Gastroenterology Commons^™

Direct Detection Of Shigella In Stool Specimens By Use Of A Metagenomic Approach, Jie Liu, Mathieu Almeida, Furqan Kabir, Sadia Shakoor, Shahida Qureshi, Anita K. M. Zaidi, Shan Li, Boubou Tamboura, Samba O. Sow, Inacio Mandomando

Department of Paediatrics and Child Health

The underestimation of Shigella species as a cause of childhood diarrhea disease has become increasingly apparent with quantitative PCR (qPCR)-based diagnostic methods versus culture. We sought to confirm qPCR-based detection of Shigella via a metagenomics approach. Three groups of samples were selected from diarrheal cases from the Global Enteric Multicenter Study: nine Shigella culture-positive and qPCR-positive (culture⁺ qPCR⁺) samples, nine culture-negative but qPCR-positive (culture^- qPCR⁺) samples, and nine culture-negative and qPCR-negative (culture^- qPCR^-) samples. Fecal DNA was sequenced using paired-end Illumina HiSeq, whereby 3.26 × 10⁸ ± 5.6 × 10 …

Cow's Milk Protein-Induced Villous Atrophy And Elevated Celiac Autoimmunity In Children With Celiac Disease On A Glutten-Free Diet: A Report Of Three Cases, Kristin Capone, Naire Sansotta, Pankaj Vohra, Stefano Guandalini

Pediatrics Research and Scholarship

Objective: To describe the serologic and histologic response of three patients with celiac disease who had persistent autoimmunity and villous atrophy despite a strict gluten-free diet, to the elimination of cow's milk protein.

Spontaneous Dna Damage To The Nuclear Genome Promotes Senescence, T Redox Imbalance And Aging, Andria R. Robinson, Matthew J. Yousefzadeh, Tania A. Rozgaja, Jin Wang, Xuesen Li, Jeremy S. Tilstra, Chelsea H. Feldman, Siobhan Q. Gregg, Caroline H. Johnson, Erin M. Skoda, Marie-Celine Frantz, Harris Bell-Temin, Hannah Pope-Varsalona, Aditi U. Gurkar, Luigi A. Nasto, Rena A.S. Robinson, Heike Fuhrmann-Stroissnigg, Jolanta Czerwinska, Sara J. Mcgowan, Nadiezhda Cantu-Madellin, Jamie B. Harris, Salony Maniar, Mark A. Ross, Christy E. Trussoni, Nicholas F. Larusso, Eugenia Cifuentes-Pagano, Patrick J. Pagano, Barbara Tudek, Nam V. Vo, Lora H. Rigatti, Patricia L. Opresko, Donna B. Stolz, Simon C. Watkins, Christin E. Burd, Claudette M. St, Croix, Gary Siuzdak, Nathan A. Yates, Paul D. Robbins, Yinsheng Wang, Peter Wipf, Eric E. Kelley, Laura J. Neidernhofer

Faculty & Staff Scholarship

Accumulation of senescent cells over time contributes to aging and age-related diseases. However, what drives senescence in vivo is not clear. Here we used a genetic approach to determine if spontaneous nuclear DNA damage is sufficient to initiate senescence in mammals. Ercc1-/Δ mice with reduced expression of ERCC1-XPF endonuclease have impaired capacity to repair the nuclear genome. Ercc1-/Δ mice accumulated spontaneous, oxidative DNA damage more rapidly than wild-type (WT) mice. As a consequence, senescent cells accumulated more rapidly in Ercc1-/Δ mice compared to repair-competent animals. However, the levels of DNA damage and senescent cells in Ercc1-/Δ mice never exceeded that …

All Ttg Positive Patient Do Not Have Celiac Disease, Pankaj Vohra, Kalyan Ray Parashette, Rajmohan Dharmaraj, Angela Deubel, Richardo Castillo, Jacqueline Fridge

Pediatrics Research and Scholarship

Tissue transglutaminase antibody IgA level (tTG) is an excellent screening test for celiac disease in the presence of adequate IgA levels. Most labs while screening for Celiac disease (CD) will do the IgA levels automatically. However the serological test is not a diagnostic test.

