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Article ; Online: Elexacaftor/Tezacaftor/Ivacaftor use in Pediatric Cystic Fibrosis Patients with Advanced Liver Disease.

Protich, Hannah E / Molleston, Jean P / Bozic, Molly / Pettit, Rebecca S

Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society

2024

Abstract: ... change in ppFEV1 from prior to ETI to highest value during therapy was 14.27 % (4.25) (p = 0.007 ... When evaluating the group as whole, AST decreased from baseline to last reported -15.18 (23.23) units/L (p = 0.054 ... and ALT slightly increased 0.73 (39.13) units/L (p = 0.96). Bilirubin increased minimally overall ...

Abstract	Background: Cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy extends the life expectancy of people with cystic fibrosis (PwCF). However, CFTR modulators have not been well studied in patients with cystic fibrosis liver disease (CFLD), specifically those with advanced liver disease with portal hypertension. The purpose of this report is to describe the use of elexacaftor/tezacaftor/ivacaftor (ETI) in pediatric CF patients with advanced CFLD. Methods: This retrospective case series included PwCF < 18 years old with baseline advanced CFLD initiated on ETI. Results: Eleven PwCF and advanced CFLD were treated with ETI; six started a reduced dose regimen. No patient required treatment interruption and four patients received dose changes related to increase in transaminase and/or bilirubin elevations. Mean (SD) change in ppFEV1 from prior to ETI to highest value during therapy was 14.27 % (4.25) (p = 0.007). When evaluating the group as whole, AST decreased from baseline to last reported -15.18 (23.23) units/L (p = 0.054) and ALT slightly increased 0.73 (39.13) units/L (p = 0.96). Bilirubin increased minimally overall for patients with mean change from baseline of 0.83 (1.33) mg/dL [range -0.5-3] (p = 0.17). A model for time on ETI showed a significant decrease in AST over time of 0.955 per month of ETI but no other liver biochemistries were significant. No patient experienced decompensation of CFLD. Conclusion: ETI therapy in pediatric CF patients with advanced CFLD can be beneficial in improving pulmonary and nutritional outcomes without negative impact on liver biochemistries or hepatic outcomes. Close monitoring is recommended to ensure safety and tolerability.
Language	English
Publishing date	2024-04-04
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2084724-5
ISSN	1873-5010 ; 1569-1993
ISSN (online)	1873-5010
ISSN	1569-1993
DOI	10.1016/j.jcf.2024.03.011
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Zs.A 6028: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Mortality, Risk Factors and Disparities Associated with Esophageal Variceal Bleeding in Children's Hospitals in the US.

Molleston, Jean P / Bennett, William E

The Journal of pediatrics

2021 Volume 232, Page(s) 176–182

Abstract: ... race (OR, 2.59; P < .001) or Hispanic ethnicity (OR, 2.31; P = .001), but not sex, household income, or ... respectively; P < .001, .005, .011, <.001, and .005, respectively).: Conclusions: The 6-week mortality rate ...

