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Combined experimental and theoretical studies are reported of the Fermi surface, band structure, generalized magnetic susceptibility, electron‐phonon enhancement factor λ and superconducting transition temperature TT of LaB6. Whereas the unusually large λ values, ranging from 1.0 to 2.5, are expected to result in high TT values, TT is observed to be only 0.122°K. These results further emphasize the need for appropriate theoretical formulations for these systems. Copyright © 1975 John Wiley & Sons, Inc.

Introduction: Cross-informant disagreement is common and results in different interpretations of a youth's behavior. Theoretical explanations for discrepancies typically rely on scale level analyses. This article explores whether caregivers and adolescents differ in when they notice and report symptoms of youth mania depending on the severity of overall manic disturbance.Method: Participants were 459 adolescent-caregiver pairs recruited at either a community mental health center or an academic medical center. Adolescents were most likely to have a primary diagnosis of unipolar depression (37%) or attention-deficit/hyperactivity disorder/disruptive behavior disorder (36%). Nineteen percent of adolescents received a bipolar spectrum disorder diagnosis (4% bipolar I and 15% bipolar II, cyclothymia, or bipolar not otherwise specificed). Caregivers were primarily biological mothers (74%) or grandparents (8%). Adolescents and caregivers independently completed the Mood Disorder Questionnaire (MDQ) about the adolescent.Results: Item response theory analyses of the entire sample indicated that in general, both caregivers and adolescents reserved endorsement of mania symptoms for the most severely ill half of participants. Comparisons of caregiver and adolescent report of symptoms on the MDQ indicated two significant differences. Caregivers were more likely to report irritability at significantly lower severity of mania than adolescents. Adolescents endorsed only increased energy or hyperactivity at lower severities than caregivers.Conclusions: Adolescents and caregivers will have different concerns and might report different symptoms consistent with whom the symptom impacts first. Caregivers are more likely to report behaviors such as irritability, whereas adolescents are more likely to report subjective feelings such as feeling more energetic or more hyperactive. [ABSTRACT FROM AUTHOR]

SummaryHepatitis C virus, a recently identified member of the family Flaviviridae, is an important cause of chronic viral hepatitis and cirrhosis. There are similarities in the nature of the immune response to this pathogen with immunity in other flavivirus and hepatotropic virus infections, such as hepatitis B. However, the high rate of viral persistence after primary hepatitis C infection, and the observation that neutralizing antibodies are not protective, would suggest that there are a number of important differences between hepatitis C, other flaviviruses, and hepatitis B. The phenomenon of quasispecies evolution and other viral factors have been proposed to contribute to immune evasion by hepatitis C virus. In the face of established persistent infection, virus-specific cytotoxic T lymphocytes may exert some control over viral replication. However, these same effectors may also be responsible for the progressive liver damage characteristic of chronic hepatitis C infection. The nature of protective immunity, including the role of innate immune responses early after hepatitis C exposure, remains to be defined. [ABSTRACT FROM AUTHOR]

The supracallosal medial frontal cortex can be divided into three functional domains: a ventral region with connections to the limbic system, an anterior dorsal region with connections to lateral prefrontal systems, and a posterior dorsal region with connections to lateral motor systems. Lesion and functional imaging studies implicate this medial frontal cortex in speech and language generation. The current functional magnetic resonance imaging (fMRI) study of word generation was designed to determine which of these three functional domains was substantially involved by mapping individual subjects' functional activity onto structural images of their left medial frontal cortex. Of 28 neurologically normal right-handed participants, 21 demonstrated a prominent paracingu- late sulcus (PCS), which lies in the anterior dorsal region with connections to lateral prefrontal system. Activity increases for word generation centered in the PCS in 18 of these 21 cases. The posterior dorsal region also demonstrated significant activity in a majority of participants (16/28 cases). Activity rarely extended into the cingulate sulcus (CS) (3/21 cases) when there was a prominent PCS. If there was no prominent PCS, however, activity did extend into the CS (6/7 cases). In no case was activity present on the crest of the cingulate gyrus, which is heavily connected to the limbic system. Thus, current findings suggest that medial frontal activity during word generation reflects cognitive and motor rather than limbic system participation. The current study demonstrates that suitably designed fMRI studies can be used to determine the functional significance of anatomic variants in human cortex. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Bipolar disorder is a common mood disorder associated with significant disability and impairment in quality of life in adults. Little research has examined the impact of the disorder on quality of life in children and adolescents. The current study examines the quality of life in children and adolescents with bipolar disorder compared with other physical and psychiatric illnesses. METHODS: This study included 529 youth and caregiver pairs who sought services at a community mental health center or an academic medical center. Diagnoses were based on semistructured interviews of caregivers and youths, and quality of life was determined by the parent-reported Revised Children Quality of Life Questioinnaire (KINDL) questionnaire and compared with published benchmarks for many medical illnesses. RESULTS: Mean age of the youths was 12.0 years, 57% were boys, 72% were black, 22% were white, and 17% had received bipolar disorder diagnoses. Youths with bipolar disorder had significantly lower quality-of-life scores than youths with asthma, atopic dermatitis, obesity, arthritis, oxygen dependence, heart surgery during infancy, depression, behavior disorders, and nonmood and nonbehavior psychiatric diagnoses. CONCLUSIONS: Youths with bipolar disorder reported lower quality of life than other youths encountered in pediatric practice. Pediatricians should attend not only to the child's mood symptoms but also to the overall impairment of the disorder. [ABSTRACT FROM AUTHOR]