Practice Survey: Adherence Monitoring And Intervention In Pediatric Gastroenterology And Hepatology., Michele H. Maddux, Shawna Ricks, Julie A. Bass, James F. Daniel, Ellen Carpenter, Kimberely Radford

Manuscripts, Articles, Book Chapters and Other Papers

Purpose: Despite significant medication nonadherence rates among youth with pediatric gastroenterology and hepatology disorders, little is known about current adherence practices in pediatric gastroenterology care. This study summarizes current practices surrounding adherence monitoring and intervention in pediatric gastrointestinal (GI) and hepatologic care in the USA.

Participants and methods: One hundred and fifty-four pediatric GI providers completed an online survey designed to examine current practices surrounding adherence monitoring and intervention, specific strategies used to monitor and treat poor adherence, and the barriers currently experienced in relation to adherence monitoring and intervention.

Results: Practices varied greatly in terms of when and how …

A Nationwide Study On The Prevalence Of Functional Gastrointestinal Disorders In School-Children., Miguel Saps, Jairo Enrique Moreno-Gomez, Carmen Rossy Ramírez-Hernández, John M. Rosen, C A. Velasco-Benitez

Manuscripts, Articles, Book Chapters and Other Papers

Introduction: Functional gastrointestinal disorders (FGIDs) are highly prevalent worldwide and are thought to result from the interplay of multiple factors that can vary from region to region. Nationwide studies can help understand the regional epidemiology and the pathogenesis of FGIDs. The objectives of this study were to determine the prevalence of FGIDs in school-children of Colombia and assess associated factors.

Methods: A cross-sectional study was carried out at twelve private and public schools in ten cities distributed through the four main geographic regions of Colombia. School-children completed a validated questionnaire to assess functional gastrointestinal disorders according to Rome III criteria. …

Re-Tubularization Of Highly-Ischemic Anti-Mesenteric Border (Rehab): A Novel Bowel Preservation Technique In Complex Gastroschisis., Richard J. Hendrickson, Ashwini S. Poola, Katherine W. Gonzalez, Joel Lim, Tolulope A. Oyetunji

Manuscripts, Articles, Book Chapters and Other Papers

Complex gastroschisis with bowel necrosis poses an operative challenge. Surgeons must weigh the decision between resection versus preservation of ischemic bowel. As one of the leading causes of short bowel syndrome, aggressive resection in complicated gastroschisis subjects children to prolonged dependence on parenteral nutrition and its attendant complications. Herein, we describe a novel technique aimed towards bowel preservation in complex gastroschisis patients with severe bowel ischemia with the ultimate goal for enteral autonomy.

Neonatal Graves' Disease With Maternal Hypothyroidism., Gangaram Akangire, Alain Cuna, Charisse I. Lachica, Ryan T. Fischer, Sripriya Raman, Venkatesh Sampath

Manuscripts, Articles, Book Chapters and Other Papers

Neonatal Graves' disease presenting as conjugated hyperbilirubinemia is a diagnostic challenge because the differential includes a gamut of liver and systemic diseases. We present a unique case of neonatal Graves' disease in a premature infant with conjugated hyperbilirubinemia born to a mother with hypothyroidism during pregnancy and remote history of Graves' disease. Infant was treated with a combination of methimazole, propranolol, and potassium iodide for 4 weeks. Thyroid function improved after 8 weeks of treatment with full recovery of thyroid function, disappearance of thyroid-stimulating antibodies, and resolution of failure to thrive and conjugated hyperbilirubinemia. This case provides several clinical vignettes …

Exome Analysis Of Rare And Common Variants Within The Nod Signaling Pathway., Gaia Andreoletti, Valentina Shakhnovich, Kathy Christenson, Tracy Coelho, Rachel Haggarty, Nadeem A. Afzal, Akshay Batra, Britt-Sabina Petersen, Matthew Mort, R Mark Beattie, Sarah Ennis

