bluuebunny/crossref_metadata_2025_split huggingface dataset:
19 ROLE OF IL-33 IN PURINE METABOLISM AND ILC2 ACTIVATION DURING COLITIS-ASSOCIATED CANCER
Authors: De Salvo Carlo , Buela Kristine-Ann , Havran Hannah , Pizarro Theresa 
Published: January 2020

Abstract
UC patients have an increased risk of developing colorectal cancer, however, the immune cells and cytokines that mediate the transition from intestinal inflammation to cancer are poorly understood. Mucosal IL-33 is increased in UC patients, in addition, IL-33 and its receptor, ST2, are expressed in polyps in AOM/DSS models of colitis-associated cancer (CAC). Therefore, several studies have implicated IL-33, which is also an important activator of Innate Lymphoid Cells type 2 (ILC2s), in the formation of tumors. Moreover, it has been shown that ecto-5’-nucleotidase (CD73), critical ectoenzyme in purine metabolism which hydrolyzes extracellular AMP to adenosine, is upregulated in cancerous tissues, and an incompetent purine metabolic pathway has been associated with inflammation and inappropriate resolution in numerous inflammatory diseases, including IBD. In order to induce colitis-associated polyposis, we performed AOM/DSS protocol on 10-wk-old C57BL/6, IL-33KO and CD73KO mice as follow: the carcinogen Azoxymethane (AOM) was injected intraperitoneally (i.p.) on day 0. After two weeks, 3% dextran sodium sulfate (DSS) was administered in drinking water for a week, followed by two weeks of recovery with normal water. DSS administration and recovery was repeated one more time before euthanizing mice for tissue collection and analysis. Flow cytometry analysis showed that all ILC2s, and more specifically CD73 expressing ILC2s were significantly decreased in mesenteric lymph nodes (MLNs) of AOM/DSS treated mice lacking IL-33, compared to WT, on the other hand, CD73 deficient mice displayed a strongly reduced number of polyps compared to WT and flow cytometry revealed an ST2 expressing ILC2 cell population that was markedly reduced in CD73 deficient mice in comparison to WT. We next injected AOM/DSS treated C57BL/6 mice with either inhibitor of CD73 or sodium polyoxotungstate 1 (POM-1) CD39 inhibitor, therefore targeting the key enzymes in the purine metabolism pathway. We injected the mice i.p. with 10 mg per Kg body weight per day of either compounds or PBS, every day during the 2 weeks of DSS, to mimic a possible therapeutic treatment to prevent purine metabolism-depentent CAC. Histologic investigation of colon tissues isolated from mice treated with CD39 or CD73 inhibitors showed a significant decrease in inflammation and polyp numbers compared to vehicle-treated mice.
The data so far collected suggest that a cell population of CD73 expressing ILC2s is involved in polyp formation in AOM/DSS-treated mice and that ILC2s expansion and activity depends on IL-33/ST2 and purine metabolism synergy. Therefore the possibility exists that blockade of IL-33/ST2 axis and purine metabolism might be effective in reducing ILC2s expansion and thus be beneficial in preventing or reducing early events promoting CAC.
P071 MODULATION OF THE MUCUS LAYER BY BIFIDOBACTERIUM DENTIUM PROVIDES PROTECTION IN A MODEL OF COLITIS
Authors: Engevik Melinda , Ruan Wenly , Ihekweazu Faith , Versalovic James 
Published: January 2020

Abstract

Background
The intestinal mucus layer serves as a critical interface between the environment and the host. Patients with inflammatory bowel disease (IBD), particularly ulcerative colitis, exhibit reduced synthesis and secretion of the mucus protein MUC2 and decreased mucus thickness. This in turn promotes immune activation and inflammation. The clinical relevance of the mucus layer emphasizes the need to address strategies to modulate this barrier. Although bifidobacteria represent only 3–6% of the healthy adult fecal microbiota, their presence has been associated with numerous health benefits, including bolstering mucus production. However, the molecular mechanisms that underlie these positive effects appear to be strain-specific and are not well defined. We hypothesized that the human-derived Bifidobacterium dentium would increase intestinal mucus synthesis and expulsion via specific metabolites. We also speculated that modulation of goblet cells would be beneficial during colitis.

