Faculty Bibliography

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!

BACKGROUND: Inconsistencies in adherence to evidence-based medicine practice guidelines and quality indicators for inflammatory bowel disease (IBD) have been a recognized limitation in the quality of care afforded to IBD patients. We designed an Objective Structured Clinical Examination (OSCE) to assess many of the core competencies and to provide GI fellows with a simulated, case-based learning experience in the management of IBD patients. To supplement this experience, we provided GI fellows with an easily accessible educational resource in the form of a pocket-sized guide to highlight key evidence-based concepts in IBD education stressed in the OSCE. We assessed the utility of the NYU Gastroenterology Fellowship Training Program Pocket Guide's usefulness, functionality, utilization, and the GI fellows' satisfaction with this educational resource. METHODS: The NYU Gastroenterology Fellowship Training Program's OSCE course included 4 real life IBD clinical scenarios. Five New York City GI training programs and 12 second-year GI fellows participated. Following the OSCE, each fellow was given a pocket guide entitled "NYU Gastroenterology Fellowship Training Program Pocket Guide: Key Concepts in Managing Patients with Inflammatory Bowel Disease." In addition, the pocket guide was given to the remaining 8 NYU GI fellows who did not participate in the OSCE. The white coat pocket-sized guide is comprised of 5 front and back laminated pages, with approximately 2 pages devoted to each OSCE case. Three months following the distribution of the pocket guide, 20 fellows were invited to participate in an online survey about the pocket guide in general as an education tool, and about its specific elements, and the fellows' answers were collected. RESULTS: Sixteen of 20 (80%) fellows responded to the survey. Nearly 94% (15/16) of responders found the pocket guide to be a useful supplement to their fellowship IBD training, and 100% agreed that the guide would have been a useful reference tool to have at the s!

Th17 cells are enriched in the gut mucosa and play a critical role in maintenance of the mucosal barrier and host defense against extracellular bacteria and fungal infections. During chronic human immunodeficiency virus (HIV) infection, Th17 cells were more depleted compared to Th1 cells, even when the patients had low or undetectable viremia. To investigate the differential effects of HIV infection on Th17 and Th1 cells, a culture system was used in which CCR6(+) CD4(+) T cells were sorted from healthy human peripheral blood and activated in the presence of interleukin 1beta (IL-1beta) and IL-23 to drive expansion of Th17 cells while maintaining Th1 cells. HIV infection of these cultures had minimal effects on Th1 cells but caused depletion of Th17 cells. Th17 loss correlated with greater levels of virus-infected cells and cell death. In identifying cellular factors contributing to higher susceptibility of Th17 cells to HIV, we compared Th17-enriched CCR6(+) and Th17-depleted CCR6(-) CD4 T cell cultures and noted that Th17-enriched CCR6(+) cells expressed higher levels of alpha4beta7 and bound HIV envelope in an alpha4beta7-dependent manner. The cells also had greater expression of CD4 and CXCR4, but not CCR5, than CCR6(-) cells. Moreover, unlike Th1 cells, Th17 cells produced little CCR5 ligand, and transfection with one of the CCR5 ligands, MIP-1beta (CCL4), increased their resistance against HIV. These results indicate that features unique to Th17 cells, including higher expression of HIV receptors and lack of autocrine CCR5 ligands, are associated with enhanced permissiveness of these cells to HIV.