dependent upon the expression of the viral E6 and E7 oncogenes. The oncogenic function of hrHPV E6 relies partially on its ability to induce p53 degradation. Since p53 is generally wildtype in hrHPV-associated cancers, p53 stabilization arrests proliferation, induces apoptosis and/or results in senescence. Here we describe a live cell, image-based high-throughput screen to identify compounds that stabilize p53 and/or affect viability in HPV-positive cancer HeLa cells. We validate the robustness and potential of this screening assay by assessing the activities of approximately 6,500 known bioactive compounds, illustrating its capability to function as a platform to identify novel therapeutics for hrHPV., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The eosinophilic esophagitis (EoE) endoscopic reference score (EREFS) is a validated system for description, recognition, and reporting of EoE findings during esophagogastroduodenoscopy (EGD). This scoring system correlates with esophageal eosinophilia and therapeutic responses and has validated diagnostic accuracy with good inter- and intraobserver reliability in pediatric and adult patients. In this study, we aimed to improve physician education on and documentation of EREFS and correlate EREFS scoring with eosinophil density on histology., Methods: Applying the "Plan, Do, Study, Act" methodology for quality improvement between October 2018 and November 2019, we established a baseline rate of EREFS completion by review of the electronic medical record (EMR). Key drivers were identified, and 3 interventions were implemented., Results: Over 12 months, 542 distinct endoscopies were performed on 410 patients for EoE surveillance. Patients were 68% male with a mean age of 10.9 years (SD 5.7 years), mean EREFS score of 2.14 (SD 1.88), and mean peak eosinophil count 30.9 eos/hpf (SD 37.1 eos/hpf). Baseline EREFS completion rate of 72.7% (90% CI, 67.4-77.4). Following all 3 PDSA cycles, EREFS completion rate significantly improved to greater than desired target of 90% (94.9%; 90% CI, 90.6-97.6; P  < 0.001)., Conclusion: Interventions including provider education and the inclusion of EREFS in documentation templates can increase adoption rates of EREFS among providers caring for patients with known EoE., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 The Author(s). Published by Wolters Kluwer on behalf of European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Objectives: The aim of the study was to validate rates of fever after pediatric gastrointestinal endoscopy, to describe clinical outcomes of postendoscopy fever (PEF) cases, and to assess the effect of a PEF clinical care guideline (CCG) on hospital use., Patients and Methods: Episodes of PEF were reviewed from a large prospective database of all adverse events following pediatric gastrointestinal endoscopy at an academic children's hospital. A CCG was implemented to standardize care of children with reported fever after endoscopy and reduce unnecessary resource use. Chi-squared analysis was performed to compare rates of hospital use for evaluation of PEF before and after implementation of the CCG., Results: PEF occurred in 0.55% of the 27,100 endoscopies performed during the present study period. In the 150 cases of reported fever, the rate of identified endoscopy-related infection was low (4.0%). The rate of PEF was significantly higher in patients who underwent interventional procedures (0.81%) than those who underwent diagnostic endoscopy (0.51%, P = 0.02). In patients who experienced PEF, the CCG significantly reduced hospital use, decreasing emergency department visits and hospital admissions by 52.1% (P < 0.0001) without leading to negative patient outcomes., Conclusion: PEF in children rarely represents clinically significant infection and may be due in part to inflammation from tissue damage and/or physiologic stress. The present study shows that implementation of a PEF CCG may reduce unnecessary care while maintaining patient safety. Furthermore, multicenter studies are required to confirm the overall safety of similar clinical algorithms., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Background and Aims: Removal of gastric button batteries (BBs) remains controversial. Our aim was to better define the spectrum of injury and to characterize clinical factors associated with injury from retained gastric BBs., Methods: In this multicenter retrospective cohort study from January 2014 through May 2018, pediatric gastroenterologists from 4 pediatric tertiary care centers identified patients, aged 0 to 18 years, who had a retained gastric BB on radiography and subsequently underwent endoscopic assessment. Demographic and