Methods & Results
In silico genome analysis revealed that B. dentium lacked the enzymatic repertoire required for degradation of mucin glycans. Consistent with these findings, we found that B. dentium could not use mucin glycans as a primary carbon source in vitro. To examine mucus modulation in vivo, germ-free mice were mono-associated with live or heat-killed B. dentium. Live B. dentium mono-associated mice exhibited increased colonic expression of goblet cell markers Krüppel-Like Factor 4 (Klf4), Relmβ, trefoil factor 3 (Tff3), Muc2, and several mucin glycosyltransferases compared to both heat-killed B. dentium and germ-free counterparts. Likewise, live B. dentium mono-associated colon had increased acidic mucin-filled goblet cells as denoted by MUC2 and PAS-AB staining. In vitro, B. dentium secreted products, including acetate, were able to increase MUC2 levels in T84 cells, mouse colonoids and human colonoids. We also identified that B. dentium secreted products, such as GABA, stimulated autophagy-mediated calcium signaling and MUC2 release. To identify whether B. dentium could enhance MUC2 production in mice harboring a complete microbiota, specific pathogen free mice were treated with live B. dentium by oral gavage. Administration of B. dentium increased the inner mucus layer compared to controls. Moreover, in a TNBS model of colitis, B. dentium treated mice had increased goblet cell numbers and MUC2 mRNA. Mirroring these findings, B. dentium treated mice lost less weight, had improved histology and had decreased levels of TNF, KC (IL-8), and IL-6.

Conclusions
This work illustrates that B. dentium enhances the intestinal mucus layer and goblet cell function via upregulation of gene expression and autophagy signaling pathways with a net increase in mucin production. Ultimately, these pathways may be targeted for the development of novel therapeutics.
P168 BACTEROIDETES SPECIES ARE USEFUL BIOMARKER OF CLINICAL ACTIVITY IN ULCERATIVE COLITIS
Authors: Nomura Kei , Ishikawa Dai , Okahara Koki , Ito Shoko , Takahashi Masahito , Haga Keiichi , Shibuya Tomoyoshi , Kobayashi Osamu , Nagahara Akihito 
Published: January 2020

Abstract

Background
We previously reported that there were 13 species of Bacteroidetes phylum with significantly higher or lower relative abundance in patients with ulcerative colitis (UC) than healthy individuals. In this study, we investigated the correlation between Bacteroidetes species components in fecal samples and clinical evaluations of UC.

Method
This study included participants above 20 years of age. Fecal samples were collected for microbial analysis from 54 patients who had active UC based on a Lichtiger’s clinical activity index (CAI) ≥ 4 or an endoscopic Mayo clinic score ≥1. DNA was extracted from the fecal samples and analyzed by next-generation sequencing (the Illumina MiSeq sequencing system) targeting hsp60. We verified associations between Bacteroidetes species and eMayo sum score (total of endoscopic Mayo clinic scores in each intestine: periphery of appendix vermiformis, cecum, ascending colon, transverse colon, descending colon, sigmoid colon, and rectum), Robarts Histopathology Index (RHI), and CAI.

Results
Bacteroides uniformis (R = -0.44, p = 0.002) and four others significantly correlated with eMayo sum score. Alistipes shahii (R = -0.35, p = 0.02) and three others significantly correlated with RHI. Bacteroides rodentium (R = -0.37, p = 0.006) and two others significantly correlated with CAI. Furthermore, three Bacteroidetes species (Bacteroides stercoris, Bacteroides uniformis, and Parabacteroides merdae) correlated with two of three clinical evaluations, and the total relative abundance of these three species showed stronger correlation with eMayo sum score (R = -0.52, p = 0.00007).