Abstract: Both the clinical management and study of recurrent acute pancreatitis and chronic pancreatitis are complicated by significant heterogeneity in the etiology, mechanisms, symptoms, and complications of pancreatitis. The National Institutes of Diabetes and Digestive and Kidney Disease recently convened a workshop to address current knowledge and knowledge gaps in the field. Preclinical models that better replicate human disease are important for development of new therapies. Pain is often the most common and most difficult symptom to treat, as the causes are multifactorial and effective treatment may vary depending on whether pain is neuropathic or nociceptive in origin, and the placebo effect can complicate evaluation of the efficacy of medical and procedural interventions. Novel technologies like functional magnetic resonance imaging and virtual reality may offer novel means for assessing and treating pain, respectively. Clinical trial designs will need to consider best approaches to addressing the heterogeneity of chronic pancreatitis, including careful attention to designing eligibility criteria, and establishing accepted and validated core outcomes criteria for the field. The latter may be informed by consensus in pain research. Recruitment of participants into clinical trials has been challenging, often requiring multiple centers. Establishment of a clinical trials network would facilitate greater opportunities for therapeutic trials in pancreatitis., Competing Interests: D.Y. is a consultant for Pfizer, Inc and has received research support from AbbVie Pharmaceuticals. M.D.B. has served on advisory or monitoring boards for Vertex, Novo Nordisk, and Bridge Bio and received research support from ViaCyte and Dexcom. C.E.F. is a consultant for Nestle Health and has received research support from AbbVie Pharmaceuticals. G.I.P. has received research support by AbbVie Pharmaceuticals. S.J.S. is a consultant for UpToDate (Wolters, Inc). J.E. is a consultant for Boston Scientific Co. L.M. is President of Mission Cure Capital but no financial support or conflict of interest. F.G.S.T. has served as consultant for Sanofi. W.G.P. is a consultant for Pfizer, Arctx Medical, Ariel Medicine, Capsovision, Horizon Therapeutics, Nestle, and Olympus, and has received research support from AbbVie. A.J.F. is a consultant for BridgeBio, has received research funding from Anagram Therapeutics, and is a board member for CAPER. V.K.S. is a consultant to Panafina and Amgen; advisory board participant to Amgen and Ionis; and equity holder and scientific advisory board to Solv Endotherapy, Origin Endoscopy, and Kyttaro. D.C.W. is a consultant for Nestlé and Ariel Precision Medicine and is co-founder and chief scientific officer at Ariel Precision Medicine, Pittsburgh, PA. V.A. is a consultant for Olympus Medical, Dragonfly Endoscopy, and is a co-founder for Origin Endoscopy Inc, Solv Endotherapy Inc, and Sotelix Endoscopy Inc. All other authors have no conflict of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Pancreatic neoplasms are uncommon in children. We assessed the incidence, treatment, and survival of children with pancreatic malignancies, and determined factors associated with mortality using a large database., Methods: The Surveillance, Epidemiology, and End Results 22 database (excluding IL and MA) was queried to identify pediatric patients diagnosed with pancreatic malignancies between 2000 and 2020. Incidence, demographics, treatment modalities, and survival data were compared between tumor groups., Results: Pancreatic malignancies were identified in 300 patients (69 % female). Patients were classified by histology into solid pseudopapillary carcinoma (SPC; n = 144, 48 %), neuroendocrine (NET; n = 77, 25.7 %), epithelial (EP; n = 27, 9 %), pancreatoblastoma (PB; n = 30, 10 %), and non-epithelial/unknown (NE/U; n = 22, 7.3 %). Overall median age at diagnosis was 14, whereas median age for pancreatoblastoma was 4 (p < 0.001). Majority of SPCs (86.8 %) were diagnosed in females (p < 0.001). At diagnosis, 95 (56.2 %), 40 (23.7 %), and 34 (20.1 %) patients had localized, regional, and metastatic disease, respectively. Overall, 225 (86.2 %) patients underwent operation. Five-year overall survival rates at 5-years for each tumor group were significantly different (p < 0.001) at 100 %, 84.2 %, 69 %, 67.2 %, and 59 % for SPC, NET, NE/U, PB, and EP types, respectively. Age-adjusted incidence of pancreatic malignancies was 0.0424 per 100,000. Annual percent change in incidence from 2000 to 2020 was 9.9 [CI: (6.8,13.1), p < 0.001). Regional and distant disease, not undergoing operation, and certain tumor types were associated with increased mortality., Conclusion: Pancreatic malignancy incidence increased over the last 20 years. Tumor type (pancreatoblastoma, neuroendocrine, and epithelial), advanced disease stage, and not undergoing surgery were independently associated with increased mortality., Type of Study: Retrospective cohort study., Level of Evidence: III., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Prepancreatic postduodenal portal vein (PPPV) is a rare anatomic variant where the portal vein (PV) runs anterior to the pancreas and posterior to the duodenum. Only 20 cases of PPPV, all in adults, have been reported in literature. We report the first case of PPPV in a pediatric patient discovered intraoperatively during total pancreatectomy with islet autotransplantation (TPIAT) and the third known case in which the PPPV could be isolated intraoperatively., Case: A 10-year-old girl with debilitating acute recurrent pancreatitis requiring daily pain medication was admitted for elective TPIAT operation. Genetic workup for hereditary causes of pancreatitis was negative. Preoperative magnetic resonance cholangiopancreatography did not identify an abnormal course of the PV. During operation, dissection of tissues anteriorly overlying the pancreas revealed the variant PV anatomy. The PV was adherent to the anterior neck of the pancreas and coursed cranially posterior to the duodenum. Although prior reports have described PPPVs as thin-walled and fragile, the morphology and caliber of the PPPV appeared normal in our patient. The pancreas was adherent to and coursed between the PV and the superior mesenteric artery. The pancreas was meticulously dissected off the vessels and resected. The PPPV was successfully isolated and preserved for islet infusion later in the procedure. After isolation, 2/3 of islets were infused into the PV, and the remaining 1/3 were placed within the peritoneum due to persistently elevated portal venous pressures. There were no complications during the case, and the patient recovered as expected after operation., Conclusion: Our case highlights the first reported case of PPPV in a pediatric patient and one of the three instances wherein it could be safely isolated intraoperatively. Recognition of such anatomic variations is crucial for the safety of operations such as TPIAT that include extensive vascular dissection in chronically scarred operative fields., 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., (© 2025 Colak, Trout, Heinzman, Freeman, Rasmussen, Abu-El-Haija and Nathan.)

