399 results on '"Magee, John C."'
Search Results
2. Serum biomarkers correlated with liver stiffness assessed in a multicenter study of pediatric cholestatic liver disease
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Leung, Daniel H, Devaraj, Sridevi, Goodrich, Nathan P, Chen, Xinpu, Rajapakshe, Deepthi, Ye, Wen, Andreev, Victor, Minard, Charles G, Guffey, Danielle, Molleston, Jean P, Bass, Lee M, Karpen, Saul J, Kamath, Binita M, Wang, Kasper S, Sundaram, Shikha S, Rosenthal, Philip, McKiernan, Patrick, Loomes, Kathleen M, Jensen, M Kyle, Horslen, Simon P, Bezerra, Jorge A, Magee, John C, Merion, Robert M, Sokol, Ronald J, Shneider, Benjamin L, Network, The Childhood Liver Disease Research, Alonso, Estella, Bass, Lee, Kelly, Susan, Riordan, Mary, Melin‐Aldana, Hector, Bezerra, Jorge, Bove, Kevin, Heubi, James, Miethke, Alexander, Tiao, Greg, Denlinger, Julie, Chapman, Erin, Sokol, Ronald, Feldman, Amy, Mack, Cara, Narkewicz, Michael, Suchy, Frederick, Van Hove, Johan, Garcia, Benigno, Kauma, Mikaela, Kocher, Kendra, Steinbeiss, Matthew, Lovell, Mark, Piccoli, David, Rand, Elizabeth, Russo, Pierre, Spinner, Nancy, Erlichman, Jessi, Stalford, Samantha, Pakstis, Dina, King, Sakya, Squires, Robert, Sindhi, Rakesh, Venkat, Veena, Bukauskas, Kathy, Haberstroh, Lori, Squires, James, Bull, Laura, Curry, Joanna, Langlois, Camille, Kim, Grace, Teckman, Jeffery, Kociela, Vikki, Nagy, Rosemary, Patel, Shraddha, Cerkoski, Jacqueline, Bozic, Molly, Subbarao, Girish, Klipsch, Ann, Sawyers, Cindy, Cummings, Oscar, Murray, Karen, Hsu, Evelyn, Cooper, Kara, Young, Melissa, Finn, Laura, Ng, Vicky, Quammie, Claudia, Putra, Juan, Sharma, Deepika, Parmar, Aishwarya, Guthery, Stephen, Jensen, Kyle, Rutherford, Ann, Lowichik, Amy, Book, Linda, and Meyers, Rebecka
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Biomedical and Clinical Sciences ,Clinical Sciences ,Chronic Liver Disease and Cirrhosis ,Rare Diseases ,Pediatric ,Liver Disease ,Digestive Diseases ,Oral and gastrointestinal ,Humans ,Child ,Liver ,Matrix Metalloproteinase 7 ,Endoglin ,Interleukin-8 ,Cholestasis ,Liver Cirrhosis ,Liver Diseases ,Biomarkers ,Alagille Syndrome ,Elasticity Imaging Techniques ,Childhood Liver Disease Research Network ,Medical Biochemistry and Metabolomics ,Immunology ,Gastroenterology & Hepatology ,Clinical sciences - Abstract
Background and aimsDetailed investigation of the biological pathways leading to hepatic fibrosis and identification of liver fibrosis biomarkers may facilitate early interventions for pediatric cholestasis.Approach and resultsA targeted enzyme-linked immunosorbent assay-based panel of nine biomarkers (lysyl oxidase, tissue inhibitor matrix metalloproteinase (MMP) 1, connective tissue growth factor [CTGF], IL-8, endoglin, periostin, Mac-2-binding protein, MMP-3, and MMP-7) was examined in children with biliary atresia (BA; n = 187), alpha-1 antitrypsin deficiency (A1AT; n = 78), and Alagille syndrome (ALGS; n = 65) and correlated with liver stiffness (LSM) and biochemical measures of liver disease. Median age and LSM were 9 years and 9.5 kPa. After adjusting for covariates, there were positive correlations among LSM and endoglin ( p = 0.04) and IL-8 ( p
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- 2023
3. Prospective study of quantitative liver MRI in cystic fibrosis: feasibility and comparison to PUSH cohort ultrasound
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Towbin, Alexander J., Ye, Wen, Huang, Suiyuan, Karmazyn, Boaz W., Molleston, Jean P., Masand, Prakash, Leung, Daniel H., Chang, Samuel, Narkewicz, Michael R., Alazraki, Adina L., Freeman, A. Jay, Otto, Randolph K., Green, Nicole, Kamel, Ihab R., Karnsakul, Wikrom W., Magee, John C., Tkach, Jean, and Palermo, Joseph J.
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- 2023
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4. Mutation Analysis and Disease Features at Presentation in a Multi‐Center Cohort of Children With Monogenic Cholestasis
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Hertel, Paula M, Bull, Laura N, Thompson, Richard J, Goodrich, Nathan P, Ye, Wen, Magee, John C, Squires, Robert H, Bass, Lee M, Heubi, James E, Kim, Grace E, Ranganathan, Sarangarajan, Schwarz, Kathleen B, Bozic, Molly A, Horslen, Simon P, Clifton, Matthew S, Turmelle, Yumirle P, Suchy, Frederick J, Superina, Riccardo A, Wang, Kasper S, Loomes, Kathleen M, Kamath, Binita M, Sokol, Ronald J, Shneider, Benjamin L, and Network, Childhood Liver Disease Research
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Paediatrics ,Biomedical and Clinical Sciences ,Clinical Sciences ,Nutrition and Dietetics ,Liver Disease ,Chronic Liver Disease and Cirrhosis ,Genetics ,Clinical Research ,Digestive Diseases ,Aetiology ,2.1 Biological and endogenous factors ,ATP-Binding Cassette Transporters ,Child ,Child ,Preschool ,Cholestasis ,Cholestasis ,Intrahepatic ,Humans ,Longitudinal Studies ,Mutation ,Childhood Liver Disease Research Network ,Medical and Health Sciences ,Gastroenterology & Hepatology ,Clinical sciences ,Nutrition and dietetics - Abstract
ObjectivesTo advance our understanding of monogenic forms of intrahepatic cholestasis.MethodsAnalyses included participants with pathogenic biallelic mutations in adenosine triphosphate (ATP)-binding cassette subfamily B member 11 (ABCB11) (bile salt export pump; BSEP) or adenosine triphosphatase (ATPase) phospholipid transporting 8B1 (ATP8B1) (familial intrahepatic cholestasis; FIC1), or those with monoallelic or biallelic mutations in adenosine triphosphate (ATP)-binding cassette subfamily B member 4 (ABCB4) (multidrug resistance; MDR3), prospectively enrolled in the Longitudinal Study of Genetic Causes of Intrahepatic Cholestasis (LOGIC; NCT00571272) between November 2007 and December 2013. Summary statistics were calculated to describe baseline demographics, history, anthropometrics, laboratory values, and mutation data.ResultsNinety-eight participants with FIC1 (n = 26), BSEP (n = 53, including 8 with biallelic truncating mutations [severe] and 10 with p.E297G or p.D482G [mild]), or MDR3 (n = 19, including four monoallelic) deficiency were analyzed. Thirty-five had a surgical interruption of the enterohepatic circulation (sEHC), including 10 who underwent liver transplant (LT) after sEHC. Onset of symptoms occurred by age 2 years in most with FIC1 and BSEP deficiency, but was later and more variable for MDR3. Pruritus was nearly universal in FIC1 and BSEP deficiency. In participants with native liver, failure to thrive was common in FIC1 deficiency, high ALT was common in BSEP deficiency, and thrombocytopenia was common in MDR3 deficiency. sEHC was successful after more than 1 year in 7 of 19 participants with FIC1 and BSEP deficiency. History of LT was most common in BSEP deficiency. Of 102 mutations identified, 43 were not previously reported.ConclusionsIn this cohort, BSEP deficiency appears to be correlated with a more severe disease course. Genotype-phenotype correlations in these diseases are not straightforward and will require the study of larger cohorts.
