A Diagnostic Conundrum: A Case of Pediatric Autoimmune Pancreatitis.

Autoimmune pancreatitis (AIP) is rare cause of abdominal pain in children who often present with obstructive jaundice, mimicking malignancy. An investigation of clinical symptoms, serology, imaging, and histopathology is necessary for diagnosis. We report a 10-year-old female presenting with abdominal pain and jaundice, ultimately found to have AIP after confirmation with tissue pathology. Our patient's prompt response to corticosteroid initiation is characteristic of this disease state. AIP has 2 subtypes, the second of which is more frequently found in children. Our patient's pathology did not fit perfectly with either subtype, but had features found in each one. While diagnostic criteria for AIP have not established in pediatrics, our case highlights the combination of clinical symptoms, imaging, and histopathology that children classically present with. While rare, the diagnosis of AIP is associated with comorbidities and must be considered in any child presenting with a pancreatic mass or biliary stricture.

Review of paediatric obesity and non-alcoholic fatty liver disease-A focus on emerging non-pharmacologic treatment strategies.

Obesity in paediatrics has become one of the most serious public health concerns worldwide. Paediatric obesity leads to increased adult obesity and is associated with several comorbidities, both physical and psychological. Within gastroenterology, non-alcoholic fatty liver disease (NAFLD) is now the most common cause of paediatric liver disease and the most common cause of liver transplantation in young adults. Treatment for NAFLD largely focuses on treatment of obesity with weight loss strategies. Unfortunately, the traditional method of weight loss using multicomponent lifestyle modification (dietary changes, increased exercise and behavioural modification) has often led to disappointing results. In adult patients with obesity, treatment strategies have evolved to include bariatric surgery and, more recently, bariatric endoscopy. In paediatrics, the obesity and NAFLD epidemics will likely require this variety of treatment to address children in a personalized manner. Here, we present a review of paediatric obesity, paediatric NAFLD and the various treatment strategies to date. We focus on non-pharmacologic and emerging therapies, including bariatric surgery and bariatric endoscopy-based treatments. With such a large population of children and adolescents with obesity, further development of these treatments, including paediatric-focused clinical trials, is essential for these emerging modalities.

A National Survey of the Training and Practice Patterns of Practicing Pediatric Advanced Endoscopists in the United States.

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.

Impact of Trainee Involvement on Pediatric ERCP Procedures: Results From the Pediatric ERCP Initiative.

This study examines the role of trainee involvement with pediatric endoscopic retrograde cholangiopancreatography (ERCP) and whether it affects the procedure's success, post-procedural adverse outcomes, and duration. A secondary analysis of the Pediatric ERCP Database Initiative, an international database, was performed. Consecutive ERCPs on children <19 years of age from 18 centers were entered prospectively into the database. In total 1124 ERCPs were entered into the database, of which 320 (28%) were performed by trainees. The results showed that the presence of trainees did not impact technical success ( P = 0.65) or adverse events rates ( P = 0.43). Rates of post-ERCP pancreatitis, pain, and bleeding were similar between groups ( P > 0.05). Fewer cases involving trainees were in the top quartile (>58 minutes) of procedural time (19% vs 26%; P = 0.02). Overall, our findings indicate trainee involvement in pediatric ERCP is safe.

Pediatric ERCP in the Setting of Acute Pancreatitis: A Secondary Analysis of an International Multicenter Cohort Study.

Previous studies have demonstrated the safety of performing endoscopic retrograde cholangiopancreatography (ERCP) in the pediatric population; however, few have addressed the outcomes of children undergoing ERCP during acute pancreatitis (AP). We hypothesize that ERCP performed in the setting of AP can be executed with similar technical success and adverse event profiles to those in pediatric patients without pancreatitis. Using the Pediatric ERCP Database Initiative, a multi-national and multi-institutional prospectively collected dataset, we analyzed 1124 ERCPs. One hundred and ninety-four (17%) of these procedures were performed in the setting of AP. There were no difference in the procedure success rate, procedure time, cannulation time, fluoroscopy time, or American Society of Anesthesiology class despite patients with AP having higher American Society of Gastrointestinal Endoscopy grading difficulty scores. This study suggests that ERCP can be safely and efficiently performed in pediatric patients with AP when appropriately indicated.

