bluuebunny/crossref_metadata_2025 huggingface dataset:
Subclinical atherosclerosis is associated with incident atrial fibrillation: a systematic review and meta-analysis
Authors: Kristensen Kit Engedal , Knage Cille Cederholm , Nyhegn Liv Havgaard , Mulder Bart A , Rienstra Michiel , Van Gelder Isabelle C , Brandes Axel
Published: January 2020

Aims

Coronary artery disease is an established risk factor for incident atrial fibrillation (AF), but it is unclear whether subclinical atherosclerosis also increases the risk of incident AF. Therefore, the aim was to assess the association between subclinical atherosclerosis, defined by increased carotid intima-media thickness (cIMT) or coronary artery calcium score (CACS), and incident AF.

Methods and results

A systematic review of MEDLINE, EMBASE, and Cochrane was done to find all cohort studies investigating the association between subclinical atherosclerosis, defined by increased cIMT or CACS, and incident AF. Eligible articles had to be available in an English full-text version; include adults over the age of 18 years; include ≥100 participants; and have a follow-up period ≥12 months. Data on cIMT were pooled using a fixed-effects model, while data on CACS (I2 >25) were pooled using a random-effects model. Five studies on cIMT including 36 333 patients and two studies on CACS including 34 603 patients were identified. All studies investigating the association between increased cIMT and incident AF showed a significant association, with an overall hazard ratio (HR) of 1.43 [95% confidence interval (CI) 1.27–1.59]. The two studies investigating the association between increased CACS and AF also showed a significant association with an overall HR of 1.07 (95% CI 1.02–1.12).

Conclusion

Data from seven observational studies suggest that subclinical atherosclerosis defined by increased cIMT or CACS is associated with an increased risk of incident AF. These findings emphasize the need for further research investigating whether treatment of subclinical atherosclerosis should be a part of the initiatives to prevent AF.
Participation of People With Impairments in Seniors’ Organizations: Conditions and Limitations on Inclusion
Authors: Raymond Émilie , Lantagne Lopez Mélanie
Published: January 2020

Background and Objectives

While older adults’ social participation has attracted sustained attention, the realities faced by seniors with impairments in this area are still understudied. Social representations are formed from socially constructed opinions regarding a given object and have four functions (knowledge, identity, orientation, justification). The purpose of this article is to document the social representations that exist within seniors’ organizations regarding participation by older people with impairments.

Research Design and Methods

In this mixed-methods study, an exploratory sequential design was applied. First, a qualitative phase involved meetings with five focus groups to explore how participants would manage difficult situations in which the inclusion of an older person with impairments must be addressed. Second, a quantitative phase consisted of a questionnaire administered to 86 respondents to examine the components of social representations about the participation of older people with impairments.

Results

Results show that, although research participants acknowledge that all seniors have the right to participate, this right confronts a collective identity infused with aging model that demands a youthful, “un-disabled” appearance and activities. In terms of the orientation function, making participation a reality is seen as relying on the efforts of people with impairments, but when there is a failure of inclusiveness, the reasons offered to justify it concern the resources available, rather than possible prejudices.

Discussion and Implications

Interpretation of the results leads to recommendations for both implementing an inclusion philosophy and practices in seniors’ organizations and revisiting the view of impairment in old age as otherness.
Visions of the future: political labour’s temporality and socialist objectives in Britain and Australia, 1918–21
Authors: Byrne Liam
Published: January 2020

This article is a comparative study of political temporality and the concept of the ‘future’ in British Labour and Australian Labor. It deepens knowledge of how Labo(u)r’s political culture has been forged through debates over socialism, focusing on the socialist objectives of 1918 and 1921. As a result, it allows an appreciation of phenomena such as the rise of Jeremy Corbyn and ‘Corbynism’. It is focused around a reading of the major conferences of each party, as sites of power negotiation, debate and ideological creation. These sources are complemented by an extensive reading of labour newspapers and pamphlets from both countries.
P057 WIRELESS ELECTRODE PATCHES SHOW INTRAPATIENT REPRODUCIBILITY IN A LONGITUDINAL STUDY OF PATIENTS WITH CROHN’S DISEASE IN REMISSION
Authors: Axelrod Steve , Axelrod Lindsay , Navalgund Anand , Spear Estelle , Patel Akshar , Li Cuiping , Habtezion Aida , Triadafilopoulos George
Published: January 2020

Background

Crohn’s disease (CD) patients would benefit from a non-invasive indicator of gut function to better predict changes in disease state, such as the onset of flare. A study of CD patients using non-invasive wireless electrode patches (G-Tech Medical, Mountain View, CA) that read myoelectric signals from the gut over 3 days is underway at Stanford University’s IBD center. The study will include 40 patients presenting in flare and 30 in remission to be tested at t=0, 1, 3 and 6 months. In addition, one-time tests will be performed on 20 healthy controls.

Aims

Herein, we report on the first 6 CD patients tested at t=0 and 1 month while in remission.

Methods

Each patient wore 3 abdominal patches (each 2.7” diameter) for 3 consecutive days while pursuing regular daily activities and meals (Figure 1). Each patch recorded 4 channels of myoelectric activity from the stomach, small intestine and colon, and transmitted the raw data to an iPod Touch, which relayed the data to a secure cloud server. Data were later downloaded and processed to remove artifacts, create frequency spectra, and search them for peaks representing rhythmic motor activity. We find that, nominally, stomach activity appears at 3 cycles/minute (cpm), small intestine at 6–12 cpm, and colon at 12–25 cpm.

