bluuebunny/crossref_metadata_2025_split huggingface dataset:
25 DONOR SELECTION OF FECAL MICROBIOTA TRANSPLANTATION IS IMPORTANT TO LONG-TERM MAINTENANCE OF ULCERATIVE COLITIS
Authors: Okahara Koki , Ishikawa Dai , Nomura Kei , Ito Shoko , Haga Keiichi , Takahashi Masahito , Shibuya Tomoyoshi , Nagahara Akihito 
Published: January 2020

Abstract

Background
Fecal microbiota transplantation (FMT) has been investigated as a potential treatment for various disease. However, the therapeutic mechanism is still unclear. We previously demonstrated that fresh-fecal microbiota transplantation following triple-antibiotic therapy [amoxicillin, fosfomycin, and metronidazole (AFM); A-FMT] for ulcerative colitis (UC) patients induced changes in the phylum Bacteroidetes, which constitutes a critical factor correlated with clinical responses. Here, we analyzed microbiota to examine the beneficial species, and observed long-term course (12 months) of the patients who treated with AFM and A-FMT. Moreover, we explore the concept of best donor for FMT success.

Methods
This prospective and non-randomized controlled study was conducted from July 2014 to March 2017 at Juntendo University Hospital. Eligible patients were at least 20 years of age, with a diagnosis of active UC which were required a Lichtiger’s clinical activity index (CAI) of 5 or more, or with an endoscopic Mayo score of 1 or more. Patients’ spouses or relatives in the family were selected as donors. AFM was administered to patients with UC for 2 weeks, and up to 2 days before fresh FMT. Clinical response was defined as a decrease of CAI of 3 points or more, and remission was defined as 3 points or less. Maintenance of efficacy was defined as no exacerbation of CAI and no intensification of treatments.

Results
Seventy-nine patients completed protocol (A-FMT; n = 47, mono-AFM; n = 32). At 4 weeks after treatment, clinical response and remission were observed in 31 and 19 patients (65.9%, 40.4%) in A-FMT, which higher than in mono-AFM respectively (56.2%, 18.7%). The maintenance rate of clinical responder was shown to be significantly higher in A-FMT than in AFM at 12 months after treatment (A-FMT vs mono-AFM, n = 13, 10; P = 0.046). Furthermore, in case that the age difference between donor and patient is more than 11 years, maintenance rate was significantly lower than 0–10 age difference in A-FMT (≧11 vs 0–10, n = 14, 16; P = 0.004). Siblings relationship has a significantly higher maintenance rate compared to parent–child relationship (Siblings vs parent-child; n = 7, 13; P = 0.009). An analysis of some cases in which the microbiota was followed for 24 months revealed a tendency that some bacterial species such as Bacteroides dorei and Bacteroides uniformis maintained their effects.

Conclusion
A-FMT exhibited reassuring clinical outcomes in terms of both short and long term. This is the first report of FMT to reveal importance of donor selection for long-term maintenance for UC.
P079 ISOLATION OF GASTROINTESTINAL PATHOGENS AFFECTS MEDICAL MANAGEMENT OF OUTPATIENTS WITH RELAPSE OF INFLAMMATORY BOWEL DISEASE
Authors: Hong Soonwook , Zaki Timothy , Main Michael , Hine Ashley , Chang Shannon , Hudesman David , Axelrad Jordan 
Published: January 2020

Abstract

Introduction
Evaluating for the presence of gastrointestinal infection is a critical component of the workup for relapse of inflammatory bowel disease (IBD). With the advent of stool multiplex gastrointestinal pathogen panels (GI PCR), infections are increasingly identified. Prior research has shown that detection of enteric infection significantly affects the management of IBD in the inpatient setting. We aimed to characterize the impact of enteric infection detection on the management of IBD therapy in outpatients with relapse of IBD.

Methods
In a cross-sectional study of IBD outpatients at an academic medical center presenting with acute gastrointestinal symptoms from September 2015 to April 2019 who received GI PCR testing, we recorded pathogens detected, demographic data, biomarkers of inflammation, presenting symptoms, IBD subtypes, and IBD therapy. Our primary outcome was dose escalation in IBD therapy, defined as the addition of a new therapeutic agent or an increase in the dose or frequency of an existing medication. Secondary outcomes included rates of endoscopy, abdominal imaging, and antibiotics in the 30-day period after the initial visit and rates of adverse outcomes, i.e. emergency room (ER) visits, hospitalizations, and abdominal surgeries in the 90-day period after the initial visit.