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- 2021
5. Renal Outcomes After Simultaneous Liver‐Kidney Transplantation: Results from the US Multicenter Simultaneous Liver‐Kidney Transplantation Consortium
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Sharma, Pratima, Sui, Zhiyu, Zhang, Min, Magee, John C, Barman, Pranab, Patel, Yuval, Schluger, Aaron, Walter, Kara, Biggins, Scott W, Cullaro, Giuseppe, Wong, Randi, Lai, Jennifer C, Jo, Jennifer, Sinha, Jasmine, VanWagner, Lisa, and Verna, Elizabeth C
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Biomedical and Clinical Sciences ,Clinical Sciences ,Digestive Diseases ,Clinical Research ,Liver Disease ,Organ Transplantation ,Kidney Disease ,Transplantation ,Hepatitis ,Prevention ,Renal and urogenital ,Good Health and Well Being ,Adolescent ,Adult ,Cohort Studies ,Female ,Graft Survival ,Humans ,Kidney ,Kidney Transplantation ,Liver ,Liver Transplantation ,Middle Aged ,Retrospective Studies ,Risk Factors ,Treatment Outcome ,United States ,Surgery ,Clinical sciences - Abstract
Simultaneous liver-kidney transplantation (SLKT) is increasingly common in the United States. However, little is known about the renal-related outcomes following SLKT, which are essential to maximize the health of these allografts. We examined the factors impacting renal function following SLKT. This is an observational multicenter cohort study from the US Multicenter SLKT Consortium consisting of recipients of SLKT aged ≥18 years of transplantations performed between February 2002 and June 2017 at 6 large US centers in 6 different United Network for Organ Sharing regions. The primary outcome was incident post-SLKT stage 4-5 chronic kidney disease (CKD) defined as
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- 2021
6. Longitudinal Outcomes in Young Patients with Alpha-1-Antitrypsin Deficiency with Native Liver Reveal that Neonatal Cholestasis is a Poor Predictor of Future Portal Hypertension
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Teckman, Jeffrey, Rosenthal, Philip, Hawthorne, Kieran, Spino, Cathie, Bass, Lee M, Murray, Karen F, Kerkar, Nanda, Magee, John C, Karpen, Saul, Heubi, James E, Molleston, Jean P, Squires, Robert H, Kamath, Binita M, Guthery, Stephen L, Loomes, Kathleen M, Sherker, Averell H, Sokol, Ronald J, ChiLDReN, Alonso, Estella, Bass, Lee, Kelly, Susan, Riordan, Mary, Melin-Aldana, Hector, Bezerra, Jorge, Bove, Kevin, Heubi, James, Miethke, Alexander, Tiao, Greg, Denlinger, Julie, Chapman, Erin, Sokol, Ronald, Feldman, Amy, Mack, Cara, Narkewicz, Michael, Suchy, Frederick, Sundaram, Shikha, Van Hove, Johan, Garcia, Benigno, Kauma, Mikaela, Kocher, Kendra, Steinbeiss, Matthew, Lovell, Mark, Loomes, Kathleen, Piccoli, David, Rand, Elizabeth, Russo, Pierre, Spinner, Nancy, Erlichman, Jessi, Stalford, Samantha, Pakstis, Dina, King, Sakya, Squires, Robert, Sindhi, Rakesh, Venkat, Veena, Bukauskas, Kathy, McKiernan, Patrick, Haberstroh, Lori, Squires, James, Bull, Laura, Curry, Joanna, Langlois, Camille, Kim, Grace, Teckman, Jeffery, Kociela, Vikki, Nagy, Rosemary, Patel, Shraddha, Cerkoski, Jacqueline, Bozic, Molly, Subbarao, Girish, Klipsch, Ann, Sawyers, Cindy, Cummings, Oscar, Horslen, Simon, Murray, Karen, Hsu, Evelyn, Cooper, Kara, Young, Melissa, Finn, Laura, Kamath, Binita, Ng, Vicky, Quammie, Claudia, Putra, Juan, Sharma, Deepika, Parmar, Aishwarya, Guthery, Stephen, Jensen, Kyle, Rutherford, Ann, Lowichik, Amy, Book, Linda, Meyers, Rebecka, Hall, Tyler, Wang, Kasper, Michail, Sonia, Thomas, Danny, Goodhue, Catherine, Kohli, Rohit, Wang, Larry, and Soufi, Nisreen
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Paediatrics ,Biomedical and Clinical Sciences ,Digestive Diseases ,Liver Disease ,Pediatric ,Hypertension ,Clinical Research ,Rare Diseases ,Transplantation ,Chronic Liver Disease and Cirrhosis ,2.1 Biological and endogenous factors ,Aetiology ,Oral and gastrointestinal ,Good Health and Well Being ,Adolescent ,Adult ,Child ,Child ,Preschool ,Cholestasis ,Intrahepatic ,Disease Progression ,Female ,Humans ,Hypertension ,Portal ,Infant ,Infant ,Newborn ,Liver Transplantation ,Longitudinal Studies ,Male ,Young Adult ,alpha 1-Antitrypsin Deficiency ,ChiLDReN ,cirrhosis ,jaundice ,liver enzymes ,liver transplant ,metabolic liver disease ,Human Movement and Sports Sciences ,Paediatrics and Reproductive Medicine ,Pediatrics - Abstract
ObjectivesTo identify predictors of portal hypertension, liver transplantation, and death in North American youth with alpha-1-antitrypsin (AAT) deficiency, and compare with patients with AAT deficiency elsewhere.Study designThe Childhood Liver Disease Research Network Longitudinal Observational Study of Genetic Causes of Intrahepatic Cholestasis is a prospective, cohort study of pediatric cholestatic liver diseases, including AAT deficiency, enrolling PIZZ and PISZ subjects 0-25 years of age seen since November 2007 at 17 tertiary care centers in the US and Canada. Data from standard-of-care baseline and annual follow-up visits were recorded from medical records, history, physical examination, and laboratory studies. Participants with portal hypertension were identified based on data collected.ResultsWe enrolled 350 participants (60% male) with a native liver; 278 (79%) entered the cohort without portal hypertension and 18 developed portal hypertension during follow-up. Thirty participants required liver transplantation; 2 patients died during 1077 person-years of follow-up. There was no difference in participants with or without preceding neonatal cholestasis progressing to transplantation or death during the study (12% vs 7%; P = .09), or in experiencing portal hypertension (28% vs 21%; P = .16); the hazard ratio for neonatal cholestasis leading to portal hypertension was P = .04. Development of portal hypertension was associated with a reduced height Z-score.ConclusionsPortal hypertension in youth with AAT deficiency impacts growth measures. Progression to liver transplantation is slow and death is rare, but the risk of complications and severe liver disease progression persists throughout childhood. A history of neonatal cholestasis is a weak predictor of severe disease.
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- 2020
7. Heterogeneous liver on research ultrasound identifies children with cystic fibrosis at high risk of advanced liver disease
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Siegel, Marilyn J, Leung, Daniel H., Molleston, Jean P, Ye, Wen, Paranjape, Shruti M, Freeman, A Jay, Palermo, Joseph J, Stoll, Janis, Masand, Prakash, Karmazyn, Boaz, Harned, Roger, Ling, Simon C, Navarro, Oscar M, Karnsakul, Wikrom, Alazraki, Adina, Schwarzenberg, Sarah Jane, Towbin, Alex J, Alonso, Estella M, Nicholas, Jennifer L., Green, Nicole, Otto, Randolph K, Magee, John C, and Narkewicz, Michael R
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- 2023
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8. PREDICTORS OF LENGTH OF STAY AND DEATH FOR SIMULTANEOUS LIVER-KIDNEY TRANSPLANT (SLKT) INDEX ADMISSION: RESULTS FROM THE US MULTICENTER SLKT CONSORTIUM
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Barman, Pranab M, Xie, Jiaheng, Zhang, Min, Jo, Jennifer, Sinha, Jasmine, Schluger, Aaron, Walter, Kara, Biggins, Scott W, Cullaro, Giuseppe, Wong, Randi, Lai, Jennifer Cindy, VanWagner, Lisa B, Magee, John C, Verna, Betsy C, Patel, Yuval, and Sharma, Pratima
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Medical Biochemistry and Metabolomics ,Clinical Sciences ,Immunology ,Gastroenterology & Hepatology - Published
- 2020
9. Addressing sex-based disparities in solid organ transplantation in the United States – a conference report
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Sawinski, Deirdre, Lai, Jennifer C., Pinney, Sean, Gray, Alice L., Jackson, Annette M., Stewart, Darren, Levine, Deborah Jo, Locke, Jayme E., Pomposelli, James J., Hartwig, Matthew G., Hall, Shelley A., Dadhania, Darshana M., Cogswell, Rebecca, Perez, Richard V., Schold, Jesse D., Turgeon, Nicole A., Kobashigawa, Jon, Kukreja, Jasleen, Magee, John C., Friedewald, John, Gill, John S., Loor, Gabriel, Heimbach, Julie K., Verna, Elizabeth C., Walsh, Mary Norine, Terrault, Norah, Testa, Guiliano, Diamond, Joshua M., Reese, Peter P., Brown, Kimberly, Orloff, Susan, Farr, Maryjane A., Olthoff, Kim M., Siegler, Mark, Ascher, Nancy, Feng, Sandy, Kaplan, Bruce, and Pomfret, Elizabeth
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- 2023
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10. Long-term follow-up and liver outcomes in children with cystic fibrosis and nodular liver on ultrasound in a multi-center study
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Leung, Daniel H., Ye, Wen, Schwarzenberg, Sarah J., Freeman, A. Jay, Palermo, Joseph J., Weymann, Alexander, Alonso, Estella M., Karnsakul, Wikrom W., Murray, Karen F., Stoll, Janis M., Huang, Suiyuan, Karmazyn, Boaz, Masand, Prakash, Magee, John C., Alazraki, Adina L., Towbin, Alexander J., Nicholas, Jennifer L., Green, Nicole, Otto, Randolph K., Siegel, Marilyn J., Ling, Simon C., Navarro, Oscar M., Harned, Roger K., Narkewicz, Michael R., and Molleston, Jean P.
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- 2023
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11. Identification of Polycystic Kidney Disease 1 Like 1 Gene Variants in Children With Biliary Atresia Splenic Malformation Syndrome
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Berauer, John‐Paul, Mezina, Anya I, Okou, David T, Sabo, Aniko, Muzny, Donna M, Gibbs, Richard A, Hegde, Madhuri R, Chopra, Pankaj, Cutler, David J, Perlmutter, David H, Bull, Laura N, Thompson, Richard J, Loomes, Kathleen M, Spinner, Nancy B, Rajagopalan, Ramakrishnan, Guthery, Stephen L, Moore, Barry, Yandell, Mark, Harpavat, Sanjiv, Magee, John C, Kamath, Binita M, Molleston, Jean P, Bezerra, Jorge A, Murray, Karen F, Alonso, Estella M, Rosenthal, Philip, Squires, Robert H, Wang, Kasper S, Finegold, Milton J, Russo, Pierre, Sherker, Averell H, Sokol, Ronald J, Karpen, Saul J, and Network, for the Childhood Liver Disease Research
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Perinatal Period - Conditions Originating in Perinatal Period ,Kidney Disease ,Digestive Diseases ,Genetics ,Chronic Liver Disease and Cirrhosis ,Liver Disease ,Rare Diseases ,Congenital Structural Anomalies ,Human Genome ,Pediatric ,Clinical Research ,2.1 Biological and endogenous factors ,Aetiology ,Congenital ,Oral and gastrointestinal ,Abnormalities ,Multiple ,Biliary Atresia ,Child ,Databases ,Factual ,Female ,Gene Expression Regulation ,Developmental ,Genetic Variation ,Humans ,Infant ,Infant ,Newborn ,Male ,Membrane Proteins ,Polycystic Kidney Diseases ,Retrospective Studies ,Spleen ,Syndrome ,Exome Sequencing ,Childhood Liver Disease Research Network ,Medical Biochemistry and Metabolomics ,Clinical Sciences ,Immunology ,Gastroenterology & Hepatology - Abstract
Biliary atresia (BA) is the most common cause of end-stage liver disease in children and the primary indication for pediatric liver transplantation, yet underlying etiologies remain unknown. Approximately 10% of infants affected by BA exhibit various laterality defects (heterotaxy) including splenic abnormalities and complex cardiac malformations-a distinctive subgroup commonly referred to as the biliary atresia splenic malformation (BASM) syndrome. We hypothesized that genetic factors linking laterality features with the etiopathogenesis of BA in BASM patients could be identified through whole-exome sequencing (WES) of an affected cohort. DNA specimens from 67 BASM subjects, including 58 patient-parent trios, from the National Institute of Diabetes and Digestive and Kidney Diseases-supported Childhood Liver Disease Research Network (ChiLDReN) underwent WES. Candidate gene variants derived from a prespecified set of 2,016 genes associated with ciliary dysgenesis and/or dysfunction or cholestasis were prioritized according to pathogenicity, population frequency, and mode of inheritance. Five BASM subjects harbored rare and potentially deleterious biallelic variants in polycystic kidney disease 1 like 1 (PKD1L1), a gene associated with ciliary calcium signaling and embryonic laterality determination in fish, mice, and humans. Heterozygous PKD1L1 variants were found in 3 additional subjects. Immunohistochemical analysis of liver from the one BASM subject available revealed decreased PKD1L1 expression in bile duct epithelium when compared to normal livers and livers affected by other noncholestatic diseases. Conclusion: WES identified biallelic and heterozygous PKD1L1 variants of interest in 8 BASM subjects from the ChiLDReN data set; the dual roles for PKD1L1 in laterality determination and ciliary function suggest that PKD1L1 is a biologically plausible, cholangiocyte-expressed candidate gene for the BASM syndrome.