Results

Figure 2 shows peak spectra for the 6 patients at t=0 and 1 month. Individual peaks represent motor activity at a specific frequency associated with the stomach, small intestine, or colon. Each patient has a unique overall pattern, or GutPrint, reflecting the frequencies and levels of activity of their GI motility. The GutPrint for each individual reproduces well at the second test and is easily recognizable for each subject. Although the peak amplitudes may vary, virtually all of the peaks that appear at specific frequencies at t=0 are also present at 1 month representing a quantifiable signature that reflects each patient’s unique motility.

Conclusion

The G-Tech patch system provides a practical and noninvasive, physiologic means of measuring motor activity of the gut over multiple days. Its intra-patient reproducibility allows for the possibility of measuring changes to gut performance over time, whether naturally- or drug-induced, showing promise in CD monitoring.
P112 CORRELATION OF FECAL CALPROTECTIN TO COLONOSCOPIC FINDINGS FOR DETECTION OF RECURRENCE OF CROHN’S DISEASE IN THE POST-OPERATIVE SETTING AT A SINGLE ACADEMIC CENTER
Authors: Sharma Anil , Morrison Georgia , Keyashian Kian , Matro Rebecca
Published: January 2020

Introduction

Patients with Crohn’s disease (CD) who undergo a first surgery are at higher risk of having a subsequent surgery in light of recurrence of disease. Significant evidence suggests that a postoperative colonoscopy evaluating recurrence at the anastomosis using the Rugeerts score (RS) can predict risk of repeat surgery. Given the invasive nature of colonoscopy, there has been increasing interest in using noninvasive biomarkers to predict disease recurrence. Studies have shown variability in the operating characteristics of the fecal calprotectin (FC) assay with sensitivities and specificities for detecting recurrence ranging widely from 48–95 and 58–79%, respectively. A recent meta-analysis demonstrated a pooled sensitivity of 70% when using an optimal FC cut-off of 150 ug/g. We sought to delineate how FC correlates with RS at our institution and to identify a cutoff for significant recurrence.

Methods

We performed a retrospective review of adult patients with CD who underwent ileocecectomy followed by a colonoscopy within 18 months of surgery, with the additional inclusion of FC testing within 2 weeks of the colonoscopy. Patients were identified at our institution via ICD 9 and 10 codes and the electronic medical record. The primary outcome of interest was a comparison of mean FC for those without endoscopic recurrence (defined as RS i0-i1) to those with significant endoscopic recurrence (defined as RS i2-i4). Other variables assessed included gender, disease location and phenotype, and extent of surgery (Table 1).

Results

A total of 12 patients met the inclusion criteria. 7 patients (58.3%) were female. Age at time of surgery ranged from 21 to 73 years (mean 37.9). Only 1 patient (8.3%) had a nonstricturing, nonpenetrating phenotype. After surgery, 11 patients were on biologic or combination therapy and 1 patient was not on any medical therapy. 5 patients (42%) demonstrated endoscopic recurrence by RS with mean FC of 883.7 ug/g, as compared to mean FC of 83.6 ug/g for those without recurrence. There was a positive correlation between FC and RS with a Spearman’s rank correlation coefficient of 0.86 (p = 0.0004).

Conclusions

Our results demonstrate a strong correlation between FC and RS. Using a cutoff for FC of 150 ug/g, we demonstrate sensitivity and specificity of 100%. This further supports the possibility of using FC as a surrogate to possibly defer colonoscopy in those post-operative CD patients with low FC. Study limitations include the retrospective nature and small sample size, recognizing that in years past FC was not as readily available or used in this setting. Future considerations include larger, prospective studies looking at FC and other noninvasive biomarkers in this post-operative setting.
P115 RELATIONS BETWEEN DISEASE STATUS AND BODY COMPOSITION IN PEDIATRIC INFLAMMATORY BOWEL DISEASE
Authors: Talathi Saurabh , Nagaraj Pooja , Jester Traci , Maclin Jeanine , Knight Taylor , Barnes Margaux
Published: January 2020

Objective

To evaluate the effect of remission status on physical activity, and body composition in pediatric patients with inflammatory bowel disease (PIBD) and healthy peers.

Methods

Single center cohort study including 54 PIBD patients and 33 healthy peers. During initial study visit, a brief demographic questionnaire, physical activity questionnaire completed by participants and instructions on recording dietary intake were given. Physicians completed the Physician Global Assessment (PGA) for disease severity. Medical chart abstraction done to obtain disease variables of interest. DEXA scan completed one week later to obtain information on body composition. Variables of interest were compared between the three groups (IBD-Remission, IBD-Active and healthy controls) using an ANOVA or Chi square test as appropriate.

Results

IBD patients were older than controls, reported lower quality of life (73.9 vs 80.9) and engaged in less MVPA (195.4 versus 361.1). IBD-Active group had a significantly lower lean body mass, bone mineral density and time spent in MVPA compared to IBD-Remission group and healthy controls. IBD-Remission group had a significantly lower percentage of biologic use (55% vs 87%) and comorbidities (26% vs 44%) compared to IBD-active group. IBD-remission group also had a lower fat mass percentage.

