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3. Isolation of Epithelial and Stromal Cells from Colon Tissues in Homeostasis and Under Inflammatory Conditions

Author

Clara Morral, Reem Ghinnagow, Tatiana Karakasheva, Yusen Zhou, Anusha Thadi, Ning Li, Benjamin Yoshor, Gloria Soto, Chia- Chen, Daniel Aleynick, Sarah Weinbrom, MaryKate Fulton, Yasin Uzun, Meenakshi Bewtra, Judith Kelsen, Chris Lengner, Kai Tan, Andy Minn, and Kathryn Hamilton

Subjects
Biology (General), QH301-705.5
Abstract

Inflammation of the gastrointestinal tract is a prevalent pathology in diseases such as inflammatory bowel disease (IBD). Currently, there are no therapies to prevent IBD, and available therapies to treat IBD are often sub-optimal. Thus, an unmet need exists to better understand the molecular mechanisms underlying intestinal tissue responses to damage and regeneration. The recent development of single-cell RNA (sc-RNA) sequencing-based techniques offers a unique opportunity to shed light on novel signaling pathways and cellular states that govern tissue adaptation or maladaptation across a broad spectrum of diseases. These approaches require the isolation of high-quality cells from tissues for downstream transcriptomic analyses. In the context of intestinal biology, there is a lack of protocols that ensure the isolation of epithelial and non-epithelial compartments simultaneously with high-quality yield. Here, we report two protocols for the isolation of epithelial and stromal cells from mouse and human colon tissues under inflammatory conditions. Specifically, we tested the feasibility of the protocols in a mouse model of dextran sodium sulfate (DSS)-induced colitis and in human biopsies from Crohn’s patients. We performed sc-RNA sequencing analysis and demonstrated that the protocol preserves most of the epithelial and stromal cell types found in the colon. Moreover, the protocol is suitable for immunofluorescence staining of surface markers for epithelial, stromal, and immune cell lineages for flow cytometry analyses. This optimized protocol will provide a new resource for scientists to study complex tissues such as the colon in the context of tissue damage and regeneration.Key features• This protocol allows the isolation of epithelial and stromal cells from colon tissues.• The protocol has been optimized for tissues under inflammatory conditions with compromised cell viability.• This protocol is suitable for experimental mouse models of colon inflammation and human biopsies.Graphical overviewGraphical representation of the main steps for the processing of colon tissue from dextran sodium sulfate (DSS)-treated mice (upper panel) and frozen biopsies from Crohn’s patients (lower panel)

Published
2023
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5. Very early-onset inflammatory bowel disease: Novel description in glycogen storage disease type Ia

Author

William B. Hannah, Ricardo C. Ong, Margarita Nieto Moreno, Surekha Pendyal, Monica Abdelmalak, Judith Kelsen, Nancy M. McGreal, and Priya S. Kishnani

Subjects
Glycogen storage disease type 1a, Very early-onset inflammatory bowel, Medicine (General), R5-920, Biology (General), QH301-705.5
Abstract

Although inflammatory bowel disease is a well-described feature of glycogen storage disease type Ib, it has been reported in only a small number of individuals with glycogen storage disease type Ia (GSDIa). We describe, to our knowledge, the first patient with GSDIa and very early-onset inflammatory bowel disease (VEO-IBD). Larger studies are needed to better understand this possible association, elucidate the mechanism of VEO-IBD in GSDIa, and inform management.

Published
2022
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6. T cell dynamics and response of the microbiota after gene therapy to treat X-linked severe combined immunodeficiency

Author

Erik L. Clarke, A. Jesse Connell, Emmanuelle Six, Nadia A. Kadry, Arwa A. Abbas, Young Hwang, John K. Everett, Casey E. Hofstaedter, Rebecca Marsh, Myriam Armant, Judith Kelsen, Luigi D. Notarangelo, Ronald G. Collman, Salima Hacein-Bey-Abina, Donald B. Kohn, Marina Cavazzana, Alain Fischer, David A. Williams, Sung-Yun Pai, and Frederic D. Bushman

Subjects
Medicine, Genetics, QH426-470
Abstract

Abstract Background Mutation of the IL2RG gene results in a form of severe combined immune deficiency (SCID-X1), which has been treated successfully with hematopoietic stem cell gene therapy. SCID-X1 gene therapy results in reconstitution of the previously lacking T cell compartment, allowing analysis of the roles of T cell immunity in humans by comparing before and after gene correction. Methods Here we interrogate T cell reconstitution using four forms of high throughput analysis. (1) Estimation of the numbers of transduced progenitor cells by monitoring unique positions of integration of the therapeutic gene transfer vector. (2) Estimation of T cell population structure by sequencing of the recombined T cell receptor (TCR) beta locus. (3) Metagenomic analysis of microbial populations in oropharyngeal, nasopharyngeal, and gut samples. (4) Metagenomic analysis of viral populations in gut samples. Results Comparison of progenitor and mature T cell populations allowed estimation of a minimum number of cell divisions needed to generate the observed populations. Analysis of microbial populations showed the effects of immune reconstitution, including normalization of gut microbiota and clearance of viral infections. Metagenomic analysis revealed enrichment of genes for antibiotic resistance in gene-corrected subjects relative to healthy controls, likely a result of higher healthcare exposure. Conclusions This multi-omic approach enables the characterization of multiple effects of SCID-X1 gene therapy, including T cell repertoire reconstitution, estimation of numbers of cell divisions between progenitors and daughter T cells, normalization of the microbiome, clearance of microbial pathogens, and modulations in antibiotic resistance gene levels. Together, these results quantify several aspects of the long-term efficacy of gene therapy for SCID-X1. This study includes data from ClinicalTrials.gov numbers NCT01410019, NCT01175239, and NCT01129544.

