bluuebunny/crossref_metadata_2025 huggingface dataset:
P055 MARKOV CHAIN ECONOMIC IMPACT MODEL FOR ANTI-TNF NON-RESPONSE STRATIFICATION OF PATIENTS WITH MODERATE TO SEVERE ULCERATIVE COLITIS
Authors: Jeter Anna , Sanchez Helia , Withers Johanna , Akmaev Viatcheslav , Chaihorsky Lena , Saleh Alif
Published: January 2020

Objective

The annual cost of ulcerative colitis (UC) in the US is estimated to be as high as $14.9 billion, of which therapeutics account for up to 45%. The mean annual drug cost per patient with moderate to severe UC is $28,586. However, only 49% of patients achieve endoscopic healing on their first anti-tumor necrosis factor (anti-TNF) therapy and up to half of UC patients on biologics discontinue therapy within 12 months of initiation which leads to high rates of hospitalization and surgery. We performed a health care payer budget impact analysis to assess the influence of a precision medicine RNA-based classifier (PrismUC) that predicts, at baseline, anti-TNF non-response in patients with moderate to severe UC.

Methods

We developed a 12-month budget impact model for a 1-million-member health plan by analyzing peer-reviewed literature of treatment patterns in commercial and Medicare populations moderate to severe UC patients. Inputs included drug and medical costs, UC prevalence, biologic assignment patterns, therapy response rates, therapy persistence, therapy cycling, endoscopic healing rates, and risk of surgery. Drug and medical costs were obtained from published literature. A Markov model was created to estimate indirect effects of treatment efficacy, timing and cost of disease progression in subjects identified as anti-TNF non-responders (patients who fail to achieve endoscopic healing). Non-responders were assigned either to an alternative first-line therapy (vedolizumab) or to the standard of care (SOC) as determined by clinician judgments and payer formularies. The SOC included cycling patients through various biologics such as anti-TNF, vedolizumab, tofacitinib and ustekinumab. The cost of SOC was compared that of implementing a classifier to stratify patients by primary non-response to anti-TNF. Final cost savings included the cost of drugs, hospitalizations, and surgeries.

Results

Introducing a classifier that identifies anti-TNF non-responder UC patients to a 1-million-member health plan resulted in annual cost savings ranging from $6.8 to $9.6 million total (Table 1) within a 12-month period with and $9.0 to $12.7 thousand per patient (Table 2), depending on classifier performance metrics.

Conclusion

The PrismUC precision medicine classifier test that identifies non-responders to anti-TNF therapy will provide significant economic savings to payers by decreasing expenditures on unnecessary drugs and shortening times to endoscopic healing. These savings provide an economic incentive for payers to proactively engage with diagnostics manufacturers and encourage development of such tools to improve care management. A subsequent classifier that predicts response to therapies with alternative mechanisms of action is in development and expected to yield even higher cost savings.
P110 ASSOCIATION OF FECAL CALPROTECTIN WITH ENDOSCOPIC AND HISTOLOGY ACTIVITY IN PEDIATRIC INFLAMMATORY BOWEL DISEASE PATIENTS
Authors: Crawford Erin , Gestrich Catherine , Malay Sindhoosha , Sferra Thomas , Saab Shahrazad , Moses Jonathan
Published: January 2020

Background

Inflammatory bowel disease (IBD) treatment strategies have evolved to target mucosal healing, which has been shown to be associated with clinical remission and reduced complications. Fecal calprotectin (FC) is a non-invasive marker of intestinal inflammation, and has been shown to correlate with disease activity in IBD patients, though values which correlate with mucosal healing vary across studies. We aim to examine the association of quantitative FC levels with endoscopic and histologic severity, and compare FC in IBD patients with endoscopic remission with a control population.

Methods

We conducted a retrospective chart review of patients who had a FC completed between 30 and 1 days before colonoscopy at UH Rainbow Babies and Children’s Hospital between 2014 and 2018. IBD patients had disease severity endoscopically graded using the SES-CD or Mayo UC score, and had disease severity histologically graded using the Geboes method. Severity was classed as no disease, mild, moderate or severe. FC values of IBD patients with mucosal healing and the control population (those without gastrointestinal pathology or diagnosis on evaluation) were compared.