Abstract	Objectives: To use a large administrative database to determine the mortality, risk factors, and comorbidities of esophageal variceal bleeding in children. Study design: Retrospective cohort study using Pediatric Health Information System data from 50 tertiary children's hospitals in the US. International Classification of Diseases (ICD) codes (FY 2020 ICD-10 update and revision 10 of ICD-9) from 2004 through 2019 identified children 18 years and younger with variceal bleeding and complications. Univariate analyses used the Student t -test for continuous variables (age) and the χ Results: There were 1902 patients who had 3399 encounters for esophageal variceal bleeding. The mortality rate for variceal bleeding was 7.3%, increasing to 8.8% by 6 weeks; any mortality during the study was 20.1%. Transfusion was required in 54.7% of encounters, and 42.6% were admitted to the intensive care unit. Variceal bleeding encounters were complicated by peptic ulcer disease (6.9%), bacteremia (11.4%), acute renal failure (5.1%), mechanical ventilation (18%), ascites (21.3%), and peritonitis (3.3%). Multivariable mixed-effects logistic regression showed that Black race (OR, 2.59; P < .001) or Hispanic ethnicity (OR, 2.31; P = .001), but not sex, household income, or insurance type, were associated with increased mortality. Bacteremia, peritonitis, mechanical ventilation, acute renal failure, and transfusion were associated with higher mortality (ORs of 2.29, 2.18, 1.93, 6.33, and 1.81, respectively; P < .001, .005, .011, <.001, and .005, respectively). Conclusions: The 6-week mortality rate for variceal bleeding in children is 8.8%. Black or Hispanic children are at higher risk of dying. Serious morbidities associated with variceal hemorrhage impact mortality. These data can inform consideration of prophylactic or therapeutic interventions for children at risk.
MeSH term(s)	Adolescent ; Child ; Child, Preschool ; Databases, Factual ; Esophageal and Gastric Varices/complications ; Esophageal and Gastric Varices/diagnosis ; Female ; Gastrointestinal Hemorrhage/diagnosis ; Gastrointestinal Hemorrhage/ethnology ; Gastrointestinal Hemorrhage/etiology ; Gastrointestinal Hemorrhage/mortality ; Health Status Disparities ; Hospitals, Pediatric ; Humans ; Infant ; Infant, Newborn ; Linear Models ; Logistic Models ; Male ; Prognosis ; Proportional Hazards Models ; Retrospective Studies ; Risk Factors ; Severity of Illness Index ; United States/epidemiology
Language	English
Publishing date	2021-01-12
Publishing country	United States
Document type	Journal Article
ZDB-ID	3102-1
ISSN	1097-6833 ; 0022-3476
ISSN (online)	1097-6833
ISSN	0022-3476
DOI	10.1016/j.jpeds.2020.12.082
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Article ; Online: Biomarkers of fibrosis and portal hypertension in Fontan-associated liver disease in children and adults.

Jarasvaraparn, Chaowapong / Thoe, Jessica / Rodenbarger, Andrew / Masuoka, Howard / Payne, R Mark / Markham, Larry Wayne / Molleston, Jean P

Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver

2024

Abstract: ... platelet count (151 vs. 198 K/uL, p = 0.003), higher APRI (0.64 vs. 0.32, p = 0.01), higher FIB-4 (0.64 vs. 0.32 ... p = 0.02). Liver fibrosis score correlated with APRI (0.34, p = 0.02) and FIB-4 (0.47, p = 0.001 ...

Abstract	Background: Fontan-associated liver disease (FALD) refers to structural and functional changes of the liver caused by the physiology of the Fontan palliation. Currently, liver biopsy is the gold standard to assess liver fibrosis of FALD. Aim: Investigate biomarkers correlating with severity of liver biopsy fibrosis in FALD. Methods: A retrospective study of post-Fontan patients ≥ 10 years of age who underwent liver biopsy was conducted. Advanced liver disease (ALD) was defined as bridging fibrosis and/or cirrhosis on liver biopsy. AST-to-platelet ratio index (APRI), Fibrosis-4 (FIB-4) and Liver Stiffness Measurement (LSM) from FibroScan were used as non-invasive fibrosis scores. Results: Sixty-six patients (26/47; 55.3% adults and 13/19 children; 68.4%) had ALD on biopsy. ALD was associated with lower platelet count (151 vs. 198 K/uL, p = 0.003), higher APRI (0.64 vs. 0.32, p = 0.01), higher FIB-4 (0.64 vs. 0.32, p = 0.02). Liver fibrosis score correlated with APRI (0.34, p = 0.02) and FIB-4 (0.47, p = 0.001) in adults. LSM had a high sensitivity at 81.3% with 45.5% specificity at a cut-off 18.5 kPa. Conclusions: APRI and FIB-4 had modest discrimination to identify adults with advanced liver disease, but not children, indicating that these values may be followed as a marker of FALD progression in older patients.
Language	English
Publishing date	2024-01-13
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1459373-7
ISSN	1878-3562 ; 1125-8055
ISSN (online)	1878-3562
ISSN	1125-8055
DOI	10.1016/j.dld.2023.12.017
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Article ; Online: Granulomas in Pediatric Liver Biopsies: Single Center Experience.