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.)

Background: The Cystic Fibrosis Foundation Patient Registry (CFFPR) maintains clinical data, including history of solid organ transplant, on people with cystic fibrosis (CF) who obtain care at CF Foundation-accredited care centers. The Scientific Registry of Transplant Recipients (SRTR) database is a collection of national data related to organ transplantation that supports research to evaluate solid organ transplant candidate and recipient outcomes., Methods: Individuals in the CFFPR were matched to SRTR records using an algorithm that compared names, last four digits of social security numbers, date of birth and date of death. We evaluated match quality by summarizing the extent to which transplant status agreed between the two data sources by organ and year of listing or transplant. We summarized CFFPR-reported characteristics for lung and liver transplants in the year prior to transplant., Results: A total of 7,594 individuals who participated in the CFFPR matched SRTR records with approximately 75% having at least one transplant record in SRTR. Over 97% of the matched population had a CF diagnosis reported to SRTR. In total, 5,253 people were identified as lung transplant recipients and 499 as liver transplant recipients in SRTR. Clinical characteristics for lung and liver transplants were consistent with the epidemiology of transplantation for people with CF., Conclusions: Linkage of the two data sources was successful, with high agreement between them supporting the use of the matched population as a valid resource to study transplantation in CF, particularly leveraging pre-transplant characteristics (collected in CFFPR) with detailed transplant data (collected in SRTR)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

Pancreatic mucinous cystic neoplasms (MCNs) are rare tumors predominantly identified in middle-aged females. Occurrences are extremely rare in children. We report a rare case of pancreatic MCN in an adolescent. A 14-year-old female with Smith-Magenis syndrome and steatotic liver disease (SLD) presented with abdominal discomfort. Magnetic resonance elastography obtained for SLD revealed cholelithiasis and a 0.5-cm cyst in the distal pancreas. Observation was recommended by her pediatric surgery provider. At 18 years old, contrast-enhanced abdominal magnetic resonance imaging showed a 2.4-cm mildly complex, septate, cystic lesion along the distal pancreas with no soft tissue component, pancreatic atrophy, or ductal dilation. Endoscopic ultrasound with cyst fluid cytology showed no definitive neoplasm. Carcinoembryonic antigen level of cyst fluid was markedly elevated at 11,207 ng/mL, concerning an MCN. She was referred to Hepatopancreatobiliary Surgery for evaluation and underwent robotic-assisted distal pancreatectomy. Final pathology revealed a 2.8-cm low-grade MCN with intermediate-grade dysplasia., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Author(s). JPGN Reports published by Wiley Periodicals LLC on behalf of The European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Tumour immune evasion presents a significant challenge to the effectiveness of cancer immunotherapies. Recent advances in high-throughput screening techniques have uncovered that loss of antigen presentation and cytokine signalling pathways are central mechanisms by which tumours evade T cell immunity. To uncover additional vulnerabilities in tumour cells beyond the well-recognized antigen presentation pathway, we conducted a genome-wide CRISPR/Cas9 screen to identify genes that mediate resistance to chimeric-antigen receptor (CAR)-T cells, which function independently of classical antigen presentation. Our study revealed that loss of core-binding factor subunit beta (CBFβ) enhances tumour cell resistance to T cell killing, mediated through T cell-derived TNF. Mechanistically, RNA-sequencing and elemental analyses revealed that deletion of CBFβ disrupts numerous pathways including those involved in zinc homoeostasis. Moreover, we demonstrated that modulation of cellular zinc, achieved by supplementation or chelation, significantly altered tumour cell susceptibility to TNF by regulating the levels of inhibitor of apoptosis proteins. Consistent with this, treatment of tumour cells with a membrane-permeable zinc chelator had no impact on tumour cell viability alone, but significantly increased tumour cell lysis by CD8+ T cells in a TNF-dependent but perforin-independent manner. These results underscore the crucial role of intracellular zinc in regulating tumour cell susceptibility to T cell-mediated killing, revealing a novel vulnerability in tumour cells that might be exploited for the development of future cancer immunotherapeutics., Competing Interests: Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: All animal studies were performed in accordance with the NHMRC Australian Code for the Care and Use of Animals for Scientific Purposes 8th edition (2013) and with approval from the Peter MacCallum Cancer Centre Animal Experimentation Ethics Committee (Ethics approvals E548, E638, 2023-17)., (© 2024. The Author(s).)

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.)