Results

331 cases were included in the study; 107 IBD cases and 224 controls. 63 patients (19%) had a diagnosis of Crohn’s disease (CD) and 44 patients (13%) had ulcerative colitis (UC). When assessing endoscopic scoring of IBD patients, the median FC was lowest in those with no disease (181 ug/g), followed by those with mild and moderate disease (499, 599 ug/g) and highest in those with severe disease (921 ug/g). There was significance comparing no disease to moderate and severe disease (p=0.019, 0.003), and between mild and severe disease (p=0.012). When assessing histology, the median FC was lowest in IBD patients with no disease (328 ug/g), followed by those with mild and moderate disease (399 ug/g, 674 ug/g) and highest in those with severe disease (895 ug/g). There was significance comparing no disease to moderate and severe disease (p=0.021, 0.018). In CD patients, there was significance in FC between no disease and moderate and severe disease (p=0.047, 0.0047) on endoscopic scoring. In UC patients, there was significance in FC between no disease and moderate disease (p=0.023) for histologic scoring. When comparing FC of endoscopically normal patients, the control group had a significantly lower median FC than the IBD population with endoscopic remission (43 ug/g vs 181 ug/g, p=0.018).

Conclusion

FC showed association with disease severity on gross endoscopy and histology and significance between severities in our IBD cohort. Additionally, normal cut-off values of FC may depend on the presence or absence of underlying disease. While larger studies are needed, this noninvasive test may help mitigate frequency of invasive procedures.
P111 CORRELATION OF FECAL CALPROTECTIN AND MUCOSAL BIOPSY IN IDENTIFYING SUBCLINICAL INFLAMMATION IN ULCERATIVE COLITIS PATIENTS: A PRELIMINARY STUDY
Authors: Hashim Mahmoud , Perry Courtney , Schaberg Kurt , Elkheshen Ahmed , Hussein Mohamed , Barrett Terrence
Published: January 2020

Background

For years, the gold standard for Ulcerative Colitis (UC) remission was mucosal appearance during endoscopy. However, recent literature suggests histological or “deep” remission is important for preventing flares and maintaining clinical remission. There are now validated histological scoring systems to identify subclinical inflammation, the simplest being the Nancy Histology Index (NHI). Colonoscopy with histological evaluation is the gold standard for UC monitoring, but frequent endoscopy is not always possible. Literature reporting the utility of fecal calprotectin (FC) in detecting subclinical inflammation is limited. We seek to evaluate the correlation of FC and C-reactive protein (CRP) with NHI scores to better assess their role in detecting subclinical UC.

Methods

We retrospectively evaluated clinical data and pathology slides of 69 UC patients that were collected over 6-months period at university of Kentucky. Pathology slides were scored according to NHI by a trained researcher and verified by an IBD pathologist. Presence of acute activity was defined as NHI>2. Mayo endoscopic scores (MES) were based on endoscopic reports from one expert endoscopist. Endoscopic remission was defined as MES <2. FC and CRP were recorded if collected within a month of endoscopy. FC was defined as elevated (≥120 mcg/g) or borderline (50.1–120 mcg/g). Elevated CRP was defined as (> 0.9 mg/dl).

Results

33 of the 69 (47.8%) patients analyzed were in endoscopic remission. 17 of those 33 (51.5%) patients in endoscopic remission had acute histological activity (NHI >2). 7 (21.2%) patients with acute histological activity completed FC testing. Of the 7 who submitted FC, 4 were elevated, and 1 was borderline. 15 of the 17 NHI positive patients submitted CRP, 4 (26%) were elevated. Finally, among the 17 patients with NHI >2, four patients flared within a year (Table 1). In these 4 flared patients, FC was abnormal in 3 patients. CRP was negative in these three patients. One patient did not complete a FC or CRP. Conversely, of the 16 patients with quiescent UC and NHI <2 only 1 patient flared within a year. FC and CRP were not completed at the time of endoscopy.

