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Nonstandard exception requests (NSERs), for which transplant centers provide patient-specific narratives to support a higher Model for End-stage Liver Disease/Pediatric End-stage Liver Disease score, are made for >30% of pediatric liver transplant candidates. We describe the justifications used in pediatric NSER narratives 2009-2014 and identify justifications associated with NSER denial, waitlist mortality, and transplant. Using United Network for Organ Sharing data, 1272 NSER narratives from 1138 children with NSERs were coded for analysis. The most common NSER justifications were failure-to-thrive (48%) and risk of death (40%); both associated with approval. Varices, involvement of another organ, impaired quality of life, and encephalopathy were justifications used more often in denied NSERs. Of the 25 most prevalent justifications, 60% were not associated with approval or denial. Waitlist mortality risk was increased when fluid overload or "posttransplant complication outside standard criteria" were cited and decreased when liver-related infection was noted. Transplant probability was increased when the narrative mentioned liver-related infections, and fluid overload for children

Nonstandard exceptions requests (NSERs), in which transplant centers appeal on a case-by-case basis for Pediatric End-Stage Liver Disease/Mayo End-Stage Liver Disease points, have been highly utilized for pediatric liver transplant candidates. We evaluated whether NSE outcomes are associated with waitlist and posttransplant mortality. United Network for Organ Sharing (UNOS) Scientific Registry of Transplant Recipients data on pediatric liver transplant candidates listed in 2009-2014 were analyzed after excluding those granted automatic UNOS exceptions. Of 2581 pediatric waitlist candidates, 44% had an NSE request. Of the 1134 children with NSERs, 93% were approved and 7% were denied. For children 2-18 years at listing, NSER denial increased the risk of waitlist mortality or removal for being too sick (subhazard ratio 2.99, 95% confidence interval [CI] 1.26-7.07, p = 0.01 in multivariate analysis). For children younger than 2 years, NSER denial did not impact waitlist mortality/removal. Children with NSER approved had reduced risk of graft loss 3 years posttransplant in univariate but not multivariable analysis (odds ratio 0.73, 95% CI 0.53-1.01, p = 06). Those with NSER denial had a higher risk of posttransplant death than those with no NSER (hazard ratio 2.43, 95% CI 0.99-5.95, p = 0.05, multivariable analysis), but NSER approval did not impact posttransplant death. Further research on NSER utilization in pediatric liver transplant is needed to optimize organ allocation and outcomes for children.

Metabolic syndrome is associated with long-term morbidity and mortality after adult liver transplantation (LT). Whether pediatric LT recipients have a higher prevalence of metabolic syndrome remains controversial. In a cross-sectional study, we evaluated pediatric LT recipients aged 8-30 years using National Health and Nutrition Examination Survey (NHANES) protocols. LT recipients were matched by gender, race/ethnicity, and age with controls from NHANES. Pediatric LT recipients (n = 83), after adjusting for overweight/obesity and glucocorticoid use, had increased prevalence of prehypertension and hypertension, impaired glucose tolerance (IGT; 2-h glucose after oral glucose tolerance test ≥140 mg/dL), and low high-density lipoprotein compared to matched NHANES controls (n = 235) despite a lower prevalence of overweight/obesity. Among LT recipients, the adjusted odds of IGT doubled for every 7.5 years taking calcineurin inhibitors (odds ratio = 2.10, 95% confidence interval 1.06-4.17 per 7.5 years taking calcineurin inhibitors, p = 0.03). Among all subjects with IGT, LT recipients had a lower prevalence of overweight/obesity and less insulin resistance (homeostatic model assessment of insulin resistance) than did controls with IGT. Among normal weight subjects, LT recipients were significantly more likely than controls to have prehypertension/hypertension, IGT, low high-density lipoprotein, and metabolic syndrome. Pediatric LT recipients have unique metabolic syndrome profiles and risk factors and will require tailored screening and management protocols.

Despite a high prevalence of pancreatic endocrine and exocrine insufficiency in cystic fibrosis (CF), pancreas transplantation is rarely reported. United Network for Organ Sharing (UNOS) data were used to examine utilization of pancreas transplant and posttransplant outcomes in CF patients. Between 1987-2014, CF patients (N = 4600) underwent 17 liver-pancreas, three lung-pancreas, one liver-lung pancreas, four kidney-pancreas, and three pancreas-only transplants. Of the 303 CF patients who received liver transplantation, 20% had CF-related diabetes (CFRD) before transplantation, and nine of those received a liver-pancreas transplant. Of 4241 CF patients who underwent lung transplantation, 33% had CFRD before transplantation, and three of those received a pancreas transplant. Of 49 CF patients who received a liver-lung transplant, 57% had CFRD before transplantation and one received a pancreas transplant. Posttransplantation diabetes developed in 7% of CF pancreas transplant recipients versus 24% of CF liver and 29% of CF lung recipients. UNOS has no data on pancreas exocrine insufficiency. Two-year posttransplantation survival was 88% after liver-pancreas transplant, 33% after lung-pancreas transplant, and 100% after pancreas-kidney and pancreas-only transplants. Diabetes is common pretransplantation and posttransplantation in CF solid organ transplant recipients, but pancreas transplantation remains rare. Further consideration of pancreas transplant in CF patients undergoing other solid organ transplant may be warranted.

Posttransplant metabolic syndrome (PTMS)-obesity, hypertension, elevated triglycerides, low HDL and glucose intolerance-is a major contributor to morbidity after adult liver transplant. This analysis of the Withdrawal of Immunosuppression in Pediatric Liver Transplant Recipients (WISP-R) pilot trial is the first prospective study of PTMS after pediatric liver transplant. Twenty children were enrolled in WISP-R, at median age 8.5 years (IQR 6.4-10.8), and weaned from calcineurin-inhibitor monotherapy. The 12 children who tolerated complete immunosuppression withdrawal were compared to matched historical controls. At baseline, 45% of WISP-R subjects and 58% of controls had at least one component of PTMS. Calcineurin-inhibitor withdrawal in the WISP-R subjects did not impact the prevalence of PTMS components compared to controls. At 5 years, despite weaning off of immunosuppression, 92% of the 12 tolerant WISP-R subjects had at least one PTMS component and 58% had at least two; 33% were overweight or obese, 50% had dyslipidemia, 33% glucose intolerance and 42% systolic hypertension. Overweight/obesity increased the risk of hypertension in all children. Compared to controls, WISP-R tolerant subjects had similar GFR at baseline but did have higher GFR at 2, 3 and 4 years. Further study of PTMS and immunosuppression withdrawal after pediatric liver transplant is warranted.

