Article
Pediatrics
L. Seddon, K. Dick, S. B. Carr, I. M. Balfour-Lynn
Summary: The majority of parents in a survey conducted in a London pediatric center believed that cystic fibrosis newborn screening results should be communicated face to face rather than over the telephone. There were mixed responses regarding whether parents should be informed of the genotype and CF diagnosis before the confirmatory sweat test.
EUROPEAN JOURNAL OF PEDIATRICS
(2021)
Article
Pediatrics
Iolo Doull, Christopher William Course, Ruth E. Hanks, Kevin W. Southern, Julian T. Forton, Lena P. Thia, Stuart J. Moat
Summary: The study aimed to determine the causes of false negative cases in CF newborn screening and found that the majority of false negatives were associated with poor quality DBS samples. Improving the quality of DBS samples would be the optimal way to enhance the sensitivity of the CF NBS programme.
ARCHIVES OF DISEASE IN CHILDHOOD
(2021)
Article
Critical Care Medicine
Mirjam Stahl, Eva Steinke, Simon Y. Graeber, Cornelia Joachim, Christoph Seitz, Hans-Ulrich Kauczor, Monika Eichinger, Susanne Haemmerling, Olaf Sommerburg, Mark O. Wielpuetz, Marcus A. Mall
Summary: The study showed that MRI can detect the progression of lung disease and the benefits of early diagnosis using NBS in preschool children with CF. Increase in MRI global score was associated with symptoms like cough and pulmonary exacerbations. MRI is suggested as a sensitive outcome measure for diagnostic monitoring and early intervention trials in preschool children with CF.
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(2021)
Review
Pediatrics
Ioanna Loukou, Maria Moustaki, Konstantinos Douros
Summary: The aim of this study was to familiarize clinicians with the terms cystic fibrosis transmembrane conductance regulator related metabolic syndrome (CRMS) and cystic fibrosis screen positive inconclusive diagnosis (CFSPID), and to highlight the monitoring and outcomes of children with these designations. A literature review was performed to gather relevant articles, and the results showed that despite newborn screening programs for cystic fibrosis, the diagnosis remains uncertain for some infants. CRMS/CFSPID was established as a unified definition in 2016, but longer longitudinal studies are needed to determine the appropriate follow-up for these children. It is important for pediatricians to be knowledgeable about this condition and for children to be in contact with their local CF center.
Review
Biology
Joan Kathleen DeCelie-Germana, Lynn Bonitz, Elinor Langfelder-Schwind, Catherine Kier, Barry Lawrence Diener, Maria Berdella
Summary: As of December 2009, cystic fibrosis (CF) newborn screening (NBS) is performed in all 50 US states and the District of Columbia. Widespread implementation of CF newborn screening (CFNBS) in the US and internationally has brought about new and varied challenges. Advances in genetic testing have provided an opportunity for earlier identification of babies with CF through CFTR sequencing, improving long-term outcomes through prompt treatment and intervention.
Article
Pediatrics
Heather J. Stalker, Amy R. Jonasson, Sidney M. Hopfer, Melanie Sue Collins
Summary: Genetic counseling through telemedicine was well received by families, leading to improved understanding of CF-related risks for their child and other family members. The study also showed that parents demonstrated better comprehension of the genetic implications of an abnormal CF newborn screen after receiving counseling via telemedicine. Additionally, the use of trained CF genetic counselors through telemedicine proved to be feasible and effective in improving parent understanding of CF genetics across a wide geographical area.
PEDIATRIC PULMONOLOGY
(2023)
Article
Pediatrics
Tugba Ramasli Gursoy, Pelin Asfuroglu, Tugba Sismanlar Eyuboglu, Ayse Tana Aslan, Asli Imran Yilmaz, Gokcen Unal, Busra Sultan Kibar, Sevgi Pekcan, Melih Hangul, Mehmet Kose, Isil Irem Budakoglu, Deniz Acican
Summary: This cross-sectional study aimed to evaluate the cutoff values of immunoreactive trypsinogen (IRT) and investigate the relationship between IRT values and clinical characteristics in children with cystic fibrosis (CF). The study included data from children with positive newborn screening (NBS) from 2015 to 2021. Sensitivity and specificity of IRT cutoff values were assessed, and the positive predictive value (PPV) was determined. The study found that while the sensitivity of CF NBS was high, the PPV was significantly lower than expected. Revising the NBS strategy may help overcome false-positive results.