Published
2018
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7. Optimizing methods and dodging pitfalls in microbiome research

Author

Dorothy Kim, Casey E. Hofstaedter, Chunyu Zhao, Lisa Mattei, Ceylan Tanes, Erik Clarke, Abigail Lauder, Scott Sherrill-Mix, Christel Chehoud, Judith Kelsen, Máire Conrad, Ronald G. Collman, Robert Baldassano, Frederic D. Bushman, and Kyle Bittinger

Subjects
Metagenomics, 16S rRNA gene, Shotgun metagenomics, Environmental contamination, Methods, Study design, Microbial ecology, QR100-130
Abstract

Abstract Research on the human microbiome has yielded numerous insights into health and disease, but also has resulted in a wealth of experimental artifacts. Here, we present suggestions for optimizing experimental design and avoiding known pitfalls, organized in the typical order in which studies are carried out. We first review best practices in experimental design and introduce common confounders such as age, diet, antibiotic use, pet ownership, longitudinal instability, and microbial sharing during cohousing in animal studies. Typically, samples will need to be stored, so we provide data on best practices for several sample types. We then discuss design and analysis of positive and negative controls, which should always be run with experimental samples. We introduce a convenient set of non-biological DNA sequences that can be useful as positive controls for high-volume analysis. Careful analysis of negative and positive controls is particularly important in studies of samples with low microbial biomass, where contamination can comprise most or all of a sample. Lastly, we summarize approaches to enhancing experimental robustness by careful control of multiple comparisons and to comparing discovery and validation cohorts. We hope the experimental tactics summarized here will help researchers in this exciting field advance their studies efficiently while avoiding errors.

Published
2017
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8. 2092 A multicenter study of fecal microbiota transplantation for Clostridium difficile infection in children

Author

Maribeth R. Nicholson, Erin Alexander, Mark Bartlett, Penny Becker, Zev Davidovics, Elizabeth E. Knackstedt, Michael Docktor, Michael Dole, Grace Felix, Jonathan Gisser, Suchitra Hourigan, Kyle Jensen, Jess Kaplan, Judith Kelsen, Melissa Kennedy, Sahil Khanna, McKenzie Leier, Jeffery Lewis, Ashley Lodarek, Sonia Michail, Paul Mitchell, Maria Oliva‐Hemker, Tiffany Patton, Karen Queliza, Namita Singh, Aliza Solomon, David Suskind, Steven Werlin, Richard Kellermayer, and Stacy Kahn

Subjects
Medicine
Abstract

OBJECTIVES/SPECIFIC AIMS: Clostridium difficile infection (CDI) is the most common cause of antibiotic-associated diarrhea and an increasingly common infection in children in both hospital and community settings. Between 20% and 30% of pediatric patients will have a recurrence of symptoms in the days to weeks following an initial infection. Multiple recurrences have been successfully treated with fecal microbiota transplantation (FMT), though the body of evidence in pediatric patients is limited primarily to case reports and case series. The goal of our study was to better understand practices, success, and safety of FMT in children as well as identify risk factors associated with a failed FMT in our pediatric patients. METHODS/STUDY POPULATION: This multicenter retrospective analysis included 373 patients who underwent FMT for CDI between January 1, 2006 and January 1, 2017 from 18 pediatric centers. Demographics, baseline characteristics, FMT practices, C. difficile outcomes, and post-FMT complications were collected through chart abstraction. Successful FMT was defined as no recurrence of CDI within 60 days after FMT. Of the 373 patients in the cohort, 342 had known outcome data at two months post-FMT and were included in the primary analysis evaluating risk factors for recurrence post-FMT. An additional six patients who underwent FMT for refractory CDI were excluded from the primary analysis. Unadjusted analysis was performed using Wilcoxon rank-sum test, Pearson χ2 test, or Fisher exact test where appropriate. Stepwise logistic regression was utilized to determine independent predictors of success. RESULTS/ANTICIPATED RESULTS: The median age of included patients was 10 years (IQR; 3.0, 15.0) and 50% of patients were female. The majority of the cohort was White (89.0%). Comorbidities included 120 patients with inflammatory bowel disease (IBD) and 14 patients who had undergone a solid organ or stem cell transplantation. Of the 336 patients with known outcomes at two months, 272 (81%) had a successful outcome. In the 64 (19%) patients that did have a recurrence, 35 underwent repeat FMT which was successful in 20 of the 35 (57%). The overall success rate of FMT in preventing further episodes of CDI in the cohort with known outcome data was 87%. Unadjusted predictors of a primary FMT response are summarized. Based on stepwise logistic regression modeling, the use of fresh stool, FMT delivery via colonoscopy, the lack of a feeding tube, and a lower number of CDI episodes before undergoing FMT were independently associated with a successful outcome. There were 20 adverse events in the cohort assessed to be related to FMT, 6 of which were felt to be severe. There were no deaths assessed to be related to FMT in the cohort. DISCUSSION/SIGNIFICANCE OF IMPACT: The overall success of FMT in pediatric patients with recurrent or severe CDI is 81% after a single FMT. Children without a feeding tube, who receive an early FMT, FMT with fresh stool, or FMT via colonoscopy are less likely to have a recurrence of CDI in the 2 months following FMT. This is the first large study of FMT for CDI in a pediatric cohort. These findings, if confirmed by additional prospective studies, will support alterations in the practice of FMT in children.