Conclusion
All eight Bacteroidetes species identified in this study represented negative correlation with the clinical activity, so these species are suggested to be lost by exacerbation. Bacteroidetes species, especially total relative abundance of three Bacteroidetes species (Bacteroides stercoris, Bacteroides uniformis, and Parabacteroides merdae) may become a biomarker for evaluating the clinical activity of UC.
3 MECHANSISMS OF INTESTINAL FUNGI RECOGNITION AND CONTROL
Authors: Leonardi Irina , Iliev Iliyan 
Published: January 2020

Abstract

Background and Objectives
Intestinal fungal communities are perturbed in several autoimmune diseases and have been shown to influence disease outcome. We have shown that intestinal resident CX3CR1+ mononuclear phagocytes (MNPs) can sense gut fungi and are crucial for the initiation of immune responses both locally and at distant sites. These results suggest that recognition of fungi by gut phagocytes might be involved in the pathogenesis of immune-related diseases such as IBD. Despite the identification of a few molecules involved in the recognition and immunity to intestinal fungi the cellular mechanisms governing the initiation and regulation of the mucosal immune responses to the mycobiota remain unknown. We sought to identify the functional role of distinct phagocytic subsets in the response to fungal communities in the gut during health and intestinal disease.

Methods
We used Candida albicans, the main opportunistic fungus found in IBD patients, as model fungal colonizer, with a focus on the mechanisms mediating the adaptive response. To elucidate the mechanisms and consequences of the recognition of fungi by phagocytic subsets in the lamina propria we used genetic models of depletion and deletion of specific subtypes of phagocytes. We further targeted fungal recognition and antigen presentation in phagocytes to investigate the mechanisms leading to the induction of adaptive anti-fungal responses.

Results
C. albicans colonization induced a consistent increase in Th17 cells in the intestinal mucosa that was decreased upon depletion of CX3CR1+ MNPs. Genetic depletion of CX3CR1+ MNPs in mice led to changes in gut fungal communities and to severe chemically induced intestinal inflammation that was rescued by antifungal treatment. Recognition of fungi through a C-type lectin/Syk pathways and antigen presentation via MHC-II were necessary for the induction of adaptive T cell in responses to C. albicans colonization.

Conclusion
Our work aims at defining the role of CX3CR1+ MNPs and cDCs in the initiation of anti-fungal immune responses in the intestine at the steady state. We have demonstrated the essential role of CX3CR1+ MNPs in the initiation of antifungal responses in the intestine at steady state and for the control of fungi at steady state and during inflammation. We have demonstrated the importance of CX3CR1+ MNPs in the control of the intestinal mycobiota.
P004 A PERSPECTIVE ON PORTRAYAL: MEN AND MINORITIES ARE UNDER-REPRESENTED ON BIOLOGIC WEBSITES
Authors: Rao Vinay , Baumgartner Scott , Khan Ali , Borum Marie 
Published: January 2020

Abstract

Introduction
Biologics are important options for inflammatory bowel disease (IBD) management. It has been reported that people of color (POC) with IBD are less frequently prescribed biologics compared to whites. Drug manufacturers’ websites are often designed to improve patient awareness and understanding of medical conditions and treatment. There is a paucity of information evaluating racial minorities depicted on pharmaceutical websites focused on biologic therapy. This study evaluated minority representation on websites of common biologic therapies used for IBD.

Methods
Websites for 4 major biologics were evaluated (Humira, Remicade, Stelara, Entyvio) for minority representation. Stock photos and videos were analyzed. Individuals were categorized based upon perceived ethnicity (person of color [POC], racially ambiguous [RA], white), gender, and role (patient, provider). Individuals were categorized independently by 3 investigators. Repeat images, incomplete facial images, inactive background role in videos, or images in which there was disagreement among all investigators were excluded. Statistical analysis was performed using two-sample t-test with significance set at p&lt;0.05.

Results
In the 4 websites, there were 102 total subjects (49 photos, 53 videos). There were 89 white, 11 POC, and 2 RA subjects with 33 males (32 white, 1 POC, 0 RA) and 69 females (57 white, 10 POC, 2 RA). There were significantly less POC compared to whites in photos (14.2% vs 81.6%; p=0.0003) and videos (7.0% vs 93.0%; p=0.001). Males were less frequently represented than females in photos (33.3% vs 66.7%; p=0.0096) and videos (32.3% vs 67.7%; p=0.0238). There were no males of color in photos. Humira portrayed 10 POC, Entyvio portrayed 1 POC and none were identified on Remicade and Stelara websites. Humira included 1 white, male provider, and Remicade 1 female POC provider. Stelara and Entyvio included no providers in either photos or videos. There were no images or videos about which all 3 reviewing investigators disagreed. All websites included at least 1 image with which a single investigator disagreed. Only Humira and Vedolizumab included a video with single investigator disagreement.