clinical information were abstracted from electronic health records using a standard data collection form., Results: Sixty-eight patients with a median age of 2.5 years underwent endoscopic retrieval of a gastric BB. At presentation, 17 (25%) were symptomatic. Duration from ingestion to endoscopic removal was known for 65 patients (median, 9 hours [interquartile range, 5-19]). Median time from ingestion to first radiographic evaluation was 2 hours. At endoscopic removal, 60% of cases had visual evidence of mucosal damage, which correlated with duration of BB retention (P = .0018). Time to retrieval of the BB was not statistically significant between symptomatic and asymptomatic subjects (P = .12). After adjusting for age and symptoms, the likelihood of visualizing gastric damage among patients who had BBs removed 12 hours post ingestion was 4.5 times that compared with those with BB removal within 12 hours of ingestion., Conclusions: In this study, swallowed BBs posed a risk of damage to the stomach, including a single case of impaction and perforation of the gastric wall. Clinicians may want to consider retrieval within 12 hours of ingestion of gastric BBs. Larger prospective studies to assess risk of injury are needed., (Copyright © 2020 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Outbreaks of infections transmitted by duodenoscopes have prompted changes to duodenoscope cleaning protocols. However, little is known about effectiveness of clinical cleaning practices. We present culture data after duodenoscope manufacturer-recommended high-level disinfection (HLD) and quarantine., Methods: Our institution adopted a combination of manufacturer-recommended cleaning with the Centers for Disease Control and Prevention-recommended culture and quarantine in 2015. Duodenoscopes (models TJF-Q180V, TJF-160, and PJF-160; Olympus, Center Valley, Penn, USA) underwent HLD according to the manufacturer's reprocessing manual protocols after use. Two culture specimens were then obtained using a sterile brush from the distal tip, including elevator mechanism, and by flushing sterile water through the working channel. Duodenoscopes were quarantined until cultures resulted. Positive cultures were defined as >10 colony-forming units (CFUs) of low-concern organisms or any CFUs of high-concern organisms according to Centers for Disease Control and Prevention recommendations. If either culture specimen was positive, the process was repeated until cultures were negative. Data were collected from December 2015 to July 2018., Results: There were 140 instances of duodenoscope cleaning with 280 specimens. Twenty-eight of 234 (12%) initial culture specimens (18% of cultured duodenoscopes) were positive. Five of 36 (14%) second cultures were positive. Two of 8 (25%) third cultures were positive. Ninety-eight percent of organisms cultured were gram positive. In 8 instances both culture methods (brushing and flush) were positive; otherwise, only 1 method was positive. In 11 instances (8%) duodenoscopes were removed from quarantine before final culture results. No patient had infections related to ERCP., Conclusions: Eighteen percent of duodenoscopes had a positive culture after initial HLD. Only 3% were gram-negative bacteria. Repeated HLD was 86% and 75% effective at eliminating initial and repeat positive cultures, respectively. Initial HLD per manufacturer recommendations is not always effective at eliminating bacterial contamination. Additional steps are necessary to decrease risks of duodenoscope-transmitted infections., (Copyright © 2020 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Evaluation and treatment of children with eosinophilic esophagitis (EoE) requires serial endoscopic, visual, and histologic assessment by sedated esophagogastroduodenoscopy (EGD). Unsedated transnasal endoscopy (TNE) was reported to be successful in a pilot study of children. We evaluated video goggle and virtual reality-based unsedated TNE in children with EoE, collecting data on rates of completion, adverse events, and adequacy of visual and histologic findings., Methods: We performed a retrospective study of 190 children and young adults (age, 3-22 y) who underwent video goggle or virtual reality-based unsedated TNE from January 2015 through February 2018. We analyzed data on patient demographics, procedure completion, endoscope type, adverse events, visual and histologic findings, estimated costs, and duration in the facility. Esophageal biopsies from the first 173 subjects who underwent TNE were compared with those from previous EGD evaluations., Results: During 300 attempts, 294 TNEs were performed (98% rate of success). Fifty-four patients (age, 6-18 y) underwent multiple