This study was designed to examine how cultural values affected mothers' perceptions of internalizing symptoms in youth, comparing Taiwanese and U.S. samples. We hypothesized that mothers' self-reported East Asian cultural values (e.g., conformity, emotional self-control, face culture) would mediate the relationship between their country of residence and perceptions of youth's depressed mood and anhedonia. Participants were 310 mothers from the United States and 294 mothers from Taiwan. All participants responded to questions regarding their adherence to specific East Asian cultural values. Four brief vignettes about a male adolescent experiencing internalizing symptoms were presented to all participants. After reading each vignette, participants rated their perceptions of the adolescent's symptoms. Results from a series of multilevel structural equation models indicated that Taiwan mothers reported more East Asian cultural values (conformity, emotional self-control, face culture) compared to U.S. mothers, which in turn led to rating youth internalizing problems as less acceptable, more impairing, and more problematic to the family, and feeling less proud and more ashamed of the youth. There was also an inconsistent mediation effect of East Asian cultural values on the relationship between country and rating of anhedonia. The mediation pathway was non-significant for the rating of depressed mood. In conclusion, to improve cultural understanding, researchers and clinicians should consider the driving force of the observed between-group differences to ensure appropriate conceptual frameworks in a cross-cultural context. Cross-cultural differences in ratings of youth symptoms highlight the importance of a culturally sensitive approach to assessing symptoms and functional impairment in different cultural groups., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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.)

Cystic fibrosis-related hepatobiliary involvement (CFHBI) is a term used to describe a spectrum of hepatobiliary involvement ranging from a transient elevation of transaminase levels to advanced cystic fibrosis-associated liver disease (aCFLD). While CFHBI is common among people with cystic fibrosis (PwCF), aCFLD is rare impacting only approximately 5%-10% of the CF population. After respiratory/cardiorespiratory issues and transplant-related complications, aCFLD is now the 4th leading cause of mortality among PwCF. Additionally, aCFLD is an independent predictor of all-cause mortality and is associated with significant morbidity. Despite this recognition, our ability to predict those patients at greatest risk for aCFLD, identify early aCFLD, and monitor the incremental progression of CFHBI is lacking. Here, we review the strengths and weaknesses of the common biomarkers and imaging modalities used in the evaluation and monitoring of CFHBI, as well as the current understanding of genetic modifiers related to aCFLD., (© 2024 Wiley Periodicals LLC.)

Background: Minimal clinically important difference (MCID) is important to establish as a meaningful outcome in research when using patient reported outcome measures (PROMs). We determined the MCID using the distribution-based approach for three measurements used as part of the GALAXY study, which is an observational prospective study on gastrointestinal (GI) symptoms in cystic fibrosis (CF)., Methods: Four hundred and two persons with cystic fibrosis (PwCF) participated in the GALAXY study, all with baseline values available for all questionnaires. Mean age was 20.9 years (2.1- 61.1) with 75 females and 94 males under the age of 18 (42.04 %) and 118 females and 115 males aged 18 or older (57.99 %). MCID was measured for Patient Assessment of Constipation Symptoms (PAC-SYM), Patient Assessment of Upper Gastrointestinal Symptoms (PAGI-SYM), Patient Assessment of Constipation-Quality of Life (PAC-QOL) and their subscales. Two distribution-based approaches, defined as multiplications of the standard deviation (SD) or standard error of the mean (SEM), were used to approximate the MCID., Results: The two distribution-based approaches for determining the MCID estimates produced comparable results in trends in MCIDs across the subscales and total scores. In general, MCID estimates of subscales for all three measurements were higher than their total score MCIDs. The one-half SD- and SEM-based MCID estimates for total scores of each questionnaire are as follows: PAC-SYM: 0.26 and 0.14; PAGI-SYM: 0.32 and 0.15; PAC-QOL: 0.27 and 0.18, respectively., Conclusion: This paper establishes initial MCIDs estimated by the distribution-based approach for the PAC-SYM, PAGI-SYM and PAC-QOL that can now be used to evaluate interventional studies that may impact gastrointestinal symptoms in PwCF., Competing Interests: Declaration of competing interest Dr. Meghana Sathe has received research support from Anagram Therapeutics, Inc and the Cystic Fibrosis Foundation. Dr. Sarah Jane Schwarzenberg consults with Abbvie, Renexxion, and UpToDate. Dr. Baha Moshiree has the following COI to report: She is a consultant for Salix Pharmaceuticals, Ardelyx, and Ironwood. She is on advisory boards for AbbVie, Takeda and Salix and has grant support from Restalsis, ATMO, CF Foundation and Medtronic. She has served as speaker for Ardelyx, Ironwood, Nestle Foundation and QOL Medical. She also has two patents through University of Miami and Wake Forest Medical University pertaining to small bowel capsule (Gut capsule) and blue muffin stool transit test. Dr. A Jay Freeman serves as a consultant for AbbVie and Takeda. He has received research support from the CFF, NIH, Allergan and Travere Therapeutics., (Copyright © 2024. Published by Elsevier B.V.)

