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Integrated Analysis of Biopsies from Inflammatory Bowel Disease Patients Identifies SAA1 as a Link Between Mucosal Microbes with TH17 and TH22 Cells

Tang, Mei San; Bowcutt, Rowann; Leung, Jacqueline M; Wolff, Martin J; Gundra, Uma M; Hudesman, David; Malter, Lisa B; Poles, Michael A; Chen, Lea Ann; Pei, Zhiheng; Neto, Antonio G; Abidi, Wasif M; Ullman, Thomas; Mayer, Lloyd; Bonneau, Richard A; Cho, Ilseung; Loke, P'ng
BACKGROUND: Inflammatory bowel diseases (IBD) are believed to be driven by dysregulated interactions between the host and the gut microbiota. Our goal is to characterize and infer relationships between mucosal T cells, the host tissue environment, and microbial communities in patients with IBD who will serve as basis for mechanistic studies on human IBD. METHODS: We characterized mucosal CD4 T cells using flow cytometry, along with matching mucosal global gene expression and microbial communities data from 35 pinch biopsy samples from patients with IBD. We analyzed these data sets using an integrated framework to identify predictors of inflammatory states and then reproduced some of the putative relationships formed among these predictors by analyzing data from the pediatric RISK cohort. RESULTS: We identified 26 predictors from our combined data set that were effective in distinguishing between regions of the intestine undergoing active inflammation and regions that were normal. Network analysis on these 26 predictors revealed SAA1 as the most connected node linking the abundance of the genus Bacteroides with the production of IL17 and IL22 by CD4 T cells. These SAA1-linked microbial and transcriptome interactions were further reproduced with data from the pediatric IBD RISK cohort. CONCLUSIONS: This study identifies expression of SAA1 as an important link between mucosal T cells, microbial communities, and their tissue environment in patients with IBD. A combination of T cell effector function data, gene expression and microbial profiling can distinguish between intestinal inflammatory states in IBD regardless of disease types.
PMID: 28806280
ISSN: 1536-4844
CID: 2669222

Using the Objective Structured Clinical Examination to Assess ACGME Competencies in Pediatric Gastroenterology Fellows

Solomon, Aliza B; Reed, Rachel; Benkov, Keith; Kingsbery, Joseph; Lusman, Sarah S; Malter, Lisa B; Levine, Jeremiah; Rabinowitz, Simon S; Wolff, Martin; Zabar, Sondra; Weinshel, Elizabeth
BACKGROUND:The Accreditation Council for Graduate Medical Education has described 6 core competencies with which trainees should demonstrate proficiency. Using the Objective Structured Clinical Examination (OSCE), we aimed to assess 4 of these competencies among Pediatric Gastrointestinal (GI) fellows (PGs). METHODS:Eight first-year PGs from 6 medical centers in the New York area participated in a 4-station OSCE with trained standardized patient (SP) actors. The cases included an emergency department (ED) consult, or "ED Consult" for lower gastrointestinal bleeding; "Breaking Bad News" focusing on CF nutritional complications; "Second Opinion" for abdominal pain; "Transition of Care" for inflammatory bowel disease. At each station, attending faculty observed the encounters behind a 1-way mirror. SPs and faculties provided immediate feedback to the examined fellows. Previously validated OSCE checklists were used to assess performance. On completion, fellows attended debriefing sessions and completed surveys about the educational value. RESULTS:Median overall milestone competency scores were 6.9 (PC1), 4.8 (PC2), 5.9 (MK1), 5.7 (MK2), 6.4 (ICS1), 6.9 (Prof1), and 6.7 (Prof3). Overall, fellows score highest (7/9) on the inflammatory bowel disease "Transition of Care" case, found the "Breaking Bad News" Cystic Fibrosis OSCE to be the most challenging, and were most comfortable with the "ED Consult" OSCE, as a commonly encountered scenario. Overall, the fellows rated the educational value of the program highly. CONCLUSIONS:To our knowledge, although the OSCE has been validated in other medical fields, this is the first OSCE program developed for PGs fellows. These OSCEs have included Accreditation Council for Graduate Medical Education competencies, serving to assess fellows' skills in these areas while exposing them to challenging medical and psychosocial cases that they may not frequently encounter.
PMID: 27782961
ISSN: 1536-4801
CID: 2956102

Isolation and cytokine analysis of lamina propria lymphocytes from mucosal biopsies of the human colon

Bowcutt, Rowann; Malter, Lisa B; Chen, Lea Ann; Wolff, Martin J; Robertson, Ian; Rifkin, Daniel B; Poles, Michael; Cho, Ilseug; Loke, P'ng
Much of our understanding of gut-microbial interactions has come from mouse models. Intestinal immunity is complex and a combination of host genetics and environmental factors play a significant role in regulating intestinal immunity. Due to this complexity, no mouse model to date gives a complete and accurate representation of human intestinal diseases, such as inflammatory bowel diseases. However, intestinal tissue from patients undergoing bowel resection reflects a condition of severe disease that has failed treatment, hence a more dynamic perspective of varying inflammatory states in IBD could be obtained through the analyses of pinch biopsy material. Here we describe our protocol for analyzing mucosal pinch biopsies collected predominantly during colonoscopies. We have optimized flow cytometry panels to analyze up to 8 cytokines produced by CD4+ and CD8+ cells, as well as for characterizing nuclear proteins and transcription factors such as Ki67 and Foxp3. Furthermore, we have optimized approaches to analyze the production of cytokines, including TGF-beta from direct ex vivo cultures of pinch biopsies and LPMCs isolated from biopsies. These approaches are part of our workflow to try and understand the role of the gut microbiota in complex and dynamic human intestinal diseases.
PMID: 25769417
ISSN: 0022-1759
CID: 1495252