TNEs for dietary or medical management of EoE. There were no significant adverse events. Visual and histologic findings were adequate for assessment of EoE. TNE reduced costs by 53.4% compared with EGD (TNE $4393.00 vs EGD $9444.33). TNE was used increasingly from 2015 through 2017, comprising 31.8% of endoscopies performed for EoE. The total time spent in the clinic (front desk check-in to check-out) in 2018 was 71 minutes., Conclusions: In a retrospective study of 190 children and young adults (age, 3-22 y) who underwent video goggle or virtual reality-based unsedated TNE, TNE was safe and effective and reduced costs of EoE monitoring. Advantages of TNE include reduced risk and cost associated with anesthesia as well as decreased in-office time, which is of particular relevance for patients with EoE, who require serial EGDs., (Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Introduction: From 2009 to 2016, the Centers for Disease Control and Prevention (CDC) activated its Incident Management System for a public health emergency 91 percent of the time. The CDC must ensure its workforce is prepared for the evolving nature of emergencies., Objectives: The purpose of this assessment was to identify perceived preparedness and response training needs for the CDC responder workforce., Methods: Between November 2012 and January 2013, focus groups and in-depth interviews were conducted with CDC responders, including senior leaders. The evaluation questions were: (1) How well does the current training system prepare CDC staff to respond to emergency events? (2) What gaps exist in the current training system? and (3) What trainings are essential and should be included in the training system?, Results: Eight focus groups were conducted with 51 responders and 18 interviews with response leaders. Themes were identified for each main outcome measure and translated to training improvements., Conclusions: The CDC workforce received foundational training. Recommendations are provided to better prepare responders during an emergency. Periodic assessments are necessary to expand training and remain responsive to the complexities of emerging threats.

Background: Pneumatic balloon and bougie dilation are widely used methods for pediatric esophageal dilation. There are no studies directly comparing the safety of these techniques in pediatric patients. This study compared adverse events (AEs) of balloon and bougie dilation in children at a single institution., Methods: AEs were identified by means of a prospective clinical registry of all procedure related AEs from 2012 to 2015 at a single institution. Identified AEs underwent retrospective review of procedural and clinical details. The category of each AE was recorded and severity was assigned using a 5-point scoring system. AEs were compared between balloon and bougie dilation for different severities., Results: There were 105 patients who underwent 246 dilation sessions. Balloon dilation was performed more commonly (n = 190, 77%) as compared to Maloney dilators (n = 56, 23%). Patients with balloon dilation were younger (3.0 vs 14.5 years, P = 0.0001) and more likely to have strictures from caustic ingestion (42% vs 2%, P < 0.0001) or surgical anastomoses (34% vs 5% P < 0.0001). Bougie dilation was used more commonly in patients with eosinophilic esophagitis (77% vs 7%, P < 0.0001)). In multivariate analysis, each year of increasing age was associated with a 12% increase in any AEs (P = 0.015), but no difference in clinically significant AEs (grade 2 or higher) was identified between dilation methods., Conclusions: Bougie and balloon dilation did not have significant differences in AE rates, but the patient populations differed between the 2 methods. The dilation method should depend on stricture characteristics and endoscopist expertise with each method.

Chronic abdominal pain (CAP) is a common and challenging problem in pediatric primary and specialty care. We developed a diagnostic algorithm to organize workup for gastrointestinal causes of CAP and improve identification of patients who are low suspicion (LS) or high suspicion (HS) to have significant intestinal pathology identified with endoscopy. We retrospectively used this algorithm to categorize 150 outpatients with CAP as LS (n = 99) or HS (n = 51) and examined subsequent endoscopic findings for all patients. There were 6% significant diagnoses in the LS group compared with 34% in the HS group ( P < .0001). The LS group had no patients with celiac or inflammatory bowel disease. These results can be used to help a clinician approach CAP, and discuss with families the likelihood of endoscopy finding a cause for CAP based on LS or HS designation.