EUS in Pediatrics: A Multicenter Experience and Review.

Background/Aim: Endoscopic ultrasound (EUS) is a well-established tool used in the evaluation and treatment of a wide range of pathologies in adult medicine. EUS in pediatrics has been shown to be safe and technically effective, and its use continues to evolve. This article aims to describe the EUS experience at our tertiary-care centers with regard to safety, technical success, and its impact in clinical management. We also discuss the current and developing diagnostic and therapeutic uses for EUS in pediatrics such as in pancreaticobiliary disease, congenital anomalies, eosinophilic esophagitis, inflammatory bowel disease, and liver disease. Methods: This is a retrospective review of EUS performed by two pediatric gastroenterologists trained as endosonographers between April 2017 and November 2020. Patient demographics, procedure indication, procedure characteristics, technical success, and complications were collected. Literature review was performed to describe current and future uses of EUS in pediatrics. Results: Ninety-eight EUS were performed with 15 (15.3%) including fine needle aspiration/biopsy and 9 (9.2%) cases being therapeutic. Most common indications include choledocholithiasis (n = 31, 31.6%), pancreatic fluid collections (n = 18, 18.4%), chronic and acute recurrent pancreatitis (n = 14, 14.3%), and acute pancreatitis characterization (n = 13, 13.3%). Notable indications of pancreatic mass (n = 6, 6.1%) and luminal lesions/strictures (n = 6, 6.1%) were less common. Complications were limited with one instance of questionable GI bleeding after cystgastrostomy creation. Ninety-eight of 98 (100%) cases were technically successful. Conclusion/Discussion: EUS has been shown to be performed safely and successfully in the pediatric population by pediatric endosonographers. This study and review support its use in pediatric practice and demonstrate the wide variety of indications for EUS such as pancreatic cystgastrostomy, celiac plexus neurolysis, and evaluation of chronic pancreatitis. This literature review also demonstrates areas of potential development for EUS within the practice of pediatric gastroenterology.

Medical Management of Chronic Pancreatitis in Children: A Position Paper by the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition Pancreas Committee.

ABSTRACT: This position paper summarizes the current understanding of the medical management of chronic pancreatitis (CP) in children in light of the existing medical literature, incorporating recent advances in understanding of nutrition, pain, lifestyle considerations, and sequelae of CP. This article complements and is intended to integrate with parallel position papers on endoscopic and surgical aspects of CP in children. Concepts and controversies related to pancreatic enzyme replacement therapy (PERT), the use of antioxidants and other CP medical therapies are also reviewed. Highlights include inclusion of tools for medical decision-making for PERT, CP-related diabetes, and multimodal pain management (including an analgesia ladder). Gaps in our understanding of CP in children and avenues for further investigations are also reviewed.

A Mobile Infliximab Dosing Calculator for Therapy Optimization in Inflammatory Bowel Disease.

