Faculty Bibliography

OBJECTIVES: To evaluate the impact of HIV infection on colonization resistance in the proximal gut. DESIGN: It was a case-control study. METHODS: We contrasted microbiota composition between eight HIV-1-infected patients and eight HIV-negative controls to characterize community alteration and detect exogenous bacteria in the esophagus, stomach, and duodenum, as well as the mouth using a universal 16s ribosomal RNA gene survey and correlated the findings with HIV serostatus and peripheral blood T-cell counts. RESULTS: HIV infection was associated with an enrichment of Proteobacteria (P=0.020) and depletion of Firmicutes (P = 0.005) in the proximal gut. In particular, environmental species Burkholderia fungorum and Bradyrhizobium pachyrhizi colonized the duodenum of HIV patients who had abnormal blood CD4 T-cell counts but were absent in HIV-negative controls or HIV patients whose CD4 cell counts were normal. The two species coexisted and exhibited a decreasing trend proximally toward the stomach and esophagus and were virtually absent in the mouth. B. fungorum always outnumbered B. pachyrhizi in a ratio of approximately 15 to 1 regardless of the body sites (P < 0.0001, r = 0.965). Their abundance was inversely correlated with CD4 cell counts (P = 0.004) but not viral load. Overgrowth of potential opportunistic pathogens for example, Prevotella, Fusobacterium, and Ralstonia and depletion of beneficial bacteria, for example, Lactobacillus was also observed in HIV patients. CONCLUSIONS: The colonization of the duodenum by environmental bacteria reflects loss of colonization resistance in HIV infection. Their correlation with CD4 cell counts suggests that compromised immunity could be responsible for the observed invasion by exogenous microbes.

Over half of patients with human immunodeficiency virus (HIV) experience diarrhea that contributes negatively to quality of life and adherence to antiretroviral therapy (ART). Opportunistic infectious agents that cause diarrhea in patients with HIV span the array of protozoa, fungi, viruses, and bacteria. With global use of ART, the incidence of diarrhea because of opportunistic infections has decreased; however, the incidence of noninfectious diarrhea has increased. The etiology of noninfectious diarrhea in patients with HIV is multifactorial and includes ART-associated diarrhea and gastrointestinal damage related to HIV infection (i.e., HIV enteropathy). A basic algorithm for the diagnosis of diarrhea in patients with HIV includes physical examination, a review of medical history, assessment of HIV viral load and CD4+ T cell count, stool microbiologic assessment, and endoscopic evaluation, if needed. For patients with negative diagnostic results, the diagnosis of noninfectious diarrhea may be considered. Pharmacologic options for the treatment of noninfectious diarrhea are primarily supportive; however, the use of many unapproved agents is based on unstudied and anecdotal information. In addition, these agents can be associated with treatment-limiting adverse events (AEs), such as drug-drug interactions with ART regimens, abuse liability, and additional gastrointestinal AEs. Currently, crofelemer, an antisecretory agent, is the only therapy approved in the USA for the symptomatic relief of noninfectious diarrhea in patients with HIV on ART.

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.