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- 2019
12. Evidence of Chronic Allograft Injury in Liver Biopsies From Long-term Pediatric Recipients of Liver Transplants
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Feng, Sandy, Bucuvalas, John C, Demetris, Anthony J, Burrell, Bryna E, Spain, Katherine M, Kanaparthi, Sai, Magee, John C, Ikle, David, Lesniak, Andrew, Lozano, Juan J, Alonso, Estella M, Bray, Robert A, Bridges, Nancy E, Doo, Edward, Gebel, Howard M, Gupta, Nitika A, Himes, Ryan W, Jackson, Annette M, Lobritto, Steven J, Mazariegos, George V, Ng, Vicky L, Rand, Elizabeth B, Sherker, Averell H, Sundaram, Shikha, Turmelle, Yumirle P, and Sanchez-Fueyo, Alberto
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Biomedical and Clinical Sciences ,Clinical Sciences ,Chronic Liver Disease and Cirrhosis ,Transplantation ,Liver Disease ,Clinical Research ,Rare Diseases ,Digestive Diseases ,Genetics ,Organ Transplantation ,Oral and gastrointestinal ,Adolescent ,Allografts ,Biopsy ,Child ,Chronic Disease ,Cross-Sectional Studies ,Female ,Graft Rejection ,Humans ,Liver ,Liver Function Tests ,Liver Transplantation ,Male ,Time Factors ,Young Adult ,ALT ,DSA ,Immune Response ,Prognostic Factor ,Neurosciences ,Paediatrics and Reproductive Medicine ,Gastroenterology & Hepatology ,Clinical sciences ,Nutrition and dietetics - Abstract
Background & aimsA substantial proportion of pediatric liver transplant recipients develop subclinical chronic allograft injury. We studied whether there are distinct patterns of injury based on histopathologic features and identified associated immunologic profiles.MethodsWe conducted a cross-sectional study of 157 stable, long-term pediatric recipients of transplanted livers (70 boys; > 6 years old at time of transplantation; mean, 8.9 ± 3.46 years after liver transplantation) who underwent liver biopsy analysis from August 13, 2012, through May 1, 2014. Participants had received livers from a living or deceased donor and had consistently normal results from liver tests. Liver biopsy specimens were scored by a central pathologist; an unsupervised hierarchical cluster analysis of histologic features was used to sort biopsy samples into 3 clusters. We conducted transcriptional and cytometric analyses of liver tissue samples and performed a systems biology analysis that incorporated clinical, serologic, histologic, and transcriptional data.ResultsThe mean level of alanine aminotransferase in participants was 27.6 ± 14.57 U/L, and the mean level of γ-glutamyl transferase was 17.4 ± 7.93 U/L. Cluster 1 was characterized by interface activity (n = 34), cluster 2 was characterized by periportal or perivenular fibrosis without interface activity (n = 45), and cluster 3 had neither feature (n = 78). We identified a module of genes whose expression correlated with levels of alanine aminotransferase, class II donor-specific antibody, portal inflammation, interface activity, perivenular inflammation, portal and perivenular fibrosis, and cluster assignment. The module was enriched in genes that regulate T-cell-mediated rejection (TCMR) of liver and other transplanted organs. Functional pathway analysis showed overrepresentation of TCMR gene sets for cluster 1 but not clusters 2 or 3.ConclusionIn an analysis of biopsies from an apparently homogeneous group of stable, long-term pediatric liver transplant recipients with consistently normal liver test results, we found evidence of chronic graft injury (inflammation and/or fibrosis). Biopsy samples with interface activity had a gene expression pattern associated with TCMR.
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- 2018
13. Inflammation, Active Fibroplasia, and End-stage Fibrosis in 172 Biliary Atresia Remnants Correlate Poorly With Age at Kasai Portoenterostomy, Visceral Heterotaxy, and Outcome
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Bove, Kevin E, Thrasher, Andrew D, Anders, Robert, Chung, Catherine T, Cummings, Oscar W, Finegold, Milton J, Finn, Laura, Ranganathan, Sarangarajan, Kim, Grace E, Lovell, Mark, Magid, Margret S, Melin-Aldana, Hector, Russo, Pierre, Shehata, Bahig, Wang, Larry, White, Francis, Chen, Zhen, Spino, Catherine, and Magee, John C
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Biomedical and Clinical Sciences ,Clinical Sciences ,Pediatric ,Digestive Diseases ,Liver Disease ,2.1 Biological and endogenous factors ,Aetiology ,Oral and gastrointestinal ,Age Factors ,Biliary Atresia ,Biopsy ,Cholangitis ,Databases ,Factual ,Female ,Heterotaxy Syndrome ,Humans ,Infant ,Infant ,Newborn ,Liver Cirrhosis ,Biliary ,Male ,North America ,Portoenterostomy ,Hepatic ,Risk Factors ,Severity of Illness Index ,Treatment Outcome ,biliary atresia ,extrahepatic bile ducts ,histogenesis ,hilar plate ,Kasai portoenterostomy ,age ,heterotaxy ,outcome ,Pathology ,Clinical sciences - Abstract
Published histologic studies of the hilar plate or entire biliary remnant at the time of Kasai portoenterostomy (KHPE) have not provided deep insight into the pathogenesis of biliary atresia, relation to age at surgery, prognosis or the basis for successful drainage. We report detailed histologic findings in 172 centrally reviewed biliary remnants with an average of 6 sections per subject. Active lesions were classified as either necroinflammatory (rare/clustered in a few subjects) or active concentric fibroplasia with or without inflammation (common). Inactive lesions showed bland replacement by collagen and fibrous cords with little or no inflammation. Heterogeneity was common within a given remnant; however, relatively homogenous histologic patterns, defined as 3 or more inactive or active levels in the hepatic ducts levels, characterized most remnants. Homogeneity did not correlate with age at KHPE, presence/absence of congenital anomalies at laparotomy indicative of heterotaxy and outcome. Remnants from youngest subjects were more likely than older subjects to be homogenously inactive suggesting significantly earlier onset in the youngest subset. Conversely remnants from the oldest subjects were often homogenously active suggesting later onset or slower progression. More data are needed in remnants from subjects
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- 2018
14. Health-related quality of life in a prospective study of ultrasound to detect cystic fibrosis-related liver disease in children
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Schwarzenberg, Sarah Jane, Palermo, Joseph J., Ye, Wen, Huang, Suiyuan, Magee, John C., Alazraki, Adina, Freeman, A. Jay, Harned, Roger, Karmazyn, Boaz, Karnsakul, Wikrom, Leung, Daniel H., Ling, Simon C., Masand, Prakash, Molleston, Jean P., Murray, Karen F., Navarro, Oscar M., Nicholas, Jennifer L., Otto, Randolph K., Paranjape, Shruti M., Siegel, Marilyn J., Stoll, Janis, Towbin, Alexander J., Narkewicz, Michael R., and Alonso, Estella M.
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- 2022
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15. Initial assessment of the infant with neonatal cholestasis—Is this biliary atresia?
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Shneider, Benjamin L, Moore, Jeff, Kerkar, Nanda, Magee, John C, Ye, Wen, Karpen, Saul J, Kamath, Binita M, Molleston, Jean P, Bezerra, Jorge A, Murray, Karen F, Loomes, Kathleen M, Whitington, Peter F, Rosenthal, Philip, Squires, Robert H, Guthery, Stephen L, Arnon, Ronen, Schwarz, Kathleen B, Turmelle, Yumirle P, Sherker, Averell H, and Sokol, Ronald J
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Rare Diseases ,Liver Disease ,Perinatal Period - Conditions Originating in Perinatal Period ,Infant Mortality ,Digestive Diseases ,Pediatric ,Good Health and Well Being ,Biliary Atresia ,Bilirubin ,Biopsy ,Cholestasis ,Diagnosis ,Differential ,Female ,Follow-Up Studies ,Gallbladder ,Humans ,Infant ,Infant ,Newborn ,Prospective Studies ,Childhood Liver Disease Research Network ,General Science & Technology - Abstract
IntroductionOptimizing outcome in biliary atresia (BA) requires timely diagnosis. Cholestasis is a presenting feature of BA, as well as other diagnoses (Non-BA). Identification of clinical features of neonatal cholestasis that would expedite decisions to pursue subsequent invasive testing to correctly diagnose or exclude BA would enhance outcomes. The analytical goal was to develop a predictive model for BA using data available at initial presentation.MethodsInfants at presentation with neonatal cholestasis (direct/conjugated bilirubin >2 mg/dl [34.2 μM]) were enrolled prior to surgical exploration in a prospective observational multi-centered study (PROBE-NCT00061828). Clinical features (physical findings, laboratory results, gallbladder sonography) at enrollment were analyzed. Initially, 19 features were selected as candidate predictors. Two approaches were used to build models for diagnosis prediction: a hierarchical classification and regression decision tree (CART) and a logistic regression model using a stepwise selection strategy.ResultsIn PROBE April 2004-February 2014, 401 infants met criteria for BA and 259 for Non-BA. Univariate analysis identified 13 features that were significantly different between BA and Non-BA. Using a CART predictive model of BA versus Non-BA (significant factors: gamma-glutamyl transpeptidase, acholic stools, weight), the receiver operating characteristic area under the curve (ROC AUC) was 0.83. Twelve percent of BA infants were misclassified as Non-BA; 17% of Non-BA infants were misclassified as BA. Stepwise logistic regression identified seven factors in a predictive model (ROC AUC 0.89). Using this model, a predicted probability of >0.8 (n = 357) yielded an 81% true positive rate for BA;
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- 2017
16. Key Histopathologic Features of Liver Biopsies That Distinguish Biliary Atresia From Other Causes of Infantile Cholestasis and Their Correlation With Outcome
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Russo, Pierre, Magee, John C, Anders, Robert A, Bove, Kevin E, Chung, Catherine, Cummings, Oscar W, Finegold, Milton J, Finn, Laura S, Kim, Grace E, Lovell, Mark A, Magid, Margret S, Melin-Aldana, Hector, Ranganathan, Sarangarajan, Shehata, Bahig M, Wang, Larry L, White, Frances V, Chen, Zhen, and Spino, Catherine
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Pediatric ,Chronic Liver Disease and Cirrhosis ,Perinatal Period - Conditions Originating in Perinatal Period ,Transplantation ,Rare Diseases ,Liver Disease ,Digestive Diseases ,Clinical Research ,4.2 Evaluation of markers and technologies ,Detection ,screening and diagnosis ,Oral and gastrointestinal ,Biliary Atresia ,Bilirubin ,Biomarkers ,Biopsy ,Needle ,Cholestasis ,Diagnosis ,Differential ,Female ,Humans ,Infant ,Infant ,Newborn ,Kaplan-Meier Estimate ,Liver ,Logistic Models ,Longitudinal Studies ,Male ,Portoenterostomy ,Hepatic ,Proportional Hazards Models ,Prospective Studies ,Sensitivity and Specificity ,Single-Blind Method ,infant cholestasis ,liver biopsy ,biliary atresia ,large duct obstruction ,laterality defects ,Childhood Liver Disease Research Network ,Clinical Sciences ,Pathology - Abstract
The liver biopsy guides diagnostic investigation and therapy in infants with undiagnosed cholestasis. Histologic features in the liver may also have prognostic value in the patient with biliary atresia (BA). We assessed the relative value of histologic features in 227 liver needle biopsies in discriminating between BA and other cholestatic disorders in infants enrolled in a prospective Childhood Liver Disease Research Network (ChiLDReN) cohort study by correlating histology with clinical findings in infants with and without BA. In addition, we reviewed 316 liver biopsies from clinically proven BA cases and correlated histologic features with total serum bilirubin 6 months after hepatoportoenterostomy (the Kasai procedure, HPE) and transplant-free survival up to 6 years. Review pathologists were blinded to clinical information except age. Semiquantitative scoring of 26 discrete histologic features was based on consensus. Bile plugs in portal bile ducts/ductules, moderate to marked ductular reaction, and portal stromal edema had the largest odds ratio for predicting BA versus non-BA by logistic regression analysis. The diagnostic accuracy of the needle biopsy was estimated to be 90.1% (95% confidence interval [CI]: 85.2%, 94.9%), whereas sensitivity and specificity for a diagnosis of BA are 88.4% (95% CI: 81.4, 93.5) and 92.7% (95% CI: 84.8, 97.3), respectively. No histologic features were associated with an elevated serum bilirubin 6 months after HPE, although it (an elevated serum bilirubin) was associated with an older age at HPE. Higher stages of fibrosis, a ductal plate configuration, moderate to marked bile duct injury, an older age at HPE, and an elevated international normalized ratio were independently associated with a higher risk of transplantation.