Results
We identified 134 IBD outpatients tested with GI PCR. A pathogen was identified in 35 (26%) patients, of whom 9 (27%) had an increase in their medication regimen; 2 (22%) were prescribed an additional mesalamine, 3 (33%) a biologic, and none glucocorticoids. In contrast, 49/99 (45%, p=0.03) patients without an infection had an increase in their medication regimen, with 3 (7%, p=0.49) prescribed mesalamines, 11 (24%, p=0.67) biologics, and 7 (16%, p=0.04) glucocorticoids (Table 1). No patient received immunomodulators. Patients with an infection received more antibiotics (49% vs. 12%, p&lt;0.01). They were also more likely to present with vomiting (11% vs. 3%, p=0.06) and undergo less post-visit endoscopy (6% vs. 16%, p=0.13), but these differences were near significant. There were no significant differences in demographics, initial IBD medications on testing, presenting symptoms, lab markers, abdominal imaging, or adverse outcomes. The most commonly isolated organisms were Escherichia coli subtypes, with 22/35 (63%) patients having at least one species isolated on testing (Table 2).

Conclusion
Detection of an enteric infection in outpatients with relapse of IBD was associated with significantly fewer dose escalations in IBD therapy, including glucocorticoids, and increased exposure to antibiotics, and a marginal decrease in endoscopy. These changes in management were not associated with a difference in adverse outcomes.
2 EFFECTS OF AN IBD-ASSOCIATED MICROBIAL COMMUNITY STATE ON INTESTINAL INFLAMMATION IN HUMANIZED GNOTOBIOTIC MICE
Authors: Lagishetty Venu , Arias Nerea , Dong Tien , Hauer Meg , Katzka William , Dubinsky Marla , Braun Jonathan , Jacobs Jonathan 
Published: January 2020

Abstract

Background and Aims
We previously reported that 20% of unaffected first-degree relatives of pediatric IBD patients share the same microbial community structure (OTU-type) as IBD patients. This suggests that a preexisting dysbiosis can predispose to the development of IBD. The aims of this study were to establish that microbial community types identified in the family cohort could be reconstituted in gnotobiotic mice for further translational studies and to assess for any direct effects of this microbiota on intestinal inflammation.

Methods
Over 100 germ-free wild-type C57/BL6 mice were colonized for 4 weeks in the UCLA gnotobiotic facility with fecal microbiota from 30 human donors belonging to each of four groups from the pediatric family cohort: unaffected first-degree relatives with OTU-type 1, unaffected first-degree relatives with the IBD-associated OTU-type 2, Crohn’s disease (CD) with OTU-type 1, CD with OTU-type 2. Each group was represented by 8 human donors (n=3–4 mice/donor) with the exception of CD OTU-type 1 (only 5 donors available in the cohort). In addition, 35 eight week old germ-free IL-10-/- C57/BL6 mice were colonized for 12 weeks with fecal microbiota from 4 CD OTU-type 2 donors and 4 unaffected OTU-type 1 donors (n=4–5/donor). Luminal and mucosal microbial composition in the colon and small intestine was evaluated by 16S rRNA sequencing. Intestinal inflammation was assessed in the small intestine and colon by semiquantitative scoring of H&E stained sections.

Results
Donor-specific microbial composition was observed in the humanized gnotobiotic mice with clear separation between recipients of donor OTU-type 1 vs. OTU-type 2 stool. Parallel differences in differentially abundant microbes and microbial diversity were seen in these gnotobiotic mice as in the original human donors. No histologic evidence was found for colitis, enteritis, or fibrosis in wild-type colonized mice. However, fecal lipocalin was increased two-fold increase in recipients of OTU-type 2 microbiota from CD patients relative to the other three groups. CD humanized IL-10-/- mice exhibited lower microbial diversity and distinct microbial composition compared to non-IBD humanized IL-10-/- mice, mirroring differences in the human donors. Mice colonized with CD microbiota had increased histological disease severity in the colon and cecum (p=0.05) compared to mice colonized with non-IBD microbiota.