EUROPEAN JOURNAL OF PEDIATRICS
(2023)
Article
Multidisciplinary Sciences
Jennifer A. Scott, Elliot Jokl, Timothy Gordon-Walker, Neil A. Hanley, Karen Piper Hanley, Varinder S. Athwal, Andrew M. Jones, Peter J. Barry
Summary: This study assessed diagnostic tools for liver fibrosis in patients with cystic fibrosis, finding that current guidelines may underestimate fibrosis while newer methods provide more accurate results. The authors proposed a new diagnostic criterion, which was validated in an independent cohort and accurately predicted liver disease in cystic fibrosis patients.
Review
Gastroenterology & Hepatology
Jennifer Scott, Andrew M. Jones, Karen Piper Hanley, Varinder S. Athwal
Summary: This review provides a summary of the current understanding of cystic fibrosis-related liver disease (CFLD) in terms of its epidemiology, pathology, diagnosis, and management. The review highlights the heterogeneity of CFLD and the challenges in its diagnosis and treatment. The authors emphasize the lack of precise diagnostic strategies and effective therapies for CFLD, and the need for further research on its pathogenesis and disease detection.
ALIMENTARY PHARMACOLOGY & THERAPEUTICS
(2022)
Article
Gastroenterology & Hepatology
Shruti Sakhuja, Heather M. Staples, Charles G. Minard, Louise E. Ramm, Peter J. Lewindon, Grant A. Ramm, Daniel H. Leung
Summary: This study aimed to evaluate the clinical utility of lung function and liver biomarkers assessed years prior to liver biopsy-proven CFLD in predicting the risk of severe fibrosis development. The findings suggest that mild-moderate pulmonary dysfunction and higher liver biomarker indices at baseline may be associated with faster progression of CFLD.
LIVER INTERNATIONAL
(2023)
Article
Genetics & Heredity
Sevcan Tug Bozdogan, Cem Mujde, Ibrahim Boga, Ozge Sonmezler, Abdullah Hanta, Cagla Rencuzogullari, Dilek Ozcan, Derya Ufuk Altintas, Atil Bisgin
Summary: This study evaluates the genetic testing results of 1595 newborns in Turkey with positive CF NBS program results, showing that 35.1% of patients carried at least one CF-related variant. The most common findings included compound heterozygosity for two mutations and the identification of novel variants. The study highlights the impact of NBS on genetic diagnosis centers and the diversity of CFTR mutations in the Turkish population.
Article
Pediatrics
Michael J. J. Rock, Mei Baker, Nicholas Antos, Philip M. M. Farrell
Summary: Using next generation sequencing (NGS) in combination with immunoreactive trypsinogen (IRT) can effectively identify infants at risk for cystic fibrosis (CF) without significantly increasing the rate of detecting carriers. NGS has the potential to enhance equity, sensitivity, and detection of more CF patients with 2 variants during the screening process.
PEDIATRIC PULMONOLOGY
(2023)
Article
Pediatrics
Annemarie G. Wolfe, Stephanie P. Gilley, Stephanie W. Waldrop, Christina Olson, Emma Harding, Kaitlin Widmer, Lindsey B. Gumer, Matthew Haemer, Jordana E. Hoppe
Summary: Universal newborn screening has changed the way CF is diagnosed, with nearly all cases being detected shortly after birth. However, clinicians should still be aware of the possibility of CF in newborns with normal screening results.
FRONTIERS IN PEDIATRICS
(2023)
Article
Respiratory System
Susanna A. McColley, Stacey L. Martiniano, Clement L. Ren, Marci K. Sontag, Karen Rychlik, Lauren Balmert, Alexander Elbert, Runyu Wu, Philip M. Farrell
Summary: This study evaluated whether the implementation of cystic fibrosis newborn screening leads to equitable timeliness of initial evaluation. The study compared the age at the first event (AFE) between infants of different races and ethnicities (Group 1) and white non-Hispanic infants (Group 2). The study found that differences in AFE for infants with CF from historically marginalized groups may exacerbate long-standing health disparities.
JOURNAL OF CYSTIC FIBROSIS
(2023)
Article
Pediatrics
Halime Nayir Buyuksahin, Nagehan Emiralioglu, Beste Ozsezen, Dilber Ademhan Tural, Birce Sunman, Ismail Guzelkas, Basak Tezel, Didem Dayangac Erden, Ebru Yalcin, Deniz Dogru, Ugur Ozcelik, Nural Kiper
Summary: The study found low sensitivity and positive predictive value of NBS for cystic fibrosis, with infants who tested negative showing symptoms such as feeding reluctance and Pseudobartter syndrome. Early diagnosis did not significantly impact nutritional outcomes, highlighting the need for further large-scale studies to optimize care for infants diagnosed through NBS.