Background/objective: Recurrent acute pancreatitis (RAP) and chronic pancreatitis (CP) lack effective therapies. There is no consensus or guidance on which endpoints or outcome measures should be used in clinical trials. This study aimed to develop a core outcome set aligned with both patient and provider priorities for RAP and CP. Utilizing the Outcomes Measures in Rheumatology (OMERACT) framework, a multi-stakeholder approach was adopted to identify and prioritize outcome domains., Methods: A two-round Delphi poll was conducted among four stakeholder groups: adult patients, parents and pediatric patients, adult health care providers and pediatric health care providers. Steering committee consensus further refined the core outcome domains, categorizing them as mandatory, important but optional, or research agenda domains, with full consensus achieved., Results: Pain severity, ability to participate in social roles and activities, pancreatitis related hospitalization/ER visits and acute pancreatitis flare-ups were recommended as mandatory outcome domains for future clinical trials in RAP/CP., Conclusions: Using the OMERACT framework, we developed a core outcome set for RAP and CP. Future research will focus on identifying validated measures for each domain, facilitating standardized assessments across clinical trials., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest for this article., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background/objectives: Hope is a universal, multidimensional, and nuanced concept that may have specific meaning for young people living with chronic health conditions anticipated to last into adulthood. We previously identified definitions of hope for youth living with chronic health conditions derived from young people's and their caregivers' own words. Here, we aimed to develop a hope assessment tool to facilitate the future evaluation of interventions to support wellness and health for young people growing up with chronic health conditions; Methods: We developed Likert-type scale questions using the young people's and caregivers' definitions of hope and applied the think-aloud cognitive interview method to assess understanding and to inform sequential iteration. Interviews were recorded and insights from participant interviews were analyzed thematically., Results: In total, 11 youth (age 12-16 years) with various chronic health conditions completed surveys and interviews over three iteration cycles. Responses to the six-point Likert-scale questions ranged from 1 (none of the time) to 6 (all of the time) (median 5). All of the young people (n = 11) reported that they do things they enjoy, either all of the time or most of the time. In contrast, only 36% felt energetic, either all or most of the time. Three themes were identified: my body and hope; my identity, self-image, and hope; and my world and hope., Conclusions: In addition to gaining important feedback that allowed us to improve item word choice to maximize assessment tool understanding, we gained valuable insights into the multidimensional construct of hope. Thematic analysis revealed the importance of physical symptoms and identity to the meaning of hope in the context of a young person's life. Our new hope assessment tool derived from the young people's own definition of hope has face and content validity for use in clinical and research settings to evaluate hope among pediatric patients living with chronic health conditions.

Introduction: Among children who suffer from acute recurrent pancreatitis (ARP) or chronic pancreatitis (CP), acute pancreatitis (AP) episodes are painful, often require hospitalization, and contribute to disease complications and progression. Despite this recognition, there are currently no interventions to prevent AP episodes. In this retrospective cohort study, we assessed the impact of pancreatic enzyme therapy (PERT) use on clinical outcomes among children with pancreatic-sufficient ARP or CP., Methods: Children with pancreatic-sufficient ARP or CP in the INSPPIRE-2 cohort were included. Clinical outcomes were compared for those receiving vs not receiving PERT, as well as frequency of AP before and after PERT. Logistic regression was used to study the association between development of AP episodes after starting PERT and response predictors., Results: Among 356 pancreatic-sufficient participants, 270 (76%) had ARP, and 60 (17%) received PERT. Among those on PERT, 42% did not have a subsequent AP episode, during a mean 2.1 years of follow-up. Children with a SPINK1 mutation ( P = 0.005) and those with ARP (compared with CP, P = 0.008) were less likely to have an AP episode after starting PERT. After initiation of PERT, the mean AP annual incidence rate decreased from 3.14 down to 0.71 ( P < 0.001)., Discussion: In a retrospective analysis, use of PERT was associated with a reduction in the incidence rate of AP among children with pancreatic-sufficient ARP or CP. These results support the need for a clinical trial to evaluate the efficacy of PERT to improve clinical outcomes among children with ARP or CP., (Copyright © 2024 by The American College of Gastroenterology.)

Objective: To determine if mild-moderate hypertriglyceridemia (HTG) is associated with increased development of chronic pancreatitis (CP) or pancreatitis-associated complications in children with acute recurrent or CP., Study Design: Longitudinal data from the INternational Study group of Pediatric Pancreatitis: In search for a cuRE-2 (INSPPIRE-2) cohort of children with acute recurrent or CP (n = 559) were analyzed. Subjects were divided into normal triglycerides (<150 mg/dL; 1.7 mmol/L), any HTG (≥150 mg/dL; ≥1.7 mmol/L), mild-moderate HTG (150-499 mg/dL; 1.7-5.6 mmol/L), moderate HTG (500-999 mg/dL; 5.6-11.3 mmol/L), and severe HTG groups (≥1000 mg/dL; ≥11.3 mmol/L), based on highest serum triglyceride value. Laboratory, imaging, pancreatitis and hospital events, complications, and quality of life data were analyzed., Results: In children with acute recurrent or CP and HTG, there was no increase in the number of pancreatitis attacks per person-years, nor an increase in CP prevalence. However, HTG severity was associated with increased pancreatic inflammation, pancreatic cysts, pain, hospital days, number of hospitalizations, intensive care, and missed school days., Conclusions: Mild-moderate HTG in children with acute recurrent or CP was not associated with increased pancreatitis frequency, nor increased development of CP, but was associated with increased pancreatitis complications and disease burden. As a treatable condition, treatment of mild-moderate HTG may be considered to reduce pancreatitis-associated complications and medical burden in children with acute recurrent or CP., Competing Interests: Declaration of Competing Interest Z.M.S. is currently an employee of 4D Molecular Therapeutics Inc and a consultant for BridgeBio Pharma and Renexxion. M.A.H. is the president of CAPER, a board member of CAPER, and a board member of the National Pancreas Foundation. T.G. received a research grant from Vertex Pharmaceuticals, and she is a consultant for Cystic Fibrosis Foundation (CFF). C.Y.O. is a consultant for and has received research grant from Vertex Pharmaceuticals. E.R.P. is a consultant for BridgeBio and Ultragenyx. S.J.S. is a consultant for UpToDate, Nestle, Abbvie, Renexxion, and the CFF. A.J.F. is a consultant for Takeda and AbbVie, CFF, and is a member of the CAPER board. V.D.M. is an Associate Editor for JPGN Reports. D.M.T. is an Associate Editor for JPGN. M.W. is a consultant for and has received research grants from Vertex Pharmaceuticals. M.E.L. receives royalties from Millipore Inc and UpToDate and consults for CFF. A.U. is a consultant for CFF and Abbvie Inc. The other authors declare no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease among US children. Studies have associated food insecurity with MASLD in adults, but there are few studies of pediatric MASLD, particularly in high-risk populations. We assessed the impact of household food insecurity at 4 years of age on MASLD in Latinx children., Methods: Using a prospective cohort design, Latina mothers were recruited during pregnancy and followed with their children until early to mid-childhood. Our primary exposure was household food insecurity at 4 years of age measured using the validated US Household Food Security Food Module. Our primary outcome, MASLD, was defined as alanine transaminase (ALT) ≥95th% for age/gender plus body mass index (BMI) ≥85% at time of ALT measurement (assessed between ages 5-12). We used multivariable logistic regression models to test for independent associations between household food insecurity and pediatric MASLD., Results: Among 136 children, 28.7% reported household food insecurity at 4 years of age and 27.2% had MASLD in early to middle childhood. Approximately 49% of children with MASLD and 21% of children without MASLD were food insecure (p < 0.01). Exposure to household food insecurity at age 4 was independently associated with a 3.7-fold higher odds of MASLD later in childhood (95% CI: 1.5-9.0, p < 0.01)., Conclusions: Exposure to household food insecurity at 4 years of age was associated with increased risk for MASLD later in childhood. Further studies are needed to explore mechanism(s) and impact of reducing food insecurity on risk for MASLD., (© 2024 The Authors. Pediatric Obesity published by John Wiley & Sons Ltd on behalf of World Obesity Federation.)