Conclusion

We successfully identified an important subset of UC patients in clinical and endoscopic remission with active histological activity. Most patients in this subset had elevated fecal calprotectin levels. This suggests fecal calprotectin can be used for disease monitoring to proactively identify subclinical activity before disease flare. Our findings suggest that biopsies should be performed in all UC patients even in the absence of endoscopic abnormality, and fecal calprotectin should be ordered at regular intervals to pre-emptively detect and prevent UC flares.
P113 EVALUATION OF THE EFFICACY OF TOFACITINIB IN PATIENTS WITH ULCERATIVE COLITIS UTILIZING THE MODIFIED MAYO SCORE: DATA FROM THE OCTAVE PROGRAM
Authors: Sandborn William , Sands Bruce , Steinwurz Flavio , Vermeire Séverine , Guo Xiang , Maller Eric , Modesto Irene , Su Chinyu , Wang Wenjin , Woodworth Deborah , Panes Julian
Published: January 2020

Introduction

Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of ulcerative colitis (UC). Safety and efficacy of tofacitinib were evaluated in 2 Phase 3 induction studies (OCTAVE Induction 1 & 2, NCT01465763 & NCT01458951), a 52-week (wk), Phase 3 maintenance study (OCTAVE Sustain, NCT01458574),1 and an ongoing open-label, long-term extension study (NCT01470612).2 In these trials, endpoint definitions were based on the conventional Mayo score comprising 4 subscores (stool frequency, rectal bleeding, endoscopic findings, Physician Global Assessment [PGA]). The FDA recommend the use of a modified Mayo (mMayo) score in which the PGA subscore is omitted (a subjective measure, and a recognized Mayo score limitation) as an endpoint measure for UC clinical trials.3 In this post hoc analysis, we assessed the efficacy of tofacitinib using endpoint definitions based on mMayo score.

Methods

In OCTAVE Induction 1 & 2, patients received placebo or tofacitinib 10 mg twice daily (BID) for 8 wks; clinical responders were re-randomized into OCTAVE Sustain for 52 wks and received placebo, tofacitinib 5 or 10 mg BID. Trial endpoints included remission, symptomatic remission, and clinical remission (Table), assessed at Wk 8 in OCTAVE Induction 1 & 2 and Wk 52 in OCTAVE Sustain. Treatment effects (ie difference from placebo) using mMayo and Mayo scores were evaluated and compared.

Results

In OCTAVE Induction 1 & 2, numerically more patients achieved remission using the mMayo score (7.7% placebo; 24.8% tofacitinib 10 mg BID) compared with the Mayo score (6.0% placebo; 17.6% tofacitinib 10 mg BID), with a greater difference from placebo with mMayo scores (Table). Likewise, the proportion of patients achieving clinical remission was numerically greater with mMayo scores (7.7% placebo; 25.0% tofacitinib 10 mg BID) compared with Mayo scores (6.0% placebo; 17.7% tofacitinib 10 mg BID), whereas the same proportion of patients achieved symptomatic remission with both scores. The same trends were noted in OCTAVE Sustain, with numerically more patients in placebo and tofacitinib groups achieving remission and clinical remission using mMayo scores compared with Mayo scores (Table), and symptomatic remission achieved by the same proportion of patients with both scores.

Conclusion

In this post hoc analysis, a statistically significant effect of tofacitinib treatment vs placebo was demonstrated across endpoints based on the mMayo score, agreeing with previously reported data based on the Mayo score.1 Treatment effect sizes for endpoints based on the mMayo score without PGA were the same or numerically greater than corresponding endpoints based on the Mayo score.

References
P109 PASSIVE ECCRINE SWEAT SENSING FOR DUPLEX TEMPORAL DETECTION OF CYTOKINES
Authors: Jagannath Badrinath , Muthukumar Sriram , Prasad Shalini
Published: January 2020

Introduction

Sweat based wearable sensors have shown a lot of promise in the recent years due to the ability of tracking the biomarkers in real-time. Among the various biomarkers present in sweat, cytokine concentrations have been shown in comparable range to the blood cytokines. Detection of sweat cytokines can help in monitoring of inflammation in real-time. In this work, we demonstrate a duplex cytokine sweat based sensor for real-time monitoring. The developed sensor can detect interleukin-6 (IL-6) and interleukin-10 (IL-10) in real-time that can aid in prognosis or recovery of inflammation.

Materials and Methods

The sweat based sensor was developed with semiconducting electrode on porous polymeric substrate on a porous polymer substrate. Affinity capture probes were immobilized on the sensor surface via a thiol-cross linking chemistry. ATR-IR was used to validate immobilization of the capture probes. Electrochemical impedance measurements technique was used to detect the interaction between the specific antibody and target analyte. The impedance response based on the binding interaction was used to quantify the sensor metrics.