Conclusion
Our results demonstrate that human microbial community states identified in the pediatric IBD cohort could be reconstituted in gnotobiotic mice for translational studies. Moreover, CD-associated dysbiosis exacerbated colitis severity. These data support the concept that dysbiosis plays a direct role in promoting intestinal inflammation and provide an experimental framework for further mechanistic studies of IBD-associated microbial communities.
8 ROLE OF THE HOST IMMUNE RESPONSE TO ENTERIC PROKARYOTIC VIRUSES IN INFLAMMATORY BOWEL DISEASE
Authors: Angkeow Julia , Monaco Daniel , Handley Scott , Larman H B 
Published: January 2020

Abstract

Background
Gut microbiota comprise important environmental exposures that influence human immune systems and may alter the clinical course of inflammatory bowel disease (IBD). Little is known about the role of gut bacteriophages (viral components that infect prokaryotic bacteria) and their interactions with the host’s immune responses. We tested the hypotheses that (1) immune responses of individuals with IBD to phages differ from those without IBD and (2) immune responses to phages are associated with disease type (i.e. those with Crohn’s disease have different responses than those with ulcerative colitis).

Methods
We have constructed the first bacteriophage peptidome library (“phageome”), based on sequencing of environmental phages and large-scale metagenomic sequencing of virus-like particles isolated from stool samples from IBD patients and their non-IBD household contacts. Using Phage ImmunoPrecipitation Sequencing (PhIP-Seq) technology, we generated complete serum antibody binding profiles of 48 IBD patients (16 ulcerative colitis, 11 Crohn’s, and 11 indeterminate), 9 of their non-IBD household contacts, and an independent non-IBD cohort of 674 volunteers collected by the Vaccine Research Center (VRC) at the National Institutes of Health. Antibody binding profiles were compared among groups using nonparametric statistics.

Results
IBD patients as a group had lower antibody responses to specific phages compared to both non-IBD household contacts and the non-IBD VRC controls; this difference was significant and remained after control for unequal sample sizes [Figure 1]. Patients with Crohn’s disease compared to those with ulcerative colitis had similar antibody responses. Particularly for phages of the genera Phifelvirus, the immune responses of Crohn’s patients were significantly reduced compared to their non-IBD household contacts, while the immune responses of patients with ulcerative colitis did not significantly differ from non-IBD household contacts [Figure 2]. IBD disease type comparisons to the VRC controls yielded similar results.

Conclusion
PhIP-Seq with a phageome library can be used to study the relationship between immune responses and gut bacteriophages in IBD. Our results suggest that IBD patients may have lower antibody responses to specific phages compared to non-IBD individuals. Differential antibody reactivities in Crohn’s disease vs. ulcerative colitis compared to their household contacts and VRC controls suggest disease-specific response to the gut phageome that warrant further study.
P120 PRE-POUCH ILEITIS IS A RISK FACTOR FOR DEVELOPMENT OF CROHN’S DISEASE-LIKE COMPLICATIONS, NEED FOR BIOLOGIC THERAPY AND POUCH FAILURE
Authors: Shemtov Ron , Fleshner Phil , Syal Gaurav 
Published: January 2020

Abstract

Introduction
Pre-pouch ileitis or afferent limb inflammation is generally considered to be suggestive of de novo Crohn’s disease in patients with ileal pouch. However, the data on whether these patients progress to develop CD-like complications is limited. We aim to study the evolution of pre-pouch ileitis in this study.

Methods
All patients who underwent an IPAA surgery by an expert surgeon between 1990 and 2018 for diagnosis of ulcerative colitis (UC) or inflammatory bowel disease-unclassified (IBD-U) at our institution and later went to develop pre-pouch ileitis were included. Patient charts were reviewed were reviewed subsequent to the diagnosis of pre-pouch ileitis to assess development of CD-like complications (non-anastomotic strictures and fistulae developing &gt;6 months after ileostomy closure) or requirement of J-pouch surgery or ileostomy. Pre-pouch ileitis was defined by presence of erosions or ulcers in the afferent limb.

Results
58 patients with J-pouch developed pre-pouch ileitis at a median of 21 months (range 1–216 months) from ileostomy closure. Baseline characteristics are shown in table 1.
Median follow up duration after the diagnosis of pre-pouch ileitis was 48 months (range 2–204 months). 54/58 (93%) patients had concomitant pouchitis with pre-pouch ileitis. 36/58 (62%) patients were initiated on biologic therapy during their follow up course and 3/58 (5%) were treated with an immunomodulator. 20/58 (35%) patients developed Crohn’s disease-like complications (10 developed non-anastomotic strictures and 10 developed perianal complications) at a median follow up of 17 months (range 2–85 months) from the diagnosis of pre-pouch ileitis. 5/58 (8.6%) needed endoscopic stricture dilation and 6/58 (10%) needed perianal surgery for fistula or abscess. Pouch failure occurred in 5/58 (9%) of patients (3 with pouch resection, 1 with pouch revision and 1 with permanent ileostomy), while 3/58 (5%) patients required temporary ileostomy.

