Acute Liver Failure Secondary to Remdesivir in the Treatment of COVID-19.

Remdesivir has been the mainstay of coronavirus disease 2019 treatment since the start of the severe acute respiratory syndrome coronavirus 2 pandemic. Despite its growing use, safety data are limited. We present the case of an elderly man with obesity and coronavirus disease 2019 who developed acute liver failure after initiation of remdesivir. This report broadens our knowledge of the side effect profile of remdesivir and discusses potential risk factors and an approach to remdesivir-induced liver failure. Our case also highlights the importance of monitoring hepatic function after initiation of therapy with remdesivir.

Progressive dysbiosis of human orodigestive microbiota along the sequence of gastroesophageal reflux, Barrett's esophagus and esophageal adenocarcinoma.

The incidence of esophageal adenocarcinoma (EA) has drastically increased in the United States since 1970s for unclear reasons. We hypothesized that the widespread usage of antibiotics has increased the procarcinogenic potential of the orodigestive microbiota along the sequence of gastroesophageal reflux (GR), Barrett's esophagus (BE) and EA phenotypes. This case control study included normal controls (NC) and three disease phenotypes GR, BE and EA. Microbiota in the mouth, esophagus, and stomach, and rectum were analyzed using 16S rRNA gene sequencing. Overall, we discovered 44 significant pairwise differences in abundance of microbial taxa between the four phenotypes, with 12 differences in the mouth, 21 in the esophagus, two in the stomach, and nine in the rectum. Along the GR→BE→EA sequence, oral and esophageal microbiota were more diversified, the dominant genus Streptococcus was progressively depleted while six other genera Atopobium, Actinomyces, Veillonella, Ralstonia, Burkholderia and Lautropia progressively enriched. In NC, Streptococcus appeared to control populations of other genera in the foregut via numerous negative and positive connections, while in disease states, the rich network was markedly simplified. Inferred gene functional content showed a progressive enrichment through the stages of EA development in genes encoding antibiotic resistance, ligands of Toll-like and NOD-like receptors, nitrate-nitrite-nitric oxide pathway and acetaldehyde metabolism. The orodigestive microbiota is in a progressive dysbiotic state along the GR-BE-EA sequence. The increasing dysbiosis and antibiotic and procarcinogenic genes in the disease states warrants further study to define their roles in EA pathogenesis.

Acute Kidney Injury Presenting as Hepatorenal Syndrome in the Setting of Glecaprevir/Pibrentasvir Treatment for Hepatitis C.

A 65-year-old man with chronic hepatitis C virus and hepatocellular carcinoma, after surgical resection and chemotherapy, was started on a regimen of glecaprevir and pibrentasavir for treatment of his hepatitis C virus. Ten days later, he developed hepatotoxicity with subsequent progression to hepatorenal syndrome (HRS). On discontinuation of glecaprevir/pibrentasavir and initiation of HRS treatment, he had improvement in his renal and hepatic function. Although there have been recent safety concerns surrounding hepatocellular injury secondary to glecaprevir/pibrentasavir, this is the first case report of HRS secondary to severe hepatotoxicity induced by glecaprevir/pibrentasavir.

Endoscopic part-task training box scores correlate with endoscopic outcomes.

BACKGROUND: Competency in endoscopy has traditionally been based on number of procedures performed. With movement towards milestone-based accreditation, new standards of establishing competency are required. The Thompson Endoscopic Skills Trainer (TEST) is a training device previously shown to differentiate between novice and expert endoscopists. This study aims to correlate TEST scores to other markers of performance in endoscopy. METHODS: Trainees of a gastroenterology fellowship program were guided through the TEST. Their scores and sub-scores were correlated to their endoscopic metrics of performance, including adenoma detection rate, cecal intubation rate, cecal intubation time, withdrawal time, fentanyl usage, midazolam usage, pain score, overall procedure time, and performance on the ASGE Assessment of Competency in Endoscopy Tool (ACE Tool). RESULTS: The Overall Score positively correlated with the ACE Tool Total Score (r = 0.707, p = 0.010) and sub-scores (Cognitive Skills Score: r = 0.624, p = 0.030; Motor Skills Score: r = 0.756, p = 0.004), and negatively correlated with cecal intubation time (r = - 0.591, p = 0.043). The Gross Motor Score positively correlated with cecal intubation rate (r = 0.593, p = 0.042), ACE Tool Total Score (r = 0.594, p = 0.042) and Motor Skills Score (r = 0.623, p = 0.031), and negatively correlated with cecal intubation time (r = - 0.695, p = 0.012). The Fine Motor Score positively correlated with the ACE Tool Polypectomy Score (r = 0.601, p = 0.039), and negatively correlated with procedure time (r = - 0.640, p = 0.025), cecal intubation time (r = - 0.645, p = 0.024), and withdrawal time (r = - 0.629, p = 0.028). CONCLUSION: This study demonstrates that performance on the TEST correlate to endoscopic measures. Given these results, the TEST may be used in conjunction with existing assessment tools for demonstrating competency in endoscopy.

