Faculty Bibliography

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.

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.

AIM: To assess and teach cultural competency skills at the fellowship training level through the use of objective structured clinical examinations (OSCEs). METHODS: We revised four scenarios to infuse a specific focus on cross-cultural care, and to render them appropriate for gastroenterology fellows. Three are discussed here: (1) Poor Health Literacy; (2) Disclosing/Apologizing for a Complication to a Patient Who Mistrusts the Healthcare System; and (3) Breaking Bad News to a Fatalistic Patient. A fourth case emphasizing shared decision-making will be described elsewhere. Four stations were completed by fellows and observed live by four faculty members, and the fellows' performance was assessed. RESULTS: Eleven fellows from four programs participated in the four OSCE. In the "Poor Health Literacy" case, 18% (2/11) of participants recognized that the standardized patient (SP) had below-basic health literacy. None successfully evaluated the SP's reading skills in a culturally-sensitive manner. In "Disclosing/Apologizing for a Complication", 4/11 (36%) personally apologized for the complication. 1/11 recognized the SP's mistrust of the medical system. With "Breaking Bad News", 27% (3/11) explored the patient's values to identify her fatalistic beliefs. CONCLUSION: OSCEs can be used to assess deficiencies in culturally-competent care at the fellowship level. OSCEs also afford fellowships the opportunity to inform future training curricula.

Portal hypertensive gastropathy (PHG) is a painless condition of gastric mucosal ectasia and impaired mucosal defense, commonly seen in patients with elevated portal pressures. While it is typically asymptomatic and incidentally discovered on upper endoscopy, acute and chronic bleeding may occur. There are no definitive recommendations for treatment of asymptomatic PHG. Non-selective beta-blockers represent the mainstay of therapy for chronic bleeding, while somatostatin and vasopressin and their derivatives may be used in conjunction with supportive measures for acute bleeding. Salvage therapy with transjugular intrahepatic portosystemic shunt or rarely surgical shunt is appropriate when medical management fails. The role of endoscopic therapy for PHG is controversial. Liver transplantation should be considered as a final resort in cases of refractory bleeding due to PHG.

T helper type (Th17) cytokines such as interleukin (IL)-17A and IL-22 are important in maintaining mucosal barrier function and may be important in the pathogenesis of inflammatory bowel diseases (IBDs). Here, we analyzed cells from the colon of IBD patients and show that Crohn's disease (CD) patients had significantly elevated numbers of IL-17+, CD4+ cells compared with healthy controls and ulcerative colitis (UC) patients, but these numbers did not vary based on the inflammatory status of the mucosa. By contrast, UC patients had significantly reduced numbers of IL-22+ cells in actively inflamed tissues compared with both normal tissue and healthy controls. There was a selective increase in mono-IL-17-producing cells from the mucosa of UC patients with active inflammation together with increased expression of transforming growth factor (TGF)-beta and c-Maf. Increasing concentrations of TGF-beta in lamina propria mononuclear cell cultures significantly depleted Th22 cells, whereas anti-TGF-beta antibodies increased IL-22 production. When mucosal microbiota was examined, depletion of Th22 cells in actively inflamed tissue was associated with reduced populations of Clostridiales and increased populations of Proteobacteria. These results suggest that increased TGF-beta during active inflammation in UC may lead to the loss of Th22 cells in the human intestinal mucosa.

INTRODUCTION: The impaired host defense system in HIV infection impacts the oral and gastrointestinal microbiota and associated opportunistic infections. Antiretroviral treatment is predicted to partially restore host defenses and decrease the oral manifestation of HIV/AIDS. Well-designed longitudinal studies are needed to better understand the interactions of soluble host defense proteins with bacteria and virus in HIV/AIDS. "Crosstalk" was designed as a longitudinal study of host responses along the gastrointestinal (GI) tract and interactions between defense molecules and bacteria in HIV infection and subsequent therapy. PURPOSE: The clinical core formed the infrastructure for the study of the interactions between the proteome, microbiome and innate immune system. The core recruited and retained study subjects, scheduled visits, obtained demographic and medical data, assessed oral health status, collected samples, and guided analysis of the hypotheses. This manuscript presents a well-designed clinical core that may serve as a model for studies that combine clinical and laboratory data. METHODS: Crosstalk was a case-control longitudinal clinical study an initial planned enrollment of 170 subjects. HIV+ antiretroviral naive subjects were followed for 9 visits over 96 weeks and HIV uninfected subjects for 3 visits over 24 weeks. Clinical prevalence of oral mucosal lesions, dental caries and periodontal disease were assessed. RESULTS: During the study, 116 subjects (47 HIV+, 69 HIV-) were enrolled. Cohorts of HIV+ and HIV- were demographically similar except for a larger proportion of women in the HIV- group. The most prevalent oral mucosal lesions were oral candidiasis and hairy leukoplakia in the HIV+ group. DISCUSSION: The clinical core was essential to enable the links between clinical and laboratory data. The study aims to determine specific differences between oral and GI tissues that account for unique patterns of opportunistic infections and to delineate the differences in their susceptibility to infection by HIV and their responses post-HAART.

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 (ACGME) has identified OSCEs as an ideal method for assessing the core competency of interpersonal and communication skills. The field of inflammatory bowel disease (IBD) challenges clinicians to communicate effectively due to the complex multidisciplinary nature of its management. Here, we describe a novel educational tool (the IBD OSCE) to assess and improve this clinical skillset in Gastroenterology (GI) fellows. METHODS: Twelve second-year GI fellows from 5 fellowship programs participated in a 4-station OSCE. Previously validated OSCE checklists were used to assess the GI fellows' performance in IBD-specific cases. In the first case ("New Diagnosis") the goal of the GI fellow was to educate a patient on her recent diagnosis of ulcerative colitis and to navigate a complex conversation about her risk of colon cancer. In the second case ("Shared Decision Making") the objective was to evaluate a patient with Crohn's disease who would benefit from combination therapy with infliximab and azathioprine. A third case ("Emergency Department Flare") involved evaluating how the fellow performs in the initial triage and management of an ulcerative colitis patient in flare through an observed telephone encounter with an actual emergency department physician. In the final case ("Pre-conception Counseling"), the fellow was asked to discuss the pre-conceptive management of active ulcerative colitis with a "real-life" obstetrician/gynecologist. Each station was videotaped and observed live by faculty gastroenterologists. Checklists were scored independently by a physician-observer and the Standardized Patient (SP), who both provided feedback to the fellow immediately following each case. Fellow performance was scored across multiple domains and individ!