The broad spectrum of hepatobiliary involvement in cystic fibrosis (CF) has been commonly referred to as cystic fibrosis liver disease (CFLD). However, differences in the definitions of CFLD have led to variations in reported prevalence, incidence rates, and standardized recommendations for diagnosis and therapies. Harmonizing the description of the spectrum of hepatobiliary involvement in all people with CF (pwCF) is deemed essential for providing a reliable account of the natural history, which in turn supports the development of meaningful clinical outcomes in patient care and research. Recognizing this necessity, The European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) and the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) commissioned and tasked a committee to develop and propose a systematic classification of the CF hepatobiliary manifestations to increase uniformity, accuracy, and comparability for clinical, registry, and research purposes. This report describes the committee's combined expert position statement on hepatobiliary involvement in CF, which has been endorsed by NASPGHAN and ESPGHAN. We recommend using CFHBI (Cystic Fibrosis Hepato-Biliary Involvement) as the updated term to describe and classify all hepatobiliary manifestations in all pwCF. CFHBI encompasses the current extensive spectrum of phenotypical, clinical, or diagnostic expressions of liver involvement observed in pwCF. We present a schematic categorization of CFHBI, which may also be used to track and classify the changes and development of CFHBI in pwCF over time. The proposed classification for CFHBI is based on expert consensus and has not been validated for clinical practice and research purposes. Achieving validation should be an important aim for future research., (© 2023 European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Objectives: This study benchmarks quality of life (QoL) of youth with bipolar disorder (BD) against healthy youth, youth with chronic medical conditions, and youth with other psychiatric disorders. The relative impacts of depressive, (hypo)manic, mixed, and externalizing symptoms on QoL are tested for youth with BD., Method: In total, 657 youth completed the Schedule for Affective Disorders and Schizophrenia for Children (KSADS), the KSADS depression and mania scales, the Parent General Behavior Inventory (PGBI), and the Child Behavior Checklist (CBCL). Youth-reported QoL was determined by the Revised Children Quality of Life Questionnaire (KINDL) and was compared to healthy youth, youth with chronic medical conditions, and youth with other psychiatric disorders., Results: Youth with BD reported poorer QoL overall and on most subscales compared to healthy youth, youth with chronic medical conditions, youth with behavior disorders, and youth with other non-behavior/non-mood disorders. QoL in youth with BD did not differ significantly from QoL in youth with unipolar depression. Parent-report and interview-rated depressive symptoms were associated with decreases in Total QoL and all QoL subscales except Family. Externalizing symptoms were associated with decreases in Family QoL and increases in Friend QoL, and (hypo)manic symptoms were associated with increases in Emotional Well-Being QoL., Conclusions: Depressive symptoms may drive the decline in QoL causing youth with BD to rate their QoL worse than healthy youth, youth with chronic medical conditions, and youth with behavior disorders, but not worse than youth with unipolar depression., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: Drug-associated acute pancreatitis (DAP) studies typically focus on single acute pancreatitis (AP) cases. We aimed to analyze the (1) characteristics, (2) co-risk factors, and (3) reliability of the Naranjo scoring system for DAP using INSPPIRE-2 (the INternational Study group of Pediatric Pancreatitis: In search for a cuRE-2) cohort study of acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP) in children., Methods: Data were obtained from ARP group with ≥1 episode of DAP and CP group with medication exposure ± DAP. Physicians could report multiple risk factors. Pancreatitis associated with Medication (Med) (ARP+CP) was compared to Non-Medication cases, and ARP-Med vs CP-Med groups. Naranjo score was calculated for each DAP episode., Results: Of 726 children, 392 had ARP and 334 had CP; 51 children (39 ARP and 12 CP) had ≥1 AP associated with a medication; 61% had ≥1 AP without concurrent medication exposure. The Med group had other risk factors present (where tested): 10 of 35 (28.6%) genetic, 1 of 48 (2.1%) autoimmune pancreatitis, 13 of 51 (25.5%) immune-mediated conditions, 11 of 50 (22.0%) obstructive/anatomic, and 28 of 51 (54.9%) systemic risk factors. In Med group, 24 of 51 (47%) had involvement of >1 medication, simultaneously or over different AP episodes. There were 20 ARP and 4 CP cases in "probable" category and 19 ARP and 7 CP in "possible" category by Naranjo scores., Conclusions: Medications were involved in 51 of 726 (7%) of ARP or CP patients in INSPPIRE-2 cohort; other pancreatitis risk factors were present in most, suggesting a potential additive role of different risks. The Naranjo scoring system failed to identify any cases as "definitive," raising questions about its reliability for DAP., Competing Interests: Dr Lowe is on the Board of Directors of the National Pancreas Association and receives royalties from Millipore Inc and UpToDate. Dr Gonska received a research grant from Vertex Pharmaceuticals, and she is a consultant for Cystic Fibrosis Foundation (CFF). Dr Uc is a member of American Board of Pediatrics, Subboard of Pediatric Gastroenterology, Associate Editor of Pancreatology , and consultant for CFF. Dr Schwarzenberg is a consultant for UpToDate, Nestle, AbbVie, and the CFF, and she has a grant from Gilead. Dr Troendle is an Associate Editor for JPGN . Dr Morinville is an Associate Editor for JPGN Reports . The remaining authors report no conflicts of interest., (Copyright © 2023 by European Society for European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Background: Pediatric radiologists can identify a liver ultrasound (US) pattern predictive of progression to advanced liver disease. However, reliably discriminating these US patterns remains difficult. Quantitative magnetic resonance imaging (MRI) may provide an objective measure of liver disease in cystic fibrosis (CF)., Objective: The purpose of this study was to determine if quantitative MRI, including MR elastography, is feasible in children with CF and to determine how quantitative MRI-derived metrics compared to a research US., Materials and Methods: A prospective, multi-institutional trial was performed evaluating CF participants who underwent a standardized MRI. At central review, liver stiffness, fat fraction, liver volume, and spleen volume were obtained. Participants whose MRI was performed within 1 year of US were classified by US pattern as normal, homogeneous hyperechoic, heterogeneous, or nodular. Each MRI measure was compared among US grade groups using the Kruskal-Wallis test., Results: Ninety-three participants (51 females [54.8%]; mean 15.6 years [range 8.1-21.7 years]) underwent MRI. MR elastography was feasible in 87 participants (93.5%). Fifty-eight participants had an US within 1 year of MRI. In these participants, a nodular liver had significantly higher stiffness (P<0.01) than normal or homogeneous hyperechoic livers. Participants with a homogeneous hyperechoic liver had a higher fat fraction (P<0.005) than others., Conclusion: MR elastography is feasible in children with CF. Participants with a nodular pattern had higher liver stiffness supporting the US determination of advanced liver disease. Participants with a homogeneous hyperechoic pattern had higher fat fractions supporting the diagnosis of steatosis., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: The authors used a machine-learning approach to model clinician decision making regarding psychiatric hospitalization of children and youths in crisis and to identify factors associated with the decision to hospitalize., Methods: Data consisted of 4,786 mobile crisis response team assessments of children and youths, ages 4.0-19.5 years (mean±SD=14.0±2.7 years, 56% female), in Nevada. The sample assessments were split into training and testing data sets. A random-forest machine-learning algorithm was used to identify variables related to the decision to hospitalize a child or youth after the crisis assessment. Results from the training sample were externally validated in the testing sample., Results: The random-forest model had good performance (area under the curve training sample=0.91, testing sample=0.92). Variables found to be important in the decision to hospitalize a child or youth were acute suicidality, followed by poor judgment or decision making, danger to others, impulsivity, runaway behavior, other risky behaviors, nonsuicidal self-injury, psychotic or depressive symptoms, sleep problems, oppositional behavior, poor functioning at home or with peers, depressive or schizophrenia spectrum disorders, and age., Conclusions: In crisis settings, clinicians were found to mostly focus on acute factors that increased risk for danger to self or others (e.g., suicidality, poor judgment), current psychiatric symptoms (e.g., psychotic symptoms), and functioning (e.g., poor home functioning, problems with peer relationships) when deciding whether to hospitalize or stabilize a child or youth. To reduce psychiatric hospitalization, community-based services should target interventions to address these important factors associated with the need for a higher level of care among youths in psychiatric crisis., Competing Interests: The authors report no financial relationships with commercial interests.