A Theory-based Educational Pamphlet With Low-residue Diet Improves Colonoscopy Attendance and Bowel Preparation Quality.

GOALS/BACKGROUND: Patients who "no-show" for colonoscopy or present with poor bowel preparation waste endoscopic resources and do not receive adequate examinations for colorectal cancer (CRC) screening. Using the Health Belief Model, we modified an existing patient education pamphlet and evaluated its effect on nonattendance rates and bowel preparation quality. STUDY: We implemented a color patient education pamphlet to target individual perceptions about CRC and changed bowel preparation instructions to include a low-residue diet instead of the previous clear liquid diet. We compared the nonattendance rate over a 2-month period before and after the introduction of the pamphlet, allowing for a washout period during which pamphlet use was inconsistent. We compared the Boston Bowel Preparation Scale (BBPS) in 100 consecutive patients who underwent colonoscopy during each of the 2 periods. RESULTS: Baseline characteristics between the 2 groups were similar, although patients who received the pamphlet were younger (P=0.03). The nonattendance rate was significantly lower in patients who received the pamphlet (13% vs. 21%, P=0.01). The percentage of patients with adequate bowel preparation increased from 82% to 86% after introduction of the pamphlet, although this was not statistically significant (P=0.44). The proportion of patients with a BBPS score of 9 was significantly higher in the pamphlet group (41% vs. 27%, P=0.03). There was no difference in adenoma and sessile serrated adenoma detection rates before and after pamphlet implementation. CONCLUSIONS: After implementing a theory-based patient education intervention with a low-residue diet, our absolute rate for colonoscopy nonattendance decreased by 8% and the proportion of patients with a BBPS score of 9 increased by 14%. The Health Belief Model appears to be a useful construct for CRC screening interventions.

Split- versus single-dose preparation tolerability in a multiethnic population: decreased side effects but greater social barriers.

BACKGROUND: This study was performed to compare patient-reported tolerability and its barriers in single- vs. split-dose 4-L polyethylene glycol (PEG) bowel preparation for colonoscopy in a large multiethnic, safety-net patient population. METHODS: A cross-sectional, dual-center study using a multi-language survey was used to collect patient-reported demographic, medical, socioeconomic, and tolerability data from patients undergoing outpatient colonoscopy. Univariate and multivariate analyses were used to identify demographic and clinical factors significantly associated with patient-reported bowel preparation tolerability. RESULTS: A total of 1023 complete surveys were included, of which 342 (33.4%) completed single-dose and 681 (66.6%) split-dose bowel preparation. Thirty-nine percent of the patients were Hispanic, 50% had Medicaid or no insurance, and 34% had limited English proficiency. Patients who underwent split-dose preparation were significantly more likely to report a tolerable preparation, with less severe symptoms, than were patients who underwent single-dose preparation. Multiple logistic regression revealed that male sex and instructions in the preferred language were associated with tolerability of the single-dose preparation, while male sex and concerns about medications were associated with tolerability of the split-dose preparation. CONCLUSIONS: In a large multiethnic safety-net population, split-dose bowel preparation was significantly more tolerable and associated with less severe gastrointestinal symptoms than single-dose preparation. The tolerability of split-dose bowel preparation was associated with social barriers, including concerns about interfering with other medications.

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

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.

Disruptive behavior in the workplace: Challenges for gastroenterology fellows.

AIM: To assess first-year gastroenterology fellows' ability to address difficult interpersonal situations in the workplace using objective structured clinical examinations (OSCE). METHODS: Two OSCEs ("distracted care team" and "frazzled intern") were created to assess response to disruptive behavior. In case 1, a fellow used a colonoscopy simulator while interacting with a standardized patient (SP), nurse, and attending physician all played by actors. The nurse and attending were instructed to display specific disruptive behavior and disregard the fellow unless requested to stop the disruptive behavior and focus on the patient and procedure. In case 2, the fellow was to calm an intern managing a patient with massive gastrointestinal bleeding. The objective in both scenarios was to assess the fellows' ability to perform their duties while managing the disruptive behavior displayed by the actor. The SPs used checklists to rate fellows' performances. The fellows completed a self-assessment survey. RESULTS: Twelve fellows from four gastrointestinal fellowship training programs participated in the OSCE. In the "distracted care team" case, one-third of the fellows interrupted the conflict and refocused attention to the patient. Half of the fellows were able to display professionalism despite the heated discussion nearby. Fellows scored lowest in the interprofessionalism portion of post-OSCE surveys, measuring their ability to handle the conflict. In the "frazzled intern" case, 68% of fellows were able to establish a calm and professional relationship with the SP. Despite this success, only half of the fellows were successfully communicate a plan to the SP and only a third scored "well done" in a domain that focused on allowing the intern to think through the case with the fellow's guidance. CONCLUSION: Fellows must receive training on how to approach disruptive behavior. OSCEs are a tool that can assess fellow skills and set a culture for open discussion.

Assessment of Abilities of Gastroenterology Fellows to Provide Information to Patients With Liver Disease.