Background: Data on oral vancomycin for primary sclerosing cholangitis (PSC)-associated inflammatory bowel disease (IBD) are limited., Aims: Using data from the Paediatric PSC Consortium, to examine the effect of vancomycin on IBD activity., Methods: In this retrospective multi-centre cohort study, we matched vancomycin-treated and untreated patients (1:3) based on IBD duration at the time of primary outcome assessment. The primary outcome was Physician Global Assessment (PGA) of IBD clinical activity after 1 year (±6 months) of vancomycin. We used generalised estimating equations (GEE) to examine the association between vancomycin and PGA remission, adjusting for IBD type, severity and medication exposures. Secondary outcomes included serum labs and endoscopic remission (global rating of no activity) among those with available data and also analysed with GEE., Results: 113 PSC-IBD patients received vancomycin (median age 12.7 years, 63% male). The matched cohort included 70 vancomycin-treated and 210 untreated patients. Vancomycin was associated with greater odds of IBD clinical remission (odds ratio [OR] 3.52, 95% CI 1.97-6.31; adjusted OR [aOR] 5.24, 95% CI 2.68-10.22). Benefit was maintained in sensitivity analyses restricted to non-transplanted patients and those with baseline moderate-severe PGA. Vancomycin was associated with increased odds of endoscopic remission (aOR 2.76, 95% CI 1.002-7.62; N = 101 with data), and with lower CRP (p = 0.03) and higher haemoglobin and albumin (both p < 0.01)., Conclusion: Vancomycin was associated with greater odds of IBD clinical and endoscopic remission. Additional, preferably randomised, controlled studies are needed to characterise efficacy using objective markers of mucosal inflammation, and to examine safety and define optimal dosing., (© 2024 John Wiley & Sons Ltd.)

Pediatric liver transplant (LT) recipients navigate a lifelong journey that includes constant monitoring and challenges. Research priorities and questions in LT have traditionally been provider-driven. This project was a novel partnership between a learning health system dedicated to pediatric LT (Starzl Network for Excellence in Pediatric Transplantation) and a parent-led advocacy group (Transplant Families) that aimed to prepare families and providers for collaborative patient-centered outcomes research (PCOR). We developed 5 virtual modules to (1) teach participants about PCOR, and (2) elicit ideas for PCOR priorities and processes in pediatric LT. Parents and providers participated via self-guided online modules or focus groups. Participants included 240 patient partners and 133 pediatric LT providers from 16 centers over 2 years. We held 20 focus groups, including 5 to amplify underrepresented voices: young adults, Spanish speakers, and African Americans. Feedback was summarized to create a PCOR Roadmap, a guide for future PCOR in the Starzl Network, which was disseminated back to participants online and via webinars. Feedback from a diverse group of stakeholders allowed us to develop PCOR priorities and processes for the pediatric LT community. Our engagement strategies could be adapted by other transplant communities to facilitate patient and provider research partnerships., Competing Interests: Declaration of competing interest The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: No study has explored whether availability of endoscopic retrograde cholangiopancreatography (ERCP) is adequate and equitable across US children's hospitals. We hypothesized that ERCP availability and utilization differs by geography and patient factors., Methods: Healthcare encounter data from 2009 to 2019 on children with pancreatic and biliary diseases from the Pediatric Health Information System were analyzed. ERCP availability was defined as treatment at a hospital that performed pediatric ERCP during the year of service., Results: From 2009 to 2019, 37,946 children (88,420 encounters) had a potential pancreatic or biliary indication for ERCP; 7066 ERCPs were performed. The commonest pancreatic diagnoses leading to ERCP were chronic (47.2%) and acute pancreatitis (43.2%); biliary diagnoses were calculus (68.3%) and obstruction (14.8%). No ERCP was available for 25.0% of pancreatic encounters and 8.1% of biliary encounters. In multivariable analysis, children with public insurance, rural residence, or of Black race were less likely to have pancreatic ERCP availability; those with rural residence or Asian race were less likely to have biliary ERCP availability. Black children or those with public insurance were less likely to undergo pancreatic ERCP where available. Among encounters for calculus or obstruction, those of Black race or admitted to hospitals in the West were less likely to undergo ERCP when available., Conclusions: One-in-four children with pancreatic disorders and one-in-12 with biliary disorders may have limited access to ERCP. We identified racial and geographic disparities in availability and utilization of ERCP. Further studies are needed to understand these differences to ensure equitable care., (© 2024 The Authors. Journal of Pediatric Gastroenterology and Nutrition published by Wiley Periodicals LLC on behalf of European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Background: Adult patients with biliary acute pancreatitis (BAP) or choledocholithiasis who do not undergo cholecystectomy on index admission have worse outcomes. Given the paucity of data on the impact of cholecystectomy during index hospitalization in children, we examined readmission rates among pediatric patients with BAP or choledocholithiasis who underwent index cholecystectomy versus those who did not., Methods: Retrospective study of children (< 18 years old) admitted with BAP, without infection or necrosis (ICD-10 K85.10), or choledocholithiasis (K80.3x-K80.7x) using the 2018 National Readmission Database (NRD). Exclusion criteria were necrotizing pancreatitis with or without infected necrosis and death during index admission. Multivariable logistic regression was performed to identify factors associated with 30-day readmission., Results: In 2018, 1122 children were admitted for index BAP (n = 377, 33.6%) or choledocholithiasis (n = 745, 66.4%). Mean age at admission was 13 (SD 4.2) years; most patients were female (n = 792, 70.6%). Index cholecystectomy was performed in 663 (59.1%) of cases. Thirty-day readmission rate was 10.9% in patients who underwent cholecystectomy during that index admission and 48.8% in those who did not (p < 0.001). In multivariable analysis, patients who underwent index cholecystectomy had lower odds of 30-day readmission than those who did not (OR 0.16, 95% CI 0.11-0.24, p < 0.001)., Conclusions: Index cholecystectomy was performed in only 59% of pediatric patients admitted with BAP or choledocholithiasis but was associated with 84% decreased odds of readmission within 30 days. Current guidelines should be updated to reflect these findings, and future studies should evaluate barriers to index cholecystectomy., (© 2024. The Author(s).)

The exception point system for liver allocation in the United States allows for additional waitlist priority for candidates where the Model for End-Stage Liver Disease or Pediatric End-stage Liver Disease does not effectively represent their urgency or need for a transplant. In May 2019, the review process for liver exception cases transitioned from 11 Regional Review Boards (RRBs) to 1 National Liver Review Board (NLRB), intended to increase consistency nationwide, improve efficiency, and balance transplant access for candidates with and without exception scores. This report provides a review of liver exception request and review practices, waitlist outcomes, and transplant activity in the first 2 years after implementation of the NLRB and acuity circle-based distribution in the United States. We compared initial and extension exception request forms submitted from May 13, 2017 to May 13, 2019 (prepolicy or RRB era) to the period from February 4, 2020 to February 3, 2022 (postpolicy or NLRB era). During this time, the NLRB reviewed 10,083 initial exception requests and 12,686 extension requests. Notable postpolicy highlights include (1) an increase in the proportion of initial and extension requests that were automatically approved instead of manually reviewed; (2) a decrease in the overall approval rates of initial exception requests (87.8% for adult HCC, 64.3% for adult other diagnoses, and 71.5% for pediatric); and (3) reduction in the time from exception request submission to adjudication to a median of 3.73 days. The proportions of waitlist registration and deceased donor liver transplants for patients with exception scores decreased, and waitlist outcomes between patients with and without exception scores are now comparable. Implementation of the NLRB improved efficiency, reduced case workloads, and standardized criteria for exception cases, with similar waitlist outcomes between patients with and without exception scores and improved equity in terms of access to liver transplants., (Copyright © 2023 American Association for the Study of Liver Diseases.)