Background: This study examines whether heterogeneous (HTG) pattern on liver ultrasound (US) identifies children at risk for advanced cystic fibrosis liver disease (aCFLD)., Methods: Prospective 6-year multicenter case-controlled cohort study. Children with pancreatic insufficient cystic fibrosis (CF) aged 3-12 years without known cirrhosis underwent screening US. Participants with HTG were matched (by age, Pseudomonas infection status and center) 1:2 with participants with normal (NL) US pattern. Clinical status and laboratory data were obtained annually and US bi-annually for 6 years. Primary endpoint was development of nodular (NOD) US pattern consistent with aCFLD., Results: 722 participants underwent screening US, with 65 HTG and 592 NL. Final cohort included 55 HTG and 116 NL with ≥ 1 follow-up US. ALT, AST, GGTP, FIB-4, GPR and APRI were higher, and platelets were lower in HTG compared to NL. HTG had a 9.5-fold increased incidence (95% confidence interval [CI]:3.4, 26.7, p<0.0001, 32.7% vs 3.4%) of NOD versus NL. HTG had a sensitivity of 82% and specificity of 75% for subsequent NOD. Negative predictive value of a NL US for subsequent NOD was 96%. Multivariate logistic prediction model that included baseline US, age, and log(GPR) improved the C-index to 0.90 compared to only baseline US (C-index 0.78). Based on survival analysis, 50% of HTG develop NOD after 8 years., Conclusions: Research US finding of HTG identifies children with CF with a 30-50% risk for aCFLD. A score based on US pattern, age and GPR may refine the identification of individuals at high risk for aCFLD., Clinical Trial Registration: Prospective Study of Ultrasound to Predict Hepatic Cirrhosis in CF: NCT 01,144,507 (observational study, no consort checklist)., Competing Interests: Declaration of Competing Interest The authors disclosure the following Sarah Jane Schwarzenberg serves as a: consultant for AbbVie, Michael R Narkewicz serves as a consultant for Vertex, and has received research grants from Gilead, AbbVie and has a family member with stock in Merck. Jean Molleston has research funding from Abbvie, Albireo, Gillead, Shire. Daniel H. Leung has served as a consultant for Merck, Gilead and Vertex and has received research grants from Gilead, Abbvie and Mirum. A. Jay Freeman has done consulting work for AbbVie and Takeda and has received research support from Allergan and Travere Therapeutics. Wikrom Karnsakul has received grants from Albireo Pharma, Gilead, and Travere Therapeutics. Alexander J Towbin received author royalites from Elsevier, served as a consultant to Applied Radiology and received grant funding from the Cystic Fibrosis Foundation. Simon Ling has received research grants from Abbvie and Gilead. The remaining authors disclose no conflicts., (Copyright © 2023 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

Living hominoids are distinguished by upright torsos and versatile locomotion. It is hypothesized that these features evolved for feeding on fruit from terminal branches in forests. To investigate the evolutionary context of hominoid adaptive origins, we analyzed multiple paleoenvironmental proxies in conjunction with hominoid fossils from the Moroto II site in Uganda. The data indicate seasonally dry woodlands with the earliest evidence of abundant C 4 grasses in Africa based on a confirmed age of 21 million years ago (Ma). We demonstrate that the leaf-eating hominoid Morotopithecus consumed water-stressed vegetation, and postcrania from the site indicate ape-like locomotor adaptations. These findings suggest that the origin of hominoid locomotor versatility is associated with foraging on leaves in heterogeneous, open woodlands rather than forests.