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- 2016
17. Longitudinal Outcomes in Young Patients with Alpha-1-Antitrypsin Deficiency with Native Liver Reveal that Neonatal Cholestasis is a Poor Predictor of Future Portal Hypertension
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Alonso, Estella, Bass, Lee, Kelly, Susan, Riordan, Mary, Melin-Aldana, Hector, Bezerra, Jorge, Bove, Kevin, Heubi, James, Miethke, Alexander, Tiao, Greg, Denlinger, Julie, Chapman, Erin, Sokol, Ronald, Feldman, Amy, Mack, Cara, Narkewicz, Michael, Suchy, Frederick, Sundaram, Shikha, Van Hove, Johan, Garcia, Benigno, Kauma, Mikaela, Kocher, Kendra, Steinbeiss, Matthew, Lovell, Mark, Loomes, Kathleen, Piccoli, David, Rand, Elizabeth, Russo, Pierre, Spinner, Nancy, Erlichman, Jessi, Stalford, Samantha, Pakstis, Dina, King, Sakya, Squires, Robert, Sindhi, Rakesh, Venkat, Veena, Bukauskas, Kathy, McKiernan, Patrick, Haberstroh, Lori, Squires, James, Rosenthal, Philip, Bull, Laura, Curry, Joanna, Langlois, Camille, Kim, Grace, Teckman, Jeffery, Kociela, Vikki, Nagy, Rosemary, Patel, Shraddha, Cerkoski, Jacqueline, Molleston, Jean P., Bozic, Molly, Subbarao, Girish, Klipsch, Ann, Sawyers, Cindy, Cummings, Oscar, Horslen, Simon, Murray, Karen, Hsu, Evelyn, Cooper, Kara, Young, Melissa, Finn, Laura, Kamath, Binita, Ng, Vicky, Quammie, Claudia, Putra, Juan, Sharma, Deepika, Parmar, Aishwarya, Guthery, Stephen, Jensen, Kyle, Rutherford, Ann, Lowichik, Amy, Book, Linda, Meyers, Rebecka, Hall, Tyler, Wang, Kasper, Michail, Sonia, Thomas, Danny, Goodhue, Catherine, Kohli, Rohit, Wang, Larry, Soufi, Nisreen, Thomas, Daniel, Karpen, Saul, Gupta, Nitika, Romero, Rene, Jr., Vos, Miriam B., Tory, Rita, Berauer, John-Paul, Abramowsky, Carlos, McFall, Jeanette, Shneider, Benjamin, Harpavat, Sanjiv, Hertel, Paula, Leung, Daniel, Tessier, Mary, Schady, Deborah, Cavallo, Laurel, Olvera, Diego, Banks, Christina, Tsai, Cynthia, Thompson, Richard, Doo, Edward, Hoofnagle, Jay, Sherker, Averell, Torrance, Rebecca, Hall, Sherry, Magee, John, Merion, Robert, Spino, Cathie, Ye, Wen, Teckman, Jeffrey, Hawthorne, Kieran, Bass, Lee M., Murray, Karen F., Kerkar, Nanda, Magee, John C., Heubi, James E., Squires, Robert H., Kamath, Binita M., Guthery, Stephen L., Loomes, Kathleen M., Sherker, Averell H., and Sokol, Ronald J.
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- 2020
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18. Diagnostic accuracy of serum matrix metalloproteinase-7 as a biomarker of biliary atresia in a large North American cohort.
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Pandurangi, Sindhu, Mourya, Reena, Nalluri, Shreya, Fei, Lin, Dong, Shun, Harpavat, Sanjiv, Guthery, Stephen L., Molleston, Jean P., Rosenthal, Philip, Sokol, Ronald J., Wang, Kasper S., Ng, Vicky, Alonso, Estella M., Hsu, Evelyn K., Karpen, Saul J., Loomes, Kathleen M., Magee, John C., Shneider, Benjamin L., Horslen, Simon P., and Teckman, Jeffrey H.
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- 2024
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19. Heterogeneous Liver on Research Ultrasound Identifies Children with Cystic Fibrosis at High Risk of Advanced Liver Disease: Interim Results of a Prospective Observational Case-Controlled Study
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Siegel, Marilyn J., Freeman, A. Jay, Ye, Wen, Palermo, Joseph J., Molleston, Jean P., Paranjape, Shruti M., Stoll, Janis, Leung, Daniel H., Masand, Prakash, Karmazyn, Boaz, Harned, Roger, Ling, Simon C., Navarro, Oscar M., Karnsakul, Wikrom, Alazraki, Adina, Schwarzenberg, Sarah Jane, Seidel, Frank Glen, Towbin, Alex, Alonso, Estella M., Nicholas, Jennifer L., Murray, Karen F., Otto, Randolph K., Sherker, Averell H., Magee, John C., and Narkewicz, Michael R.
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- 2020
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20. Quality of Life and Its Determinants in a Multicenter Cohort of Children with Alagille Syndrome
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Kamath, Binita M, Chen, Zhen, Romero, Rene, Fredericks, Emily M, Alonso, Estella M, Arnon, Ronen, Heubi, James, Hertel, Paula M, Karpen, Saul J, Loomes, Kathleen M, Murray, Karen F, Rosenthal, Philip, Schwarz, Kathleen B, Subbarao, Girish, Teckman, Jeffrey H, Turmelle, Yumirle P, Wang, Kasper S, Sherker, Averell H, Sokol, Ronald J, Magee, John C, and Network, Childhood Liver Disease Research
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Clinical Research ,Liver Disease ,Pediatric ,Digestive Diseases ,Chronic Liver Disease and Cirrhosis ,Adolescent ,Alagille Syndrome ,Case-Control Studies ,Child ,Child ,Preschool ,Cohort Studies ,Emotions ,Female ,Health Status ,Humans ,Male ,Quality of Life ,Social Behavior ,Surveys and Questionnaires ,alpha 1-Antitrypsin Deficiency ,Childhood Liver Disease Research Network ,Human Movement and Sports Sciences ,Paediatrics and Reproductive Medicine ,Pediatrics - Abstract
ObjectivesTo assess health-related quality of life (HRQOL) in children with Alagille syndrome (ALGS) in comparison with healthy and other liver disease cohorts, and to identify determinants of HRQOL in patients with ALGS.Study designWithin the Childhood Liver Disease Research Network prospective study of cholestasis, Pediatric Quality of Life Inventory (PedsQL) questionnaires were administered to 70 children with ALGS, 95 children with alpha-1-antitrypsin deficiency (A1ATD), and 49 children with other causes of chronic intrahepatic cholestasis (IHC) aged 5-18 years. Parent proxy PedsQL scores were recorded for children aged 2-18 years (98 ALGS, 123 A1ATD, and 68 IHC).ResultsMean ages and total bilirubin (mg/dL) were ALGS 9.4 years; 4.4, A1ATD 9.5 years; 0.7, and IHC 10.3 years; 2.9. ALGS child PedsQL scores were lower than in healthy children and children with A1ATD (mean 73 vs 83; P = .001). Children with ALGS and IHC were similar, except in physical scores (73 vs 79; P = .05). Parents of children with ALGS perceived their children to have worse HRQOL than A1ATD (P ≤ .001) and marginally lower compared with IHC. Univariate analysis revealed ALGS child-reported scores were positively associated with better growth and inversely with total bilirubin. Growth failure, elevated international normalized ratio, and an intracardiac defect were predictive of poor parental scores (P ≤ .05). In multivariate analysis, only weight z-score remained significant for child- and parent-reported scores.ConclusionsHRQOL is impaired in children with ALGS compared with healthy and children with A1ATD, similar to children with IHC and is associated with growth failure, which is a potentially treatable cause of impaired HRQOL.