Discussion
Biologic therapy has a significant role in IBD treatment and should be considered for all IBD patients who have the appropriate indications. Pharmaceutical websites can have a role in increasing patient understanding and acceptance of therapy. Patients may have increased acceptance of treatment based upon portrayed images. While this study revealed that males and POC were significantly less represented on biologic websites, it may reflect gender and minority group IBD prevalence. However, consideration should be given to increase minority representation on biologic websites to enhance male and POC acceptance of therapeutic options and potentially improve clinical outcomes.
P005 A SURVEY STUDY OF GASTROENTEROLOGISTS’ VIEWS ON DYSPLASIA SURVEILLANCE AND CHROMOENDOSCOPY IN IBD
Authors: Grossberg Laurie , Farraye Francis , Papamichail Konstantinos , Cheifetz Adam , Feuerstein Joseph 
Published: January 2020

Abstract

Background
Patients with inflammatory bowel disease (IBD) have an increased risk of colon cancer. Current guidelines are equivocal in their recommendations for chromoendoscopy. The objective of this study is to assess gastroenterologists’ current attitudes and barriers toward chromoendoscopy in IBD.

Methods
A 23 question survey was distributed to members of the Crohn’s & Colitis Foundation via email. We collected physician characteristics, practice demographics, and data regarding chromoendoscopy use and barriers to chromoendoscopy.

Results
A total of 57 gastroenterologists from 22 US states [male, n=42 (74%); practicing in an academic university n=44 (77%)] met inclusion criteria. All respondents agree that patients with IBD involving more than 1/3 of the colon have increased risk of colon cancer. Most gastroenterologists agree that patients with extensive UC (100%), left-sided UC (80%), or Crohn’s involving more than 1/3 of the colon (98%) should be in a surveillance protocol, however, 37%, 9%, and 2% also believe that patients with distal ulcerative proctosigmoiditis, ulcerative proctitis, and ileal Crohn’s disease should be in a surveillance protocol respectively. All gastroenterologists perform surveillance in patients without other risk factors within 3 years, however the interval varies: 28% every year, 47% every 2 years, and 25% every 3 years. 61% believe that chromoendoscopy is the preferred method for dysplasia surveillance, but 72% use white light endoscopy most often for surveillance in their clinical practice. Two-thirds (38/57) of gastroenterologists reported ever performing chromoendoscopy. The most common reasons to use chromoendoscopy were history of dysplasia found on random biopsy (89%), history of nonpolypoid dysplasia (76%), or history of primary sclerosing cholangitis (76%). Only 8 gastroenterologists reported using chromoendoscopy for all IBD surveillance. Physicians agree that the top barriers to chromoendoscopy use include longer procedure time (43), lack of standardized training in chromoendoscopy (42), and lack of reimbursement for chromoendoscopy (36); however, most would be likely or very likely to use chromoendoscopy if data showed which patients would benefit most from chromoendoscopy (95%) and if data showed benefits of chromoendoscopy compared to other techniques (93%).

Conclusion
Most gastroenterologists believe that chromoendoscopy is the ideal method for IBD surveillance, yet white light endoscopy is used most often. Physicians agree that longer procedure times and lack of reimbursement deter chromoendoscopy use, but the majority would be willing to use chromoendoscopy if data showed superiority of chromoendoscopy compared to other techniques and identified patients that would benefit the most.
P001 PHARMACIST ROLE IN IBD MEDICATION OPTIMIZATION (PRIMO-IBD)
Authors: Kim Nari , Chu Chau , Tran Hai , Shane Rita , Melmed Gil 
Published: January 2020

Abstract

Introduction
Inflammatory bowel disease (IBD) is a chronic disease state with growing focus, due to its significant medical and economic health burden. Although targeted therapy against tumor necrosis factor (anti-TNF), interleukin receptors, and integrin receptors have established roles in ulcerative colitis and Crohn’s disease management, medication accessibility and literacy contribute to medication non-adherence. Non-adherence to IBD therapy is associated with 62% higher costs for hospitalizations, along with increased disease mortality, relapse, loss of response, and antibody formation. IBD centers recognize the collaborative importance of a pharmacist’s role in medication optimization, patient adherence, and transitions of care.