Objective: Compare long-term mortality, secondary intervention and secondary rupture following elective endovascular aneurysm repair (EVAR) and open surgical repair (OSR)., Background: EVAR has surpassed OSR as the most common procedure used to repair abdominal aortic aneurysm (AAA), but evidence regarding long-term outcomes is inconclusive., Methods: We included patients in linked clinical registry and administrative data undergoing EVAR or OSR for intact AAA between January 2010 and June 2019. We used an inverse probability of treatment-weighted survival analysis to compare all-cause mortality, cause-specific mortality, secondary interventions and secondary rupture, and evaluate the impact of secondary interventions and secondary rupture on all-cause mortality., Results: The study included 3460 EVAR and 427 OSR patients. Compared to OSR, the EVAR all-cause mortality rate was lower in the first 30 days [adjusted hazard ratio (HR) = 0.22, 95% confidence interval (CI) 0.140.33], but higher between 1 and 4 years (HR = 1.29, 95% CI 1.12-1.48) and after 4years (HR = 1.41, 95% CI 1.23-1.63). Secondary intervention rates were higher over the first 30 days (HR = 2.26, 95% CI 1.11-4.59), but lower between 1 and 4years (HR = 0.59, 95% CI 0.48-0.74). Secondary aortic intervention rates were higher across the entire follow-up period (HR = 2.52, 95% CI 2.06-3.07). Secondary rupture rates did not differ significantly (HR = 1.06, 95% CI 0.73-1.55). All-cause mortality beyond 1 year remained significantly higher for EVAR after adjusting for any secondary interventions, or secendary rupture., Conclusions: EVAR has an early survival benefit compared to OSR. However, elevated long-term mortality and higher rates of secondary aortic interventions and subsequent aneurysm repair suggest that EVAR may be a less durable method of aortic aneurysm exclusion., Competing Interests: Conflicts of interest and Source of Funding: This study was partially supported by the US Food and Drug Administration (Grant number U01FD005478, PI, Sedrakyan), and a National Health and Medical Council (NHMRC) Project Grant (no: 1162833). The funders had no influence on the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. M.O.F. is supported by a NHMRC Early Career Research Fellowship (no: 1139133). R.L.V. is a consultant to Abbott Vascular, Medtronic, Intervene, Surmodics, Intact Vascular, Boston Scientific and BD Bard receiving modest honoraria. The authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Aims: People with cystic fibrosis (PwCF) suffer from gastrointestinal (GI) symptoms affecting their quality of life (QOL). Despite the relevance of GI symptoms to the overall health of PwCF, a paucity of studies only have comprehensively assessed the prevalence, severity and QOL of GI symptoms in both children and adults with Cystic Fibrosis (CF)., Methods: Eligible participants ≥2 years of age across 26 US CF centers were followed for 4 weeks. Three validated GI electronic patient-reported outcome measures (ePROMs) with a recall period of 2 weeks and a stool-specific questionnaire were administered weekly over four weeks. Total and domain scores of ePROMs were evaluated overall and in subgroups using linear mixed-effect models., Results: Of 402 enrolled, 58% were ≥ 18 years of age (52% male). The mean (SD) of the total score for PAC-SYM was 0.52 (0.55), for PAGI-SYM was 0.63 (0.67), and for PAC-QOL was 0.67 (0.55). For specific ePROM questions, prevalence of moderate to very severe symptoms were as follows: straining (20.3%), fullness (18.3%), incomplete bowel movements (17.1%), bloating (16.4%), distension (16.4%), abdominal pain (upper-5.1%, lower-7.5%). Comparing participants ≥18 versus <18, a higher prevalence of bloating (63.7% versus 27.3%), lower abdominal pain (39.8% vs 26.2%), stomach fullness (75.6% versus 56.2%), and abdominal distension (60.2% versus 34.9%) was found. Both age groups reported high treatment dissatisfaction as measured with PAC-QOL, mean 1.39 (95% CI: 1.30, 1.47)., Conclusion: GI symptoms were reported in all age ranges irrespective of gender, with higher prevalence observed amongst older and female subgroups. Dissatisfaction with GI targeted treatments were reported in a large proportion of participants despite therapy, highlighting an unmet need for clinical interventions., Clinicaltrials: GOV: NCT03801993., (Copyright © 2022 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

Introduction: The success of highly effective modulator therapy (HEMT) has led to consideration of simpler regimens for people with CF (PwCF) with opportunities to modify burdensome regimens. Despite the intuitive appeal of discontinuing chronic therapies no longer necessary, this process should be pursued systematically to ensure safety, adherence, and validate patient-centered preferences. We designed a questionnaire to determine the state of use of acid-suppressive medications (ASM) and pancreatic enzyme therapy (PERT), current self-withdrawal and provider-directed withdrawal practices, and interest in a standardized withdrawal study., Methods: In collaboration with CF Foundation (CFF), a questionnaire was developed and distributed to members of Community Voice (CV, comprised of PwCF and their loved ones), and CF providers regarding the need to study simplifying the gastrointestinal (GI) regimen for PwCF on HEMT., Results: Approximately 20-40% of CV or CF providers have decreased or stopped ASM for those on HEMT. For PERT, CV and CF providers have decreased dose (34%-48% and approximately 25%, respectively) more often than having stopped it altogether (13%-24% and 3%-12%, respectively). Cumulatively, there is interest in pursuing research in this area (86% CV and 89% CF providers) and willingness to enroll in such a study (80% CV and 89% CF providers)., Conclusion: Systematically studying the withdrawal of common GI medications, ASM and PERT, is important to CV and CF providers. Decreases in dosing and withdrawal are already taking place without evidence to support this practice. This questionnaire is the first step in designing a GI medication simplification study in PwCF on HEMT., (© 2022 Wiley Periodicals LLC.)