Published
2018
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9. Multicenter Cohort Study of Infliximab Pharmacokinetics and Therapy Response in Pediatric Acute Severe Ulcerative Colitis

Author

Kaitlin G. Whaley, Ye Xiong, Rebekah Karns, Jeffrey S. Hyams, Subra Kugathasan, Brendan M. Boyle, Thomas D. Walters, Judith Kelsen, Neal LeLeiko, Jason Shapiro, Amanda Waddell, Sejal Fox, Ramona Bezold, Stephanie Bruns, Robin Widing, Yael Haberman, Margaret H. Collins, Tomoyuki Mizuno, Phillip Minar, Geert R. D’Haens, Lee A. Denson, Alexander A. Vinks, Michael J. Rosen, Gastroenterology and Hepatology, and AGEM - Amsterdam Gastroenterology Endocrinology Metabolism

Subjects
Hepatology, Trough Serum Concentration, Anti-TNF Biological Drug, Inflammatory Bowel Disease, Gastroenterology
Abstract

Background & aims: We aimed to model infliximab (IFX) pharmacokinetics (PK) in pediatric acute severe ulcerative colitis (ASUC) and assess the association between PK parameters, including drug exposure, and clinical response. Methods: We studied a multicenter prospective cohort of hospitalized children initiating IFX for ASUC or IBD-unclassified. Serial IFX serum concentrations over 26 weeks were used to develop a PK model. We tested the association of PK parameter estimates with day 7 clinical response, week 8 clinical remission, week 26 corticosteroid-free clinical remission (CSF-CR) (using the Pediatric Ulcerative Colitis Activity Index), and colectomy-free survival. Results: Thirty-eight participants received IFX (median initial dose, 9.9 mg/kg). Day 7 clinical response, week 8 clinical remission, and week 26 CSF-CR occurred in 71%, 55%, and 43%, respectively. Albumin, C-reactive protein, white blood cell count, platelets, weight, and antibodies to IFX were significant covariates incorporated into a PK model. Week 26 non-remitters exhibited faster IFX clearance than remitters (P =.013). However, cumulative IFX exposure did not differ between clinical response groups. One (2.7%) and 4 (10.8%) participants underwent colectomy by week 26 and 2 years, respectively. Day 3 IFX clearance >0.02 L/h was associated with colectomy (hazard ratio, 58.2; 95% confidence interval, 6.0–568.6; P

Published
2022

10. Single cell RNA sequencing of a biopsy specimen v1

Author

Tatiana Karakasheva, Anusha Thadi, Ning Li, Yasin Uzun, Chia-Hui Chen, Daniel Aleynick, Shraimr not provided, Sarah Weinbrom, Gloria Soto, Judith Kelsen, Chris Lengner, Kai Tan, and Kathryn E Hamilton

Abstract

This protocol describes dissociation of a human intestinal biopsy tissue into single cells, followed by depletion of dead cells via annexin V MACS beads. The outcome is a single-cell suspension with viability ≥ 90% that is used for single-cell sequencing or establishemt of enteroid/colonoid culture.

Published
2021
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11. ANTI-TNF PHARMACOKINETICS AND RESPONSE TO THERAPY IN PEDIATRIC ACUTE SEVERE ULCERATIVE COLITIS (THE ARCH STUDY)

Author

Kaitlin Whaley, Vivian Xiong, Rebekah Karns, Jeffrey Hyams, Subra Kugathasan, Brendan Boyle, Tom Walters, Judith Kelsen, Neal LeLeiko, Jason Shapiro, Amanda Waddell, Sejal Fox, Yael Haberman, Phillip Minar, Lee Denson, Geert D’Haens, Alexander Vinks, and Michael Rosen

Subjects
Gastroenterology, Immunology and Allergy
Abstract

Background and Aims 25% of children hospitalized with acute severe ulcerative colitis (ASUC) rescued with infliximab (IFX) at labeled dosing undergo a colectomy prior to discharge. Our aim was to determine whether IFX pharmacokinetics (PK) are associated with treatment response in pediatric ASUC. Methods We prospectively enrolled hospitalized pediatric patients initiating IFX for ASUC or IBD-U (PUCAI ≥65) at 7 North American centers and followed for 26 weeks in this pilot and feasibility cohort study. Serial IFX levels (Prometheus Biosciences, Inc.) were obtained and individual PK parameter estimates, such as volume of distribution, clearance (CL), elimination half-life (T1/2) and IFX exposure (area under the concentration-time curve) were estimated using Bayesian methodology. The primary outcome was Day 7 clinical response (CR-D7, PUCAI Results 38 participants (mean age 14.5 years, 50% female, 95% UC, 87% extensive/pancolitis) were treated with IFX at a mean higher than labeled dosing of 9.9 [9.3,10.3] mg/kg, and 16% received an early second dose 4–6 days after the first infusion. CR-D7, CR-W8, and CFR-W26 were achieved in 71%, 55%, and 41%, respectively. Only one participant (2.7%) underwent colectomy by week 26. Using 304 IFX level measurements, we developed a novel pediatric population PK model for IFX in ASUC that incorporated albumin, antibodies to IFX, CRP, and height to characterize the PK profile for participants. The median IFX T1/2 was 5.8 [4.2,7.0] days at Day 7 and lengthened to 7.4 [5.4,8.4] days by Week 26 (P=0.014), but notably remained below the median 10.8 [8.6, 15.4] days reported in a randomized controlled trial of IFX for moderate to severe pediatric UC (Fig. 1). IFX exposure was not associated with CR-D7, CR-W8, or CSR-W26. More rapid IFX CL at Week 26 was significantly associated with inability to achieve CFR-W26 (P=.013). This finding was in line with a higher, but not statistically significant, median trough IFX level nearest Week 26 in those with (19.5 [13.6, 30.3]) versus without (14.2 [6.0, 21.3] μg/ml) CFR-W26 (P=.13) (Fig. 2). Conclusion At the higher than standard IFX dosing used to treated children with ASUC in this observational study, we observed a lower colectomy rate compared to prior studies but did not observe a positive association between IFX exposure and clinical outcomes. Albumin, CRP, height, and ATI were associated with IFX PK and incorporated into a new pediatric ASUC PK model. Initial 10 mg/kg IFX dosing may be sufficient to optimize early outcomes in pediatric ASUC. Additional studies are needed to determine if sustained intensification of maintenance IFX regimens can overcome persistent rapid clearance and improve later outcomes in pediatric ASUC.