Objective: The aim of the study is to analyze a large series of esophageal balloon dilations in patients with epidermolysis bullosa (EB) to determine procedural approach and frequency of post-endoscopic adverse events (AEs)., Methods: Retrospective chart review for AE occurrence and clinical outcomes in children and adolescents with EB, age 1 to 19, who underwent esophageal dilation for esophageal stricture(s) from January 2003 to April 2016 at an academic, tertiary care, free-standing children's hospital. The primary outcome measure was occurrence of procedural AEs (defined as events occurring within 72 hours after endoscopic dilation procedure)., Results: A total of 231 fluoroscopy-guided esophageal balloon dilation procedures (209 anterograde, 20 retrograde, 2 both) were performed in 24 patients. Strictures were more common in the proximal portion of the esophagus with median stricture location 13 cm from the lips. From 2003 to 2012, 4.1% of dilations were retrograde. From 2013 to 2016, 20.2% of dilations were retrograde. AEs attributable to dilation occurred after 10.0% of procedures, and the most common AEs were vomiting, pain, and fever. No esophageal perforations, serious bleeding events, or deaths occurred secondary to dilation. The rate of post-dilation hospitalization was 6.9%. Dilation approach (anterograde vs retrograde) did not impact the likelihood of AEs., Conclusions: The characteristic esophageal lesion in EB is a single, proximal esophageal stricture. EB patients can safely undergo repeat pneumatic esophageal balloon dilations with minimal risk for severe complication. We observed a trend towards increased use of retrograde esophageal dilation.

Background and Aims: Previous studies on pediatric endoscopic training have not examined in detail if adverse events (AEs) are affected by the fellow's training level. We aimed to determine whether trainee presence and educational level increase AEs or operative time (OT) for pediatric intestinal endoscopy., Methods: This was a prospective observational study of AEs for all endoscopic procedures and retrospective analysis of OT (time of endoscope insertion until removal) for a sample of specified procedures at a tertiary children's hospital. AEs were categorized by severity grades: 1, home management; 2, outpatient evaluation; 3, hospitalization and/or repeat endoscopy; 4, surgery and/or intensive care unit admission; and 5, death., Results: A total of 15,886 procedures (6257 with trainee) including 1627 therapeutic procedures (733 with trainee) were analyzed for AEs. Four hundred thirteen total AEs (2.60%) and 213 AEs grade 2 to 4 (1.34%) were identified. Fellow presence at any training level did not increase AE rates for any procedures. Median OT for 3762 EGDs decreased from 17 to 11 minutes from the first quarter to the fourth quarter of first-year fellowship and then remained stable. EGDs without fellows were shorter (9 minutes, P < .0001) compared with any training level. Median times of 1291 colonoscopies with EGD decreased from 55 to 51 to 47 minutes for fellows in the first half, second half of first-year fellowship, and second and third year, respectively. Attendings alone were faster (37 minutes, P < .0001)., Conclusions: Current pediatric endoscopic training for is safe regardless of fellow training level. Trainee efficiency improves during and after fellowship., (Copyright © 2018 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Toys entering the marketplace may have unrecognized hazard risks until data on injury become known. The fidget spinner is a new popular toy mass marketed to children and is primarily sold without warning labels. The US Consumer Product Safety Commission has recently issued a formal statement on potential safety concerns related to ingestion of the toy parts and other hazards. Button batteries within this toy pose the greatest danger to children as ingestion can lead to lethal injury. We report 2 cases of children who swallowed a button battery from a fidget spinner, causing severe esophageal injury. Various aspects of this type of ingestion important for clinicians to be aware of are reviewed.