Objective structured clinical examination as a novel tool in inflammatory bowel disease fellowship education

Wolff, Martin J; Balzora, Sophie; Poles, Michael; Zabar, Sondra; Mintah, Afua; Wong, Lillian; Weinshel, Elizabeth; Malter, Lisa B
BACKGROUND: Experiential learning in medical education, as exemplified by objective structured clinical examinations (OSCEs), is a well-validated approach for improving trainee performance. Furthermore, the Accreditation Council for Graduate Medical Education has identified OSCEs as an ideal method for assessing the core competency of interpersonal and communication skills. Here, we describe a novel educational tool, the inflammatory bowel disease OSCE (IBD OSCE), to assess and improve this clinical skill set in Gastroenterology fellows. METHODS: We developed a 4-station IBD OSCE that assessed shared decision making, physician-physician communication, and physician-patient consultative skills specifically related to the care of patients with IBD. Each station was videotaped and observed live by faculty gastroenterologists. Behaviorally anchored checklists were scored independently by a faculty observer and the standardized patient/physician, who both provided feedback to the fellow immediately after each case. Post-OSCE, fellows attended a debriefing session on patient communication and were surveyed to assess their perspective on the examination's educational value. RESULTS: Twelve second-year gastroenterology fellows from 5 fellowship programs participated in the IBD OSCE. Fellows performed well in all measured domains and rated the experience highly for its educational value. Fellows cited IBD as an area of relative deficiency in their education compared with other knowledge areas within gastroenterology. CONCLUSIONS: To our knowledge, this is the first OSCE designed specifically for the evaluation of skills as they relate to IBD management. Using OSCEs for IBD education provides an opportunity to robustly assess core competencies and the role of the physician as an educator.
PMID: 25633560
ISSN: 1078-0998
CID: 1506802

Inferred metagenomic comparison of mucosal and fecal microbiota from individuals undergoing routine screening colonoscopy reveals similar differences observed during active inflammation

Tang, Mei San; Poles, Jordan; Leung, Jacqueline M; Wolff, Martin J; Davenport, Michael; Lee, Soo Ching; Lim, Yvonne A L; Chua, Kek Heng; Loke, P'ng; Cho, Ilseung
Abstract The mucosal microbiota lives in close proximity with the intestinal epithelium and may interact more directly with the host immune system than the luminal/fecal bacteria. The availability of nutrients in the mucus layer of the epithelium is also very different from the gut lumen environment. Inferred metagenomic analysis for microbial function of the mucosal microbiota is possible by PICRUSt. We recently found that by using this approach, actively inflamed tissue of ulcerative colitis (UC) patients have mucosal communities enriched for genes involved in lipid and amino acid metabolism, and reduced for carbohydrate and nucleotide metabolism. Here, we find that the same bacterial taxa (e.g. Acinetobacter) and predicted microbial pathways enriched in actively inflamed colitis tissue are also enriched in the mucosa of subjects undergoing routine screening colonoscopies, when compared with paired samples of luminal/fecal bacteria. These results suggest that the mucosa of healthy individuals may be a reservoir of aerotolerant microbial communities expanded during colitis.
PMID: 25559083
ISSN: 1949-0976
CID: 1428792

Assessing the Usefulness of a Digital Educational Resource for Managing Inflammatory Bowel Disease During Fellowship [Meeting Abstract]

Dikman, Andrew; Balzora, Sophie; Shroff, Hersh; Wolff, Martin; Malter, Lisa
ISSN: 1572-0241
CID: 1854372

Immune response to helminth infections and its role in treatment for autoimmune disorders

Chapter by: Bowcutt, R; Wolff, MJ; Loke, P
in: The Th2 Type Immune Response in Health and Disease: From Host Defense and Allergy to Metabolic Homeostasis and Beyond by
pp. 131-154
ISBN: 9781493929115
CID: 2228962

Adapting Lugasi's Core Conditions for Optimizing Transition of Pediatric to Adult Care in Inflammatory Bowel Disease

Kingsbery, Joseph; Wolff, Martin J.; McGreal, Nancy; Malter, Lisa B.
ISSN: 0277-4208
CID: 4519622

Optimizing Transition of Pediatric to Adult Care in Inflammatory Bowel Disease (IBD) Through the Use of an Observed Structured Clinical Examination (OSCE) [Meeting Abstract]

Kingsbery, Joseph; Wolff, Martin; Zabar, Sondra; Gillespie, Colleen; Weinshel, Elizabeth; Soloman, Aliza; Malter, Lisa
ISSN: 1572-0241
CID: 1443812

Inflammatory Bowel Disease: The Bellevue Experience

Ali, Rabia; Wolff, Martin J; Malter, Lisa B
The Bellevue IBD clinic serves a radically different patient population than is treated in most US healthcare settings, represented in most clinical trials, or reflected in current management guidelines. Here we discuss the complexity of providing care to these individuals, areas of disparity in IBD care and resources to assist our patient population
ISSN: 0277-4208
CID: 1654192