Discussion

In this study, we report significantly favorable LBM, BMD, and time spent in MVPA in patients with IBD in remission compared to those not in remission with the former demonstrating a body composition resembling to that of healthy peers. While an improvement in BMD was observed with remission, the scores were still lower than controls.
P116 SMALL BOWEL INVOLVEMENT IN CHRONIC GRANULOMATOUS DISEASE COLITIS
Authors: Bhattacharya Sumona , Taneja Sonia , Zerbe Christa , DeRavin Suk See , Malech Harry , Holland Steven , Koh Christopher , Heller Theo
Published: January 2020

Chronic granulomatous disease (CGD) is a rare disorder caused by genetic mutations of the nicotinamide adenine dinucleotide phosphate oxidase complex (NADPH), occurring in approximately 1/200,000 individuals. These mutations decrease residual reactive oxygen species (ROS) levels, leading to dysregulated inflammation. Inflammatory manifestations can be widespread, including severe and recurrent infections. The gastrointestinal tract is the most commonly affected organ with resultant inflammatory bowel disease, termed CGD colitis. Manifestations include abdominal pain, diarrhea with or without blood, nausea/vomiting, obstructions, and fistulas which can occur in a perianal distribution. Patients are often misdiagnosed with Crohn’s disease or ulcerative colitis, especially in the absence of extensive infectious history. We aimed to characterize the small bowel involvement in CGD.

Data is presented from a combined retrospective and ongoing prospective observational study of patients with genetically-confirmed CGD who underwent wireless video capsule endoscopy (VCE) at the National Institutes of Health Clinical Center (n = 8). VCEs were performed for clinical indications including abdominal pain (88%), diarrhea (75%), bloody stools (38%), and/or nausea/vomiting (25%). One patient (13%) underwent VCE for otherwise unexplained high inflammatory markers. Laboratory evaluation was significant for leukopenia/leukocytosis (75%), anemia (63%), and elevated C reactive-protein levels (63%). Seven patients (88%) had prior small bowel imaging, however none showed evidence of any abnormality in this organ. The most common VCE findings were ulcers and/or erosions (88%). Most patients also displayed other mucosal changes consistent with inflammation such as erythema and/or edema (88%). There was also evidence of blood or hematin on 63% of the endoscopies.

While therapies for CGD colitis are targeted towards colonic involvement, our findings show that the vast majority of symptomatic patients also have active small bowel disease including ulcers, erosions, evidence of bleeding, and other signs of inflammation. These findings, however, are not specific to CGD. Given that certain biologic medications used for Crohn’s disease and ulcerative colitis have been shown to increase the risk of life-threatening infections in patients with CGD, it is important to keep other forms of IBD, especially CGD-related IBD, in mind when interpreting small bowel capsule endoscopy in patients with suspected IBD. Lastly, in patients with confirmed CGD colitis, small bowel disease should be rigorously investigated, and therapy should also seek to address small bowel involvement. Of note, our patients did not display any radiographic abnormalities of the small bowel. Due to our small sample size, we aim to study additional patients in the future to augment our data.
P107 SINUSITIS IS A RISK FOR SUBSEQUENT INFLAMMATORY BOWEL DISEASE
Authors: Rai Victoria , Traboulsi Cindy , Gulotta George , Rubin David
Published: January 2020

Introduction

The relationship between sinusitis and inflammatory bowel disease (IBD) has not yet been established. Though the two are characterized by dysfunction of the epithelial barrier, there lacks evidence on the relative contributions of infection or inflammation to this co-morbidity in IBD patients. Previous analysis from our group (ACG 2019) identified an increased prevalence of sinusitis among patients with IBD, but that work did not include a stratified analysis of IBD patients with sinusitis based on the order in which these conditions were diagnosed.

Methods

This is a retrospective study at our tertiary IBD center. We utilized our institution’s electronic medical record data warehouse of 2.4 million patients to identify those with diagnostic codes for both sinusitis (J32) and IBD (K50.90 and K51.90). Patients with a confirmed diagnosis of IBD and/or sinusitis between January 2000 and May 2019 and age ≥18 years were included. Demographic and disease related information were collected, including dates of diagnosis for both sinusitis and IBD. Categorical variables were analyzed using Fisher’s exact test and continuous variables were analyzed using Wilcoxon rank sum test.

Results

Of 14,366 patients with IBD, 386 patients (2.69%) were diagnosed with both IBD and sinusitis (IBD+S). The average age of IBD diagnosis in the IBD only group was 37.30 (18.76) years and IBD+S group was 38.36 (19.81) years (p = 0.27). Of the 386 patients with IBD+S, 268 (69.4%) were diagnosed with IBD before sinusitis and 118 (30.6%) were diagnosed with IBD after sinusitis (Table 1). The average age of IBD diagnosis in the IBD before sinusitis group was 33.2 ± 17.3 years, which was significantly younger than patients in the IBD after sinusitis group of 50.2 ± 20.2 years (p < 0.001). The average time between diagnoses was significantly more in the group diagnosed with IBD before sinusitis compared with the group diagnosed with IBD after sinusitis (7.64 ± 8.89 years vs 3.73 ± 3.16 years, respectively; p < 0.001). In addition, patients diagnosed with IBD after sinusitis were significantly less likely to be of white race, never smokers, have Crohn’s disease, bowel obstruction, or be receiving immunosuppressive medications.