Objectives: Endoscopic retrograde cholangiopancreatography is used to manage biliary pathology in pediatric patients. Plastic biliary stents have been used in this population for obstructive lesions and bile leaks; however, they are sometimes not effective due to migration, occlusion, or ineffective sealing. Fully covered self-expanding metal stents (FCSEMS) have larger diameters making them more suitable for some situations. Their use in pediatrics has, however, not been defined. The aim of the present study is to describe our experience with FCSEMS at our institution., Methods: We present a series of all patients who underwent FCSEMS placement at Children's Hospital Colorado including 3 adolescents and 1 young adult with complex medical needs., Results: Patient age range was 12 to 24 years and the weight ranged between 36 and 75 kg. All patients underwent previous endoscopic retrograde cholangiopancreatography and 1 or more rounds of plastic stenting without adequate clinical response before consideration of FCSEMS placement. Indications included recalcitrant biliary anastomotic stricture after liver transplant, persistent bile leak after needle perforation, recurrent obstructive choledocholithiasis after cholecystectomy, and malignant biliary stricture. Sizes of FCSEMS depended on patient bile duct size and biliary pathology. Dwell time was 6 to 8 weeks. Three patients had resolution of biliary pathology after FCSEMS therapy. One patient had distal migration of FCSEMS necessitating repeat stenting. There were no adverse events from FCSEMS placement or removal., Conclusions: FCSEMS therapy should be considered in appropriate pediatric patients when plastic biliary stents are not effective. Further studies are needed to evaluate the safety and efficacy of FCSEMS in the pediatric age group.

Monitoring therapy in esophageal inflammatory disorders such as eosinophilic esophagitis and reflux esophagitis often requires frequent endoscopic evaluation. We recently reported the effective use of unsedated in-office transnasal esophagoscopy that significantly decreased costs and anesthetic exposure associated with pediatric esophagoscopy in eosinophilic esophagitis. Here we report a series of pediatric patients with esophagitis with gastrostomy tubes who underwent unsedated transgastrostomy esophagoscopy (TGE) in an office setting. Nine patients (ages 16 months-21 years) tolerated TGE without significant adverse events. Biopsy specimens were adequate for evaluation. This series confirms that unsedated in-office TGE can be used to successfully obtain mucosal biopsies to monitor esophageal inflammatory conditions in children without the use of sedation.

Purpose/objectives: To evaluate whether survivorship of multiple primary cancers (MPCs) is associated with psychological distress, positive health behaviors, and benefit finding.
., Design: Secondary analysis of the 2010 Livestrong cross-sectional survey.
., Setting: Online survey.
., Sample: 238 MPC survivors and 3,295 single cancer survivors.
., Methods: Chi-square and t tests for group comparisons were used. Multivariate linear regression, adjusted for covariates, was used to determine associations between variables.
., Main Research Variables: MPC versus single cancer; psychological distress, health behavior (healthy lifestyle and positive healthcare utilization), and benefit-finding scores.
., Findings: Survivors of MPCs (compared to single cancer survivors) were significantly older, less likely to have a spouse or partner, further out from original cancer diagnosis, and less likely to be employed full-time, and they differed by cancer diagnoses and survivorship stage. Having MPCs was associated with significantly higher psychological distress and healthcare utilization but not healthy lifestyle or benefit finding.
., Conclusions: Relative to those with single cancers, MPC survivors are at increased risk for psychological distress and are more likely to receive recommended cancer screenings. Additional research is needed to understand mechanisms surrounding psychological distress in MPC survivors.
., Implications for Nursing: Targeted distress screening in MPC survivors may allow for early identification and interventions to ameliorate distress and reduce negative downstream health effects.