Background: Inadequate infliximab (IFX) drug exposure remains a clinical challenge and leads to high loss of response rates and therapy failure in inflammatory bowel disease (IBD). We aimed to determine the feasibility and pilot effectiveness of a novel, web-based, mobile IFX dosing calculator (mIDC) for therapy optimization. Methods: We developed an mIDC leveraging the known clinical variables of C-reative protein (CRP), albumin, patient's weight, disease activity indices, calprotectin, drug trough levels, and antibodies to IFX that significantly affect pharmacokinetics and/or outcomes. A prospective observational cohort study in pediatric and young adult IBD patients receiving maintenance IFX was performed. System-wide practice adoption of mIDC was achieved through a quality improvement (QI) initiative within a hospital-based infusion unit. Results: Forty-nine patients (median age: 16.0 years; 55% female; 65% Crohn's disease) were followed over 9 months. mIDC recommendations for dose optimization were followed by the treating physicians in 198 (89%) out of 222 infusions. Twenty-eight (13%) of 222 mIDC recommendations were to escalate IFX dosing; 15 (54%) of 28 escalation recommendations were declined, and these patients were more likely to already be receiving IFX dose intensification compared with those in whom escalation recommendations were followed (P < 0.05). From mIDC initiation to end of follow-up, mean albumin levels remained unchanged at 3.8 g/dL. Median CRP remained unchanged at 2 g/L. Median calprotectin levels showed a downward trend from 30 to 27 µg/g (n = 9, P < 0.05). The percentage of patients undergoing therapeutic drug monitoring in clinical care increased from 34% to 86% with the QI initiative. The target median IFX trough goal of >5 µg/mL was achieved with 81% probability throughout the QI initiative, an increase of 12% compared with pre-QI values. Conclusions: The use of a novel mIDC is feasible and potentially effective, facilitating both standardization and individualization of therapy in clinical care. mIDC appears to be a practical IFX dosing tool for point-of-care use, leveraging individual pharmacokinetic considerations.

Application of Population Pharmacokinetic Modeling for Individualized Infliximab Dosing Strategies in Crohn Disease.

OBJECTIVES: The pharmacokinetics of infliximab (IFX) is highly variable in children with Crohn disease (CD), and a one-size-fits-all approach to dosing is inadequate. Model-based drug dosing can help individualize dosing strategies. We evaluated the predictive performance and clinical utility of a published population pharmacokinetic model of IFX in children with CD. METHODS: Within a cohort of 34 children with CD who had IFX trough concentrations measured, the pharmacokinetics of each patient was estimated in NONMEM using a published population pharmacokinetic model. Infliximab concentrations were then predicted based on each patient's dosing history and compared with actual measured concentrations (n = 59). In addition, doses 5 to 10 mg/kg and dosing intervals every 4 to 8 weeks were simulated in each patient to examine dose-trough relationships. RESULTS: Predicted concentrations were within ±1.0 µg/mL of actual measured concentrations for 88% of measurements. The median prediction error (ie, measure of bias) was -0.15 µg/mL (95% confidence interval -0.37 to -0.05 µg/mL) and absolute prediction error (ie, measure of precision) was 0.26 µg/mL (95% confidence interval 0.15 to 0.40 µg/mL). At standard maintenance dosing of 5 mg/kg every 8 weeks, a trough >3 µg/mL was predicted to be achieved in 32% of patients. To achieve a trough >3 µg/mL, a dosing interval ≤every 6 weeks was predicted to be required in 29% of patients. CONCLUSIONS: A published IFX population pharmacokinetic model demonstrated accurate predictive performance in a pediatric CD population. Individualized IFX dosing strategies in children with CD will be critical to consistently achieve trough concentrations associated with optimal outcomes.

Infliximab Dosing Strategies and Predicted Trough Exposure in Children With Crohn Disease.

OBJECTIVES: Standard infliximab maintenance dosing of 5 mg/kg every 8 weeks may be inadequate to consistently achieve sufficient drug exposure to minimize loss of response or treatment failure in pediatric Crohn disease (CD). We aimed to determine the predicted infliximab trough concentrations in children with CD during maintenance therapy and the percentage of patients achieving target trough concentration >3 µg/mL. METHODS: A Monte Carlo simulation analysis was constructed using a published population pharmacokinetic model based on data from 112 children in the REACH trial. We assessed maintenance dosing strategies of 5, 7.5, and 10 mg/kg at dosing intervals of every 4, 6, and 8 weeks for children that differed by age, weight, albumin level, and concomitant immunomodulator therapy. RESULTS: Based on the index case of a 10-year-old with CD receiving standard infliximab dosing with concomitant immunomodulator therapy, the median (interquartile range) simulated infliximab trough concentration at week 14 was 1.3 (0.5-2.7) µg/mL and 2.4 (1.0-4.8) µg/mL for albumin levels of 3 and 4 g/dL, respectively. Among 1000 simulated children in the model, trough concentration >3 µg/mL at week 14 was achieved 21% and 41% of the time for albumin levels of 3 and 4 g/dL, respectively. CONCLUSIONS: Standard infliximab maintenance dosing in children with CD is predicted to frequently result in inadequate exposure, especially when albumin levels are low. Optimized dosing strategies for individual patients are needed to achieve sufficient drug exposure during infliximab maintenance therapy.