Manuscripts, Articles, Book Chapters and Other Papers

Pediatric inflammatory bowel disease (pIBD) is a chronic heterogeneous disorder. This study looks at the burden of common and rare coding mutations within 41 genes comprising the NOD signaling pathway in pIBD patients. 136 pIBD and 106 control samples underwent whole-exome sequencing. We compared the burden of common, rare and private mutation between these two groups using the SKAT-O test. An independent replication cohort of 33 cases and 111 controls was used to validate significant findings. We observed variation in 40 of 41 genes comprising the NOD signaling pathway. Four genes were significantly associated with disease in the discovery cohort …

Novel Genetic Variants Associated With Child Refractory Esophageal Stricture With Food Allergy By Exome Sequencing., Min Yang, Min Xiong, Huan Chen, Lanlan Geng, Peiyu Chen, Jing Xie, Shui Qing Ye, Ding-You Li, Sitang Gong

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Refractory esophageal stricture (RES) may be attributed to food allergy. Its etiology and pathogenesis are not fully understood. Identification of novel genetic variants associated with this disease by exome sequencing (exome-seq) may provide new mechanistic insights and new therapeutic targets.

METHODS: To identify new and novel disease-associating variants, whole-exome sequencing was performed on an Illumina NGS platform in three children with RES as well as food allergy.

RESULTS: A total of 91,024 variants were identified. By filtering out 'normal variants' against those of the 1000 Genomes Project, we identified 12,741 remaining variants which are potentially associated with RES plus …

Causal Pathways From Enteropathogens To Environmental Enteropathy: Findings From The Mal-Ed Birth Cohort Study, Margaret N. Kosek, Zulfiqar Ahmed Bhutta, Anita K. M. Zaidi, Imran Ahmed, Syed Asad Ali, Muneera Rasheed, Sajid Bashir Soofi, Ali Turab, Didar Alam, Shahida Qureshi

Department of Paediatrics and Child Health

Background: Environmental enteropathy (EE), the adverse impact of frequent and numerous enteric infections on the gut resulting in a state of persistent immune activation and altered permeability, has been proposed as a key determinant of growth failure in children in low- and middle-income populations. A theory-driven systems model to critically evaluate pathways through which enteropathogens, gut permeability, and intestinal and systemic inflammation affect child growth was conducted within the framework of the Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) birth cohort study that included children from eight countries. …

Mortality Associated With Gastrointestinal Bleeding In Children: A Retrospective Cohort Study., Thomas M. Attard, Mikaela Miller, Chaitanya Pant, Ashwath Kumar, Mike Thomson

Manuscripts, Articles, Book Chapters and Other Papers

AIM: To determine the clinical characteristics of children with gastrointestinal bleeding (GIB) who died during the course of their admission.

METHODS: We interrogated the Pediatric Hospital Information System database, including International Classification of Diseases, Current Procedural Terminology and Clinical Transaction Classification coding from 47 pediatric tertiary centers extracting the population of patients (1-21 years of age) admitted (inpatient or observation) with acute, upper or indeterminate GIB (1/2007-9/2015). Descriptive statistics, unadjusted univariate and adjusted multivariate analysis of the associations between patient characteristics and treatment course with mortality was performed with mortality as primary and endoscopy a secondary outcome of interest. All …

Outcomes From A 12-Week, Open-Label, Multicenter Clinical Trial Of Teduglutide In Pediatric Short Bowel Syndrome., Beth A. Carter, Valeria C. Cohran, Conrad R. Cole, Mark R. Corkins, Reed A. Dimmitt, Christopher Duggan, Susan Hill, Simon Horslen, Joel D. Lim, David F. Mercer, Russell J. Merritt, Peter F. Nichol, Luther Sigurdsson, Daniel H. Teitelbaum, John Thompson, Charles Vanderpool, Juliana F. Vaughan, Benjamin Li, Nader N. Youssef, Robert S. Venick, Samuel A. Kocoshis

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: To determine safety and pharmacodynamics/efficacy of teduglutide in children with intestinal failure associated with short bowel syndrome (SBS-IF).