Shaheen, Muhammad / Lei, Guang-Sheng / Relich, Ryan F / Jarasvaraparn, Chaowapong / Tolliver, Kyla M / Molleston, Jean P / González, Iván A

Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society

2024 , Page(s) 10935266231221908

Abstract: Background: Granulomas in pediatric liver biopsies (GPLB) are rare with the largest pediatric cohort reported over 25 years ago.: Methods: Single-center retrospective study of GPLB.: Results: Seventeen liver biopsies from 16 patients with ... ...

Abstract	Background: Granulomas in pediatric liver biopsies (GPLB) are rare with the largest pediatric cohort reported over 25 years ago. Methods: Single-center retrospective study of GPLB. Results: Seventeen liver biopsies from 16 patients with granulomas were identified (9 boys, 56%) with a median age of 13 years (range: 1-18) for which the most common indication was the presence of a nodule/mass (47%). Significant comorbidities were seen in 13 patients (81%) and included: liver transplant (25%), history of a neoplasm (25%), autoimmune hepatitis (6%), Crohn disease (6%), bipolar disorder (6%), severe combined immunodeficiency (6%), and sickle cell disease (6%). Eleven patients were taking multiple medications at the time of biopsy. Granulomas were more commonly pan-acinar (11 cases) followed by subcapsular (4 cases), portal (1 case), and periportal (1 case). Necrosis was seen in 10 cases (59%). GMS stain was positive in 2 cases for Conclusion: In our experience, GPLB are heterogenous with only 3 cases having an identifiable infectious etiology and many of the remaining cases being associated to multiple medications, suggesting drug-induced liver injury as possible etiology.
Language	English
Publishing date	2024-01-14
Publishing country	United States
Document type	Journal Article
ZDB-ID	1463498-3
ISSN	1615-5742 ; 1093-5266
ISSN (online)	1615-5742
ISSN	1093-5266
DOI	10.1177/10935266231221908
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Zs.A 5063: Show issues

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Article ; Online: Cholangitis in Patients With Biliary Atresia Receiving Hepatoportoenterostomy: A National Database Study.

Cheng, Katherine / Molleston, Jean P / Bennett, William E

Journal of pediatric gastroenterology and nutrition

2020 Volume 71, Issue 4, Page(s) 452–458

Abstract: ... odds ratio (OR) 1.51, P = 0.044) and presence of PH (OR 2.24, P < 0.001) were associated with increased risk ... of ≥ 2 episodes of cholangitis, whereas HPE at >90 days was associated with less risk (OR 0.46, P = 0.001 ... Among those with ≥5 episodes, Asian race (OR 2.66, P = 0.038), public insurance (OR 1.72, P = 0.043), EV (OR 1.81, P ...