The current era of healthcare reform emphasizes the provision of effective, safe, equitable, high-quality, and cost-effective care. Within the realm of gastrointestinal endoscopy in adults, renewed efforts are in place to accurately define and measure quality indicators across the spectrum of endoscopic care. In pediatrics, however, this movement has been less-defined and lacks much of the evidence-base that supports these initiatives in adult care. A need, therefore, exists to help define quality metrics tailored to pediatric practice and provide a toolbox for the development of robust quality improvement (QI) programs within pediatric endoscopy units. Use of uniform standards of quality reporting across centers will ensure that data can be compared and compiled on an international level to help guide QI initiatives and inform patients and their caregivers of the true risks and benefits of endoscopy. This report is intended to provide pediatric gastroenterologists with a framework for the development and implementation of endoscopy QI programs within their own centers, based on available evidence and expert opinion from the members of the NASPGHAN Endoscopy Committee. This clinical report will require expansion as further research pertaining to endoscopic quality in pediatrics is published.

Objectives: Although several studies report on the experience with adult eosinophilic esophagitis (EoE)-related stricture, outcomes for pediatric patients with EoE-associated fibrostenosis and stricture is more limited. To address this, we aim to identify the adverse event (AE) rate and short-term outcomes of the largest reported cohort of children with EoE to undergo esophageal dilation for management of symptomatic esophageal narrowing., Methods: A retrospective assessment of all children, 18 years and younger, who underwent esophageal dilation at an academic children's hospital during a 5-year period was conducted. Clinical, endoscopic, histologic, and outcomes of dilation were extracted from the medical record. AEs were captured within a standardized endoscopic AE database. Grade 2 AEs (requiring unanticipated medical intervention) were termed significant. Dilation-related events were compared between patients with EoE, without EoE, and those undergoing standard upper endoscopy., Results: Of the 451 total dilations, 68 dilations were performed in 40 EoE patients (mean age 13.8 years, standard deviation 3.3 years [4.6-18.9 years]). Forty-three percent (17/40) had repeat dilation during the study period. Dilation-related grade 2 AE rates in EoE and in non-EoE patients were 2.9% and 3.1%, respectively (P > 0.5). Chest pain (any grade AE) was reported in 14.7% of EoE dilations. No significant associations were found between postprocedural pain and dilation method, final dilator size, medical therapy, or esophageal eosinophilia. No perforations or significant hemorrhage were reported., Conclusions: We conclude that dilation can be performed safely in children with EoE. In the appropriate clinical setting, cautious dilation may be considered in the management of fibrostenotic EoE.

Wireless capsule endoscopy (CE) was introduced in 2000 as a less invasive method to visualize the distal small bowel in adults. Because this technology has advanced it has been adapted for use in pediatric gastroenterology. Several studies have described its clinical use, utility, and various training methods but pediatric literature regarding CE is limited. This clinical report developed by the Endoscopic and Procedures Committee of the North American Society of Pediatric Gastroenterology, Hepatology and Nutrition outlines the current literature, and describes the recommended current role, use, training, and future areas of research for CE in pediatrics.

Objectives: Anesthesia can alter gastric and small intestinal motility, but its effect on gastroesophageal reflux (GER) is unclear. We set out to evaluate the effect of anesthesia on pH-multichannel intraluminal impedance (pH impedance) evaluation of GER., Methods: Retrospective single-center analysis of 95 pH impedance probe studies performed in patients both with anesthesia exposure and esophagogastroduodenoscopy (n = 50) and without (n = 45)., Results: Increased acid reflux per hour, nonacid reflux per hour, and total reflux per hour were observed in the first 4 hours, both overall and in children 1 year or older and in both sedation groups. This difference remained for the older children without sedation by multiple regression analysis for nonacid reflux per hour and total reflux per hour. Patients using proton pump inhibitors had more nonacid reflux events per hour and total reflux events per hour regardless of sedation., Conclusions: Based on the results of the present study, there is no need to eliminate the data collected immediately after placement of the probe in children younger than 1 year of age, but in those who are 1 year or older without sedation, there may be a greater number of reflux events in the first 4 hours. The first 4 hours, therefore, should be carefully evaluated in patients older than 1 year of age. Further study is needed to provide normative data for the first 4 hours versus the later time period, both for those undergoing sedation and for unsedated patients, to validate the findings from the present study and to better understand the mechanism of GER.