Pharmacologic modification to resuscitation fluid after thermal injury--is drotrecogin alfa the answer to arrest burn depth progression?

HYPOTHESIS: The addition of drotrecogin alfa (DA), an anti-inflammatory useful in septic shock, to standard burn shock resuscitation fluids will protect burned, injured skin from further injury. METHODS: Anesthetized animals were subjected to a standardized burn pattern by applying a branding iron to 10 different locations on the back of the rat for 1 seconds to 14 seconds, creating a range of burn depths and severities. DESIGN: Animal burn shock and resuscitation model. PARTICIPANTS: Thirty-one male adult Sprague-Dawley rats. INTERVENTIONS: Control animals were resuscitated with lactated Ringer's solution (LRS) at 2 mL/kg/percent total body surface area/24 h; experimental animals received LRS plus DA 24 microg/kg/h (LRS + DA). OUTCOME MEASURES: Perfusion to each burned area was assessed using a laser Doppler imaging technology. Punch biopsies at each burned area were stained with hematoxylin and eosin and assessed for burn depth and for inflammation using previously reported measures. Samples from 14 animals were stained for terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling and caspase-3 (apoptosis markers). RESULTS: Increasing branding iron contact times worsened perfusion, burn depth, and apoptotic ratios. There was no correlation between inflammatory markers and burn contact time. The addition of DA leads to worse perfusion, deeper burns, worse inflammation, and decreased apoptotic ratios. CONCLUSIONS: Laser Doppler imaging is a useful technology to assess burn depth. The addition of DA to traditional resuscitation fluids for burn shock is deleterious to the injured, burned skin. Modifying the traditional burn shock resuscitation fluids, although intellectually attractive, needs to be rigorously studied.

Morphological parameters for assessment of burn severity in an acute burn injury rat model.

Determination of burn severity (i.e. burn depth) is important for effective medical management and treatment. Using a recently described acute burn model, we studied various morphological parameters to detect burn severity. Anaesthetized Sprague-Dawley rats received burns of various severity (0- to 14-s contact time) followed by standard resuscitation using intravenous fluids. Biopsies were taken from each site after 5 h, tissues fixed in 10% neutral-buffered formalin, processed and stained with haematoxylin and eosin. Superficial burn changes in the epidermis included early keratinocyte swelling progressing to epidermal thinning and nuclear elongation in deeper burns. Subepidermal vesicle formation generally decreased with deeper burns and typically contained grey foamy fluid. Dermal burns were typified by hyalinized collagen and a lack of detectable individual collagen fibres on a background of grey to pale eosinophilic seroproteinaceous fluid. Intact vascular structures were identified principally deep to the burn area in the collagen. Follicle cell injury was identified by cytoplasmic clearing/swelling and nuclear pyknosis, and these follicular changes were often the deepest evidence of burn injury seen for each time point. Histological scores (epidermal changes) or dermal parameter depths (dermal changes) were regressed on burn contact time. Collagen alteration (r(2) = 0.91) correlated best to burn severity followed by vascular patency (r(2) = 0.82), epidermal changes (r(2) = 0.76), subepidermal vesicle formation (r(2) = 0.74) and follicular cell injury was useful in all but deep burns. This study confirms key morphological parameters can be an important tool for the detection of burn severity in this acute burn model.