Conclusions

There are significant differences in the characteristics of patients with IBD and sinusitis from IBD only patients, and even greater differences when stratifying the IBD+S group based on the order of diagnoses. Within the subgroup of IBD+S, most notably, patients with sinusitis first have an older age of IBD diagnosis. These findings suggest that a diagnosis of sinusitis should prompt consideration of co-existing or subsequent risk of IBD.
P148 COLONIC SPROUTY2 IS ELEVATED IN INFLAMMATORY BOWEL DISEASE PATIENTS
Authors: Appel Keren , Schumacher Michael , Frey Mark
Published: January 2020

Background

The intestinal epithelium plays a central role in protecting against the development of colitis, and is disrupted in inflammatory bowel disease (IBD). It serves as the physical barrier that, when breached, allows luminal contents (i.e. bacteria, antigens) to stimulate inflammatory responses. Sprouty2 (SPRY2) is an intracellular regulator of growth factor receptor signaling that is downregulated in a compensatory response to inflammatory stimuli in cell lines and a mouse model of colitis. Additionally, mice with intestine-specific Spry2 deletion are protected against colitis and have elevated tuft and goblet cell numbers, cell types thought to protect the intestinal epithelium. This may represent a feedback mechanism to reinforce the intestinal epithelium during the initial stages of injury. However, the regulation of SPRY2 in IBD patients is unknown. We hypothesized that SPRY2 expression might be dysregulated in patients with IBD.

Methods

SPRY2 levels were measured by quantitative PCR analysis of human colonic tissue from endoscopic biopsies and surgical resection specimens from pediatric IBD and non-IBD patients. Human colonoids (primary cultures of colonic epithelium) were grown from surgical resection specimens of non-IBD control patients. SPRY2 expression was measured via qPCR in response to treatment with TNF for 24 hrs.

Results

SPRY2 expression decreased by an average of 24.41% (p = 0.0002, n =4) in colonoids from non-IBD patients treated with tumor necrosis factor (TNF) 10 ng/mL and 18.13% (p = 0.0016) for 100 ng/mL. However, SPRY2 expression in endoscopic biopsies from IBD patients was 2.325 ± 0.9846 fold higher in ulcerative colitis (UC) patients (p= 0.0242, n =8) and 9.825 ± 2.800 fold higher in Crohn’s disease patients (p= 0.0014, n=6) compared to non-IBD controls (n=27). In surgical specimens, SPRY2 levels were 37.10 ± 21.96 (p= 0.0459) fold higher in IBD (n=6) vs. non-IBD (n=4) patients. Furthermore, data mining of Gene Expression Omnibus dataset GDS3268 (biopsies from UC patients) revealed a significant negative correlation between SPRY2 and the protective tuft cell markers DCLK1 and TRPM5.

Conclusion

Acute TNF signaling repressed SPRY2 expression in a human colonoid model. In contrast, SPRY2 levels appear to be increased in human IBD and negatively correlate with tuft cell markers. Together these data suggest that, while acute inflammation can downregulate SPRY2 to drive increased numbers of protective secretory cells, in chronic disease this response either does not occur or is lost. A failure to down-regulate SPRY2 in response to early mucosal damage may be a factor in the development of IBD.
P149 DECREASED COLONIC ACTIVIN RECEPTOR-LIKE KINASE 1 DISRUPTS EPITHELIAL BARRIER INTEGRITY AND IS ASSOCIATED WITH A POOR CLINICAL OUTCOME IN CROHN’S DISEASE
Authors: Toyonaga Takahiko , Keith Benjamin , Barrow Jasmine , Schaner Matthew , Wolber Elizabeth , Beasley Caroline , Huling Jeniffer , Wang Yuli , Allbritton Nancy , Furey Terrence , Sethupathy Praveen , Sheikh Shehzad
Published: January 2020

Background and Aims

Intestinal epithelial cell (IEC) barrier dysfunction is critical to the development of Crohn’s disease (CD). Mechanisms controlling colonocyte differentiation and barrier defects are understudied in CD. We recently reported increased expression of microRNA-31-5p (miR-31-5p) in colonic IECs of CD patients compared to non-IBD (NIBD) controls. In this study we identify and characterize the miR-31-5p target gene Activin Receptor-Like Kinase 1 (ALK1) as a key regulator of colonocyte maturation and IEC barrier integrity, specifically the functional impact of aberrant ALK1 signaling on colonocyte differentiation, barrier integrity, and clinical disease outcomes in CD.

Methods

MiR-31-5p target genes were identified in CD patients by integrative analysis of RNA- and small RNA-sequencing data from colonic mucosa and confirmed by quantitative RT-PCR (qPCR) in isolated colonic IECs. Functional characterization of ALK1 in colonic IECs was performed ex vivo using 2- or 3-dimensional cultured human primary colonic IECs. The impact of altered colonic ALK1 signaling for the risk of surgery and endoscopic relapse was evaluated by a multivariate regression analysis and a Kaplan-Meier estimator among CD patients.

Results

Integrative analysis of RNA- and small RNA-sequencing and follow-up qPCR identified ALK1 as a candidate target of miR-31-5p in the colonic IECs of CD patients. A 3’-UTR reporter assay with site-directed mutagenesis confirmed the direct regulation of ALK1 expression by miR-31-5p in HEK293T cells. Increased activation of ALK1 restricted the proliferation of primary colonic IECs in an EdU proliferation assay and down-regulated the expression of stemness-related genes, such as LGR5 and ASCL2. Activated ALK1 signaling directed the fate of human colonic IEC differentiation toward colonocytes. Down-regulated ALK1 signaling was associated with increased stemness-related gene expression and decreased colonocyte-specific gene expression in the isolated colonic IECs of CD patients compared to non-IBD controls. Activation of ALK1 did not affect colonic IEC migration in a wound healing assay, but enhanced epithelial barrier integrity in a trans-epithelial electrical resistance (TEER)-based permeability assay. Lower colonic ALK1 expression was associated with higher risks of surgery and endoscopic relapse in CD patients.