Published
2021
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12. Autoinflammatory diseases predominantly affecting the gastrointestinal tract

Author

Kaan Boztug and Judith Kelsen

Subjects
Gastrointestinal tract, Gastrointestinal disease, business.industry, medicine.medical_treatment, fungi, medicine, food and beverages, Identification (biology), Bioinformatics, medicine.disease, business, Targeted therapy
Abstract

Autoinflammatory diseases can present in a myriad of ways, affecting nearly any organ. This chapter focuses on those autoinflammatory conditions where the gastrointestinal tract is often involved. These children can have severe and refractory gastrointestinal disease. Over the last decade, the advent and widespread availability of next generation sequencing technologies has allowed identification of these monogenic defects (de Ridder et al., 2007; Biank et al., 2007; Begue et al., 2011). Identification of the causative defect is critical, as it can lead to targeted therapy and in some cases curative approaches.

Published
2020
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13. Contributors

Author

Michael S. Abers, Daria V. Babushok, Mark Ballow, Bertrand Boisson, Vincent Robert Bonagura, Francisco A. Bonilla, João Bosco de Oliveira Filho, Kaan Boztug, Lori Broderick, Manish J. Butte, Fabio Candotti, Jean-Laurent Casanova, Shanmuganathan Chandrakasan, Antonio Condino-Neto, Yanick J. Crow, Charlotte Cunningham-Rundles, Virgil A.S.H. Dalm, Adriana A. de Jesus, Emma de Maio, Geneviève de Saint Basile, Esther de Vries, Inderjeet Dokal, Christopher J.A. Duncan, A. Durandy, Stephan Ehl, Amos Etzioni, Polly J. Ferguson, Thomas A. Fleisher, Lisa R. Forbes-Satter, Michael M. Frank, Alexandra F. Freeman, Marie-Louise Frémond, John W. Frew, Mathieu Fusaro, Eleonora Gambineri, Rebecca D. Ganetzky, Andrew R. Gennery, Raphaela Goldbach-Mansky, Amy C. Goldstein, John M. Graham, Stephanie E. Gupton, Elie Haddad, Sophie Hambleton, Eric P. Hanson, Jennifer Heimall, Miep Helfrich, Sarah E. Henrickson, Steven M. Holland, Amy P. Hsu, Soma Jyonouchi, Sara Kashef, Judith Kelsen, Maya Khalil, Christoph Klein, Lisa Kobrynski, Donald B. Kohn, S. Kracker, James G. Krueger, Pascal M. Lavoie, Heather K. Lehman, Jennifer W. Leiding, Michael J. Lenardo, Ofer Levy, Allison Pecha Lim, Michail S. Lionakis, Andrea Lisco, Vassilios Lougaris, Saul O. Lugo Reyes, M. Louise Markert, Rebecca A. Marsh, Elizabeth A. McCarthy, Isabelle Meyts, Cinzia Milito, Joshua D. Milner, Jeffrey E. Ming, Despina Moshous, Ludmila Müller, Kristina Navrazhina, Kim E. Nichols, Luigi D. Notarangelo, Eric Oksenhendler, Jordan S. Orange, Roberto Paganelli, Graham Pawelec, Tancredi Massimo Pentimalli, Elena E. Perez, Capucine Picard, Alessandro Plebani, Oscar Porras, Amanda C. Przespolewski, Anne Puel, Federica Pulvirenti, Isabella Quinti, Nima Rezaei, Ger T. Rijkers, David Walter Rosenthal, Sergio D. Rosenzweig, Brahm H. Segal, Mikko R.J. Seppänen, Irini Sereti, Anna Shcherbina, Cristina Sobacchi, Jacqueline D. Squire, Polina Stepensky, Helen C. Su, Kathleen E. Sullivan, Troy R. Torgerson, Gulbu Uzel, Mirjam van der Burg, Anna Villa, Jean-Pierre de Villartay, Klaus Warnatz, Richard L. Wasserman, Corry M.R. Weemaes, Joyce E. Yu, Shen-Ying Zhang, and John B. Ziegler

Published
2020
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14. A Simple Endoscopic Score Modified for the Upper Gastrointestinal Tract in Crohn's Disease [UGI-SES-CD]: A Report From the ImageKids Study