SARS-CoV-2 infection during the Omicron period was frequent amongst a cohort of vaccinated pediatric solid organ transplant recipients (pSOTRs) despite robust anti-receptor-binding domain (anti-RBD) antibody response, suggesting poor neutralizing capacity against Omicron subvariants. Breakthrough infections among pSOTRs were overall limited in severity., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Adolescent solid organ transplant recipients (aSOTRs) who received three doses of the COVID-19 mRNA vaccine experience high seroconversion rates and antibody persistence for up to 3 months. Long-term antibody durability beyond this timeframe following three doses of the SARS-CoV-2 mRNA vaccine remains unknown. We describe antibody responses 6 months following the third vaccine dose (D3) of the BNT162b2 mRNA vaccination among aSOTRs., Methods: Participants in a multi-center, observational cohort who received the third dose of the vaccine were analyzed for antibodies to the SARS-CoV-2 spike protein receptor-binding domain (Roche Elecsys anti-SARS-CoV-2-S positive: ≥0.8, maximum: >2500 U/mL). Samples were collected at 1-, 3-, and 6-months post-D3. Participants were surveyed at each timepoint and at 12-months post-D3., Results: All 34 participants had positive anti-RBD antibody titers 6 months post-D3. Variations in titers occurred between 3 and 6 months post-D3, with 8/28 (29%) having decreased antibody levels at 6 months compared to 3 months and 2/28 (7%) reporting increased titers at 6 months. The remaining 18/28 (64%) had unchanged antibody titers compared to 3-month post-D3 levels. A total of 4/34 (12%) reported breakthrough infection within 6 months and 3/32 (9%) reported infection after 6-12 months following the third dose of the SARS-CoV-2 mRNA vaccine., Conclusions: The results suggest that antibody durability persists up to 6 months following three doses of the SARS-CoV-2 mRNA in aSOTRs. Demography and transplant characteristics did not differ for those who experienced antibody weaning. Breakthrough infections did occur, reflecting immune-evasive nature of novel variants such as Omicron., (© 2024 Wiley Periodicals LLC.)

Objectives: The Starzl Network for Excellence in Pediatric Transplantation identified optimizing immunosuppression (IS) as a priority practice improvement area for patients, families, and providers. We aimed to evaluate associations between clinical characteristics, early IS, and outcomes., Methods: We analyzed pediatric liver transplant (LT) data from 2013 to 2018 in the United Network for Organ Sharing (UNOS) and the Society of Pediatric Liver Transplantation (SPLIT) registries., Results: We included 2542 LT recipients in UNOS and 1590 in SPLIT. IS choice varied between centers with steroid induction and mycophenolate mofetil (MMF) use each ranging from 0% to 100% across centers. Clinical characteristics associated with early IS choice were inconsistent between the two data sets. T-cell depleting antibody use was associated with improved 1-year graft (hazard ratio [HR] 0.50, 95% confidence interval [CI] 0.34-0.76) and patient (HR 0.40, 95% CI 0.20-0.79) survival in UNOS but decreased 1-year patient survival (HR 4.12, 95% CI 1.31-12.93) and increased acute rejection (HR 1.58, 95% CI 1.07-2.34) in SPLIT. Non-T-cell depleting antibody use was not associated with differential risk of survival nor rejection. MMF use was associated with improved 1-year graft survival (HR 0.73, 95% CI 0.54-0.99) in UNOS only., Conclusions: Variation exists in center choice of early IS regimen. UNOS and SPLIT data provide conflicting associations between IS and outcomes in multivariable analysis. These results highlight the need for future multicenter collaborative work to identify evidence-based IS best practices., (© 2024 European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Children from minoritized/socioeconomically deprived backgrounds suffer disproportionately high rates of uninsurance and graft failure/death after liver transplant. Medicaid expansion was developed to expand access to public insurance. Our objective was to characterize the impact of Medicaid expansion policies on long-term graft/patient survival after pediatric liver transplantation. All pediatric patients (<19 years) who received a liver transplant between January 1, 2005, and December 31, 2020 in the US were identified in the Scientific Registry of Transplant Recipients (N = 8489). Medicaid expansion was modeled as a time-varying exposure based on transplant and expansion dates. We used Cox proportional hazards models to evaluate the impact of Medicaid expansion on a composite outcome of graft failure/death over 10 years. As a sensitivity analysis, we conducted an intention-to-treat analysis from time of waitlisting to death (N = 1 1901). In multivariable analysis, Medicaid expansion was associated with a 30% decreased hazard of graft failure/death (hazard ratio, 0.70; 95% confidence interval, 0.62, 0.79; P < .001) after adjusting for Black race, public insurance, neighborhood deprivation, and living in a primary care shortage area. In intention-to-treat analyses, Medicaid expansion was associated with a 72% decreased hazard of patient death (hazard ratio, 0.28; 95% confidence interval, 0.23-0.35; P < .001). Policies that enable broader health insurance access may help improve outcomes and reduce disparities for children undergoing liver transplantation., (Copyright © 2023 American Society of Transplantation & American Society of Transplant Surgeons. Published by Elsevier Inc. All rights reserved.)

Background/objectives: Bone health of children with acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP) is not well studied., Methods: This retrospective study was performed at three sites and included data from INSPPIRE-2., Results: Of the 87 children in the study: 46 had ARP (53%), 41 had CP (47%). Mean age was 13.6 ± 3.9 years at last DXA scan. The prevalence of low height-for-age (Z-score < -2) (13%, 10/78) and low bone mineral density (BMD) adjusted for height (Z-score < -2) (6.4%, 5/78) were higher than a healthy reference sample (2.5%, p < 0.0001 and p = 0.03, respectively)., Conclusion: Children with ARP or CP have lower height and BMD than healthy peers. Attention to deficits in growth and bone mineral accrual in children with pancreatic disease is warranted., (Copyright © 2023 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Objective: To inform approaches to pediatric medical traumatic stress (PMTS) by exploring providers' (1) perception of the impact of PMTS on the medical care of patients with pediatric-onset chronic illnesses, (2) self-reported competencies and practices of PMTS prevention, treatment, and counseling, and (3) perception of the barriers influencing the adoption of these practices., Study Design: A convenience sample of multidisciplinary healthcare providers was recruited through a multimodal recruitment strategy to participate in an electronic survey adapted from the Trauma-Informed Care Provider Survey., Results: Among participants (n = 304), 99% agreed that PMTS impacts patient health. Participants report altering medical care plans due to PMTS, including deferring or stopping treatments (n = 98 [32%]) and changing medication regimens (n = 88 [29%]). Sixty-eight percent (n = 208) report negative impact of PMTS on patient implementation of medical care plans, including medication nonadherence (n = 153 [50%]) and missed appointments (n = 119 [39%]). Although participants agreed it is their job to decrease patient stress (n = 292 [96%]) and perform PMTS assessments (n = 268 [88%]), few practiced PMTS-focused trauma informed care. Systems-level barriers to practice included insufficient training, absent clinical workflows, and lack of access to mental health experts., Conclusions: Our findings have helped inform a conceptual framework for understanding the relationship between PMTS and health outcomes. Systems-level opportunities to optimize PMTS-focused trauma-informed care include (1) dissemination of provider training, (2) integrated workflows for PMTS mitigation, and (3) enhanced accessibility to mental health providers. Further work is required to determine if these interventions can improve health outcomes in patients with pediatric-onset chronic illnesses., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interests. Conflicts and support: The authors declare no conflicts of interest. This work was supported by a Harry Shwachman Clinical Investigator Award from the Cystic Fibrosis Foundation (AC, Grant # CUNEO20Q0). Study sponsors played no role in the (1) study design, (2) collection, analysis, and interpretation of data, (3) writing of the report, or (4) decision to submit the paper for publication., (Published by Elsevier Inc.)