STUDY DESIGN: This 12-week, open-label study enrolled patients aged 1-17 years with SBS-IF who required parenteral nutrition (PN) and showed minimal or no advance in enteral nutrition (EN) feeds. Patients enrolled sequentially into 3 teduglutide cohorts (0.0125 mg/kg/d [n = 8], 0.025 mg/kg/d [n = 14], 0.05 mg/kg/d [n = 15]) or received standard of care (SOC, n = 5). Descriptive summary statistics were used.

RESULTS: All patients experienced ≥1 treatment-emergent adverse event; most were mild or moderate. No serious teduglutide-related …

A Novel Compound-Heterozygous Epithelial Cell Adhesion Molecule Mutation In Tufting Enteropathy., Valentina Shakhnovich, Darrell Dinwiddie, Amber Hildreth, Thomas M. Attard, Stephen Kingsmore

Manuscripts, Articles, Book Chapters and Other Papers

No abstract provided.

Bleeding Meckel's Diverticulum In Children: The Diagnostic Value Of Double-Balloon Enteroscopy., Lan-Lan Geng, Pei-Yu Chen, Qiang Wu, Hui-Wen Li, Ding-You Li, Min Yang, Si-Tang Gong

Manuscripts, Articles, Book Chapters and Other Papers

Background. Meckel's diverticulum (MD) is the most common congenital anomaly of the gastrointestinal tract. The purpose of this study was to evaluate the diagnostic value and safety of double-balloon enteroscopy (DBE) for bleeding MD in children. Methods. We included consecutive children who were highly suspected of MD between 2012 and 2013. All patients underwent Meckel's scan. DBE was performed for patient with negative Meckel's scan. An exploratory laparoscopy was performed in children with positive Meckel's scan or DBE. Results. 42 patients met the inclusion criteria. 40 patients were confirmed to have MD by exploratory laparoscopy. Meckel's scan …

Ibd Live Case Series-Case 6., Dhyan Rajan, Julia B. Greer, Miguel D. Regueiro, Leonard Baidoo, David G. Binion, Hans H. Herfarth, Corey A. Siegel, Douglas J. Hartman, Francis A. Farraye, Ioannis E. Koutroubakis, Myron H. Brand, Emmanuelle D. Williams, Alka Goyal, Raymond K. Cross

Manuscripts, Articles, Book Chapters and Other Papers

No abstract provided.

Celiac Disease Presenting As Intussusception From Giardia Lamblia, Adam R. Paul Do

Department of Pediatrics

No abstract provided.

Decreased Pregnane X Receptor Expression In Children With Active Crohn's Disease, Valentina Shakhnovich, Carrie A. Vyhlidal, Craig A. Friesen, Amber Hildreth, Vivekanand Singh, James Daniel, Gregory L. Kearns, J Steven Leeder

Manuscripts, Articles, Book Chapters and Other Papers

Copyright © 2016 The Author(s). Expression of the pregnane X receptor (PXR) has been reported to be decreased in animal models of inflammatory bowel disease (IBD). To investigate the differential expression of PXR in children with Crohn's disease, a type of IBD, RNA was extracted from archived intestinal biopsies from 18 children with Crohn's disease (CD) and 12 age- and sex-matched controls (aged 7-17yrs). The aim of this investigation was to compare the relative mRNA expression of PXR, cytochrome p450 3A4 (CYP3A4), and villin 1 (VIL1) (a marker of epithelial cell integrity) in the inflamed terminal ileum (TI) versus noninflamed …

Treatment And Prevention Of Human Rotavirus (Hrv) In Developing Countries: The Potential Of Avian Immunoglobulin Y, Christa Brown

Senior Honors Theses

Rotavirus gastroenteritis is a leading cause of childhood mortality, killing ~1400 children younger than five daily, primarily through severe diarrheal dehydration. Eighty-five percent of this mortality occurs in developing countries where rotavirus vaccines are not widely implemented and are only partially effective. In those countries, it has proven difficult to implement the recommended supportive therapies like oral rehydration therapy (ORT) on a wide scale due to lack of both medical infrastructure and private economic investment combined with cultural bias against ORT. IgY targeting human rotavirus (anti-HRV IgY) shows potential as a passive immunotherapy that reduces rotavirus-associated morbidity and mortality, augments …

Therapeutic Effect Of Melatonin On Pediatric Functional Dyspepsia: A Pilot Study., Katherine Zybach, Craig A. Friesen, Jennifer V. Schurman

Manuscripts, Articles, Book Chapters and Other Papers

AIM: To study the effectiveness of melatonin vs placebo in children with functional dyspepsia (FD).