BACKGROUND & AIMS: Patient education is critical in ensuring patient compliance and good health outcomes. Fellows must be able to effectively communicate with their patients, delivering enough information for the patient to understand their medical problem and maximize patient compliance. We created an objective structured clinical examination (OSCE) with 4 liver disease cases to assess fellows' knowledge and ability to inform standardized patients (SPs) about their clinical condition. METHODS: We developed 4 cases highlighting different aspects of liver disease and created a 4-station OSCE: hepatitis B, acute hepatitis C, new diagnosis of cirrhosis, and an end-stage cirrhotic nontransplant candidate. The SP with hepatitis B was minimizing the fact that she could not read English. The acute hepatitis C SP was a nursing student who is afraid that having hepatitis C might jeopardize her career. The SP with the new diagnosis of alcoholic cirrhosis needed to stop drinking, and the end-stage liver disease patient had to grapple with his advanced directives. Twelve fellows from 4 GI training programs participated. Our focus was to assess the fellows' knowledge about liver diseases and the Accreditation Council for Graduate Medical Education competencies of health literacy, shared decision making, advanced directives, and goals of care. The goal for the fellows was to communicate effectively with the SPs, and acknowledge that each patient had an emotionally charged issue to overcome. The SPs used a checklist to rate fellows' performance. Faculty and the SPs observed the cases and provided feedback. The fellows were surveyed on their performance regarding the case. RESULTS: The majority of fellows were able to successfully summarize findings and discuss a plan with the patient in the new diagnosis of cirrhosis (76.92%) and hepatitis C case (100%), but were less successful in the hepatitis B case (30.77%) and the end-of-life case (41.67%). Overall, a small percentage of fellows reflected that they did a good job (22%-33%), except at the end-of-life case (67%). The fellows' greatest challenge was trying to cover a lot of information in a single outpatient visit. CONCLUSIONS: Caring for patients with liver diseases can be complex and time consuming. The patients and fellows' observations were discordant in several areas: for example, the fellows believed they excelled in the end-of-life case, but the SP thought only a small percentage of fellows were able to successfully summarize and discuss the plan. This discrepancy and others highlight important areas of focus in training programs. OSCEs are important to help the fellows facilitate striking the right balance of information delivery and empathy, and this will lead to better patient education, compliance, rapport, and satisfaction.

Perceptions of fecal microbiota transplantation for Clostridium difficile infection: factors that predict acceptance.

BACKGROUND: Despite the effectiveness of fecal microbiota transplantation (FMT) for treating recurrent Clostridium difficile (C. difficile) infection, some patients are reluctant to accept this therapy. Our study examined attitudes towards FMT and factors that contribute to patients' acceptance of this treatment. METHODS: We distributed patient surveys at a Veterans Affairs hospital, a public hospital, and an academic faculty practice. Multivariable logistic regression was performed, adjusting for factors associated with FMT acceptance on univariate analysis and prior experience with C. difficile infection. RESULTS: Of 267 patients, only 12% knew of FMT prior to the survey, but 77% would undergo the procedure if medically indicated. On multivariable analysis, those with children and with college degrees or higher were more likely to agree to FMT (odds ratio [OR] 2.11, 95% confidence interval [CI] 1.02-4.35; OR 2.27, 95% CI 1.11-4.60 respectively). Sixty-five respondents (71%) chose colonoscopy as the preferred vehicle for FMT, while nasogastric tube was least preferred. Disease transmission was the most common concern (30%, n=242), and FMT success rate was the least selected concern (9.1%). CONCLUSIONS: Most patients in a diverse sample of gastroenterology clinics had no prior knowledge of FMT, but were receptive to the procedure. Having children and higher education levels were predictors for FMT acceptance. Our findings suggest that barriers to FMT utilization may be overcome with counseling about safety concerns. More data on the risk of transmitting diseases or clinical characteristics, such as obesity, through FMT are needed and will be important for the acceptance of this procedure.

HIV-induced immunosuppression is associated with colonization of the proximal gut by environmental bacteria.

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.

Portal hypertensive gastropathy with a focus on management.

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 ß-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.

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

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.

Human Immunodeficiency Virus-Associated Diarrhea: Still an Issue in the Era of Antiretroviral Therapy.

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.

Assessing cultural competency skills in gastroenterology fellowship training.

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.

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

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.

Design aspects of a case-control clinical investigation of the effect of HIV on oral and gastrointestinal soluble innate factors and microbes.

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 naïve 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.

Preferential HIV infection of CCR6+ Th17 cells is associated with higher levels of virus receptor expression and lack of CCR5 ligands.

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 1ß (IL-1ß) 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 α4ß7 and bound HIV envelope in an α4ß7-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-1ß (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.

Clash of the microbes: let's bring back the good guys.

A 38-year-old man with a history of HIV infection virologically suppressed on antiretroviral therapy presents to his gastroenterologist for evaluation of iron deficiency anemia and weight loss. A diagnostic colonoscopy demonstrates a two-centimeter ulcerated mass in the cecum. Biopsies of the lesion return moderately differentiated adenocarcinoma that is wild type for the KRAS mutation by real-time PCR.