PEDIATRIC PULMONOLOGY
(2022)
Article
Respiratory System
Susanna A. McColley, Stacey L. Martiniano, Clement L. Ren, Marci K. Sontag, Karen Rychlik, Lauren Balmert, Alexander Elbert, Runyu Wu, Philip M. Farrell
Summary: This study evaluated whether the implementation of cystic fibrosis newborn screening leads to equitable timeliness of initial evaluation. The study compared the age at the first event (AFE) between infants of different races and ethnicities (Group 1) and white non-Hispanic infants (Group 2). The study found that differences in AFE for infants with CF from historically marginalized groups may exacerbate long-standing health disparities.
JOURNAL OF CYSTIC FIBROSIS
(2023)
Article
Critical Care Medicine
Matthew K. Wynia, Laurel E. Beaty, Tellen D. Bennett, Nichole E. Carlson, Christopher B. Davis, Bethany M. Kwan, David A. Mayer, Toan C. Ong, Seth Russell, Jeffrey D. Steele, Heather R. Stocker, Adane F. Wogu, Richard D. Zane, Ronald J. Sokol, Adit A. Ginde
Summary: This observational cohort study found that treatment with neutralizing monoclonal antibodies (mAbs) was associated with reduced hospitalization and deaths among COVID-19 outpatients. The benefits of mAb treatment persisted during the Delta variant phase.
Article
Gastroenterology & Hepatology
Daniel H. Leung, Sridevi Devaraj, Nathan P. Goodrich, Xinpu Chen, Deepthi Rajapakshe, Wen Ye, Victor Andreev, Charles G. Minard, Danielle Guffey, Jean P. Molleston, Lee M. Bass, Saul J. Karpen, Binita M. Kamath, Kasper S. Wang, Shikha S. Sundaram, Philip Rosenthal, Patrick McKiernan, Kathleen M. Loomes, M. Kyle Jensen, Simon P. Horslen, Jorge A. Bezerra, John C. Magee, Robert M. Merion, Ronald J. Sokol, Benjamin L. Shneider
Summary: This study investigated biomarkers for hepatic fibrosis in pediatric cholestasis patients. The researchers found that endoglin, IL-8, and MMP-7 were positively correlated with liver stiffness in children with biliary atresia, while CTGF was negatively correlated in alpha-1 antitrypsin deficiency patients. These biomarkers may enhance the prediction of liver stiffness and facilitate early interventions.
Article
Gastroenterology & Hepatology
Sanjiv Harpavat, Kieran Hawthorne, Kenneth D. R. Setchell, Monica Narvaez Rivas, Lisa Henn, Charlotte A. Beil, Saul J. Karpen, Vicky L. Ng, Estella M. Alonso, Jorge A. Bezerra, Stephen L. Guthery, Simon Horslen, Kathy M. Loomes, Patrick McKiernan, John C. Magee, Robert M. Merion, Jean P. Molleston, Philip Rosenthal, Richard J. Thompson, Kasper S. Wang, Ronald J. Sokol, Benjamin L. Shneider
Summary: Serum bile acid levels may help predict outcomes in infants with normalized bilirubin levels after Kasai portoenterostomy.
Article
Gastroenterology & Hepatology
Ronald J. Sokol, Emmanuel M. Gonzales, Binita M. Kamath, Alastair Baker, Pamela Vig, Douglas B. Mogul, Will Garner, Bettina E. Hansen, Emmanuel Jacquemin, Richard J. Thompson
Summary: Improvement in pruritus by 48 weeks, and lower W48 bilirubin and serum bile acid levels were associated with fewer events in patients with Alagille syndrome (ALGS) treated with maralixibat (MRX).
Article
Gastroenterology & Hepatology
James E. Squires, Alexander G. Miethke, C. Alexander Valencia, Kieran Hawthorne, Lisa Henn, Johan L. K. H. Van Hove, Robert Squires, Kevin Bove, Simon Horslen, Rohit Kohli, Jean P. Molleston, Rene Romero, Estella M. Alonso, Jorge A. Bezerra, Stephen L. Guthery, Evelyn Hsu, Saul J. Karpen, Kathleen M. Loomes, Vicky L. Ng, Philip Rosenthal, Krupa Mysore, Kasper S. Wang, Marisa W. Friederich, John C. Magee, Ronald J. Sokol
Summary: This study aims to enhance the understanding of pathogenesis and natural history of mitochondrial hepatopathies (MH), a range of liver-based conditions caused by alterations in mitochondrial DNA and nuclear DNA genes. The study found differences in clinical presentation, genetic etiology, and survival between acute liver failure (ALF) and chronic liver disease (Chronic) phenotypes of MH. In addition, a subset of patients could not be identified with a specific genetic or enzymatic diagnosis, highlighting the need for further research.