Author

Martin Wasser, Osnat Konen, David R Mack, Bob Baldassano, Oren Ledder, Maarten H. Lequin, Jorge Davila, J. Hyams, Johanna C. Escher, Tony Otley, Lissy de Ridder, Shehzad Ahmed Saeed, Emily J. Stenhouse, Daniel A. Lemberg, Victor Navas, Jessie M. Hulst, Eric I Benchimol, Ted Denson, Jared Silverstein, Kathy O'Brien, Anat Ilivitzki, Judith Kelsen, Izabela Herman-Sucharska, Frank M. Ruemmele, Neal Leleiko, Lucia Riaza, Sibylle Koletzko, Elhamy Bekhit, Raanan Shamir, David J. Grand, Doug Moote, Daniel Moses, Sudha Anupindi, Richard K. Russell, Dan Turner, Laureline Berteloo, and Michal Amitai

Subjects
Male, Crohn’s disease, medicine.medical_specialty, paediatric, Adolescent, Gastroenterology, Severity of Illness Index, 03 medical and health sciences, 0302 clinical medicine, Crohn Disease, Predictive Value of Tests, Internal medicine, medicine, Upper gastrointestinal, Humans, Clinical significance, Endoscopy, Digestive System, Prospective Studies, endoscopy, Child, Antrum, Crohn's disease, medicine.diagnostic_test, business.industry, Age Factors, General Medicine, medicine.disease, Magnetic resonance enterography, Faecal calprotectin, Endoscopy, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Child, Preschool, Duodenum, 030211 gastroenterology & hepatology, Female, business
Abstract

Objective: There is no standardized endoscopic description of upper gastrointestinal [UGI] disease in Crohn's disease [CD]. We prospectively applied the Simple Endoscopic Score for CD [SES-CD] to the UGI tract as a planned sub-study of the multicentre prospective ImageKids study. We aimed to assess the utility of the UGI-SES-CD and its clinical significance in paediatric CD. Design: Patients underwent an oesophagogastroduodenoscopy [EGD], ileocolonoscopy, and magnetic resonance enterography [MRE] with explicit clinical data recorded. SES-CD was scored at each region [oesophagus, stomach body, antrum, and duodenum]. Half of the patients were followed for 18 months, when a repeat MRE was performed. Results: A total of 202 children were included 56% males, mean age 11.5 +/- 3.2 years, median weighted Paediatric Crohn's Disease Activity Index [wPCDAI 25]). UGI-SES-CD score ranged 0-17, with 95 [47%] having a UGI-SES-CD = 1; no narrowing was detected. UGI-SES-CD = 1 was associated with higher: wPCDAI [32.5 vs 20; p = 0.03]; Physician's Global Assessment [PGA] of inflammation (45 mm visual analogue score [VAS] vs 30 mm VAS; p = 0.04); ileocolonoscopic SES-CD [10 vs 7; p = 0.004], faecal calprotectin [717 mu g/g vs 654 mu/g; p= 0.046]; and radiological global assessment of damage by MRE [7 mm VAS vs 0; p = 0.04]. In all, 81 patients were followed for 18 months and no association was identified between initial UGI SES-CD and markers of disease course such as surgery, MRE assessment, or treatment escalation. Conclusion: UGI-SES-CD is an easily reported objective scoring system and is associated with a more severe disease phenotype but not with disease course.

Published
2018

15. 2346. Cost Savings Associated with Implementation of Clinical Decision Support for Clostridiodes difficile Testing

Author

Eric Shelov, Cindy L Hoegg, Judith Kelsen, Ana Maria Cardenas, Handy K Lori, Katie L Williams, Talene A Metjian, and Molly Hayes

Subjects
medicine.medical_specialty, Isolation (health care), business.industry, Best practice, Clinical decision support system, Discontinuation, Cost savings, Abstracts, Infectious Diseases, Oncology, Poster Abstracts, Medicine, Vancomycin, Antibiotic use, business, Intensive care medicine, Personal protective equipment, medicine.drug
Abstract

Background Clinical decision support for Clostridioides difficile infection (CDI) diagnostics reduces inappropriate testing, leading to decreased need for isolation and antibiotic use. Our institution utilized manual discontinuation by laboratory staff of CDI testing for inappropriate specimens, including formed stool and age < 1 year. We aimed to assess the financial impact of instituting a CDI best practice alert at a quaternary care children’s hospital. Methods A multidisciplinary team mapped inappropriate testing criteria identified from literature review with discrete fields in our electronic health record (EHR, EpicCare) to design an alert. The exclusion criteria identified included: (1) age < 1 year; (2) positive C. difficile test within past 14 days; (3) less than or equal to 3 unformed stools in past 24 hours; (4) current receipt of CDI-directed therapy; or (5) laxative use or barium exposure in prior 48 hours. 6 months of data prior to implementation were reviewed to estimate impact of the alert. At implementation, any exclusion criteria detected in the EHR at the time of order entry triggered an alert to deter CDI testing. Cost estimates for averted tests (Quick Check Complete Assay/Illumigene) included cost of test ($50), cost of isolation/personal protective equipment ($159/day), and cost of treatment with oral vancomycin in false-positives ($2250/treatment course). Results In a 6-month pre-implementation period, 586 tests for CDI were ordered; of which, 23% were identified by our criteria as inappropriate. During the first 3 months of alert implementation, 256 tests were ordered, of which 105 (41%) caused the alert to fire. Of those, 56 tests were not ordered, for a 22% reduction in testing. Laboratory staff continued to manually stop tests not meeting criteria, such as patient age Conclusion Implementation of an alert for select patients using a bioinformatics algorithm reduced inappropriate CDI testing. Clinical decision support for CDI can lead to substantial cost savings for both antibiotic use and isolation precautions. Disclosures All authors: No reported disclosures.