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- 2015
21. Baseline Analysis of a Young α‐1‐Antitrypsin Deficiency Liver Disease Cohort Reveals Frequent Portal Hypertension
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Teckman, Jeffrey H, Rosenthal, Philip, Abel, Robert, Bass, Lee M, Michail, Sonia, Murray, Karen F, Rudnick, David A, Thomas, Daniel W, Spino, Cathie, Arnon, Ronen, Hertel, Paula M, Heubi, James, Kamath, Binita M, Karnsakul, Wikrom, Loomes, Kathleen M, Magee, John C, Molleston, Jean P, Romero, Rene, Shneider, Benjamin L, Sherker, Averell H, Sokol, Ronald J, and Network, Childhood Liver Disease Research
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Biomedical and Clinical Sciences ,Clinical Sciences ,Clinical Research ,Digestive Diseases ,Liver Disease ,Rare Diseases ,Chronic Liver Disease and Cirrhosis ,Pediatric ,Aetiology ,2.1 Biological and endogenous factors ,Oral and gastrointestinal ,Adolescent ,Adult ,Child ,Child ,Preschool ,Cohort Studies ,Female ,Humans ,Hypertension ,Portal ,Infant ,Infant ,Newborn ,Jaundice ,Liver ,Longitudinal Studies ,Male ,Prospective Studies ,Young Adult ,alpha 1-Antitrypsin ,alpha 1-Antitrypsin Deficiency ,cirrhosis ,jaundice ,liver enzymes ,liver transplant ,metabolic liver disease ,Childhood Liver Disease Research Network ,Medical and Health Sciences ,Gastroenterology & Hepatology ,Clinical sciences ,Nutrition and dietetics ,Paediatrics - Abstract
Objectivesα-1-Antitrypsin (A1AT) deficiency is a common genetic disease with an unpredictable and highly variable course. The Childhood Liver Disease Research and Education Network is a National Institutes of Health, multicenter, longitudinal consortium studying pediatric liver diseases, with the objective of prospectively defining natural history and identifying disease modifiers.MethodsLongitudinal, cohort study of A1AT patients' birth through 25 years diagnosed as having liver disease, type PIZZ or PISZ. Medical history, physical examination, laboratory, imaging, and standardized survey tool data were collected during the provision of standard of care.ResultsIn the present report of the cohort at baseline, 269 subjects were enrolled between November 2008 and October 2012 (208 with their native livers and 61 postliver transplant). Subjects with mild disease (native livers and no portal hypertension [PHT]) compared to severe disease (with PHT or postliver transplant) were not different in age at presentation. A total of 57% of subjects with mild disease and 76% with severe disease were jaundiced at presentation (P = 0.0024). A total of 29% of subjects with native livers had PHT, but age at diagnosis and growth were not different between the no-PHT and PHT groups (P > 0.05). Subjects with native livers and PHT were more likely to have elevated bilirubin, ALT, AST, INR, and GGTP than the no-PHT group (P <
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- 2015
22. Factors Determining δ‐Bilirubin Levels in Infants With Biliary Atresia
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Ye, Wen, Rosenthal, Philip, Magee, John C, Whitington, Peter F, and Network, Childhood Liver Disease Research and Education
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Paediatrics ,Biomedical and Clinical Sciences ,Digestive Diseases ,Pediatric ,Rare Diseases ,Chronic Liver Disease and Cirrhosis ,Clinical Research ,Perinatal Period - Conditions Originating in Perinatal Period ,Liver Disease ,Biliary Atresia ,Bilirubin ,Cholestasis ,Female ,Humans ,Infant ,Male ,Prospective Studies ,Serum Albumin ,Time Factors ,biliary atresia ,delta-bilirubin ,conjugated bilirubin ,Childhood Liver Disease Research and Education Network ,Medical and Health Sciences ,Gastroenterology & Hepatology ,Clinical sciences ,Nutrition and dietetics - Abstract
Objectivesδ-Bilirubin (Bδ) forms when bilirubin conjugates covalently bind to albumin by way of nonenzymatic transesterification in patients with cholestasis. Infants with cholestasis with biliary atresia form Bδ. The aim of the present study was to investigate the factors determining serum Bδ concentrations in infants with biliary atresia.MethodsStudy patients were infants enrolled in a prospective study (PROBE: Clinicaltrials.gov NCT00061828) of biliary atresia. We acquired data of concurrently measured serum bilirubin analytes (total bilirubin [TB], conjugated bilirubin [Bc], and unconjugated bilirubin) and applied graphical methods and linear mixed effects model to study factors contributing to Bδ variability.ResultsBδ level increased with increasing levels of Bc and TB. In addition, the length of time cholestasis persisted partially determined the level of Bδ. An increase of 1 mg/dL in Bc is related to approximately 0.36 mg/dL increase in Bδ (P
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- 2015
23. Total Serum Bilirubin Predicts Fat‐Soluble Vitamin Deficiency Better Than Serum Bile Acids in Infants With Biliary Atresia
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Venkat, Veena L, Shneider, Benjamin L, Magee, John C, Turmelle, Yumirle, Arnon, Ronen, Bezerra, Jorge A, Hertel, Paula M, Karpen, Saul J, Kerkar, Nanda, Loomes, Kathleen M, Molleston, Jean, Murray, Karen F, Ng, Vicky L, Raghunathan, Trivellore, Rosenthal, Philip, Schwartz, Kathleen, Sherker, Averell H, Sokol, Ronald J, Teckman, Jeffrey, Wang, Kasper, Whitington, Peter F, Heubi, James E, and Network, Childhood Liver Disease Research and Education
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Biomedical and Clinical Sciences ,Nutrition and Dietetics ,Digestive Diseases ,Clinical Research ,Nutrition ,Chronic Liver Disease and Cirrhosis ,Liver Disease ,Perinatal Period - Conditions Originating in Perinatal Period ,Rare Diseases ,Pediatric ,Avitaminosis ,Bile Acids and Salts ,Biliary Atresia ,Bilirubin ,Dietary Supplements ,Double-Blind Method ,Female ,Humans ,Infant ,Infant ,Newborn ,Male ,National Institute of Diabetes and Digestive and Kidney Diseases (U.S.) ,Placebos ,Prospective Studies ,United States ,Vitamin A ,Vitamin D ,Vitamin E ,Vitamin K ,Vitamins ,biliary atresia ,bilirubin ,cholestasis ,fat-soluble vitamin ,serum bile acid ,Childhood Liver Disease Research and Education Network ,Medical and Health Sciences ,Gastroenterology & Hepatology ,Clinical sciences ,Nutrition and dietetics ,Paediatrics - Abstract
ObjectiveFat-soluble vitamin (FSV) deficiency is a well-recognized consequence of cholestatic liver disease and reduced intestinal intraluminal bile acid. We hypothesized that serum bile acid (SBA) would predict biochemical FSV deficiency better than serum total bilirubin (TB) level in infants with biliary atresia.MethodsInfants enrolled in the Trial of Corticosteroid Therapy in Infants with Biliary Atresia after hepatoportoenterostomy were the subjects of this investigation. Infants received standardized FSV supplementation and monitoring of TB, SBA, and vitamin levels at 1, 3, and 6 months. A logistic regression model was used with the binary indicator variable insufficient/sufficient as the outcome variable. Linear and nonparametric correlations were made between specific vitamin measurement levels and either TB or SBA.ResultsThe degree of correlation for any particular vitamin at a specific time point was higher with TB than with SBA (higher for TB in 31 circumstances vs 3 circumstances for SBA). Receiver operating characteristic curve shows that TB performed better than SBA (area under the curve 0.998 vs 0.821). Including both TB and SBA did not perform better than TB alone (area under the curve 0.998).ConclusionsWe found that TB was a better predictor of FSV deficiency than SBA in infants with biliary atresia. The role of SBA as a surrogate marker of FSV deficiency in other cholestatic liver diseases, such as progressive familial intrahepatic cholestasis, α-1-antitrypsin deficiency, and Alagille syndrome in which the pathophysiology is dominated by intrahepatic cholestasis, warrants further study.
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- 2014
24. Neurodevelopmental Outcomes in Children With Inherited Liver Disease and Native Liver
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Leung, Daniel H., Sorensen, Lisa G., Ye, Wen, Hawthorne, Kieran, Ng, Vicky L., Loomes, Kathleen M., Fredericks, Emily M., Alonso, Estella M., Heubi, James E., Horslen, Simon P., Karpen, Saul J., Molleston, Jean P., Rosenthal, Philip, Sokol, Ronald J., Squires, Robert H., Wang, Kasper S., Kamath, Binita M., and Magee, John C.
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- 2022
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25. Medical Status of 219 Children with Biliary Atresia Surviving Long-Term with Their Native Livers: Results from a North American Multicenter Consortium
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Ng, Vicky Lee, Haber, Barbara H, Magee, John C, Miethke, Alexander, Murray, Karen F, Michail, Sonia, Karpen, Saul J, Kerkar, Nanda, Molleston, Jean P, Romero, Rene, Rosenthal, Philip, Schwarz, Kathleen B, Shneider, Benjamin L, Turmelle, Yumirle P, Alonso, Estella M, Sherker, Averell H, Sokol, Ronald J, and Network, Childhood Liver Disease Research and Education
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Biomedical and Clinical Sciences ,Clinical Sciences ,Rare Diseases ,Clinical Research ,Liver Disease ,Pediatric ,Digestive Diseases ,Chronic Liver Disease and Cirrhosis ,Perinatal Period - Conditions Originating in Perinatal Period ,Oral and gastrointestinal ,Good Health and Well Being ,Biliary Atresia ,Canada ,Child ,Enterostomy ,Female ,Health Status ,Humans ,Liver ,Male ,Quality of Life ,Survivors ,Time Factors ,United States ,Childhood Liver Disease Research and Education Network ,Human Movement and Sports Sciences ,Paediatrics and Reproductive Medicine ,Pediatrics ,Paediatrics - Abstract
ObjectivesTo examine the medical status of children with biliary atresia (BA) with their native livers after hepato- portoenterostomy (HPE) surgery.Study designThe Childhood Liver Disease Research and Education Network database was utilized to examine subjects with BA living with their native livers 5 or more years after HPE and to describe the prevalence of subjects with BA with an "ideal" outcome, defined as no clinical evidence of chronic liver disease, normal liver biochemical indices (aspartate aminotransferase, alanine aminotransferase, γ-glutamyl transpeptidase, platelet count, total bilirubin, international normalized ratio, and albumin), and normal health-related quality of life 5 or more years after HPE.ResultsChildren with BA (n = 219; 43% male) with median age 9.7 years were studied. Median age at HPE was 56 (range 7-125) days. Median age- and sex-adjusted height and weight z-scores at 5-year follow-up were 0.487 (IQR -0.27 to 1.02) and 0.00 (IQR -0.74 to 0.70), respectively. During the 12 preceding months, cholangitis and bone fractures occurred in 17% and 5.5%, respectively. Health-related quality of life was reported normal by 53% of patients. However, only 1.8% met the study definition of "ideal" outcome. Individual tests of liver synthetic function (total bilirubin, albumin, and international normalized ratio) were normal in 75%, 85%, and 73% of the study cohort.ConclusionCholangitis and fractures in long-term survivors underscore the importance of ongoing medical surveillance. Over 98% of this North American cohort of subjects with BA living with native livers 5 or more years after HPE have clinical or biochemical evidence of chronic liver disease.
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- 2014
26. Impact of Steroid Therapy on Early Growth in Infants with Biliary Atresia: The Multicenter Steroids in Biliary Atresia Randomized Trial
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Alonso, Estella M., Ye, Wen, Hawthorne, Kieran, Venkat, Veena, Loomes, Kathleen M., Mack, Cara L., Hertel, Paula M., Karpen, Saul J., Kerkar, Nanda, Molleston, Jean P., Murray, Karen F., Romero, Rene, Rosenthal, Philip, Schwarz, Kathleen B., Shneider, Benjamin L., Suchy, Frederick J., Turmelle, Yumirle P., Wang, Kasper S., Sherker, Averell H., Sokol, Ronald J., Bezerra, Jorge A., and Magee, John C.