Introduction: Although clinicians repeatedly measure ALT to assess allograft health in children with liver transplants, they generally make decisions based on single values or qualitative trends without quantitative aggregation or synthesis. We therefore aimed to derive and test a holistic ALT metric for the 5th post-transplant year (Yr 4-5) that may better guide clinical decision-making and/or population comparisons., Methods: We derived the "adjusted mean Yr 4-5 ALT" for children transplanted in 2005-2016 by averaging the median ALT from each month. Patients in quartiles (Q1-4) defined by the adjusted mean Yr 4-5 ALT were compared by clinical variables, Yr 5-8 outcomes, and tacrolimus standard deviation (MLVI)., Results: For 97 children [49 male; 77 deceased donors; median (IQR) age at LT 2.5 (0.8-11.7) years], the 25th, 50th, and 75th percentile thresholds for adjusted mean Yr 4-5 ALT were 19, 28, and 47 U/L, respectively. Age, donor type, LT indication, rejection history, and mean tacrolimus levels did not differ between quartiles (Q). Children in Q4 had more Yr 4-5 acute rejection episodes (p < .01), higher Yr 4-5 MLVI (p < .01), and more Yr 5-8 for-cause liver biopsies (p < .01) than those in Q1 + Q2. Children in Q3 also had higher Yr 4-5 MLVI than Q1 + Q2 (p = .047). Rates of chronic rejection and therapeutic liver-related procedures were higher in Q4 but the difference did not reach significance., Conclusion: An integrated ALT metric calculated utilizing all available ALT values correlates with MLVI and future for-cause biopsies. Further study of this novel ALT metric as a predictor of clinical outcomes and descriptor of populations is warranted., (© 2023 Wiley Periodicals LLC.)

To assess the impact of technical variant grafts (TVGs) [including living donor (LD) and deceased donor split/partial grafts] on waitlist (WL) and transplant outcomes for pediatric liver transplant (LT) candidates, we performed a retrospective analysis of Organ Procurement and Transplantation Network (OPTN) data on first-time LT or liver-kidney pediatric candidates listed at centers that performed >10 LTs during the study period, 2004-2020. Center variance was plotted for LT volume, TVG usage, and survival. A composite center metric of TVG usage and WL mortality was developed to demonstrate the existing variation and potential for improvement. Sixty-four centers performed 7842 LTs; 657 children died on the WL. Proportions of WL mortality by center ranged from 0% to 31% and those of TVG usage from 0% to 76%. Higher TVG usage, from deceased donor or LD, independently or in combination, significantly correlated with lower WL mortality. In multivariable analyses, death from listing was significantly lower with increased center TVG usage (HR = 0.611, CI: 0.40-0.92) and LT volume (HR = 0.995, CI: 0.99-1.0). Recipients of LD transplants (HR = 0.637, CI: 0.51-0.79) had significantly increased survival from transplant compared with other graft types, and recipients of deceased donor TVGs (HR = 1.066, CI: 0.93-1.22) had statistically similar outcomes compared with whole graft recipients. Increased TVG utilization may decrease WL mortality in the US. Hence, policy and training to increase TVG usage, availability, and expertise are critical., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: People living with cystic fibrosis (PwCF) face a lifetime of potentially traumatic illness-related experiences that can lead to posttraumatic stress symptoms. Existing criteria for this type of posttraumatic stress, called medical traumatic stress (MTS), may not fully capture the CF experience. In this study we aimed to explore: 1) illness-related experiences perceived as traumatic in the setting of CF, 2) perceived MTS symptoms in PwCF, and 3) perceived health-related functional impairments from MTS., Methods: Informed by our aims, we developed and piloted guides for semi-structured interviews and focus groups with PwCF, family members of PwCF, and CF medical providers. We then conducted a series of interviews and focus groups. The qualitative analytical process followed Deterding and Waters' three stages of flexible coding for in-depth interviews, generating key themes and sub-themes in each domain of study inquiry., Results: We recruited 51 participants, including 24 PwCF, 7 family members of PwCF, and 20 CF care team members. Illness-related experiences perceived as traumatic were often characterized by themes of loss of agency, threats of bodily harm, and shifts in identity. Prominent MTS symptoms included shame, survivor guilt, burden guilt, germaphobia, and symptom panic. Health-related themes of functional impairments perceived to result from MTS included poor adherence and strained relationships between providers and patients/families., Conclusions: This is the first study to explore the specific experiences of MTS in PwCF. It highlights the need for screening that includes these specific exposure types and symptoms, which may be mitigatable with medical trauma-focused interventions., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest. This work was supported by a Harry Shwachman Clinical Investigator Award from the Cystic Fibrosis Foundation (AC, Grant # CUNEO20Q0). MBH is supported in part by the Ed and Liliane Schneider family. Funders have played no role in study design, collection of data, analysis, and interpretation of the data, writing of the report, or in the decision to submit the article for publication., (Copyright © 2022. Published by Elsevier B.V.)

Introduction: In October 2021, the American Society of Transplantation (AST) hosted a virtual consensus conference aimed at identifying and addressing barriers to the broader, safe expansion of living donor liver transplantation (LDLT) throughout the United States (US)., Methods: A multidisciplinary group of LDLT experts convened to address issues related to financial implications on the donor, transplant center crisis management, regulatory and oversight policies, and ethical considerations by assessing the relative significance of issues in preventing LDLT growth, with proposed strategies to overcome barriers., Results: Living liver donors endure multiple obstacles including financial instability, loss of job security, and potential morbidity. These concerns, along with other center, state, and federal specific policies can be perceived as significant barriers to expanding LDLT. Donor safety is of paramount importance to the transplant community; however, regulatory and oversight policies aimed at ensuring donor safety can be viewed as ambiguous and complicated leading to time-consuming evaluations that may deter donor motivation and program expansion., Conclusion: Transplant programs need to establish appropriate crisis management plans to mitigate potential negative donor outcomes and ensure program viability and stability. Finally, ethical aspects, including informed consent for high-risk recipients and use of non-directed donors, can be perceived as additional barriers to expanding LDLT., (© 2023 The Authors. Clinical Transplantation published by John Wiley & Sons Ltd.)

Competing Interests: The authors declare no conflicts of interest.