Conclusion

Decreased colonic ALK1 signaling disrupts colonic IEC barrier integrity and is associated with a poor clinical outcome in CD patients.
P145 MECHANISMS OF ACTION FOR THE IBD-RISK GENE C1ORF106/INAVA
Authors: Luong Phi , Lencer Wayne , Chang Denis , Li Qian
Published: January 2020

C1ORF106, also named INAVA (Innate Immune Activator), was identified as a risk gene for the chronic inflammatory bowel diseases (IBD) by genome-wide association studies and targeted exome sequencing. INAVA is highly enriched in polarized simple epithelia, the cell type that lines the intestine and interfaces most directly with the outside world. We discover that INAVA provides a direct mechanistic link between mucosal barriers and inflammation. This is driven by INAVA’s signature Domain of Unknown Function DUF3338, which we newly defined as an enhancer of IL-1β-TRAF6 polyubiquitination cascades. Our work shows that DUF3338 stably binds the GTP-exchange factor cytohesin-2 (ARNO), in one case blocking the formation of INAVA stress puncta and its effect on ubiquitination, and in another case acting at lateral membranes where the INAVA-ARNO complex regulates cortical F-actin dynamics and epithelial barrier function. We thus rename the DUF3338 domain CUPID for Cytohesin Ubiquitin Protein Inducing Domain. We performed a high throughput small molecule screen to identify molecules that modulated INAVA function in cells. Compounds hits identified in the screen links INAVA’s role in barrier and stress response mechanisms involving actin dynamics and proteostasis.
15 LONGITUDINAL EVALUATION OF MUCOSAL DNA METHYLATION IN ULCERATIVE COLITIS SHOWS DISEASE-SPECIFIC CHANGES
Authors: Venkateswaran Suresh , Kilaru Varun , Somineni Hari , Matthews Jason , Hyams Jeffrey , Investigators Protect , Cutler David , Smith Alicia , Conneely Karen , Kugathasan Subra
Published: January 2020

Background

Although inflammatory bowel disease (IBD) is heritable, the heritability is still largely unexplained despite substantial progress through GWAS and WGS. However, recent advances in epigenetics (gene environmental interactions), including DNA methylation (DNAm) analysis, has identified new disease-specific mechanisms controlling gene expression. We recently showed that IBD-associated blood DNAm patterns strongly correlated with inflammation (CRP as surrogate marker) and reverted to patterns seen in healthy controls following treatment, regardless of whether or not the underlying IBD was in remission, suggesting blood DNAm is more representative of the systemic inflammatory status rather than disease status (Gastroenterology, 2019, 156 (8): 2254–2265). Thus, we aimed to study DNAm patterns in rectal biopsies hypothesizing that DNAm in rectal biopsies will reflect disease status rather than systemic inflammatory status alone.

Method

Genome-wide DNA methylation was measured using the Illumina MethylationEPIC array on rectal biopsy DNA samples of 85 non-inflammatory, non-IBD controls and 215 newly diagnosed ulcerative colitis (UC) patients prior to therapy, along with 49 one-year follow-up UC cases (PROTECT cohort) to identify disease specific methylation patterns. Epigenome wide association studies (EWAS) were performed with UC and CRP as the outcomes in linear models adjusted for age, gender, race and five genotype-based principal components.

Results

At diagnosis, 2446 disease-specific CpG sites in rectal tissue (FDR<0.05) were identified. At baseline, the disease-associated DNAm signature in rectal tissue is distinct from our previous study from blood as only 15 CpGs were common between rectal tissue DNAm and blood DNAm. In contrast to what was observed in blood DNAm where the initial DNAm signature reverted back to control levels upon treatment, rectal tissue DNAm signatures remained persistent during follow-up (Figure 1). The majority of the disease-specific CpG sites identified in rectal biopsies showed a strong positive correlation with CRP. This evidence suggests that the treatment affects systemic measures of inflammation more strongly than disease tissues.

Conclusion

When studied longitudinally, the UC-specific DNA methylation patterns in rectal tissue are distinct from blood samples. In contrast to blood DNAm which normalizes after therapy during follow-up, rectal tissue DNAm changes persist after treatment in UC. This suggests the currently available therapies control the systemic inflammation effectively, but have less direct effect on the disease itself. Future therapies targeting disease-specific DNAm may be more effective in disease management and long-term remission.
10 THE ROLE OF DIETARY L-SERINE IN THE REGULATION OF INTESTINAL MUCUS BARRIER DURING INFLAMMATION
Authors: Sugihara Kohei , Kamada Nobuhiko
Published: January 2020

Background

Recent accumulating evidence suggests that amino acids have crucial roles in the maintenance of intestinal homeostasis. In inflammatory bowel disease (IBD), amino acid metabolism is changed in both host and the gut microbiota. Among amino acids, L-serine plays a central role in several metabolic processes that are essential for the growth and survival of both mammalian and bacterial cells. However, the role of L-serine in intestinal homeostasis and IBD remains incompletely understood. In this study, we investigated the effect of dietary L-serine on intestinal inflammation in a murine model of colitis.

Methods

Specific pathogen-free (SPF) mice were fed either a control diet (amino acid-based diet) or an L-serine-deficient diet (SDD). Colitis was induced by the treatment of dextran sodium sulfate (DSS). The gut microbiome was analyzed by 16S rRNA sequencing. We also evaluate the effect of dietary L-serine in germ-free mice and gnotobiotic mice that were colonized by a consortium of non-mucolytic bacterial strains or the consortium plus mucolytic bacterial strains.