METHODS: The study was conducted as a double blind, randomized, placebo controlled crossover trial. Subjects were aged 8-17 years and diagnosed with FD based on Rome III criteria. All subjects had failed to respond to 4 wk of acid suppression. Subjects receive a continuous two weeks of placebo and a continuous two weeks of melatonin in an order blinded to the participant and the study team. A Global Clinical Score was obtained to assess changes in abdominal pain. Pain was self-reported to be worse (grade …

Genomic Diversity Of Epec Associated With Clinical Presentations Of Differing Severity, Tracy H. Hazen, Michael S. Donnenberg, Sandra Panchalingam, Martin Antonio, Anowar Hossain, Inacio Mandomando, John Benjamin Ochieng, Shahida Qureshi, Farheen Quadri, Anita K. M. Zaidi

Department of Paediatrics and Child Health

Enteropathogenic Escherichia coli (EPEC) are diarrhoeagenic E. coli, and are a significant cause of gastrointestinal illness among young children in developing countries. Typical EPEC are identified by the presence of the bundle-forming pilus encoded by a virulence plasmid, which has been linked to an increased severity of illness, while atypical EPEC lack this feature. Comparative genomics of 70 total EPEC from lethal (LI), non-lethal symptomatic (NSI) or asymptomatic (AI) cases of diarrhoeal illness in children enrolled in the Global Enteric Multicenter Study was used to investigate the genomic differences in EPEC isolates obtained from individuals with various clinical outcomes. A …

Investigation Of Potential Early Histologic Markers Of Pediatric Inflammatory Bowel Disease, Julie A. Bass, Craig A. Friesen, Amanda D. Deacy, Nancy Neilan, Julia M. Bracken, Valentina Shakhnovich, Vivekanand Singh

Manuscripts, Articles, Book Chapters and Other Papers

© 2015 Bass et al. Background: Early manifestations of pediatric inflammatory bowel disease (IBD) can be relatively nonspecific. Initial mucosal biopsies may not be conclusive, delaying the diagnosis until subsequent biopsies demonstrate typical histologic features of IBD. We hypothesized that certain inflammatory cell types may be utilized as early histologic indicators of IBD in children. Methods: A retrospective analysis compared histologic findings from initially inconclusive or negative endoscopic studies in 22 patients who were subsequently diagnosed with IBD (after diagnostic endoscopy) to those of 20 comparison patients with functional abdominal pain matched for age, gender, and study type. A pediatric …

Pathogen-Specific Burdens Of Community Diarrhoea In Developing Countries: A Multisite Birth Cohort Study (Mal-Ed), Sadia Shakoor, Shahida Qureshi, Furqan Kabir, Anita K. M. Zaidi, Zulfiqar Ahmed Bhutta, Imran Ahmed, Didar Alam, Syed Asad Ali, Muneera Rasheed, Sajid Bashir Soofi, Ali Turab, Aisha Khizar Yousafzai

Department of Pathology and Laboratory Medicine

Background: Most studies of the causes of diarrhoea in low-income and middle-income countries have looked at severe disease in people presenting for care, and there are few estimates of pathogen-specific diarrhoea burdens in the community.
Methods: We undertook a birth cohort study with not only intensive community surveillance for diarrhoea but also routine collection of non-diarrhoeal stools from eight sites in South America, Africa, and Asia. We enrolled children within 17 days of birth, and diarrhoeal episodes (defined as maternal report of three or more loose stools in 24 h, or one loose stool with visible blood) were identified through …

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Rare Presentation Of Pancreatitis Secondary To Intussusception Of Duodenal Duplication Cyst, A Pediatric Case Report, Valentina Shakhnovich, Jennifer Colombo, Amita A. Desai, Shawn D. St Peter

Manuscripts, Articles, Book Chapters and Other Papers

No abstract provided.