Background: Nodular liver (NOD) in cystic fibrosis (CF) suggests advanced CF liver disease (aCFLD); little is known about progression of liver disease (LD) after detection of sonographic NOD., Methods: Clinical, laboratory, and ultrasound (US) data from Prediction by Ultrasound of the Risk of Hepatic Cirrhosis in CFLD Study participants with NOD at screening or follow-up were compared with normal (NL). Linear mixed effects models were used for risk factors for LD progression and Kaplan-Meier estimator for time-to-event., Results: 54 children with NOD (22 screening, 32 follow-up) and 112 NL were evaluated. Baseline (BL) and trajectory of forced expiratory volume, forced vital capacity, height/BMI z-scores were similar in NOD vs NL. Platelets were lower in NOD at BL (250 vs 331×10 3 /microL; p < 0.001) and decreased by 8600/year vs 2500 in NL. Mean AST to Platelet Ratio Index (1.1 vs 0.4; p < 0.001), Fibrosis-4 Index (0.4 vs 0.2, p < 0.001), and spleen size z-score (SSZ) [1.5 vs 0.02; p < 0.001] were higher in NOD at BL; SSZ increased by 0.5 unit/year in NOD vs 0.1 unit/year in NL. Median liver stiffness (LSM) by transient elastography was higher in NOD (8.2 kPa, IQR 6-11.8) vs NL (5.3, 4.2-7, p < 0.0001). Over 6.3 years follow-up (1.3-10.3), 6 NOD had esophageal varices (cumulative incidence in 10 years: 20%; 95% CI: 0.0%, 40.0%), 2 had variceal bleeding, and 2 underwent liver transplantation; none had ascites or hepatic encephalopathy. No NL experienced liver-related events., Conclusions: NOD developed clinically evident portal hypertension faster than NL without worse growth or lung disease., (Copyright © 2022. Published by Elsevier B.V.)

Objective: To compare rates of mortality, rupture, and secondary intervention following endovascular repair (EVAR) of intact abdominal aortic aneurysms (AAA) using contemporary endograft devices from three major manufacturers., Methods: This was a retrospective cohort study using linked clinical registry (Australasian Vascular Audit) and all payer administrative data. Patients undergoing EVAR for intact AAA between 2010 and 2019 in New South Wales, Australia were identified. Rates of all cause death, secondary rupture, and secondary intervention (subsequent aneurysm repair; other secondary aortic intervention) were compared for patients treated with Cook, Medtronic, and Gore standard devices. Inverse probability of treatment weighted proportional hazards and competing risk regression were used to adjust for patient, clinical, and aneurysm characteristics, using Cook as the referent device., Results: This study identified 2 874 eligible EVAR patients, with a median follow up of 4.1 (maximum 9.5) years. Mortality rates were similar for patients receiving different devices (ranging between 7.0 and 7.3 per 100 person years). There was no statistically significant difference between devices in secondary rupture rates, which ranged between 0.4 and 0.5 per 100 person years. Patients receiving Medtronic and Gore devices tended to have higher crude rates of subsequent aneurysm repair (1.5 per 100 person years) than patients receiving Cook devices (0.8 per 100 person years). This finding remained in the adjusted analysis, but was only statistically significant for Medtronic devices (HR 1.57, 95% CI 1.02 - 2.47; HR 1.73, 95% CI 0.94 - 3.18, respectively)., Conclusion: Major endograft devices have similar overall long term safety profiles. However, there may be differences in rates of secondary intervention for some devices. This may reflect endograft durability, or patient selection for different devices based on aneurysm anatomy. Continuous comparative assessments are needed to guide evidence for treatment decisions across the range of available devices., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: Cystic fibrosis liver disease (CFLD) begins early in life. Symptoms may be vague, mild, or nonexistent. Progressive liver injury may be associated with decrements in patient health before liver disease is clinically apparent. We examined Health-Related Quality of Life (HRQOL) in children enrolled in a multi-center study of CFLD to determine the impact of early CFLD on general and disease-specific QOL., Methods: Ultrasound (US) patterns of normal (NL), heterogeneous (HTG), homogeneous (HMG), or nodular (NOD) were assigned in a prospective manner to predict those at risk for advanced CFLD. Parents were informed of results. We assessed parent/child-reported (age ≥5 years) HRQOL by PedsQL 4.0 Generic Core and CF Questionnaire-revised (CFQ-R) prior to US and annually. HRQOL scores were compared by US pattern at baseline (prior to US), between baseline and 1 year and at 5 years. Multivariate analysis of variance (MANOVA) with Hotelling-Lawley trace tested for differences among US groups., Results: Prior to US, among 515 participants and their parents there was no evidence that HTG or NOD US was associated with reduced PedsQL/CFQ-R at baseline. Parents of NOD reported no change in PedsQL/CFQ-R over the next year. Child-report PedsQL/CFQ-R (95 NL, 20 NOD) showed improvement between baseline and year 5 for many scales, including Physical Function. Parents of HMG children reported improved CFQ-R scores related to weight., Conclusions: Early undiagnosed or pre-symptomatic liver disease had no impact on generic or disease-specific HRQoL, and HRQoL was remarkably stable in children with CF regardless of liver involvement., Competing Interests: S.J.S. serves as a consultant for Nestle, UpToDate, and AbbVie. A.J.F. has grant/research support through Travere Therapeutics and Allergan; serves as an advisor for Abbvie and Takeda. W.K. has received research grants from Gilead Sciences and Albireo Pharma; serves as an advisor for Mirum and Travere Therapeutics. D.H.L. has grant/research support from Abbvie, Gilead, and Mirum; serves as a consultant for Gilead, Vertex, and Merck. S.C.L. receives research funding from Abbvie and Gilead and serves as a consultant for Abbvie JPM has research funding from Gillead, Abbvie, Albireo, Mirum. K.F.M. is a consultant for Albireo and Gilead. M.R.N. serves as a consultant for Vertex, has received research grants from Gilead, AbbVie, and has a family member with stock in Merck. 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.)