Objective: To conduct a comprehensive study of postendoscopic adverse events (AEs) in children, categorizing them by the level of intervention required., Background: Previous studies of endoscopic AE in children have focused on intraprocedural and short-term outcomes, such as bleeding, perforation, and infection, and may underestimate the incidence of AEs., Design: Prospective observational study tracking AEs in pediatric patients within 72 hours of an endoscopic procedure., Setting: Single-center study performed at an academic, tertiary care, free-standing children's hospital over a 48-month period, from July 2010 through June 2014., Patients and Interventions: Of 9577 pediatric endoscopic procedures, cases identified as having an AE during or following endoscopy were subject to additional chart review for abstraction of relevant data., Main Outcome Measurements: Type, severity, and subsequent interventions of AEs were the primary outcome measures. Events were categorized by severity grade, with grade 1, no intervention; grade 2, outpatient evaluation; grade 3, hospitalization or repeat endoscopy; grade 4, surgery or intensive care unit admission; and grade 5, death., Results: In total, 249 endoscopic AEs were recognized of 9577 procedures performed, yielding a rate of 2.6%. Of these, 160 were identified to result in medical evaluation and costs (≥grade 2) for a rate of 1.7%. Rates of endoscopic AE after advanced or interventional endoscopic procedures were higher, with 65 of 1167 events, resulting in a total AE rate of 5.6% and a rate of 4.4% for AE ≥ grade 2. There were 10 cases of significant bleeding (0.1%), 9 cases of infection (0.09%), and 12 cases of perforation (0.13%), primarily occurring with advanced/interventional procedures., Limitations: Single-center study, lack of standardized criteria for ED referral., Conclusions: AEs presenting within 72 hours of endoscopy and resulting in medical intervention, occur more commonly than previously recognized in children. Standardized postendoscopy surveillance systems and definitions of AEs are needed.

Background and Aims: Unsedated transnasal endoscopy (TNE) is safer and less costly than sedated EGD. The aim of this study was to evaluate the performance of TNE with biopsies in monitoring the esophageal mucosa of pediatric patients with eosinophilic esophagitis., Methods: Patients between 8 and 17 years of age with eosinophilic esophagitis and their parents were enrolled. Unsedated TNE was performed. A 2.8-mm (1.2-mm channel) or a 4-mm flexible bronchoscope (2-mm channel) was used, and esophageal biopsy specimens were obtained. Biopsy specimen analysis, duration, adverse events, and billing charges of TNE were assessed. Immediately after TNE and a minimum of 2 weeks later, a modified Group Health Association of America 9 survey and a preference questionnaire were completed, respectively., Results: Twenty-one of 22 enrolled patients underwent TNE. TNE was performed with no serious adverse events. Histopathological analysis revealed 0 eosinophils per high-power field (n = 12), fewer than 15 eosinophils per high-power field (n = 4), and more than 15 eosinophils per high-power field (n = 5). The total epithelial surface area of mucosal biopsy samples from either TNE Forceps (1.2 mm or 2 mm biopsy channel forceps) compared with those obtained during the subject's previous EGD by using standard endoscopic forceps was not statistically different (P = .308 [1.2 mm]/P = .492 [2 mm]). All parents and 76.2% of subjects would undergo the TNE again. TNE was preferred over EGD by 85.7% of parents and 52.4% of subjects. The modified Group Health Association of America 9 survey revealed a high degree of satisfaction (average, 43.19 ± 2.6; maximum score, 45). Charges associated with TNE were 60.1% lower than for previous EGDs., Conclusions: Unsedated TNE is an effective, lower-cost procedure for monitoring the esophageal mucosa of children with eosinophilic esophagitis., (Copyright © 2016 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Gastrointestinal injuries secondary to button battery ingestions in children have emerged as a dangerous and difficult management problem for pediatricians. Implementation of a multidisciplinary team approach, with rapid and coordinated care, is paramount to minimize the risk of negative outcomes. In addition to providing a comprehensive review of the topic, this article outlines the authors' referral center's experience with patients with severe battery ingestion, highlighting the complications, outcomes, and important lessons learned from their care. The authors also propose an algorithm for clinical