Effects Of Whole Body Therapeutic Hypothermia On Gastrointestinal Morbidity And Feeding Tolerance In Infants With Hypoxic Ischemic Encephalopathy., Kimberly M. Thornton, Hongying Dai, Seth Septer, Joshua E. Petrikin

Manuscripts, Articles, Book Chapters and Other Papers

Objective. This retrospective cohort study evaluated the effects of whole body therapeutic hypothermia (WBTH) on gastrointestinal (GI) morbidity and feeding tolerance in infants with moderate-to-severe hypoxic ischemic encephalopathy (HIE). Study Design. Infants ≥ 35 weeks gestational age and ≥1800 grams birth weight with moderate-to-severe HIE treated from 2000 to 2012 were compared. 68 patients had documented strictly defined criteria for WBTH: 32 historical control patients did not receive WBTH (non-WBTH) and 36 cohort patients received WBTH. Result. More of the non-WBTH group infants never initiated enteral feeds (28% versus 6%; P = 0.02), never reached full enteral feeds (38% versus …

Household Food Access And Child Malnutrition: Results From The Eight-Country Mal-Ed Study, Zulfiqar Ahmed Bhutta, Maled Network Investigators, Anita K. M. Zaidi, Sajid Bashir Soofi, Ali Turab, Didar Alam, Shahida Qureshi, Aisha Khizar Yousafzai, Syed Asad Ali, Imran Ahmed, Sajad Memon, Muneera Rasheed

Woman and Child Health

Background: Stunting results from decreased food intake, poor diet quality, and a high burden of early childhood infections, and contributes to significant morbidity and mortality worldwide. Although food insecurity is an important determinant of child nutrition, including stunting, development of universal measures has been challenging due to cumbersome nutritional questionnaires and concerns about lack of comparability across populations. We investigate the relationship between household food access, one component of food security, and indicators of nutritional status in early childhood across eight country sites.
Methods: We administered a socioeconomic survey to 800 households in research sites in eight countries, including a …

Mast Cell Activation And Clinical Outcome In Pediatric Cholelithiasis And Biliary Dyskinesia., Craig A. Friesen, Nancy Neilan, James F. Daniel, Kim Radford, Jennifer Verrill Schurman, Ding-You Li, Linda Andre, Shawn D. St Peter, G W. Holcomb Iii

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: The current study was undertaken to determine the degree of activation of gallbladder mucosal mast cells, whether mast cell (MC) density or activation differ between patients with and without a positive clinical response to cholecystectomy, and whether either density or activation correlate with gallbladder emptying.

RESULTS: Fifteen biliary dyskinesia (BD) and 13 symptomatic cholelithiasis (CL) patients undergoing cholecystectomy were prospectively enrolled. Gallbladder wall MC density (by immunohistochemistry) and activation (by electron microscopy) were determined. Clinical response was evaluated 30 days post-cholecystectomy on a 5-point Likert-type scale. A complete or nearly complete clinical response was seen in 100% of CL …

Helicobacter Pylori Infection Rate Decreases In Symptomatic Children: A Retrospective Analysis Of 13 Years (1993-2005) From A Gastroenterology Clinic In West Virginia, Yoram Elitsur, Yulia Dementieva, Mary Rewalt, Zanda Lawrence

Pediatrics

Background: The rate of Helicobacter pylori is decreasing in the developed countries, but few long-term studies are available from the United States. We retrospectively assessed the annual H. pylori infection rate in symptomatic children seen in our clinic over a 13-year study period.

Study: A retrospective analysis of all children who had histologic diagnosis of H. pylori infection between January 1993 and December 2005 in our pediatric gastroenterology clinic was performed. The annual infection rate and the overall infection rate were calculated.

Results: A total of 1743 upper endoscopy reports were reviewed, of which 212 (12.1%) were diagnosed with H. …