Conclusions
Patients who develop pre-pouch ileitis are at high risk of developing CD-like complications (non-anastomotic strictures and perianal complications). The risk of pouch failure and requirement for endoscopic procedures or surgery in this cohort also appears to higher than traditionally reported in patients with pouchitis. Hence, pre-pouch ileitis should be considered suggestive of Crohn’s disease and treated aggressively.
P121 REAL WORLD PREVALENCE OF BOWEL MOVEMENT URGENCY – A SNAPSHOT OF SYMPTOM EXPERIENCE REPORTED BY PATIENTS WITH ULCERATIVE COLITIS PARTICIPATING IN SPARC IBD
Authors: Naegeli April , Dong Yan , Zhou Xian , Morris Nathan , Arora Vipin , Lissoos Trevor 
Published: January 2020

Abstract

Background
Urgency, also referred to as bowel movement urgency or bowel urgency, is the sudden need for a bowel movement. Bowel urgency is one of the most bothersome and important symptoms experienced by patients with ulcerative colitis (UC), contributing to decrements in quality of life. Bowel urgency is distinct from the common symptoms associated with UC, namely stool frequency and rectal bleeding, however patients often experience all symptoms, urgent, frequent bowel movements with bleeding, concurrently. Bowel movement urgency is a key symptom for triggering clinical consideration of UC diagnosis and for defining more severe disease activity in clinical practice.

Methods
The results published here are based on data obtained from the IBD Plexus program of the Crohn’s & Colitis Foundation. To better understand the prevalence of bowel movement urgency in patients with UC, an ad hoc analysis was performed using data from a Study of a Prospective Adult Research Cohort with IBD (SPARC IBD), a multicenter longitudinal study of adult patients with IBD that collects and links clinical data, patient-reported outcome (PRO) data, and serial bio-samples throughout the course of the patients’ disease. The enrollment visit was defined as 7 days from the patients’ date of enrollment in SPARC IBD. At study enrollment, patients were asked to answer questions based on their symptom experiences. Patients reported how much urgency they experienced before bowel movements on average during the past 3 days (none, mild, moderate, moderately severe, severe, not applicable). Descriptive analyses for patient demographic and disease characteristics were conducted. Additionally, contingency table analyses were conducted exploring the association of urgency with other UC symptoms and other measures of UC disease severity.

Results
Of 1,833 patients included in the SPARC IBD data cutoff of May 13, 2019 (Enrolled from 08 November 2016 to 15 May 2019), 582 were patients with UC, of which 514 had urgency data available. Overall, 51.8% of patients were male, and the mean age is 42.4 years (Table 1). At enrollment, 59.7% of patients reported some level (mild, moderate, moderately severe/severe) of urgency. Forty-six percent of UC patients with urgency data were receiving biologic treatment with 31% still reporting mild urgency, and 32% reporting moderate to severe urgency (Table 1). The severity of urgency was associated with patient reported severity of other UC symptoms and disease activity (Table 2).

Conclusion
Results from ad hoc analyses using a real-world sample of patients with UC suggest that bowel movement urgency is a prevalent symptom of UC which varies with disease activity.
P007 CROHN’S DISEASE: PREDICTORS OF HOSPITAL DISPOSITION AND COSTS USING DEMOGRAPHIC, CLINICAL, AND TREATMENT DATA
Authors: Brunt Hartman , Adams Mason , Barker Michael , Hamer Diana , Chapman J C 
Published: January 2020

Abstract

Purpose
Crohn’s disease (CD) is an inflammatory bowel disease (IBD) caused by an abnormal immune response to intestinal microbes in a genetically susceptible host. The objective of this cohort analysis is to compare demographic characteristics, cost difference, and treatment modalities between patients who were discharged from the Emergency Department (ED) and those who were admitted to the hospital.

Methods
This study is a retrospective chart review of adult patients diagnosed with CD who were discharged from the ED and those who were admitted to the hospital between January 1, 2014 and January 1, 2017. We compared demographic and clinical characteristics as well as total charges incurred by these patients. A chi square test of independence and a Mann Whitney U-Test were used to compare categorical variables. Linear and logistic regression analyses were utilized to identify predictors of hospitalization and total charges.