Background: For children with liver transplants (LT), achieving an "ideal outcome" is a balancing act: too little immunosuppression begets graft injury; too much begets systemic complications. We aimed to delineate the parental perspective on this tightrope., Methods: Parents of children with LT completed an internet-based survey about their child's immunosuppression., Results: Children of respondents (n = 82) were a median 4 years from primary LT (range 0-22); 73% were on immunosuppression monotherapy. Parents' top concerns were related to immunosuppression complications; 46% were more concerned about immunosuppression complications than rejection; only 17% were more concerned about rejection than immunosuppression complications. Among parents of children on immunosuppression monotherapy, 29% still worried more about immunosuppression complications than rejection, 48% expressed equal concern for both. Time since LT (0-4 vs. >4 years) was not associated with concern level for rejection or immunosuppression complications. Caregivers were significantly more certain that their child's immunosuppression regimen was correct to prevent rejection than to mitigate complications (p < .005)., Conclusion: Caregivers of children with LTs reported higher levels of concern and uncertainty about immunosuppression complications than rejection risk. Understanding parent and patient perspectives on IS, and incorporating them into immunosuppression counseling and decision-making, is critical to achieving truly "ideal" long-term outcomes., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: The prevalence of liver disorders and metabolic syndrome has increased among youth. Glyphosate, the most widely used herbicide worldwide, could contribute to the development of these conditions., Objective: We aimed to assess whether lifetime exposure to glyphosate and its degradation product, aminomethylphosphonic acid (AMPA), is associated with elevated liver transaminases and metabolic syndrome among young adults., Methods: We conducted a prospective cohort study ( n = 480 mother-child dyads) and a nested case-control study ( n = 60 cases with elevated liver transaminases and 91 controls) using data from the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS). We measured glyphosate and AMPA concentrations in urine samples collected during pregnancy and at child ages 5, 14, and 18 y from cases and controls. We calculated glyphosate residue concentrations: [ glyphosate  +   ( 1.5 × AMPA ) ]. We estimated the amount of agricultural-use glyphosate applied within a 1 - km radius of every residence from pregnancy to age 5 y for the full cohort using California Pesticide Use Reporting data. We assessed liver transaminases and metabolic syndrome at 18 y of age., Results: Urinary AMPA at age 5 y was associated with elevated transaminases [relative risk (RR) per 2 - fold increase = 1.27 , 95% confidence interval (CI): 1.06, 1.53] and metabolic syndrome ( RR = 2.07 , 95% CI: 1.38, 3.11). Urinary AMPA and glyphosate residues at age 14 y were associated with metabolic syndrome [ RR = 1.80 (95% CI: 1.10, 2.93) and RR = 1.88 (95% CI: 1.03, 3.42), respectively]. Overall, a 2-fold increase in urinary AMPA during childhood was associated with a 14% and a 55% increased risk of elevated liver transaminases and metabolic syndrome, respectively. Living near agricultural glyphosate applications during early childhood (birth to 5 y of age) was also associated with metabolic syndrome at age 18 y in the case-control group ( RR = 1.53 , 95% CI: 1.16, 2.02)., Discussion: Childhood exposure to glyphosate and AMPA may increase risk of liver and cardiometabolic disorders in early adulthood, which could lead to more serious diseases later in life. https://doi.org/10.1289/EHP11721.

Background: Patient-reported outcome measures (PROMs) are not routinely used in clinical care by pediatric liver transplant (LT) teams. The Starzl Network for Excellence in Pediatric Transplantation (SNEPT) assessed feasibility of using a disease-specific Quality of Life (QoL) questionnaire in the ambulatory setting at 10 SNEPT sites., Methods: A mixed methods feasibility project assessing administration processes, barriers, and user experiences with the Pediatric Liver Transplant Quality of Life (PeLTQL) tool. Iterative processes sought stakeholder feedback across four phases (Pilot, Extended Pilot, Development of a Mobile App PeLTQL version, and Pilot App use)., Results: A total of 149 patient-parent dyads completed the PeLTQL during LT clinic follow-up. Clinicians, parents, and patients evaluated and reported on feasibility of operationalization. Only two of 10 SNEPT sites continued PeLTQL administration after the initial two pilot phases. Reasons include limited clinical time and available personnel aggravated by the COVID-19 pandemic. In response, a mobile application version of the PeLTQL was initiated. Providing PeLTQL responses electronically was "very easy" or "easy" as reported by 96% (22/23) parents., Conclusions: Administration of a PROM into post-pediatric LT clinical care was feasible, but ongoing utilization stalled. Use of a mobile app towards facilitating completion of the PeLTQL outside of clinic hours may address the time and work-flow barriers identified., (© 2022 Wiley Periodicals LLC.)

Background: The Centers for Disease Control and Prevention and the American Academy of Pediatrics recommend that symptomatic children remain home and get tested to identify potential coronavirus disease 2019 (COVID-19) cases. As the pandemic moves into a new phase, approaches to differentiate symptoms of COVID-19 versus other childhood infections can inform exclusion policies and potentially prevent future unnecessary missed school days., Methods: Retrospective analysis of standardized symptom and exposure screens in symptomatic children 0-18 years tested for SARS-CoV-2 at three outpatient sites April to November 2020. Likelihood ratios (LR), number needed to screen to identify one COVID-19 case, and estimated missed school days were calculated., Results: Of children studied (N = 2,167), 88.9% tested negative. Self-reported exposure to COVID-19 was the only factor that statistically significantly increased the likelihood of a positive test for all ages (Positive LR, 5-18 year olds: 5.26, 95% confidence interval (CI): 4.37-6.33; 0-4 year olds: 5.87, 95% CI: 4.67-7.38). Across ages 0-18, nasal congestion/rhinorrhea, sore throat, abdominal pain, and nausea/vomiting/diarrhea were commonly reported, and were either not associated or had decreased association with testing positive for COVID-19. The number of school days missed to identify one case of COVID-19 ranged from 19 to 48 across those common symptoms., Conclusions: We present an approach for identifying symptoms that are non-specific to COVID-19, for which exclusion would likely lead to limited impact on school safety but contribute to school-days missed. As variants and symptoms evolve, students and schools could benefit from reconsideration of exclusion and testing policies for non-specific symptoms, while maintaining testing for those who were exposed., (© 2022. The Author(s).)

Objectives: The objective of this study is to investigate risk factors and disease burden in pediatric acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP)., Methods: Data were obtained from INternational Study group of Pediatric Pancreatitis: In search for a cuRE-2 (INSPPIRE-2), the largest multi-center prospective cohort study in pediatric patients with ARP or CP., Results: Of 689 children, 365 had ARP (53%), 324 had CP (47%). CP was more commonly associated with female sex, younger age at first acute pancreatitis (AP) attack, Asian race, family history of CP, lower BMI%, genetic and obstructive factors, PRSS1 mutations and pancreas divisum. CFTR mutations, toxic-metabolic factors, medication use, hypertriglyceridemia, Crohn disease were more common in children with ARP. Constant or frequent abdominal pain, emergency room (ER) visits, hospitalizations, medical, endoscopic or surgical therapies were significantly more common in CP, episodic pain in ARP. A total of 33.1% of children with CP had exocrine pancreatic insufficiency (EPI), 8.7% had diabetes mellitus. Compared to boys, girls were more likely to report pain impacting socialization and school, medical therapies, cholecystectomy, but no increased opioid use. There was no difference in race, ethnicity, age at first AP episode, age at CP diagnosis, duration of disease, risk factors, prevalence of EPI or diabetes between boys and girls. Multivariate analysis revealed that family history of CP, constant pain, obstructive risk factors were predictors of CP., Conclusions: Children with family history of CP, constant pain, or obstructive risk factors should raise suspicion for CP., Competing Interests: M.E.L. is on the Board of Directors of the National Pancreas Association and receives royalties from Millipore Inc and UpToDate. T.G. received a research grant from Vertex Pharmaceuticals, and she is a consultant for Cystic Fibrosis Foundation (CFF). A.U. is a member of American Board of Pediatrics, Subboard of Pediatric Gastroenterology, Associate Editor of Pancreatology, and consultant for CFF. S.J.S. is a consultant for UpToDate, Nestle, Abbvie, and the Cystic Fibrosis Foundation, and she has a grant from Gilead. V.D.M. is an Associate Editor for JPGN Reports. The remaining authors report no conflicts of interest., (Copyright © 2022 by European Society for European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Objectives: Known as pediatric medical traumatic stress (PMTS), posttraumatic stress symptoms from medical experiences have not been explored in children with chronic gastrointestinal diseases. This cross-sectional study of children and adolescents with inflammatory bowel disease, chronic pancreatitis and cystic fibrosis, aimed to (1) estimate the prevalence of medical potentially traumatic events (PTEs) and PMTS, (2) explore potential risk factors for PMTS, and (3) explore potential consequences of PMTS., Methods: This cross-sectional study used validated, self-report measures to evaluate PTEs and PMTS. Descriptive statistics and regression analyses were used to achieve study objectives., Results: Over two-thirds of children reported a medical potentially traumatic event (91 of 132, 69%). Forty-eight had PMTS symptoms (36%). PMTS was associated with medication burden, emergency and intensive care visits, and parent posttraumatic stress disorder in multivariate analysis. Potential consequences associated with PMTS included school absenteeism, home opioid use, poor quality of life, and parent missed work., Conclusions: A substantial portion of our cohort reported medical PTEs and PMTS. The exploratory analysis identified potential associations between PMTS and illness factors, parent posttraumatic stress disorder, and functional impairments. Further studies of PMTS detection, prevention and treatment are integral to optimizing these children's health and quality of life., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 by European Society for European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