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- 2018
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27. Use of Corticosteroids After Hepatoportoenterostomy for Bile Drainage in Infants With Biliary Atresia: The START Randomized Clinical Trial
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Bezerra, Jorge A, Spino, Cathie, Magee, John C, Shneider, Benjamin L, Rosenthal, Philip, Wang, Kasper S, Erlichman, Jessi, Haber, Barbara, Hertel, Paula M, Karpen, Saul J, Kerkar, Nanda, Loomes, Kathleen M, Molleston, Jean P, Murray, Karen F, Romero, Rene, Schwarz, Kathleen B, Shepherd, Ross, Suchy, Frederick J, Turmelle, Yumirle P, Whitington, Peter F, Moore, Jeffrey, Sherker, Averell H, Robuck, Patricia R, and Sokol, Ronald J
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Biomedical and Clinical Sciences ,Clinical Sciences ,Clinical Trials and Supportive Activities ,Digestive Diseases ,Rare Diseases ,Liver Disease ,Patient Safety ,Clinical Research ,Pediatric ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Oral and gastrointestinal ,Administration ,Oral ,Adrenal Cortex Hormones ,Biliary Atresia ,Bilirubin ,Double-Blind Method ,Drainage ,Female ,Humans ,Infant ,Infusions ,Intravenous ,Male ,Methylprednisolone ,Portoenterostomy ,Hepatic ,Prednisolone ,Survival Analysis ,Treatment Outcome ,Childhood Liver Disease Research and Education Network ,Medical and Health Sciences ,General & Internal Medicine ,Biomedical and clinical sciences ,Health sciences - Abstract
ImportanceBiliary atresia is the most common cause of end-stage liver disease in children. Controversy exists as to whether use of steroids after hepatoportoenterostomy improves clinical outcome.ObjectiveTo determine whether the addition of high-dose corticosteroids after hepatoportoenterostomy is superior to surgery alone in improving biliary drainage and survival with the native liver.Design, setting, and patientsThe multicenter, double-blind Steroids in Biliary Atresia Randomized Trial (START) was conducted in 140 infants (mean age, 2.3 months) between September 2005 and February 2011 in the United States; follow-up ended in January 2013.InterventionsParticipants were randomized to receive intravenous methylprednisolone (4 mg/kg/d for 2 weeks) and oral prednisolone (2 mg/kg/d for 2 weeks) followed by a tapering protocol for 9 weeks (n = 70) or placebo (n = 70) initiated within 72 hours of hepatoportoenterostomy.Main outcomes and measuresThe primary end point (powered to detect a 25% absolute treatment difference) was the percentage of participants with a serum total bilirubin level of less than 1.5 mg/dL with his/her native liver at 6 months posthepatoportoenterostomy. Secondary outcomes included survival with native liver at 24 months of age and serious adverse events.ResultsThe proportion of participants with improved bile drainage was not statistically significantly improved by steroids at 6 months posthepatoportoenterostomy (58.6% [41/70] of steroids group vs 48.6% [34/70] of placebo group; adjusted relative risk, 1.14 [95% CI, 0.83 to 1.57]; P = .43). The adjusted absolute risk difference was 8.7% (95% CI, -10.4% to 27.7%). Transplant-free survival was 58.7% in the steroids group vs 59.4% in the placebo group (adjusted hazard ratio, 1.0 [95% CI, 0.6 to 1.8]; P = .99) at 24 months of age. The percentage of participants with serious adverse events was 81.4% [57/70] of the steroids group and 80.0% [56/70] of the placebo group (P > .99); however, participants receiving steroids had an earlier time of onset of their first serious adverse event by 30 days posthepatoportoenterostomy (37.2% [95% CI, 26.9% to 50.0%] of steroids group vs 19.0% [95% CI, 11.5% to 30.4%] of placebo group; P = .008).Conclusions and relevanceAmong infants with biliary atresia who have undergone hepatoportoenterostomy, high-dose steroid therapy following surgery did not result in statistically significant treatment differences in bile drainage at 6 months, although a small clinical benefit could not be excluded. Steroid treatment was associated with earlier onset of serious adverse events in children with biliary atresia.Trial registrationclinicaltrials.gov Identifier: NCT00294684.
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- 2014
28. Mutations in TJP2 cause progressive cholestatic liver disease
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Sambrotta, Melissa, Strautnieks, Sandra, Papouli, Efterpi, Rushton, Peter, Clark, Barnaby E, Parry, David A, Logan, Clare V, Newbury, Lucy J, Kamath, Binita M, Ling, Simon, Grammatikopoulos, Tassos, Wagner, Bart E, Magee, John C, Sokol, Ronald J, Mieli-Vergani, Giorgina, Smith, Joshua D, Johnson, Colin A, McClean, Patricia, Simpson, Michael A, Knisely, AS, Bull, Laura N, and Thompson, Richard J
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Biochemistry and Cell Biology ,Biological Sciences ,Genetics ,Chronic Liver Disease and Cirrhosis ,Digestive Diseases ,Liver Disease ,2.1 Biological and endogenous factors ,Oral and gastrointestinal ,Animals ,Base Sequence ,Cholestasis ,Intrahepatic ,High-Throughput Nucleotide Sequencing ,Humans ,Immunoblotting ,Immunohistochemistry ,Mice ,Mice ,Knockout ,Microscopy ,Electron ,Transmission ,Models ,Biological ,Molecular Sequence Data ,Mutation ,Pedigree ,Real-Time Polymerase Chain Reaction ,Sequence Alignment ,Species Specificity ,Tight Junctions ,Zonula Occludens-2 Protein ,University of Washington Center for Mendelian Genomics ,Medical and Health Sciences ,Developmental Biology ,Agricultural biotechnology ,Bioinformatics and computational biology - Abstract
Elucidating genetic causes of cholestasis has proved to be important in understanding the physiology and pathophysiology of the liver. Here we show that protein-truncating mutations in the tight junction protein 2 gene (TJP2) cause failure of protein localization and disruption of tight-junction structure, leading to severe cholestatic liver disease. These findings contrast with those in the embryonic-lethal knockout mouse, highlighting differences in redundancy in junctional complexes between organs and species.
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- 2014
29. A Comprehensive Mixed‐Method Approach to Characterize the Source of Diurnal Tacrolimus Exposure Variability in Children: Systematic Review, Meta‐analysis, and Application to an Existing Data Set.
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Leino, Abbie D., Magee, John C., Kershaw, David B., Pai, Manjunath P., and Park, Jeong M.
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META-analysis , *CONFIDENCE intervals , *FOOD consumption , *SYSTEMATIC reviews , *CIRCADIAN rhythms , *KIDNEY transplantation , *DRUG-food interactions , *PATIENTS , *DESCRIPTIVE statistics , *BIOTRANSFORMATION (Metabolism) , *TACROLIMUS , *TRANSPLANTATION of organs, tissues, etc. - Abstract
Tacrolimus is widely reported to display diurnal variation in pharmacokinetic parameters with twice‐daily dosing. However, the contribution of chronopharmacokinetics versus food intake is unclear, with even less evidence in the pediatric population. The objectives of this study were to summarize the existing literature by meta‐analysis and evaluate the impact of food composition on 24‐hour pharmacokinetics in pediatric kidney transplant recipients. For the meta‐analysis, 10 studies involving 253 individuals were included. The pooled effect sizes demonstrated significant differences in area under the concentration–time curve from time 0 to 12 hours (standardized mean difference [SMD], 0.27; 95% confidence interval [CI], 0.03‐0.52) and maximum concentration (SMD, 0.75; 95% CI, 0.35‐1.15) between morning and evening dose administration. However, there was significant between‐study heterogeneity that was explained by food exposure. The effect size for minimum concentration was not significantly different overall (SMD, −0.09; 95% CI, −0.27 to 0.09) or across the food exposure subgroups. A 2‐compartment model with a lag time, linear clearance, and first‐order absorption best characterized the tacrolimus pharmacokinetics in pediatric participants. As expected, adding the time of administration and food composition covariates reduced the unexplained within‐subject variability for the first‐order absorption rate constant, but only caloric composition significantly reduced variability for lag time. The available data suggest food intake is the major driver of diurnal variation in tacrolimus exposure, but the associated changes are not reflected by trough concentrations alone. [ABSTRACT FROM AUTHOR]
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- 2024
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30. Changes over time in self‐efficacy and the allocation of responsibility for health management tasks in pediatric liver transplant recipients: Targets to improve the transition process.
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Bilhartz, Jacob L., Lopez, M. James, Eder, Sally J., Magee, John C., Rea, Kelly, Sturza, Julie, and Fredericks, Emily M.
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LIVER transplantation ,TIME management ,YOUNG adults ,PRINCIPAL components analysis ,TRANSITIONAL care - Abstract
Background: The process of transition to adult‐based care encompasses a critical period in the life of an adolescent and young adult living with a chronic illness and one that comes with an increase in the risk of poor health outcomes. As yet, there is a dearth of empirical data to help optimize this process to ensure the best long‐term outcome. Methods: This study used a principal components analysis to determine specific constructs measured by a revised version of the transition readiness survey used in our clinic. We investigated changes in these constructs over time. We further investigated the relationship between the change in these constructs over time spent in a focused transition program with adherence. Results: The primary component underlying our transition readiness survey for patients and parents represented self‐efficacy. Time spent in the transition program was an independent predictor of change in self‐efficacy (rho 0.299, p =.015); however, the magnitude of that change had no relationship to adherence. Change in parent‐proxy self‐efficacy was found to have a statistically significant relationship with tacrolimus standard deviation (rho −0.301, p =.026). There was disagreement identified between patient and parent responses on the survey. Neither change in patient nor parent reports of self‐efficacy was found to have a relationship with post‐transfer adherence. Conclusions: This study reaches the novel conclusion that self‐efficacy and parent‐proxy self‐efficacy are dynamic concepts that change over time spent in a focused transition program. The patient‐parent disagreement and the relationship between parent‐proxy self‐efficacy and adherence stress the importance of involving parents/guardians in the transition process as well. [ABSTRACT FROM AUTHOR]
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- 2024
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31. Extrahepatic Anomalies in Infants With Biliary Atresia: Results of a Large Prospective North American Multicenter Study
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Schwarz, Kathleen B, Haber, Barbara H, Rosenthal, Philip, Mack, Cara L, Moore, Jeffrey, Bove, Kevin, Bezerra, Jorge A, Karpen, Saul J, Kerkar, Nanda, Shneider, Benjamin L, Turmelle, Yumirle P, Whitington, Peter F, Molleston, Jean P, Murray, Karen F, Ng, Vicky L, Romero, René, Wang, Kasper S, Sokol, Ronald J, Magee, John C, and Network, Childhood Liver Disease Research and Education
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Perinatal Period - Conditions Originating in Perinatal Period ,Congenital Structural Anomalies ,Chronic Liver Disease and Cirrhosis ,Liver Disease ,Prevention ,Pediatric ,Clinical Research ,Cardiovascular ,Rare Diseases ,Digestive Diseases ,2.1 Biological and endogenous factors ,Aetiology ,Abnormalities ,Multiple ,Adult ,Biliary Atresia ,Female ,Humans ,Male ,Prospective Studies ,United States ,Childhood Liver Disease Research and Education Network ,Medical Biochemistry and Metabolomics ,Clinical Sciences ,Immunology ,Gastroenterology & Hepatology - Abstract
UnlabelledThe etiology of biliary atresia (BA) is unknown. Given that patterns of anomalies might provide etiopathogenetic clues, we used data from the North American Childhood Liver Disease Research and Education Network to analyze patterns of anomalies in infants with BA. In all, 289 infants who were enrolled in the prospective database prior to surgery at any of 15 participating centers were evaluated. Group 1 was nonsyndromic, isolated BA (without major malformations) (n = 242, 84%), Group 2 was BA and at least one malformation considered major as defined by the National Birth Defects Prevention Study but without laterality defects (n = 17, 6%). Group 3 was syndromic, with laterality defects (n = 30, 10%). In the population as a whole, anomalies (either major or minor) were most prevalent in the cardiovascular (16%) and gastrointestinal (14%) systems. Group 3 patients accounted for the majority of subjects with cardiac, gastrointestinal, and splenic anomalies. Group 2 subjects also frequently displayed cardiovascular (71%) and gastrointestinal (24%) anomalies; interestingly, this group had genitourinary anomalies more frequently (47%) compared to Group 3 subjects (10%).ConclusionThis study identified a group of BA (Group 2) that differed from the classical syndromic and nonsyndromic groups and that was defined by multiple malformations without laterality defects. Careful phenotyping of the patterns of anomalies may be critical to the interpretation of both genetic and environmental risk factors associated with BA, allowing new insight into pathogenesis and/or outcome.