Abstract	Introduction: Biliary atresia (BA) is a progressive form of liver disease in the neonatal period usually requiring hepatoportoenterostomy (HPE). Cholangitis is a common sequelae of HPE but data about which patients are at risk for this complication are limited. Objective: The objective of the study was to determine risk factors associated with cholangitis in a large retrospective cohort after HPE. Methods: The Pediatric Health Information System (PHIS) was queried for BA (ICD-9 975.61) and HPE (ICD-9-CM 51.37) admissions from 2004 to 2013. We performed univariate analysis and linear regression with dependent variables of ≥ 2 or ≥ 5 episodes of cholangitis, and independent variables of age at time of HPE, race, ethnicity, gender, insurance, ursodeoxycholic acid (UDCA) use, steroid use, presence of esophageal varices (EV), and portal hypertension (PH). Results: We identified 1112 subjects with a median age at HPE of 63 days and median number of cholangitis episodes of 2 within 2 years. On multiple regression analysis, black race (odds ratio (OR) 1.51, P = 0.044) and presence of PH (OR 2.24, P < 0.001) were associated with increased risk of ≥ 2 episodes of cholangitis, whereas HPE at >90 days was associated with less risk (OR 0.46, P = 0.001). Among those with ≥5 episodes, Asian race (OR 2.66, P = 0.038), public insurance (OR 1.72, P = 0.043), EV (OR 1.81, P = 0.017), and PH (OR 2.88, P < 0.001) were associated with higher risk. Conclusions: Complications, such as cholangitis remain a common problem for patients, after HPE, with median of 2 episodes within 2 years. Higher rates of cholangitis are associated with portal hypertension whereas lower rate is associated with age at HPE of >90 days. Asians, patients with public insurance, and those with portal hypertension are more likely to have recurrent cholangitis.
MeSH term(s)	Biliary Atresia/complications ; Biliary Atresia/surgery ; Child ; Cholangitis/epidemiology ; Cholangitis/etiology ; Humans ; Infant ; Infant, Newborn ; Liver Transplantation ; Portoenterostomy, Hepatic ; Retrospective Studies ; Treatment Outcome
Language	English
Publishing date	2020-07-07
Publishing country	United States
Document type	Journal Article
ZDB-ID	603201-1
ISSN	1536-4801 ; 0277-2116
ISSN (online)	1536-4801
ISSN	0277-2116
DOI	10.1097/MPG.0000000000002836
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Article ; Online: Perspectives on Colon Cancer Screening-A Physician Panel Discussion for Preclinical Medical Students.

Dilly, Christen K / Craven, Hannah J / Molleston, Jean P

MedEdPORTAL : the journal of teaching and learning resources

2020 Volume 16, Page(s) 11019

Abstract: Introduction: Colon cancer is the third most common cancer in the US, and the survival rate improves drastically with early detection. It is important for medical students to understand screening options, and to be able to effectively discuss these ... ...

Abstract	Introduction: Colon cancer is the third most common cancer in the US, and the survival rate improves drastically with early detection. It is important for medical students to understand screening options, and to be able to effectively discuss these options with their patients. While basic information about colon cancer screening is ubiquitous in US medical school curricula, no published curricula describe teaching students the nuances of negotiating this discussion with patients and tailoring screening to individual patients' needs. Methods: We developed a 90-minute session for second-year medical students as part of a gastroenterology and nutrition course. We provided a short lecture on colon cancer screening. We then had a panel of practicing gastroenterologists and a primary care physician discuss their approaches to six hypothetical cases. The students reflected in writing on what they learned from the session and on their opinions of the session format. Results: Of second-year medical students, 139 attended the session and 110 submitted written reflections on the session (79% response rate). The students perceived significant gains in knowledge, communication skills, and attitudes around the discussions. Discussion: This expert panel session taught medical students knowledge and communication skills related to colon cancer screening. The session could be easily implemented at any medical school, either at the preclinical or clinical level.
MeSH term(s)	Colonic Neoplasms/diagnosis ; Early Detection of Cancer ; Education, Medical, Undergraduate ; Humans ; Physicians ; Students, Medical
Language	English
Publishing date	2020-10-30
Publishing country	United States
Document type	Journal Article
ISSN	2374-8265
ISSN (online)	2374-8265
DOI	10.15766/mep_2374-8265.11019
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Article ; Online: Drug-Induced Liver Injury Module for Medical Students.

Dilly, Christen K / Craven, Hannah J / Molleston, Jean P

MedEdPORTAL : the journal of teaching and learning resources

2020 Volume 16, Page(s) 10918

Abstract: Introduction: No published curricula exist to introduce medical students to drug-induced liver injury (DILI). However, DILI is the most common cause of acute liver failure in the US, and drug-drug interactions are tested on the USMLE Step 1.: Methods!# ...