Published
2019
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16. Reply

Author

Scott W. Canna, Charlotte Girard, Louise Malle, Adriana de Jesus, Neil Romberg, Judith Kelsen, Lea F. Surrey, Pierre Russo, Andrew Sleight, Eduardo Schiffrin, Cem Gabay, Raphaela Goldbach-Mansky, and Edward M. Behrens

Subjects
Immunology, Mutation, Immunology and Allergy, Intercellular Signaling Peptides and Proteins, Carrier Proteins
Published
2017

18. Contributors

Author

Jon S. Abramson, Mark J. Abzug, John J. Aiken, H. Hesham A-kader, Cezmi A. Akdis, Harold Alderman, Ramin Alemzadeh, Evaline A. Alessandrini, Omar Ali, Namasivayam Ambalavanan, Karl E. Anderson, Peter M. Anderson, Kelly K. Anthony, Alia Y. Antoon, Stacy P. Ardoin, Carola A.S. Arndt, Stephen S. Arnon, Stephen C. Aronoff, David M. Asher, Barbara L. Asselin, Joann L. Ater, Dan Atkins, Erika F. Augustine, Marilyn Augustyn, Ellis D. Avner, Parvin H. Azimi, Carlos A. Bacino, Robert N. Baldassano, Christina Bales, William F. Balistreri, Robert S. Baltimore, Manisha Balwani, Shahida Baqar, Christine E. Barron, Dorsey M. Bass, Mark L. Batshaw, Richard E. Behrman, Michael J. Bell, John W. Belmont, Daniel K. Benjamin, Michael J. Bennett, Daniel Bernstein, Jatinder Bhatia, Zulfiqar Ahmed Bhutta, Leslie G. Biesecker, James Birmingham, Samra S. Blanchard, Ronald Blanton, Archie Bleyer, C.D.R. Lynelle M. Boamah, Steven R. Boas, Thomas F. Boat, Walter Bockting, Mark Boguniewicz, Daniel J. Bonthius, Laurence A. Boxer, Amanda M. Brandow, David Branski, David T. Breault, Rebecca H. Buckley, Cynthia Etzler Budek, E. Stephen Buescher, Gale R. Burstein, Amaya Lopez Bustinduy, Mitchell S. Cairo, Bruce M. Camitta, Angela Jean Peck Campbell, Rebecca G. Carey, Waldemar A. Carlo, Robert B. Carrigan, Mary T. Caserta, Ellen Gould Chadwick, Lisa J. Chamberlain, Jennifer I. Chapman, Ira M. Cheifetz, Wassim Chemaitilly, Sharon F. Chen, Yuan-Tsong Chen, Russell W. Chesney, Jennifer A. Chiriboga, Robert D. Christensen, Andrew Chu, Michael J. Chusid, Theodore J. Cieslak, Jeff A. Clark, Thomas G. Cleary, John David Clemens, Joanna S. Cohen, Mitchell B. Cohen, Pinchas Cohen, Michael Cohen-Wolkowiez, Robert A. Colbert, F. Sessions Cole, Joanna C.M. Cole, John L. Colombo, Amber R. Cooper, Ronina A. Covar, Barbara Cromer, James E. Crowe, Natoshia Raishevich Cunningham, Steven J. Czinn, Toni Darville, Robert S. Daum, Richard S. Davidson, H. Dele Davies, Peter S. Dayan, Michael R. DeBaun, Guenet H. Degaffe, David R. DeMaso, Mark R. Denison, Arlene E. Dent, Nirupama K. DeSilva, Robert J. Desnick, Gabrielle deVeber, Esi Morgan DeWitt, Chetan Anil Dhamne, Anil Dhawan, Harry Dietz, Lydia J. Donoghue, Patricia A. Donohoue, Mary K. Donovan, John P. Dormans, Daniel A. Doyle, Jefferson Doyle, Stephen C. Dreskin, Denis S. Drummond, Howard Dubowitz, J. Stephen Dumler, Janet Duncan, Paula M. Duncan, LauraLe Dyner, Michael G. Earing, Elizabeth A. Edgerton, Marie Egan, Jack S. Elder, Sara B. Eleoff, Dianne S. Elfenbein, Stephen C. Eppes, Michele Burns Ewald, Jessica K. Fairley, Susan Feigelman, Marianne E. Felice, Eric I. Felner, Edward Fels, Thomas Ferkol, Jonathan D. Finder, Kristin N. Fiorino, David M. Fleece, Patricia M. Flynn, Joel A. Forman, Michael M. Frank, Melvin H. Freedman, Melissa Frei-Jones, Jared E. Friedman, Sheila Gahagan, Paula Gardiner, Luigi Garibaldi, Gregory M. Gauthier, Abraham Gedalia, Matthew J. Gelmini, Michael A. Gerber, K. Michael Gibson, Mark Gibson, Francis Gigliotti, Walter S. Gilliam, Janet R. Gilsdorf, Charles M. Ginsburg, Frances P. Glascoe, Donald A. Goldmann, Denise M. Goodman, Marc H. Gorelick, Gary J. Gosselin, Jane M. Gould, Olivier Goulet, Dan M. Granoff, Michael Green, Thomas P. Green, Larry A. Greenbaum, Marie Michelle Grino, Andrew B. Grossman, David C. Grossman, Alfredo Guarino, Lisa R. Hackney, Gabriel G. Haddad, Joseph Haddad, Joseph F. Hagan, Scott B. Halstead, Margaret R. Hammerschlag, Aaron Hamvas, James C. Harris, Mary E. Hartman, David B. Haslam, Fern R. Hauck, Gregory F. Hayden, Jacqueline T. Hecht, Sabrina M. Heidemann, J. Owen Hendley, Fred M. Henretig, Gloria P. Heresi, Andrew D. Hershey, Cynthia E. Herzog, Jessica Hochberg, Lauren D. Holinger, Jeffrey D. Hord, B. David Horn, William A. Horton, Harish S. Hosalkar, Hidekazu Hosono, Peter J. Hotez, Michelle S. Howenstine, Heather G. Huddleston, Vicki Huff, Denise Hug, Winston W. Huh, Carl E. Hunt, Anna Klaudia Hunter, Patricia Ibeziako, Richard F. Jacobs, Peter Jensen, Hal B. Jenson, Chandy C. John, Michael V. Johnston, Richard B. Johnston, Bridgette L. Jones, James F. Jones, Marsha Joselow, Anupama Kalaskar, Linda Kaljee, Deepak Kamat, Alvina R. Kansra, Sheldon L. Kaplan, Emily R. Katz, James W. Kazura, Virginia Keane, Gregory L. Kearns, Desmond P. Kelly, Judith Kelsen, Kathi J. Kemper, Melissa Kennedy, Eitan Kerem, Joseph E. Kerschner, Seema Khan, Young-Jee Kim, Charles H. King, Stephen L. Kinsman, Adam Kirton, Priya S. Kishnani, Nora T. Kizer, Martin B. Kleiman, Bruce L. Klein, Bruce S. Klein, Michael D. Klein, Robert