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- 2013
32. Neurodevelopmental Outcome of Young Children with Biliary Atresia and Native Liver: Results from the ChiLDReN Study
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Hertel, Paula M., Harpavat, Sanjiv, Brandt, Mary L., Leung, Daniel H., Karnsakul, Wikrom, Torrance, Rebecca, Hall, Sherry, Doo, Edward, Hoofnagle, Jay H., Whitington, Peter, Bass, Lee, Miethke, Alexander G., Heubi, James E., Setchell, Kenneth, Bove, Kevin E., Tiao, Greg, Mack, Cara L., Narkewicz, Michael R., Feldman, Amy G., Sundaram, Shikha S., Suchy, Frederick J., Karrer, Frederick M., Lovell, Mark, Van Hove, Johan L., Rand, Elizabeth B., Squires, James E., Venkat, Veena L., Sindhi, Rakesh, Ranganathan, Sarangarajan, Bull, Laura, Teckman, Jeffrey, Bozic, Molly, Subbarao, Girish, Horslen, Simon, Hsu, Evelyn, Finn, Laura, Healey, Patrick, Kohli, Rohit, Thomas, Danny, Soufi, Nisreen, Michail, Sonia, Clifton, Matt, Gupta, Nitika, Romero, Rene, Vos, Miriam, Caltharp, Shelley, Kamath, Binita M., Ling, Simon C., Gold, Anna, Fecteau, Annie, Guthery, Stephen L., Jensen, Kyle, Meyers, Rebecka, Lowichik, Amy, Book, Linda, Merion, Robert M., Spino, Cathie, Jones, Karen, Ng, Vicky L., Sorensen, Lisa G., Alonso, Estella M., Fredericks, Emily M., Ye, Wen, Moore, Jeff, Karpen, Saul J., Shneider, Benjamin L., Molleston, Jean P., Bezerra, Jorge A., Murray, Karen F., Loomes, Kathleen M., Rosenthal, Philip, Squires, Robert H., Wang, Kasper, Arnon, Ronen, Schwarz, Kathleen B., Turmelle, Yumirle P., Haber, Barbara H., Sherker, Averell H., Magee, John C., and Sokol, Ronald J.
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- 2018
- Full Text
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33. Health Related Quality of Life in Patients with Biliary Atresia Surviving with their Native Liver
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Sundaram, Shikha S, Alonso, Estella M, Haber, Barbara, Magee, John C, Fredericks, Emily, Kamath, Binita, Kerkar, Nanda, Rosenthal, Philip, Shepherd, Ross, Limbers, Christine, Varni, James W, Robuck, Patricia, Sokol, Ronald J, and Network, Childhood Liver Disease Research and Education
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Paediatrics ,Biomedical and Clinical Sciences ,Clinical Research ,Transplantation ,Digestive Diseases ,Organ Transplantation ,Congenital Structural Anomalies ,Minority Health ,Perinatal Period - Conditions Originating in Perinatal Period ,Liver Disease ,Pediatric ,Chronic Liver Disease and Cirrhosis ,Rare Diseases ,7.1 Individual care needs ,Adolescent ,Adult ,Biliary Atresia ,Child ,Child ,Preschool ,Cohort Studies ,Cross-Sectional Studies ,Female ,Humans ,Liver ,Liver Transplantation ,Male ,Models ,Statistical ,Multivariate Analysis ,Pediatrics ,Quality of Life ,Regression Analysis ,Young Adult ,Childhood Liver Disease Research and Education Network ,ALT ,Alanine aminotransferase ,GI ,Gastrointestinal ,HPE ,HRQOL ,Health related quality of life ,Hepatic portoenterostomy ,ICC ,Intra-class correlation coefficient ,LT ,Liver transplant ,Pediatric Quality of Life Inventory ,PedsQL ,Human Movement and Sports Sciences ,Paediatrics and Reproductive Medicine - Abstract
ObjectivesTo quantify health related quality of life (HRQOL) of patients with biliary atresia with their native livers and compare them with healthy children and patients with biliary atresia post-liver transplant (LT) and to examine the relationship between HRQOL and medical variables.Study designA cross-sectional HRQOL study of patients with biliary atresia with their native livers (ages 2-25 years) was conducted and compared with healthy and post-LT biliary atresia samples using Pediatric Quality of Life Inventory 4.0 child self and parent proxy reports, a validated measure of physical/psychosocial functioning.Results221 patients with biliary atresia with native livers (54% female, 67% white) were studied. Patient self and parent proxy reports showed significantly poorer HRQOL than healthy children across all domains (P < .001), particularly in emotional and psychosocial functioning. Child self and parent proxy HRQOL scores from patients with biliary atresia with their native livers and post-LT biliary atresia were similar across all domains (P = not significant). Child self and parent proxy reports showed moderate agreement across all scales, except social functioning (poor to fair agreement). On multivariate regression analysis, black race and elevated total bilirubin were associated with lower Total and Psychosocial HRQOL summary scores.ConclusionsHRQOL in patients with biliary atresia with their native livers is significantly poorer than healthy children and similar to children with post-LT biliary atresia. These findings identify significant opportunities to optimize the overall health of patients with biliary atresia.
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- 2013
34. Portal Hypertension in Children and Young Adults With Biliary Atresia
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Shneider, Benjamin L, Abel, Bob, Haber, Barbara, Karpen, Saul J, Magee, John C, Romero, Rene, Schwarz, Kathleen, Bass, Lee M, Kerkar, Nanda, Miethke, Alexander G, Rosenthal, Philip, Turmelle, Yumirle, Robuck, Patricia R, and Sokol, Ronald J
- Subjects
Biomedical and Clinical Sciences ,Cardiovascular Medicine and Haematology ,Clinical Research ,Liver Disease ,Chronic Liver Disease and Cirrhosis ,Perinatal Period - Conditions Originating in Perinatal Period ,Pediatric ,Digestive Diseases ,2.1 Biological and endogenous factors ,Aetiology ,Adolescent ,Alanine Transaminase ,Aspartate Aminotransferases ,Bile Ducts ,Biliary Atresia ,Bilirubin ,Child ,Child ,Preschool ,Cross-Sectional Studies ,Humans ,Hypertension ,Portal ,Leukocyte Count ,Liver ,North America ,Platelet Count ,Prevalence ,Prothrombin Time ,Serum Albumin ,Splenomegaly ,Thrombocytopenia ,ascites ,hepatopulmonary syndrome ,hypersplenism ,pediatric ,varices ,Childhood Liver Disease Research and Education Network ,Medical and Health Sciences ,Gastroenterology & Hepatology ,Clinical sciences ,Nutrition and dietetics ,Paediatrics - Abstract
ObjectiveBiliary atresia (BA) frequently results in portal hypertension (PHT), complications of which lead to significant morbidity and mortality. The Childhood Liver Disease Research and Education Network was used to perform a cross-sectional multicentered analysis of PHT in children with BA.MethodsSubjects with BA receiving medical management at a Childhood Liver Disease Research and Education Network site were enrolled. A priori, clinically evident PHT was defined as "definite" when there was either history of a complication of PHT or clinical findings consistent with PHT (both splenomegaly and thrombocytopenia). PHT was denoted as "possible" if one of the findings was present in the absence of a complication, whereas PHT was "absent" if none of the criteria were met.ResultsA total of 163 subjects were enrolled between May 2006 and December 2009. At baseline, definite PHT was present in 49%, possible in 17%, and absent in 34% of subjects. Demographics, growth, and anthropometrics were similar amongst the 3 PHT categories. Alanine aminotransferase, γ-glutamyl transpeptidase, and sodium levels were similar, whereas there were significant differences in aspartate aminotransferase (AST), AST/alanine aminotransferase, albumin, total bilirubin, prothrombin time, white blood cell count, platelet count, and AST/platelet count between definite and absent PHT. Thirty-four percent of those with definite PHT had either prothrombin time >15 seconds or albumin
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- 2012
35. Efficacy of Fat-Soluble Vitamin Supplementation in Infants With Biliary Atresia
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Shneider, Benjamin L, Magee, John C, Bezerra, Jorge A, Haber, Barbara, Karpen, Saul J, Raghunathan, Trivellore, Rosenthal, Philip, Schwarz, Kathleen, Suchy, Frederick J, Kerkar, Nanda, Turmelle, Yumirle, Whitington, Peter F, Robuck, Patricia R, and Sokol, Ronald J
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Biomedical and Clinical Sciences ,Nutrition and Dietetics ,Perinatal Period - Conditions Originating in Perinatal Period ,Nutrition ,Infant Mortality ,Clinical Research ,Pediatric ,Congenital Structural Anomalies ,Clinical Trials and Supportive Activities ,Rare Diseases ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Avitaminosis ,Biliary Atresia ,Bilirubin ,Dietary Supplements ,Double-Blind Method ,Female ,Humans ,Infant ,Male ,Polyethylene Glycols ,Portoenterostomy ,Hepatic ,Postoperative Care ,Retinol-Binding Proteins ,Vitamin A ,Vitamin D ,Vitamin E ,Vitamin K ,alpha-Tocopherol ,cholestasis ,nutrition ,liver ,vitamin deficiency ,Childhood Liver Disease Research Education Network ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Pediatrics ,Biomedical and clinical sciences ,Health sciences ,Psychology - Abstract
ObjectiveCholestasis predisposes to fat-soluble vitamin (FSV) deficiencies. A liquid multiple FSV preparation made with tocopheryl polyethylene glycol-1000 succinate (TPGS) is frequently used in infants with biliary atresia (BA) because of ease of administration and presumed efficacy. In this prospective multicenter study, we assessed the prevalence of FSV deficiency in infants with BA who received this FSV/TPGS preparation.MethodsInfants received FSV/TPGS coadministered with additional vitamin K as routine clinical care in a randomized double-blinded, placebo-controlled trial of corticosteroid therapy after hepatoportoenterostomy (HPE) for BA (identifier NCT 00294684). Levels of FSV, retinol binding protein, total serum lipids, and total bilirubin (TB) were measured 1, 3, and 6 months after HPE.ResultsNinety-two infants with BA were enrolled in this study. Biochemical evidence of FSV insufficiency was common at all time points for vitamin A (29%-36% of patients), vitamin D (21%-37%), vitamin K (10%-22%), and vitamin E (16%-18%). Vitamin levels were inversely correlated with serum TB levels. Biochemical FSV insufficiency was much more common (15%-100% for the different vitamins) in infants whose TB was ≥2 mg/dL. At 3 and 6 months post HPE, only 3 of 24 and 0 of 23 infants, respectively, with TB >2 mg/dL were sufficient in all FSV.ConclusionsBiochemical FSV insufficiency is commonly observed in infants with BA and persistent cholestasis despite administration of a TPGS containing liquid multiple FSV preparation. Individual vitamin supplementation and careful monitoring are warranted in infants with BA, especially those with TB >2 mg/dL.