BACKGROUND. Imaging findings represent key criteria for diagnosing chronic pancreatitis in children. Understanding radiologists' agreement for imaging findings is critical to standardizing and optimizing diagnostic criteria. OBJECTIVE. The purpose of this study is to evaluate the interobserver agreement among experienced pediatric radiologists for subjective, quantitative, and semiquantitative imaging findings of chronic pancreatitis in children. METHODS. In this retrospective study, CT or MRI examinations performed in children with chronic pancreatitis were submitted by six sites participating in the INSPPIRE (International Study Group of Pediatric Pancreatitis: In Search for a Cure) Consortium. One pediatric radiologist from each of the six sites reviewed examinations; three of the radiologists independently reviewed all CT examinations, and the other three radiologists independently reviewed all MRI examinations. Reviewers recorded 13 categoric imaging findings of chronic pancreatitis and measured pancreas thickness and pancreatic duct diameter. Agreement was assessed using kappa coefficients for the categoric variables and intraclass correlation coefficients (ICCs) for the continuous variables. RESULTS. A total of 76 CT and 80 MRI examinations performed in 110 children (65 girls and 45 boys; mean age, 11.3 ± 4.6 [SD] years) were reviewed. For CT, kappa coefficients for categoric findings ranged from -0.01 to 0.81, with relatively high kappa coefficients noted for parenchymal calcifications (κ = 0.81), main pancreatic duct dilatation (κ = 0.63), and atrophy (κ = 0.52). ICCs for parenchymal thickness measurements ranged from 0.57 in the pancreas head to 0.80 in the body and tail. The ICC for duct diameter was 0.85. For MRI, kappa coefficients for categoric findings ranged from -0.01 to 0.74, with relatively high kappa coefficients noted for main duct irregularity (κ = 0.74), side branch dilatation (κ = 0.70), number of dilated side branches (κ = 0.65), and main duct dilatation (κ = 0.64); kappa coefficient for atrophy was 0.52. ICCs for parenchymal thickness measurements ranged from 0.53 for the neck and body individually to 0.68 in the tail. ICC for duct diameter was 0.77. CONCLUSION. Interobserver agreement was fair to moderate for most CT and MRI findings of chronic pancreatitis in children. CLINICAL IMPACT. This study highlights challenges for the imaging diagnosis of pediatric chronic pancreatitis. Standardized and/or objective criteria are needed given the importance of imaging in diagnosis.

Abstract: Recurrent acute pancreatitis and chronic pancreatitis represent high morbidity diseases, which are frequently associated with chronic abdominal pain, pancreatic insufficiencies, and reduced quality of life. Currently, there are no therapies to reverse or delay disease progression, and clinical trials are needed to investigate potential interventions that would address this important gap. This conference report provides details regarding information shared during a National Institute of Diabetes and Digestive and Kidney Diseases-sponsored workshop on Clinical Trials in Pancreatitis that sought to clearly delineate the current gaps and opportunities related to the design and conduct of patient-focused trials in recurrent acute pancreatitis and chronic pancreatitis. Key stakeholders including representatives from patient advocacy organizations, physician investigators (including clinical trialists), the US Food and Drug Administration, and the National Institutes of Health convened to discuss challenges and opportunities with particular emphasis on lessons learned from trials in participants with other painful conditions, as well as the value of incorporating the patient perspective throughout all stages of trials., Competing Interests: The following authors disclose potential conflicts of interest: P.A.H. (honoraria for consulting from Kangen Pharmaceuticals and Sagent Pharmaceuticals paid to his institution; honorarium for advisory board from Horizon Therapeutics USA, Inc, paid to his institution); G.A.C. (honoraria for consulting from Olympus Corporation of the Americas); I.G. (honoraria from Adynxx, Biogen, Eupraxia, Novaremed and GW Research); R.H.D. (past 5 years, research grants and contracts from the US Food and Drug Administration and the US National Institutes of Health and compensation forf serving on advisory boards or consulting on clinical trial methods from Abide, Acadia, Adynxx, Analgesic Solutions, Aptinyx, Aquinox, Asahi Kasei, Astellas, Beckley, Biogen, Biohaven, Biosplice, Boston Scientific, Braeburn, Cardialen, Celgene, Centrexion, Chiesi, Chromocell, Clexio, Collegium, Concert, Confo, Decibel, Editas, Eli Lilly, Endo, Ethismos (equity), Eupraxia, Exicure, Glenmark, Gloriana, Grace, Hope, Lotus, Mainstay, Merck, Mind Medicine (also equity), Neumentum, Neurana, NeuroBo, Novaremed, Novartis, OCT, OliPass, Pfizer, Q-State, Reckitt Benckiser, Regenacy (also equity), Sangamo, Sanifit, Scilex, Semnur, SIMR Biotech, Sinfonia, SK Biopharmaceuticals, Sollis, SPRIM, Teva, Theranexus, Toray, Vertex, Vizuri, and WCG); C.E.F. (research funding from Abbvie, consulting fees from Nestlé, and board member for National Pancreas Foundation); J.A.R. (consulting for Pediatrics Steering Committee, Pacira Pharmaceuticals); and D.C.W. (cofounder and chief scientific offer of Ariel Precision Medicine, consultant to Nestlé, Regeneron, and Ariel Precision Medicine). The rest of the authors declare no conflict of interest., (Copyright © 2022 “Written work prepared by employees of the Federal Government as part of their official duties is, under the U.S. Copyright Act, a “work of the United States Government” for which copyright protection under Title 17 of the United States Code is not available. As such, copyright does not extend to the contributions of employees of the Federal Government.”.)

Previous single-center, cross-sectional studies have reported a steep increase in the prevalence and severity of fibrosis through 10 to 15 years after pediatric liver transplantation. We report a multicenter study of paired surveillance biopsies in a contemporary cohort. Children who underwent liver transplant when younger than 6 years old and had paired surveillance liver biopsies were enrolled (n = 78, 35% girls, median 1.2 years old at transplant). A central pathologist graded inflammation, assessed rejection activity index, and staged fibrosis in the portal, sinusoidal, and perivenular compartments, allowing for calculation of the Liver Allograft Fibrosis Score (LAFSc). Analysis of variance tested associations between fibrosis progression and clinical parameters. The first biopsy, at a median 8.2 years (interquartile range, 5.9-11.6 years) after transplantation, showed absent to mild fibrosis (LAFSc 0-2) in 29%, moderate (LAFSc 3-5) in 56%, and severe (LAFSc 6-7) in 14% of patients. The second biopsy, at a median 4.7 years (IQR, 4.3-5.1 years) later, showed fibrosis progression (LAFSc increased by ≥3) in 10 (13%) and regression (LAFSc decreased by ≥3) in 4 (5%) patients. After adjusting for baseline LAFSc, younger age at transplant was the only risk factor for fibrosis progression. Although fibrosis prevalence and severity 6 to 12 years after transplant was similar to previous reports, fibrosis trajectory during the next 4 to 5 years was stable. Our data may be reassuring for children with consistently normal liver tests. A comprehensive understanding of factors determining allograft health during the very long term is essential to optimizing allograft and patient health., (© 2022 by the American Association for the Study of Liver Diseases.)