M. Kliegman, William C. Koch, Patrick M. Kochanek, Eric Kodish, Stephan A. Kohlhoff, Elliot J. Krane, Peter J. Krause, Richard E. Kreipe, Steven E. Krug, John F. Kuttesch, Jennifer M. Kwon, Catherine S. Lachenauer, Stephan Ladisch, Stephen LaFranchi, Oren Lakser, Marc B. Lande, Philip J. Landrigan, Gregory L. Landry, Wendy G. Lane, Philip S. LaRussa, Brendan Lee, Chul Lee, K. Jane Lee, J. Steven Leeder, Rebecca K. Lehman, Michael J. Lentze, Norma B. Lerner, Steven Lestrud, Donald Y.M. Leung, Chris A. Liacouras, Susanne Liewer, Andrew H. Liu, Stanley F. Lo, Franco Locatelli, Sarah S. Long, Anna Lena Lopez, Steven V. Lossef, Jennifer A. Lowry, Kerith Lucco, G. Reid Lyon, Prashant V. Mahajan, Akhil Maheshwari, Joseph A. Majzoub, Asim Maqbool, Ashley M. Maranich, Mona Marin, Joan C. Marini, Morri Markowitz, Kevin P. Marks, Stacene R. Maroushek, Wilbert H. Mason, Christopher Mastropietro, Kimberlee M. Matalon, Reuben K. Matalon, Robert Mazor, Susanna A. McColley, Margaret M. McGovern, Heather S. McLean, Rima McLeod, Peter C. Melby, Joseph John Melvin, Diane F. Merritt, Ethan A. Mezoff, Marian G. Michaels, Alexander G. Miethke, Mohamad A. Mikati, Henry Milgrom, E. Kathryn Miller, Jonathan W. Mink, Grant A. Mitchell, Robert R. Montgomery, Joseph G. Morelli, Anna-Barbara Moscicki, Hugo W. Moser, Kathryn D. Moyer, James R. Murphy, Timothy F. Murphy, Thomas S. Murray, Mindo J. Natale, William A. Neal, Jayne Ness, Kathleen A. Neville, Mary A. Nevin, Jane W. Newburger, Peter E. Newburger, Linda S. Nield, Zehava Noah, Lawrence M. Nogee, Robert L. Norris, Stephen K. Obaro, Makram Obeid, Theresa J. Ochoa, Katherine A. O'Donnell, Robin K. Ohls, Jean-Marie Okwo-Bele, Keith T. Oldham, Scott E. Olitsky, John Olsson, Susan R. Orenstein, Walter A. Orenstein, Judith A. Owens, Charles H. Packman, Michael J. Painter, Priya Pais, Cynthia G. Pan, Vijay Pannikar, Diane E. Pappas, Anjali Parish, John S. Parks, Laura A. Parks, Maria Jevitz Patterson, Pallavi P. Patwari, Timothy R. Peters, Larry K. Pickering, Misha L. Pless, Laura S. Plummer, Craig C. Porter, Dwight A. Powell, David T. Price, Charles G. Prober, Linda Quan, Elisabeth H. Quint, C. Egla Rabinovich, Leslie J. Raffini, Denia Ramirez-Montealegre, Giuseppe Raviola, Ann M. Reed, Harold L. Rekate, Megan E. Reller, Gary Remafedi, Jorge D. Reyes, Geoffrey Rezvani, Iraj Rezvani, A. Kim Ritchey, Frederick P. Rivara, Angela Byun Robinson, Luise E. Rogg, Genie E. Roosevelt, David R. Rosenberg, Melissa Beth Rosenberg, David S. Rosenblatt, Cindy Ganis Roskind, Mary M. Rotar, Ranna A. Rozenfeld, Sarah Zieber Rush, Colleen A. Ryan, H.P.S. Sachdev, Ramesh C. Sachdeva, Mustafa Sahin, Robert A. Salata, Denise A. Salerno, Edsel Maurice T. Salvana, Hugh A. Sampson, Thomas J. Sandora, Tracy Sandritter, Wudbhav N. Sankar, Ajit Ashok Sarnaik, Ashok P. Sarnaik, Harvey B. Sarnat, Minnie M. Sarwal, Mary Saunders, Laura E. Schanberg, Mark R. Schleiss, Nina F. Schor, Bill J. Schroeder, Robert L. Schum, Gordon E. Schutze, Daryl A. Scott, J. Paul Scott, Theodore C. Sectish, George B. Segel, Kriti Sehgal, Ernest G. Seidman, Janet R. Serwint, Dheeraj Shah, Raanan Shamir, Bruce K. Shapiro, Richard J. Shaw, Bennett A. Shaywitz, Sally E. Shaywitz, Meera Shekar, Elena Shephard, Philip M. Sherman, Benjamin L. Shneider, Scott H. Sicherer, Richard Sills, Mark D. Simms, Eric A.F. Simões, Thomas L. Slovis, P. Brian Smith, Mary Beth F. Son, Laura Stout Sosinsky, Joseph D. Spahn, Mark A. Sperling, Robert Spicer, David A. Spiegel, Helen Spoudeas, Jürgen Spranger, Rajasree Sreedharan, Raman Sreedharan, Shawn J. Stafford, Margaret M. Stager, Sergio Stagno, Virginia A. Stallings, Lawrence R. Stanberry, Charles A. Stanley, Bonita F. Stanton, Jeffrey R. Starke, Merrill Stass-Isern, Barbara W. Stechenberg, Leonard D. Stein, William J. Steinbach, Nicolas Stettler, Barbara J. Stoll, Gregory A. Storch, Ronald G. Strauss, Frederick J. Suchy, Karen Summar, Moira Szilagyi, Norman Tinanoff, James K. Todd, Lucy S. Tompkins, Richard L. Tower, Riccardo Troncone, Amanda A. Trott, David G. Tubergen, David A. Turner, Ronald B. Turner, Christina Ullrich, George F. Van Hare, Jakko van Ingen, Heather A. Van Mater, Dick van Soolingen, Scott K. Van Why, Pankhuree Vandana, Douglas Vanderbilt, Jon A. Vanderhoof, Andrea Velardi, Elliott Vichinsky, Linda A. Waggoner-Fountain, Steven G. Waguespack, David M. Walker, Heather J. Walter, Stephanie Ware, Kimberly Danieli Watts, Ian M. Waxman, Debra E. Weese-Mayer, Kathryn Weise, Martin E. Weisse, Lawrence Wells, Jessica Wen, Steven L. Werlin, Michael R. Wessels, Ralph F. Wetmore, Randall C. Wetzel, Isaiah D. Wexler, Perrin C. White, John V. Williams, Rodney E. Willoughby, Samantha L. Wilson, Glenna B. Winnie, Paul H. Wise, Laila Woc-Colburn, Joanne Wolfe, Cynthia J. Wong, Laura L. Worth, Joseph L. Wright, Peter F. Wright, Terry W. Wright, Eveline Y. Wu, Anthony Wynshaw-Boris, Nada Yazigi, Ram Yogev, Marc Yudkoff, Peter E. Zage, Anita K.M. Zaidi, Lonnie K. Zeltzer, Maija H. Zile, Peter Zimmer, and Barry Zuckerman