Abstract	Introduction: No published curricula exist to introduce medical students to drug-induced liver injury (DILI). However, DILI is the most common cause of acute liver failure in the US, and drug-drug interactions are tested on the USMLE Step 1. Methods: We developed an independent study module to introduce students to DILI. This module consisted of a narrated PowerPoint introduction, a journal article, and four example cases. Students completed the module independently. To evaluate the effectiveness of the activity, exam data and responses to the cases were reviewed, and end-of-course survey data were used. These responses were used to modify questions for clarity and to develop a feedback rubric. Results: Mean scores on case-related questions in the module ranged from 44% to 73%. However, mean scores on test questions related to DILI ranged from 61% to 98%. It is possible that students learned from receiving feedback in the form of correct answers to the cases. On course evaluations, 52.4% of students agreed or strongly agreed that the online modules as a group (which included the DILI module) were an effective teaching method. Discussion: This module introduces students to DILI and enables them to interact with valuable resources. We hope that modifications will improve the learning experience and effectiveness of the module. Going forward, we plan to collect validity evidence for the feedback rubric and develop an advanced version of the module for gastroenterology fellows.
MeSH term(s)	Chemical and Drug Induced Liver Injury/etiology ; Curriculum ; Feedback ; Humans ; Learning ; Students, Medical
Language	English
Publishing date	2020-07-15
Publishing country	United States
Document type	Journal Article
ISSN	2374-8265
ISSN (online)	2374-8265
DOI	10.15766/mep_2374-8265.10918
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Article ; Online: Comparative analysis of whole vs. split liver transplantation in infants.

Rokop, Zachary P / Mangus, Richard S / Tolliver, Kyla / Jarasvaraparn, Chaowapong / Molleston, Jean / Mihaylov, Plamen / Kubal, Chandrashekhar

Pediatric transplantation

2023 Volume 27, Issue 6, Page(s) e14564

Abstract: ... characteristics were comparable except for donor age (19 years vs. 2 years; p < .01) and weight (64 kg vs. 14.2 kg ... p < .01). Early allograft dysfunction, primary nonfunction, and hepatic artery thrombosis developed ... and 4 days) in the WLT group. One-year graft survival (100% vs. 77%; p = .10) and patient survival ...

Abstract	Background: Liver transplantation (LT) in infants can be challenging due to their small size and small vasculature. Although both whole LT (WLT) and split LT (SLT) have been described in infants, the head-to-head comparison of these techniques in this population is sparse. Methods: We retrospectively analyzed the records of all patients with age ≤1 year at Indiana University between 2016 and 2022. All SLT were left lateral segment grafts split in situ. Results: A total of 24 infants were transplanted, with 11 SLT and 13 WLT. The median follow-up time was 52.1 months. Donor and recipient characteristics were comparable except for donor age (19 years vs. 2 years; p < .01) and weight (64 kg vs. 14.2 kg; p < .01). Early allograft dysfunction, primary nonfunction, and hepatic artery thrombosis developed more frequently in the WLT group. There were no biliary complications. There were two early deaths (2 and 4 days) in the WLT group. One-year graft survival (100% vs. 77%; p = .10) and patient survival (100% vs. 85%; p = .18) were numerically higher in the SLT group. Conclusions: SLT with LLS offers a safe and viable option for liver transplantation in infants and is associated with a trend toward superior outcomes. SLT should be considered as a strategy to reduce waitlist times for infants in the absence of small, deceased donors for WLT.
MeSH term(s)	Humans ; Infant ; Young Adult ; Adult ; Liver Transplantation/methods ; Retrospective Studies ; Treatment Outcome ; Liver Diseases ; Tissue Donors ; Graft Survival
Language	English
Publishing date	2023-07-10
Publishing country	Denmark
Document type	Journal Article
ZDB-ID	1390284-2
ISSN	1399-3046 ; 1397-3142
ISSN (online)	1399-3046
ISSN	1397-3142
DOI	10.1111/petr.14564
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Article: Management of nonalcoholic fatty liver disease in children.