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- 2012
36. Neonatal cholestasis in children with Alpha-1-AT deficiency is a risk for earlier severe liver disease with male predominance.
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Teckman, Jeffrey, Rosenthal, Philip, Ignacio, Rosalinda V., Spino, Cathie, Bass, Lee M., Horslen, Simon, Wang, Kasper, Magee, John C., Karpen, Saul, Asai, Akihiro, Molleston, Jean P., Squires, Robert H., Kamath, Binita M., Guthery, Stephen L., Loomes, Kathleen M., Shneider, Benjamin L., and Sokol, Ronald J.
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- 2023
- Full Text
- View/download PDF
37. Neurodevelopmental Outcomes in Preschool and School Aged Children With Biliary Atresia and Their Native Liver
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Squires, James E., Ng, Vicky Lee, Hawthorne, Kieran, Henn, Lisa L., Sorensen, Lisa G., Fredericks, Emily M., Alonso, Estella M., Murray, Karen F., Loomes, Kathleen M., Karpen, Saul J., Cavallo, Laurel A., Molleston, Jean P., Bezerra, Jorge A., Rosenthal, Philip, Squires, Robert H., Wang, Kasper S., Schwarz, Kathleen B., Arnon, Ronen, Magee, John C., and Sokol, Ronald J.
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- 2020
- Full Text
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38. Liver Ultrasound Patterns in Children with Cystic Fibrosis Correlate with Non-Invasive Tests of Liver Disease
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Ling, Simon C., Ye, Wen, Leung, Daniel H., Navarro, Oscar M., Weymann, Alexander, Karnsakul, Wikrom, Freeman, A. Jay, Magee, John C., and Narkewicz, Michael R.
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- 2019
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39. Total Serum Bilirubin within 3 Months of Hepatoportoenterostomy Predicts Short-Term Outcomes in Biliary Atresia
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Alonso, Estella, Kaurs, Elizabeth, Kelly, Sue, Bove, Kevin, Heubi, James, Miethke, Alexander, Tiao, Greg, Denlinger, Julie, Ferris, Andrea, Feldman, Amy, Mack, Cara, Suchy, Frederick, Sundaram, Shikha, Van Hove, Johan, Hite, Michelle, Kantor, Susanna, Miller, Todd, Smith, Julia, VanWinkle, Becky, Loomes, Kathleen, Lin, Henry, Piccoli, David, Russo, Pierre, Spinner, Nancy, Brown, Lindsay, Elgert, Emily, Erlichman, Jessi, Alissa, Feras, Lindblad, Douglas, Mazariegos, George, Ortiz-Aguayo, Roberto, Perlmutter, David, Sindhi, Rakesh, Venkat, Veena, Vockley, Jerry, Bukauskas, Kathy, Kufen, Adam, Schulte, Madeline, Bull, Laura, Fleck, Shannon, Langlois, Camille, Teckman, Jeffery, Kociela, Vikki, Postma, Stacy, Harris, Kathleen, Bozic, Molly, Subbarao, Girish, Byam, Beth, Klipsch, Ann, Sawyers, Cindy, Horslen, Simon, Hsu, Evelyn, Cooper, Kara, Young, Melissa, Kamath, Binita, DeAngelis, Maria, O'Connor, Constance, VanRoestel, Krista, Parmar, Arpita, Quammie, Claudia, Hung, Kelsey, Guthery, Stephen, Jensen, Kyle, Rutherford, Ann, Kerker, Nanda, Michail, Sonia, Thomas, Danny, Goodhue, Catherine, Gupta, Nikita, Vos, Mariam, de la Cruz-Tracey, Liezl, Hankerson-Dyson, Dana, Tory, Rita, Turner-Green, Taieshia, Wellons, Allison, Brandt, Mary, Finegold, Milton, Harpavat, Sanjiv, Hertel, Paula, Leung, Daniel, Liwanag, Loriel, Thompson, Richard, Brown, Sherry, Doo, Edward, Hoofnagle, Jay, Hall, Sherry, Torrance, Rebecca, Brown, Jameisha, Kafka, Kimberly, Merion, Robert, Spino, Cathie, Shneider, Benjamin L., Magee, John C., Karpen, Saul J., Rand, Elizabeth B., Narkewicz, Michael R., Bass, Lee M., Schwarz, Kathleen, Whitington, Peter F., Bezerra, Jorge A., Kerkar, Nanda, Haber, Barbara, Rosenthal, Philip, Turmelle, Yumirle P., Molleston, Jean P., Murray, Karen F., Ng, Vicky L., Wang, Kasper S., Romero, Rene, Squires, Robert H., Arnon, Ronen, Sherker, Averell H., Moore, Jeffrey, Ye, Wen, and Sokol, Ronald J.
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- 2016
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40. Liver Ultrasound Patterns in Children With Cystic Fibrosis Correlate With Noninvasive Tests of Liver Disease
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Ling, Simon C., Ye, Wen, Leung, Daniel H., Navarro, Oscar M., Weymann, Alexander, Karnsakul, Wikrom, Freeman, A. Jay, Magee, John C., and Narkewicz, Michael R.
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- 2019
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41. Clinically Evident Portal Hypertension: An Operational Research Definition for Future Investigations in the Pediatric Population
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Bass, Lee M., Shneider, Benjamin L., Henn, Lisa, Goodrich, Nathan P., and Magee, John C.
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- 2019
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42. A Phase I/IIa Trial of Intravenous Immunoglobulin Following Portoenterostomy in Biliary Atresia
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Mack, Cara L., Spino, Cathie, Alonso, Estella M., Bezerra, Jorge A., Moore, Jeffrey, Goodhue, Catherine, Ng, Vicky L., Karpen, Saul J., Venkat, Veena, Loomes, Kathleen M., Wang, Kasper, Sherker, Averell H., Magee, John C., and Sokol, Ronald J.
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- 2019
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43. Baseline Ultrasound and Clinical Correlates in Children with Cystic Fibrosis
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Alonso, Estella M., Nicholas, Jennifer L., Kaurs, Elizabeth, Narkewicz, Michael R., Sokol, Ronald J., Harned, Roger, Burr, Susanna, Romero, Rene, Freeman, Jay, Alazraki, Adina, Patrick, Ellen, Hunter, Eric, Ling, Simon C., Navarro, Oscar, Ling, Julie P., Palermo, Joe J., Towbin, Alex, Ferris, Andrea, Denlinger, Julie, Molleston, Jean P., Bozic, Molly A., Subbarao, Girish, Karmazyn, Boaz, Klipsch, Ann, Paranjape, Shruti M., Karnsakul, Wikrom, Benson, Jane E., Callahan, Karen A., Kafka, Kim, Murray, Karen F., Gibson, Ron, Otto, Randolph, Genatossio, Alan, Young, Melissa, Weymann, Alexander, Siegel, Marilyn J., Harris, Kathy, Leung, Daniel H., Krishnamurthy, Rajesh, Brown, Jameisha, Schwarzenberg, Sara Jane, Stacklie, Denise, Seidel, F. Glenn, Doo, Edward, Sherker, Averell H., Hall, Sherry R., Torrance, Rebecca, Ye, Wen, Ling, Simon, Palermo, Joseph, Marshall, Bruce C., and Magee, John C.
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- 2015
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44. Variceal Hemorrhage and Adverse Liver Outcomes in Patients With Cystic Fibrosis Cirrhosis
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Ye, Wen, Narkewicz, Michael R., Leung, Daniel H., Karnsakul, Wikrom, Murray, Karen F., Alonso, Estella M., Magee, John C., Schwarzenberg, Sarah Jane, Weymann, Alexander, and Molleston, Jean P.
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- 2018
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45. Peer Leaders Increase Organ Donor Designation Among Members of Historically African American Fraternities and Sororities
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Loughery, Caitlin, Zhang, Nanhua, Resnicow, Ken, Chapman, Remonia, Magee, John C., and Andrews, Ann M.
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- 2017
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46. A prospective, randomized trial of complete avoidance of steroids in liver transplantation with follow‐up of over 7 years
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Pelletier, Shawn J., Nadig, Satish N., Lee, David D., Ammori, John B., Englesbe, Michael J., Sung, Randall S., Magee, John C., Fontana, Robert J., and Punch, Jeffrey D.
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- 2013
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47. Ex Situ Perfusion of Human Limb Allografts for 24 Hours
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Werner, Nicole L., Alghanem, Fares, Rakestraw, Stephanie L., Sarver, Dylan C., Nicely, Bruce, Pietroski, Richard E., Lange, Paul, Rudich, Steven M., Mendias, Christopher L., Rojas-Pena, Alvaro, Magee, John C., Bartlett, Robert H., and Ozer, Kagan
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- 2017
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48. Serum bile acids as a prognostic biomarker in biliary atresia following Kasai portoenterostomy.
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Harpavat, Sanjiv, Hawthorne, Kieran, Setchell, Kenneth D. R., Rivas, Monica Narvaez, Henn, Lisa, Beil, Charlotte A., Karpen, Saul J., Ng, Vicky L., Alonso, Estella M., Bezerra, Jorge A., Guthery, Stephen L., Horslen, Simon, Loomes, Kathy M., McKiernan, Patrick, Magee, John C., Merion, Robert M., Molleston, Jean P., Rosenthal, Philip, Thompson, Richard J., and Wang, Kasper S.
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- 2023
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49. Quality Improvement Targeting Adherence During the Transition from a Pediatric to Adult Liver Transplant Clinic
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Fredericks, Emily M., Magee, John C., Eder, Sally J., Sevecke, Jessica R., Dore-Stites, Dawn, Shieck, Victoria, and Lopez, M. James
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- 2015
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50. Randomized Trial Using Hair Stylists as Lay Health Advisors to Increase Donation in African Americans
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Resnicow, Ken, Andrews, Ann M., Beach, Denise K., Kuhn, Latoya, Krein, Sarah L., Chapman, Remonia, and Magee, John C.
- Published
- 2010
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