HEPATOLOGY COMMUNICATIONS
(2023)
Article
Gastroenterology & Hepatology
Swati Ghosh, Michael W. Devereaux, Aimee L. Anderson, Karim C. El Kasmi, Ronald J. Sokol
Summary: The study showed that FXR activation through IL-6-STAT3 signaling in a PNAC mouse model alleviated cholestatic liver injury and prevented cholestasis.
HEPATOLOGY COMMUNICATIONS
(2023)
Article
Gastroenterology & Hepatology
Antonia Felzen, Daan B. E. van Wessel, Emmanuel Gonzales, Richard J. Thompson, Irena Jankowska, Benjamin L. Shneider, Etienne Sokal, Tassos Grammatikopoulos, Agustina Kadaristiana, Emmanuel Jacquemin, Anne Spraul, Patryk Lipinski, Piotr Czubkowski, Nathalie Rock, Mohammad Shagrani, Dieter Broering, Emanuele Nicastro, Deirdre Kelly, Gabriella Nebbia, Henrik Arnell, Bjoern Fischler, Jan B. F. Hulscher, Daniele Serranti, Cigdem Arikan, Esra Polat, Dominique Debray, Florence Lacaille, Cristina Goncalves, Loreto Hierro, Gema Munoz Bartolo, Yael Mozer-Glassberg, Amer Azaz, Jernej Brecelj, Antal Dezsofi, Pier Luigi Calvo, Enke Grabhorn, Steffen Hartleif, Wendy J. van der Woerd, Binita M. Kamath, Jian-She Wang, Liting Li, Ozlem Durmaz, Nanda Kerkar, Marianne Horby Jorgensen, Ryan Fischer, Carolina Jimenez-Rivera, Seema Alam, Mara Cananzi, Noemie Laverdure, Cristina Targa Ferreira, Felipe Ordonez Guerrero, Heng Wang, Valerie Sency, Kyung Mo Kim, Huey-Ling Chen, Elisa de Carvalho, Alexandre Fabre, Jesus Quintero Bernabeu, Aglaia Zellos, Estella M. Alonso, Ronald J. Sokol, Frederick J. Suchy, Kathleen M. Loomes, Patrick J. McKiernan, Philip Rosenthal, Yumirle Turmelle, Simon Horslen, Kathleen Schwarz, Jorge A. Bezerra, Kasper Wang, Bettina E. Hansen, Henkjan J. Verkade
Summary: This study aimed to evaluate the relationship between genetic mutations related to BSEP deficiency and clinical features. The results showed that the combination of one relatively mild mutation and one severe mutation resulted in a clinical presentation similar to patients with two severe mutations, and they had a poor response to surgical interruption of the enterohepatic circulation.
Article
Gastroenterology & Hepatology
Richard J. Thompson, Reha Artan, Ulrich Baumann, Pier Luigi Calvo, Piotr Czubkowski, Buket Dalgic, Lorenzo D'Antiga, Angelo Di Giorgio, Ozlem Durmaz, Emmanuel Gonzales, Tassos Grammatikopoulos, Girish Gupte, Winita Hardikar, Roderick H. J. Houwen, Binita M. Kamath, Saul J. Karpen, Florence Lacaille, Alain Lachaux, Elke Lainka, Kathleen M. Loomes, Cara L. Mack, Jan P. Mattsson, Patrick Mckiernan, Quanhong Ni, Hasan Ozen, Sanjay R. Rajwal, Bertrand Roquelaure, Eyal Shteyer, Etienne Sokal, Ronald J. Sokol, Nisreen Soufi, Ekkehard Sturm, Mary Elizabeth Tessier, Wendy L. van der Woerd, Henkjan J. Verkade, Jennifer M. Vittorio, Terese Wallefors, Natalie Warholic, Qifeng Yu, Patrick Horn, Lise Kjems
Summary: The ongoing PEDFIC 2 study evaluated the effectiveness of odevixibat in patients with progressive familial intrahepatic cholestasis. The study found that odevixibat can reduce serum bile acids and alleviate pruritus symptoms. This suggests that odevixibat may be a safe and effective treatment option for patients with progressive familial intrahepatic cholestasis.