Molleston, Jean P

Clinical liver disease

2012 Volume 1, Issue 4, Page(s) 129–130

Language	English
Publishing date	2012-09-25
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2657644-2
ISSN	2046-2484
ISSN	2046-2484
DOI	10.1002/cld.66
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Article ; Online: Endoscopy in Infants With Gastrointestinal Bleeding Has Limited Diagnostic or Therapeutic Benefit.

Bose, Paroma / Jacobs, Annalise S / Cordova, Jorge Gonzales / Gray, Brian W / Huff, Katie A / Molleston, Jean P

Journal of pediatric gastroenterology and nutrition

2022 Volume 75, Issue 4, Page(s) 514–520

Abstract: ... likelihood of requiring surgery ( P < 0.05 for all).: Conclusions: There was limited utility to performing ...

Abstract	Objectives: Pediatric gastroenterologists are often consulted to perform diagnostic and therapeutic endoscopy in infants with gastrointestinal bleeding (GIB). The value of endoscopy and risk of complications in this population are not well characterized. We aimed to describe findings and outcomes of infants with GIB who undergo endoscopy. Methods: Retrospective, single-center, cohort study of hospitalized infants ≤12 months who underwent esophagogastroduodenoscopy (EGD) and/or colonoscopy/flexible sigmoidoscopy (COL) for GIB. Current procedural technology codes, international classification of diseases codes, and quality control logs identified infants. Results: Fifty-six infants were identified from 2008 to 2019 (51.8% female; mean age 161.6 days). Seven endoscopies identified sources of GIB: gastric ulcers, a duodenal ulcer, gastric angiodysplasia, esophageal varices, and an anastomotic ulcer. Three infants underwent therapeutic interventions of banding/sclerotherapy of esophageal varices and triamcinolone injection of an anastomotic ulcer. Six infants underwent abdominal surgery for GIB or suspected intestinal perforation after endoscopy, where a gastric perforation, jejunal perforation at an anastomotic stricture, necrotizing enterocolitis totalis with perforation, Meckel's diverticulum, and a duodenal ulcer were identified. No source of bleeding was identified surgically in 1 infant with GIB. Respiratory failure, use of vasopressors or octreotide, administration of blood products, and high blood urea nitrogen were associated with increased likelihood of requiring surgery ( P < 0.05 for all). Conclusions: There was limited utility to performing endoscopy in infants ≤12 months old with clinical GIB. Endoscopy in these sick infants carries risk, and 3 infants in this series presented with a gastrointestinal (GI) perforation shortly after the procedure. These limitations and risks should influence clinical decision-making regarding endoscopy in infants with GIB.
MeSH term(s)	Child ; Cohort Studies ; Duodenal Ulcer/complications ; Endoscopy/adverse effects ; Endoscopy, Gastrointestinal/adverse effects ; Esophageal and Gastric Varices/diagnosis ; Esophageal and Gastric Varices/etiology ; Esophageal and Gastric Varices/therapy ; Female ; Gastrointestinal Hemorrhage/diagnosis ; Gastrointestinal Hemorrhage/etiology ; Gastrointestinal Hemorrhage/therapy ; Humans ; Infant ; Infant, Newborn ; Male ; Octreotide ; Retrospective Studies ; Triamcinolone ; Ulcer
Chemical Substances	Triamcinolone (1ZK20VI6TY) ; Octreotide (RWM8CCW8GP)
Language	English
Publishing date	2022-07-18
Publishing country	United States
Document type	Journal Article
ZDB-ID	603201-1
ISSN	1536-4801 ; 0277-2116
ISSN (online)	1536-4801
ISSN	0277-2116
DOI	10.1097/MPG.0000000000003566
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