Results

We found that the SDD exacerbated experimental colitis in SPF mice. However, the severity of colitis in SDD-fed mice was comparable to control diet-fed mice in germ-free condition, suggesting that the gut microbiota is required for exacerbation of colitis caused by the restriction of dietary L-serine. The gut microbiome analysis revealed that dietary L-serine restriction fosters the blooms of a mucus-degrading bacterium Akkermansia muciniphila and adherent-invasive Escherichia coli in the inflamed gut. Consistent with the expansion of mucolytic bacteria, SDD-fed mice showed a loss of the intestinal mucus layer. Dysfunction of the mucus barrier resulted in increased intestinal permeability, thereby leading to bacterial translocation to the intestinal mucosa, which subsequently increased the severity of colitis. The increased intestinal permeability and subsequent bacterial translocation were observed in SDD-fed gnotobiotic mice that colonized by mucolytic bacteria. In contrast, dietary L-serine restriction did not alter intestinal barrier integrity in gnotobiotic mice that colonized only by non-mucolytic bacteria.

Conclusion

Our results suggest that dietary L-serine regulates the integrity of the intestinal mucus barrier during inflammation by limiting the expansion of mucus degrading bacteria.
21 NATURAL HISTORY OF COLECTOMY AMONG HOSPITALIZED PATIENTS WITH ULCERATIVE COLITIS IN THE CONTEMPORARY ERA OF BIOLOGICS
Authors: Sedki Mai , Stram Douglas , Alam Asim , Shirazi Aida , Velayos Fernando
Published: January 2020

BACKGROUND

Despite reducing mortality, the use of intravenous (IV) corticosteroids has not significantly reduced inpatient colectomy rates among hospitalized patients with ulcerative colitis (UC). Whether the occurrence of colectomy, estimated at 20–30% in this population in the prebiologic era, remains elevated is unknown.

Methods

A retrospective cohort study was conducted among health plan members of an integrated health care delivery organization that serves approximately 4.0 million members in urban, suburban, and semi-rural regions throughout Northern California. The study population consisted of 524 health plan members age >18 years of age with a 1) diagnosis of ulcerative colitis (ICD-9 code 556; ICD-10 code K51); 2) first hospitalization between 2009 and 2017 coded with ulcerative colitis as the primary cause for admission; 3) no prior hospitalizations for UC; 4) at least 1 year of continuous membership prior to the index hospitalization; 5) No dispensing of biologic therapy (infliximab, adalimumab, golimumab, vedolizumab) recorded prior to hospitalization; 6) No record of Clostridium difficile or cytomegalovirus infection during the hospitalization or 30 days prior. The primary outcome was the occurrence of colectomy during the index hospitalization and up to 12 months after hospitalization. Additional outcomes assessed were trends in colectomy over this time period and predictors for colectomy during the index hospitalization.

Results

A total of 5.3% of UC patients underwent colectomy during the index hospitalization (95%CI 3.3–7.3%) and 11.9% underwent colectomy within the first year after hospitalization (95% CI: 9.1–14.6%). Inpatient colectomy declined from 6.5% (95%CI: 2.5–10.6%) in 2009–2010 to 3.4% (95%CI: 3.3–7.3%) in 2015–2017. Colectomy in the first year after admission declined from 15.7% (95%CI 10.0–21.4%) in 2009–2011 to (10.1%; 95% CI: 5.4–14.7) in 2015–2017. A total of 16.3% of patients received infliximab in the hospital and 36.3% received within the first year of admission. In a multivariable model, the 2015–2017 cohort experienced a 64% reduction in inpatient colectomy compared to the 2009–2011 cohort (OR 0.36; 95%CI: 0.11–1.14, p=0.082) and a 54% reduction in colectomy in the first year (OR 0.46; 95%CI: 0.22–0.96, p=0.038). A prior study between 1998–2004 in this same population showed colectomy rates of 20% during the index hospitalization and 30% at 1 year.

Conclusion

Colectomy within the first year after hospital admission for UC has declined over time in the modern era of biologics with a magnitude of colectomy that is lower than the historical rate of 20–30%. Our data imply cause for optimism that the natural history of colectomy in acute severe UC may be different and modifiable in the modern biologic era compared to the past.
P006 AFTER-HOURS PATIENT PHONE CALLS TO GI FELLOWS WITHIN AN IBD MEDICAL HOME
Authors: Rodriguez Jennifer , Dueker Jeffrey , Proksell Siobhan , Szigethy Eva , Schwartz Marc , Myers Cassie , Click Benjamin , Regueiro Miguel
Published: January 2020

Objective

The Inflammatory Bowel Disease (IBD) Medical Home is a care delivery model that provides a comprehensive, patient-centered, coordinated care environment, previously shown to lead to an approximate 50% reduction in unplanned care. However, the frequency and nature of IBD medical home patient phone calls to gastroenterology (GI) fellows after-hours, and the contribution to unplanned care from these encounters, is unknown.

Methods

We included all patients that were seen in the IBD medical home between 7/1/2015 to 6/30/2016 (n = 293) and examined all phone call activity in the subsequent year: 7/1/2016 to 6/30/2017. After-hours phone calls were defined as documented calls that were routed to on-call GI fellows when the clinic is closed. The details of each after-hours encounter were reviewed, and were categorized by the reason for call, training year of the GI fellow, advice given to patient, and unplanned care outcomes. For comparison, we also tracked frequency of patient calls for symptoms during clinic hours. Demographic information, disease type, disease activity index, quality of life (QoL), and depression/anxiety scores documented most recently to the start of the observation period were included in the analysis. Comparisons were made using Chi-square, T-tests and non-parametric median tests.