Objectives: Abdominal pain, emergency department visits, and hospitalizations impact lives of children with acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP). Data on health-related quality of life (HRQOL) in this population, however, remains limited. We aimed to evaluate HRQOL in children with ARP or CP; and test biopsychosocial risk factors associated with low HRQOL., Methods: Data were acquired from the INternational Study Group of Pediatric Pancreatitis: In search for a cuRE registry. Baseline demographic and clinical questionnaires, the Child Health Questionnaire (measures HRQOL) and Child Behavior Checklist (measures emotional and behavioral functioning) were completed at enrollment., Results: The sample included 368 children (54.3% girls, mean age = 12.7years, standard deviation [SD] = 3.3); 65.2% had ARP and 34.8% with CP. Low physical HRQOL (M = 38.5, SD = 16.0) was demonstrated while psychosocial HRQOL (M = 49.5, SD = 10.2) was in the normative range. Multivariate regression analysis revealed that clinical levels of emotional and behavioral problems (B = -10.28, P  < 0.001), episodic and constant abdominal pain (B = 04.66, P = 0.03; B = -13.25, P < 0.001) were associated with low physical HRQOL, after accounting for ARP/CP status, age, sex, exocrine, and endocrine disease (F [9, 271] = 8.34, P < 0.001). Borderline and clinical levels of emotional and behavioral problems (B = -10.18, P < 0.001; B = -15.98, P < 0.001), and constant pain (B = -4.46, P < 0.001) were associated with low psychosocial HRQOL (F [9, 271] = 17.18, P < 0.001)., Conclusions: Findings highlight the importance of assessing HRQOL and treating pain and psychosocial problems in this vulnerable group of children., Competing Interests: M.L. is on the Board of Directors of the National Pancreas Association; receives royalties from Millipore Inc and UpToDate. T.G. received a research grant from Vertex Pharmaceuticals and she is a consultant for Cystic Fibrosis Foundation. M.B. is a consultant for AbbVie Inc and ARIEL Precision Medicine. C.Y.O. is a consultant for Vertex Pharmaceuticals. A.U. is a member of American Board of Pediatrics, Subboard of Pediatric Gastroenterology and a consultant for Cystic Fibrosis Foundation. The other authors declare no conflicts of interest., (Copyright © 2022 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

For pediatric liver transplant (LT) recipients, an ideal outcome is to survive and thrive into adulthood. However, outcomes reporting for all LT recipients typically rely on much shorter-term outcomes, 1-5 years post-LT. Using Organ Procurement and Transplantation Network (OPTN) registry data from 1990 to 2018, this analysis seeks to determine if long-term follow-up and outcome data are complete for pediatric LT recipients age 0 to 12 years who survive at least 1 year post-LT without graft loss (n = 9309). Of the 7948 pediatric transplant recipients who did not die or require re-LT, 1 in 6 was reported as lost to follow-up by their transplant center during long-term follow-up. Rates of lost to follow-up were highest in those transplanted between 1990 and 1999 and increased in early adulthood for all recipients. Almost 10% of pediatric LT recipients who remained in follow-up required relisting for LT. 8% of children remaining in follow-up had graft failure. Lost to follow-up may bias estimates of long-term outcomes and risk factors for poor outcomes. For those remaining in follow-up, graft failure and death continue to occur in the decades after LT. Continued proactive monitoring, management, and innovations are needed to truly optimize post-LT survival for all children., (© 2021 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Objectives: Although pain management is central to pediatric chronic pancreatitis (CP) care, no evidence-based guidelines exist. In this scoping systematic review, we sought promising strategies for CP pain treatment in children., Methods: We systematically reviewed literature on pain management in children and adults with CP, and 2 conditions with similar pain courses: juvenile idiopathic arthritis and sickle cell disease., Results: Of 8997 studies identified, 287 met inclusion criteria. There are no published studies of analgesic medications, antioxidants, dietary modification, integrative medicine, or regional nerve blocks in children with CP. In adults with CP, studies of nonopioid analgesics, pancreatic enzymes, and dietary interventions have mixed results. Retrospective studies suggest that endoscopic retrograde cholangiopancreatography and surgical procedures, most durably total pancreatectomy with islet autotransplant, improve pain for children with CP. Follow-up was short relative to a child's life. Large studies in adults also suggest benefit from endoscopic therapy and surgery, but lack conclusive evidence about optimal procedure or timing. Studies on other painful pediatric chronic illnesses revealed little generalizable to children with CP., Conclusions: No therapy had sufficient high-quality studies to warrant untempered, evidence-based support for use in children with CP. Multicenter studies are needed to identify pain management "best practices.", Competing Interests: J.F.P. is on the speaker's bureau for Practical Gastroenterology, Inc; S.J.S. receives funds from Gilead (grant) and UpToDate (royalties). This project did not have other specific grant or other sources of funding. The rest of the authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Nutritional status is known to strongly predict health outcomes in people with cystic fibrosis (CF), but the prevalence of and consequences for CF children with growth failure and underweight CF adults on the liver transplant (LT) waitlist has not been delineated. We utilized UNOS registry data from 2003 to 2017 to investigate the impact of growth failure and underweight on outcomes in liver transplant candidates with CF. Almost 1 in 3 children and adults with CF had growth failure or were underweight, respectively, at listing. Body mass index under-estimated growth failure compared to height and weight z-scores for children. In multivariate analysis of children, growth failure (HR 2.1, 95% CI 1.7-2.6), and CF (HR 2.7, 95% CI 1.6-4.6, vs. Non-CF) were independent risk factors for waitlist death among children; having both increased death risk almost fourfold (SHR 3.88, 95% CI 1.42-10.58). However, among children who did receive a LT, CF was not associated with death within 1-year post-LT. Underweight adult CF candidates were less likely to receive LT, again suggesting the importance of nutritional evaluation and early intervention in this at-risk cohort., (© 2021 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background and Aims: Recurrent primary sclerosing cholangitis (rPSC) following liver transplant (LT) has a negative impact on graft and patient survival; little is known about risk factors for rPSC or disease course in children., Approach and Results: We retrospectively evaluated risk factors for rPSC in 140 children from the Pediatric PSC Consortium, a multicenter international registry. Recipients underwent LT for PSC and had >90 days of follow-up. The primary outcome, rPSC, was defined using Graziadei criteria. Median follow-up after LT was 3 years (interquartile range 1.1-6.1). rPSC occurred in 36 children, representing 10% and 27% of the subjects at 2 years and 5 years following LT, respectively. Subjects with rPSC were younger at LT (12.9 vs. 16.2 years), had faster progression from PSC diagnosis to LT (2.5 vs. 4.1 years), and had higher alanine aminotransferase (112 vs. 66 IU/L) at LT (all P < 0.01). Inflammatory bowel disease was more prevalent in the rPSC group (86% vs. 66%; P = 0.025). After LT, rPSC subjects had more episodes of biopsy-proved acute rejection (mean 3 vs. 1; P < 0.001), and higher prevalence of steroid-refractory rejection (41% vs. 20%; P = 0.04). In those with rPSC, 43% developed complications of portal hypertension, were relisted for LT, or died within 2 years of the diagnosis. Mortality was higher in the rPSC group (11.1% vs. 2.9%; P = 0.05)., Conclusions: The incidence of rPSC in this cohort was higher than previously reported, and was associated with increased morbidity and mortality. Patients with rPSC appeared to have a more aggressive, immune-reactive phenotype. These findings underscore the need to understand the immune mechanisms of rPSC, to lay the foundation for developing new therapies and improve outcomes in this challenging population., (© 2021 by the American Association for the Study of Liver Diseases.)