Article
Public, Environmental & Occupational Health
Ashima Singh, Marci K. Sontag, Mei Zhou, Mahua Dasgupta, Tessa Crume, Morgan McLemore, Najibah Galadanci, Eldrida Randall, Nicole Steiner, Amanda M. Brandow, Kathryn Koch, Joshua J. Field, Kathryn Hassell, Angela B. Snyder, Julie Kanter
Summary: Sickle cell disease (SCD) is a genetic condition, but there is currently no universal clinical registry to estimate its prevalence. The Sickle Cell Data Collection (SCDC) program aims to identify individuals with SCD using administrative claims. This study evaluates the ability of the SCDC administrative claims case definition to accurately identify adults with SCD.
JMIR PUBLIC HEALTH AND SURVEILLANCE
(2023)
Article
Gastroenterology & Hepatology
Sarah Kemme, Jennifer D. Canniff, Amy G. Feldman, Krystle M. Garth, Shaobing Li, Zhaoxing Pan, Ronald J. Sokol, Adriana Weinberg, Cara L. Mack
Summary: This study aimed to investigate the relationship between cytomegalovirus (CMV) infection and the severity of disease and pretransplant outcomes in infants with biliary atresia (BA). The results showed that CMV infection was associated with worse liver injury, delayed surgery, and increased risk of pretransplant death, but had no effect on native liver survival.
HEPATOLOGY COMMUNICATIONS
(2023)
Article
Gastroenterology & Hepatology
Colin T. Shearn, Aimee L. Anderson, Colin G. Miller, Reed C. Noyd, Michael W. Devereaux, Nata Balasubramaniyan, David J. Orlicky, Edward E. Schmidt, Ronald J. Sokol
Summary: This study investigates the impact of thioredoxin reductase 1 (TrxR1) on liver inflammation and injury during cholestatic liver injury. The results show that TrxR1 expression is increased in inflammatory cells and hepatocytes surrounding fibrosis in cholestatic liver injury patients and mouse models. Inhibition of TrxR1 can alleviate inflammation, necrosis, and the expression of pro-inflammatory cytokines, and increase the expression of antioxidant proteins and bile acid transporters. Therefore, the TrxR1 signaling pathway plays an important role in regulating inflammation and bile acid homeostasis in cholestatic liver injury.
HEPATOLOGY COMMUNICATIONS
(2023)
Article
Gastroenterology & Hepatology
Alexander Chaidez, Zhaoxing Pan, Shikha S. Sundaram, Julia Boster, Mark Lovell, Ronald J. Sokol, Cara L. Mack
Summary: Vibration controlled transient elastography (Fibroscan) can be used to predict the severity of liver fibrosis and steatosis. This study investigated the correlation between FibroScan measurements and liver histologic features in pediatric nonalcoholic fatty liver disease (NAFLD). The study also assessed the predictive capacity of the FibroScan-aspartate aminotransferase (FAST) score in pediatric NAFLD.
HEPATOLOGY COMMUNICATIONS
(2022)
Article
Gastroenterology & Hepatology
Benjamin L. Shneider, Catherine A. Spino, Binita M. Kamath, John C. Magee, Rosalinda Ignacio, Suiyuan Huang, Simon P. Horslen, Jean P. Molleston, Alexander G. Miethke, Rohit Kohli, Daniel H. Leung, M. Kyle Jensen, Kathleen M. Loomes, Saul J. Karpen, Cara Mack, Philip Rosenthal, Robert H. Squires, Alastair Baker, Sanjay Rajwal, Deirdre Kelly, Ronald J. Sokol, Richard J. Thompson
Summary: Maralixibat administration is associated with significant improvement in pruritus and quality of life in children with severe cholestasis secondary to Alagille Syndrome.
HEPATOLOGY COMMUNICATIONS
(2022)
Article
Gastroenterology & Hepatology
Benjamin L. Shneider, Binita M. Kamath, John C. Magee, Nathan P. Goodrich, Kathleen M. Loomes, Wen Ye, Cathie Spino, Estella M. Alonso, Jean P. Molleston, Jorge A. Bezerra, Kasper S. Wang, Saul J. Karpen, Simon P. Horslen, Stephen L. Guthery, Philip Rosenthal, Robert H. Squires, Ronald J. Sokol
Summary: Long-term conventional randomized clinical trials in rare diseases are difficult, so real-world data are being used more frequently to assess new therapeutic approaches. In this investigation, inclusion and exclusion criteria from a published trial were applied to a prospective cohort study to provide contextual comparator data for evolving clinical trials in a specific disease.
HEPATOLOGY COMMUNICATIONS
(2022)