care that may be useful for guiding best management of pediatric button battery ingestion., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Foreign body ingestions in children are some of the most challenging clinical scenarios facing pediatric gastroenterologists. Determining the indications and timing for intervention requires assessment of patient size, type of object ingested, location, clinical symptoms, time since ingestion, and myriad other factors. Often the easiest and least anxiety-producing decision is the one to proceed to endoscopic removal, instead of observation alone. Because of variability in pediatric patient size, there are less firm guidelines available to determine which type of object will safely pass, as opposed to the clearer guidelines in the adult population. In addition, the imprecise nature of the histories often leaves the clinician to question the timing and nature of the ingestion. Furthermore, changes in the types of ingestions encountered, specifically button batteries and high-powered magnet ingestions, create an even greater potential for severe morbidity and mortality among children. As a result, clinical guidelines regarding management of these ingestions in children remain varied and sporadic, with little in the way of prospective data to guide their development. An expert panel of pediatric endoscopists was convened and produced the present article that outlines practical clinical approaches to the pediatric patient with a variety of foreign body ingestions. This guideline is intended as an educational tool that may help inform pediatric endoscopists in managing foreign body ingestions in children. Medical decision making, however, remains a complex process requiring integration of clinical data beyond the scope of these guidelines. These guidelines should therefore not be considered to be a rule or to be establishing a legal standard of care. Caregivers may well choose a course of action outside of those represented in these guidelines because of specific patient circumstances. Furthermore, additional clinical studies may be necessary to clarify aspects based on expert opinion instead of published data. Thus, these guidelines may be revised as needed to account for new data, changes in clinical practice, or availability of new technology.

Unlabelled: Many of the small DNA tumor viruses encode transforming proteins that function by targeting critical cellular pathways involved in cell proliferation and survival. In this study, we have examined whether some of the functions of the polyomavirus small T antigens (ST) are shared by the E6 and E7 oncoproteins of two oncogenic papillomaviruses. Using three different assays, we have found that E7 can provide some simian virus 40 (SV40) or murine polyomavirus (PyV) ST functions. Both human papillomavirus 16 (HPV16) and bovine papillomavirus (BPV1) E7 proteins are capable of partially substituting for SV40 ST in a transformation assay that also includes SV40 large T antigen, the catalytic subunit of cellular telomerase, and oncogenic Ras. Like SV40 ST, HPV16 E7 has the ability to override a quiescence block induced by mitogen deprivation. Like PyV ST, it also has the ability to inhibit myoblast differentiation. At least two of these activities are dependent upon the interaction of HPV16 E7 with retinoblastoma protein family members. For small T antigens, interaction with PP2A is needed for each of these functions. Even though there is no strong evidence that E6 or E7 share the ability of small T to interact with PP2A, E7 provides these functions related to cellular transformation., Importance: DNA tumor viruses have provided major insights into how cancers develop. Some viruses, like the human papillomaviruses, can cause cancer directly. Both the papillomaviruses and the polyomaviruses have served as tools for understanding pathways that are often perturbed in cancer. Here, we have compared the functions of transforming proteins from several DNA tumor viruses, including two papillomaviruses and two polyomaviruses. We tested the papillomavirus E6 and E7 oncoproteins in three functional assays and found that E7 can provide some or all of the functions of the SV40 small T antigen, another well-characterized oncoprotein, in two of these assays. In a third assay, papillomavirus E7 has the same effect as the murine polyomavirus small T protein. In summary, we report several new functions for the papillomavirus E7 proteins, which will contribute new insights into the roles of viruses in cancer and the cellular pathways they perturb in carcinogenesis., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)