Results

259 of 293 patients (86.7%) had any documented phone interaction. Only 36 patients (12.3%) placed a total of 63 after-hours phone calls to GI fellows, with calls for symptoms representing the majority (71.4%). Among calls for symptoms (n = 45), patients were advised by GI fellows to present to the emergency department (ED) 44.4% of the time. There was no significant difference in ED recommendations by fellow training level (p = 0.17). Of the 20 ED encounters advised by fellows, 9 (45%) did not result in admission; and 2 patients had new cross-sectional imaging. Of the 11 admissions, 10 also had new cross-sectional imaging, with generation of 10 inpatient IBD consults, as well as 1 surgery for seton placement. After-hours callers were more likely to have Crohn’s disease and higher GAD-7 scores, with trends towards lower SIBDQ scores and higher PHQ-9 scores, but similar disease activity index scores, number of clinic visits, and demographics, compared to patients who called with symptoms during clinic hours (Table 1).

Conclusions

Among patients established within an IBD medical home model, a small population of patients called after hours resulting in frequent recommendation to present to the ED from GI fellows, however it is unknown if these encounters meaningfully changed their IBD care. Higher psychosocial complexity may influence this care behavior. Further studies of triage processes and educational initiatives aimed at GI fellows may help minimize unplanned ED and inpatient care in this patient population.
P010 FIRST SURVEILLANCE COLONOSCOPY FOR INFLAMMATORY BOWEL DISEASE – ARE WE GETTING IT RIGHT FROM THE START?
Authors: Patel Rajan , Tapper Louis , Lyne Holly , Moledina Saadiq , Cama Rigers , Besherdas Kalpesh
Published: January 2020

Background

Surveillance for colorectal cancer (CRC) is necessary in patients with inflammatory bowel disease (IBD). Patients with ulcerative colitis (UC) have a similar CRC risk to those with Crohn’s colitis (CC). British Society of Gastroenterology (BSG) guidelines from 2010 outlined recommendations for screening including surveillance intervals and pancolonic dye spraying with targeted biopsies. We aimed to identify reasons why the first surveillance colonoscopy is not being performed as advised, including the role of poor bowel preparation and disease activity.

Methods

Retrospective study of all IBD colonoscopies over a 7 year period (2011–2018) across two sites at a tertiary London based hospital trust. 214 patients were identified and exclusion criterion was applied (not first surveillance/diagnosis prior to year 2000/PSC/inadequate data). 93 patients were included for analysis.

Results

26 (28.0%) surveillance colonoscopies were performed prior to 10 years of diagnosis (ie. before BSG guideline recommendation). 22 (23.7%) surveillance colonoscopies performed after the recommended interval. Dye spray was performed in only 2 patients (2%). Reasons cited for not dying were only given in 4 (4.3%) cases, and included poor bowel prep or active disease. No reason was given in 87 (93%) cases. Targeted biopsies were performed in 24 (25.8%) patients, with random biopsies in 56 (60.2%) patients.

Conclusion

The first IBD surveillance colonoscopy is only being performed at the correct time interval in approximately 50% of cases with over a quarter being performed too soon and almost a quarter being performed too late. Pan-colonic dye spray is used in only 2% and targeted biopsies are taken in only 1 in 4 patients. Poor bowel preparation and disease activity do not appear to be limiting factors in the use of dye spray. We conclude that appropriate initial colitis surveillance is not being performed in the majority despite published guidelines. Organisational factors such as sufficient time allocated to dye spray colonoscopy, along with endoscopist skill, may be contributing factors.
P011 HIGH TIME: INCREASED INQUIRY ABOUT MARIJUANA USE IN IBD PATIENTS IS NECESSARY
Authors: Baumgartner Scott , Rao Vinay , Khan Ali , Dave Jenny , Chawla Karan , Borum Marie
Published: January 2020

Background

Marijuana use in the United States continues to increase with recreational sales legal in 11 states and the District of Columbia and medicinal approval expanded to include over two thirds of states. It is estimated that cannabinoid products are used by 15–40% of individuals with inflammatory bowel disease (IBD). However, the efficacy and safety have not been well-established. It is important that providers are aware of the extent of marijuana use in IBD patients. There is limited information about the frequency that providers inquire about recreational and medicinal use of marijuana. This study evaluated the frequency that providers screen for cannabinoid product use in individuals with IBD.

Methods

A chart review of all IBD patients seen at a university GI clinic over a 5-year period was performed. A confidential database using Microsoft Excel of patient age, gender, race, IBD diagnosis and recreational drug use was created. Charts were specifically queried for documentation of recreational or medicinal marijuana / cannabinoid (CBD) product use. Statistical analysis was performed using Fisher’s exact test with significance set at p<0.05. The study was approved by the institutional IRB.

Results

381 records were analyzed. 284 patients had UC, 95 CD, and 2 indeterminate colitis. There were 172 men and 209 women (mean age 44.1 years; range 20–82). 195 patients were white, 97 African American, 11 Asian, 38 other/unknown, and 40 declined. Providers screened for recreational drug use, including marijuana, in 182 patients (47.8%). Marijuana / CBD use (medicinal or recreational) was noted in 19 (4.9%) charts (4 for IBD symptoms, 3 recreational, 12 no reason documented; 2 had prescriptions). There was no significant difference in the rate of screening for drug or marijuana / CBD use based on gender (p=0.627), race (p=0.447), or IBD type (p=0.169).