Published
2011
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19. 35 Imaging of Inflammatory Bowel Disease in Children

Author

Petar Mamula, Sudha A. Anupindi, Rama S. Ayyala, Judith Kelsen, and Kimberly E. Applegate

Subjects
medicine.medical_specialty, business.industry, Disease, medicine.disease, Inflammatory bowel disease, Ulcerative colitis, law.invention, Primary sclerosing cholangitis, Bowel obstruction, Refractory, Capsule endoscopy, law, Medicine, Radiology, Cancer Induction, business
Abstract

Children with clinically suspected IBD should have both upper and lower endoscopies as part of the initial workup (strong evidence). Fluoroscopic small bowel follow-through (SBFT) studies are typically performed as part of the initial diagnosis (limited evidence). Wireless capsule endoscopy (WCE) is a safe, moderately sensitive test for the detection of small bowel inflammatory changes and should be utilized in patients without small bowel obstruction and when other diagnostic small bowel exams are negative. However, the specificity and positive predictive value need to be further established (limited evidence). MRI is superior to CT and is the preferred initial diagnostic and follow-up imaging exam of perirectal and perianal disease in Crohn’s disease (CD) patients (moderate–strong evidence). About 70–80% of CD patients and 30–40% of UC patients will require surgery for disease refractory to medical therapy, or severe disease with complications, or risk of malignancy (UC) (moderate evidence). Repeat imaging with SBFT and CT results in significant ionizing radiation exposure and risk of later cancer induction so that alternative imaging methods, MRI and US, should be used (limited evidence).

Published
2011
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22. O-017 Digenic Inheritance of Primary Immunodeficiency Gene Variants Identified by Whole Exome Sequence in Very Early Onset IBD Patients

Author

Judith, Kelsen, primary, Christopher, Moran, additional, Noor, Dawany, additional, Helen, Pauly-Hubbard, additional, Eric, Rapport, additional, Petar, Mamula, additional, David, Piccoli, additional, Harland, Winter, additional, Mark, Daly, additional, Gregory, Sonnenberg, additional, David, Artis, additional, Robert, Baldassano, additional, and Marcella, Devoto, additional

Published
2014
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