Methodology
From November 2017 - April 2018, patients discharged from the inpatient IBD Service received a post discharge follow-up (PDFU) call from a pharmacist within 72 hours. Concurrently, the pharmacist provided pharmacotherapy optimization and education during the 4 hour weekly clinic visits, followed by a call within 72 hours.
For all sites of care, the pharmacist performed a comprehensive evaluation for healthcare maintenance (including notable lab values, drug levels, and/or antibody levels), adherence to IBD medications, and drug interactions.
The primary outcome was 30-day readmissions. The secondary outcomes included the number and severity of drug-related problems (DRPs) identified, validated by two gastroenterologists.

Results
132 patients were included in the study (63 inpatient; 69 clinic). The inpatient 30-day readmission rate for the study period was 14.3% versus 22.1% in 2016 (P=0.15). In comparison, the 30-day hospitalization rate for clinic patients remained relatively unchanged.
123 DRPs were identified from 132 patients, averaging 0.93 DRPs per patient. There were 87 DRPs from the inpatient setting and 36 DRPs identified in clinic. Of the DRPs, 60% of DRPs were prescriber-related and 40% were patient-related. 2% (2 cases) were considered life-threatening, and 40% of cases were significant DRPs; the remaining DRPs were low risk. Potential admissions were avoided in 6 patients (11%) by early detection of a drug-related error.

Conclusion
Results demonstrate the opportunities for a pharmacist to be involved in managing biologics and health maintenance therapy in the IBD patient population. There was an overall positive trend of a pharmacist role on IBD admission rates and decrease in medication related errors.
P024 THE MORE YOU KNOW: YOUNGER IBD PATIENTS AND THOSE ON BIOLOGICS ARE MORE FREQUENTLY ASSESSED FOR HEALTH LITERACY
Authors: Baumgartner Scott , Basso Jessica , Szvarca Daniel , Tabbara Nadeem , Clarke Lindsay , Borum Marie 
Published: January 2020

Abstract

Background
Immunomodulator and biologic therapies are important options for individuals with moderate to severe inflammatory bowel disease (IBD). It is critical that IBD patients are aware of potential side effects of all medications. Health literacy can impact upon patients’ understanding of IBD management. This study evaluated the rate at which university gastroenterologists assess health literacy in IBD patients on immunomodulator and biologic treatment.

Methods
A retrospective chart review of all IBD patients seen in the gastroenterology clinic of a university medical center over a five-year period was performed. Patient age, gender, IBD diagnosis, medications (biologics, immunomodulators), and documented health literacy assessment were recorded. A database was generated using Microsoft Excel. Statistical analysis was performed using Fisher’s Exact Test with significance set at P&lt;0.05. The study was approved by the institutional IRB.

Results
392 medical records were analyzed: There were 175 men and 217 women. The mean age was 44.3 years (range 20–82), with 259 (66.1%) &lt;50 years. 278 (70.9%) had ulcerative colitis (UC), 96 (24.5%) Crohn’s disease (CD), 11 (2.8%) microscopic colitis, and 7 (1.8%) unspecified colitis. 48 were on biologics alone, 30 on biologics with an immunomodulator or aminosalicylate, 224 were on immunomodulators and / or an aminosalicylates and 90 were on other medication regimens. 18 (37.5%) on biologics and 14 (46.7%) on biologics with an immunomodulator or aminosalicylate, 63 (28.1%) on an immunomodulators and /or aminosalicylates and 15 (16.7%) on other medication regimens had a documented health literacy assessment. Patients on a biologic regimens were more often assessed for health literacy compared to those on immunomodulators and / or aminosalicylates (p=0.012) or other medication regimens (p=0.0005). Additionally, patients &lt;50 years were assessed for health literacy more frequently than those &gt;50 years (p=0.0008).

Discussion
Health literacy enables individuals to make informed medical decisions and follow treatment recommendations. It is important that individuals with IBD understand their medical regimens, especially those on immunomodulator and biologic therapy. This study revealed that health literacy was inconsistently documented, with patients &lt;50 and those on biologics more frequently evaluated. While this study is limited based on upon size, retrospective design and reliance on literacy documentation, it supports recommendations that providers assess individuals’ understanding of their condition and treatment. Ensuring patients’ IBD health literacy will optimize clinical care and outcomes.