Discussion

The efficacy and safety of marijuana use in IBD remains unestablished despite that up to 40% of patients endorse cannabinoid use. It is important that providers are aware of the frequency of marijuana / CBD use by IBD patients. Identification of self-prescribed use may prompt further evaluation and modification of medication regimen. This study revealed that providers inconsistently inquire specifically about marijuana / CBD use. The growing prevalence of recreational and medicinal marijuana use should prompt increased screening and appropriate incorporation of this information into optimizing care.

References
P013 IBD 101: AN INTRODUCTORY COURSE FOR FIRST YEAR GASTROENTEROLOGY FELLOWS
Authors: Lopatin Sarah , Kane Sunanda , Hong Simon , Hudesman David , Rubin David , Malter Lisa
Published: January 2020

Introduction

Inflammatory bowel disease (IBD) management is changing at a rapid rate, with the emergence of multiple new therapies and evolving care goals. In addition, the quality and quantity of IBD fellowship education is highly variable, based on patient populations and institutional expertise. Therefore, it is crucial to develop improved ways to educate our trainees. Here, we describe an educational initiative designed to familiarize first year gastroenterology (GI) fellows to key concepts in the management of IBD.

Methods

IBD 101 is a one-day course designed to introduce first-year GI fellows to various clinical topics relevant to the management of IBD. The program was held on September 14, 2019. Fellows from U.S. allopathic GI training programs were selected by their training directors for participation. The course included small group didactic sessions led by expert faculty members and group observed structured clinical examinations (OSCEs), in which fellows observed encounters between expert faculty and standardized patients followed immediately by debrief sessions to reinforce key concepts. The topics included need for surgery in IBD, pregnancy and IBD, escalation of care for acute severe UC, initiating biologic therapy, treatment of mild-moderate IBD, treatment of moderate-severe IBD and managing loss of response to therapy. A review of supplemental opportunities for education in IBD was presented at the conclusion of the course. Pre- and post-course surveys using Likert scoring (1=“strongly disagree” through 4=“strongly agree”) were administered to assess baseline knowledge and educational impact of the course on each addressed topic.

Results

55 fellows from 32 programs participated. 49/55 (89%) completed pre- and post-course surveys to assess the educational impact of the program on the didactic sessions and on the group OSCE format. 100% of fellows felt that the course content was appropriate for their scope of clinical practice. Substantial improvement in comfort with all addressed clinical topics was noted (figure 1). In the post-course survey, all fellows reported an improved ability to manage and treat patients with IBD. Comparing career interest in IBD, more participants expressed interest in pursuing a career in IBD after participating (pre: 63% vs post: 75%). 96% of attendees stated that they would strongly recommend this course to future GI fellows.

Conclusions

This single day course for first-year GI trainees was effective and well-received, and offers a novel intervention to address the challenges of IBD education and training. Follow-up of this cohort of trainees and expansion for next year is planned.
P036 ADULT AND PEDIATRIC PATIENT AND PARENT ATTITUDES, PERCEPTIONS, AND EXPERIENCES WITH NUTRITIONAL THERAPIES FOR INFLAMMATORY BOWEL DISEASES: A SYSTEMATIC REVIEW
Authors: Sandell Angela , Michel Hilary , Folb Barbara
Published: January 2020

Background

Nutritional therapy, including exclusive enteral nutrition (EEN), partial enteral nutrition (PEN), the Crohn’s Disease Exclusion Diet (CDED), and the Specific Carbohydrate Diet (SCD), can be used as adjunct or primary treatment for inflammatory bowel diseases (IBD). Patient and parent attitudes and experiences regarding nutritional therapy affect the decision to use them as treatment, and ultimately, their success.

Aims

We aimed to summarize existing literature exploring patient and parent attitudes and experiences regarding using nutritional therapy for IBD.

Methods

We completed a systematic review of the literature to find all publications related to pediatric and adult patient, and pediatric parent attitudes, beliefs, and experiences with implementation of four nutritional therapies for IBD: EEN, PEN, CDED and SCD. In collaboration with a research librarian, we prospectively developed a review protocol in PROSPERO; a search strategy was developed in Embase and translated for MEDLINE, CINAHL, PsycINFO, Cochrane Library, and Web of Science. Authors (AS and HM) reviewed reported titles and abstracts for inclusion for full text review. AS and HM extracted data from full texts meeting inclusion criteria. Results were qualitatively coded in an iterative process to reveal the following themes: attitudes and beliefs, experiences, barriers, and facilitators.

Results

Our search revealed 2,127 abstracts of which 276 full texts met inclusion criteria. Of these, 28 were included for data extraction and 21 for final analysis (Figure 1); 16 were non-randomized studies and 5 were randomized control trials. Regarding attitudes and beliefs, patients using EEN and PEN in several studies reported being willing to utilize this therapy again in the future. Patients using the SCD felt that the diet was superior to medications and feared long-term medication side effects. Patients using EEN, PEN, and SCD commonly experienced improved quality of life (QOL) scores. Frequently, QOL scores in those on EEN or PEN were the same as or better than those on biologic medications. Another common experience reported both by patients on EEN and SCD was occasional “cheating” on the diet or eating “illegal foods.” The most common barrier to implementation of EEN and PEN was palatability. For the SCD, time to prepare foods was a barrier. Few reports of facilitators to implementation exist. No studies of the CDED met inclusion criteria. Studies are summarized in Table 1.

Conclusions

Nutritional therapy is an essential component of IBD management, yet studies focusing on the patient and parent experience with these diets are limited. Future studies with the primary aim of exploring patient and parent perceptions of and experiences with nutritional therapy may guide appropriate therapy recommendations and allow the medical team to provide adequate support to ensure their success.