Results
Of a total 195 patients, 97 were discharged from the ED and 98 were admitted to the hospital (Table 1). Patients who presented with fever, nausea/vomiting, or abdominal pain or who had a history of a fistula or stenosis were more likely to be hospitalized, as were patients who presented on steroids, 5-ASA compounds, or narcotics (Table 2). A logistic regression adjusted for these factors showed patients presenting with abdominal pain (OR=0.239, 95% CI 0.07 – 0.77) are less likely, while patients presenting with fever (OR=7.0, 95% CI 1.9 – 24.5) and history of stenosis (OR=17.8, 95% CI 5.7 – 55.9) are more likely to have a hospital admission. An increase in age and white blood cell count was associated with an increase in likelihood of admission (OR=1.04, 95% CI 1.01 – 1.07 and OR=1.2, 95% CI 1.1 – 1.4), while an increase in HGB was associated with a decrease in likelihood of admission (OR=0.682, 95% CI 0.55 – 0.83). Patients on 5-ASA compounds had the strongest association with hospital admission (OR=4.5, 95% CI 1.03 – 20.4). A linear regression analysis predicting total charges of hospitalization identified an increase of $37,500 (95% CI 6,600 – 68,489) for obese patients and of $29,000 (95% CI 20 – 57,000) for patients on narcotics prior to hospitalization. Notably, blacks were on average 6 years younger than whites (μ=36.2, st.d.=13.2 v μ=42.7, st.d.=18.2, p=0.031, respectively). No other differences in presentation or outcomes of CD were identified between these races.

Conclusion
This study describes the difference between CD patients who were admitted to the hospital compared to those who were discharged from the ED. The impact that 5-ASA compound, steroid, and narcotic use prior to presentation has on hospital admission and charges highlights the need for consistent outpatient care to manage the symptoms and disease progression in patients with CD in Baton Rouge. The difference in age at presentation between blacks and whites should also be considered in future research.
P008 EVALUTING THE EFFECTIVENESS OF TRANSITION OF CARE FOR PEDIATRIC INFLAMMATORY BOWEL DISEASE PATIENTS USING A STANDARDIZED TRANSITION PROCESS
Authors: Shearer Jennifer , Perry Sharon , Lidyard Nicole , Burkhart Kimberly , Katz Jeffry , Apperson Carolyn , Moses Jonathan 
Published: January 2020

Abstract

Significance
The incidence of inflammatory bowel disease (IBD) is rising around the globe. As pediatric IBD patients approach adulthood, they are in jeopardy of a lapse in care. We developed a standardized a health maintenance transition visit (HMV) to supplement standard medical care visits (SMV) to prepare patients for transition. Our aim was to assess the effectiveness of the structured HMV using the Transition Readiness Assessment Questionnaire (TRAQ) to predict readiness at time of transfer to an adult gastroenterologist.

Methods
A retrospective chart review was conducted including demographics and clinical data from HMV visits and pediatric or adult SMV visits. Clinical variables included scheduling, providers, TRAQs, Patient Health Questionnaire-9 (PHQ9), health maintenance goals, and disease status. The effectiveness of the HMV was accessed by attendance, PHQ9 screening, adherence to health recommendations, and TRAQ scores.

Results
140 patients completed at least one HMV. The patient cohort was 80% white and 59% male. Mean age was 18 ± 2 years old at the time of their first HMV. The majority of patients had a primary IBD diagnosis of Crohn’s disease (75%), followed by ulcerative colitis (21%), and unclassified IBD (4%). Most patients had inactive disease (68%) around the time of the first HMV, while a minority had mild (20%) or moderate (12%) disease activity based on PGA. The average TRAQ score at the first HMV visit was 66 ± 17. Patients who completed at least 1 prior HMV (n=8) scored significantly higher on the TRAQ when transferring to the adult care compared to patients (n=29) who were transferred at their first HMV visit (92 vs 83, p&lt;0.05). Of the 56 patients who completed the PHQ9 depression screen, 22 had a positive screen. Of the patients with no prior diagnosis of depression, 36% had a positive screen with the severity of depression ranging from mild to severe. Across all visits, 45 patients were transferred into adult care following a HMV.

Conclusions
This study demonstrated that a structured HMV prior to transfer may increase transition readiness as assessed by the TRAQ. In addition, new diagnosis of depression was made in a significant portion of patients screened, emphasizing the importance of regular screening for psychological issues. Future studies are needed to validate these findings and potentially move towards a standard template for transition readiness in pediatric IBD patients.