Results

In this work, a sweat sensor platform for the duplex detection of IL-6 and IL-10 has been demonstrated. The conjugation of the antibodies to the sensor surface was confirmed using ATR-IR spectroscopy. Impedance response was used to characterize the sensor performance metrics. Calibration dose response curve was developed with decreasing impedance response for increasing concentrations of target analyte. A limit of detection of 2 pg/mL was obtained with a dynamic range from 2 pg/mL- 200 pg/mL for IL-6. IL-10 demonstrated a limit of detection of 1.5pg/mL with a dynamic range from 1.5- 150pg/mL. The developed sensor demonstrated minimal or no cross-reactivity to non-specific molecules.

Conclusion

A novel sweat-based biosensor for duplex detection of cytokine markers has been demonstrated. The developed biosensor can detect pro and anti-inflammatory cytokines that can aid in the prognosis or recovery of inflammation.
14 COLONIC EPITHELIAL CELL-SPECIFIC AFTIPHILIN KNOCKDOWN REGULATES EPITHELIAL BARRIER FUNCTION THROUGH MYOSIN LIGHT CHAIN-ASSOCIATED ACTIN ORGANIZATION IN VITRO AND INTESTINAL LENGTH IN VIVO
Authors: Man Law Ivy Ka , Rankin Carl , Pothoulakis Charalabos
Published: January 2020

Background and Aims

Colonic epithelial integrity is often compromised during colonic inflammation and Inflammatory Bowel Disease. Aftiphilin (AFTPH) is a downstream target of microRNA-133a and its expression is reduced in colonic tissues of wild type mice from experimental colitis models and colonic biopsies from patients with ulcerative colitis. We have previously shown that AFTPH is involved in regulating intestinal epithelial barrier function and actin organization in human colonic epithelial cells in vitro (DDW 2016). On the other hand, our results suggested that global aftiphilin knock-out is embryonic lethal in mouse models (DDW 2019). Here, we further examined the role of AFTPH in regulating actin organization in vitro and characterize the colonic epithelial cell-specific aftiphilin knock-out mice.

Methods

Human colonic epithelial NCM460 cells were transfected with si-RNA against AFTPH to achieve transient AFTPH gene-silencing. Stable AFTPH knock-down clones were generated by transducing Caco2-BBE cells with recombinant lentivirus carrying sh-AFTPH or control sh-RNA. To create intestinal epithelial cell-specific aftiphilin knock-out mice, Aftph flox/flox mice were cross-bred with B6.Cg-Tg(Vil1-cre)997Gum/J mice, which express Villin-driven Cre recombinase (Vil-Cre), to generate intestinal epithelial cell-specific aftiphilin knock-out mice (Aftph Vil-/Vil-). Protein expression of F- and G-actin and p70S6K were detected using Western blot. Tissues from various organs were collected with Aftph Vil-/Vil- and its wildtype counterparts at 12 weeks.

Results

Results from western blot analysis showed that F-/G-actin ratio in AFTPH gene-silenced NCM460 cells were 0.6±0.17 fold, when compared to the treatment control. In addition, AFTPH gene-silencing in human colonic epithelial cells activated p70S6K, a kinase that is involved in actin organization, when compared to treatment control (1.2±0.15 vs. 2.0±0.15, p=0.0354). Furthermore, transepithelial electric resistance (TER) of Caco2-BBE cells deficient in AFTPH is significantly lower than that of control cells (0.5±0.07 fold). Lastly, in vivo intestinal epithelial cell-specific Aftph knock-out increased the length of small intestine, when compared to that of wild type mice (30.7±0.33 vs. 34.8±0.97, p=0.02), while the tissue weight of spleen to body weight was reduced (0.30±0.011 vs. 0.26±0.006, p=0.0169).

Summary and Conclusions

Our results indicate that AFTPH directly regulates epithelial barrier function and actin organization through mediating F-/G-actin ratio in human colonic epithelial cells, possibly through p70S6K. Importantly, intestinal epithelial cell-specific knock-out in vivo increased intestinal length and reduced size of the spleen. Our results suggested that AFTPH is crucial in regulating colonic epithelial barrier function in vitro and intestinal homeostasis.
20 ELUCIDATING THE ROLE OF FUSOBACTERIUM NUCLEATUM IN INTESTINAL INFLAMMATION
Authors: Engevik Melinda , Danhof Heather , Britton Robert , Versalovic James
Published: January 2020

Background

While the direct cause of inflammatory bowel disease (IBD) is unknown, the gut microbiota is speculated to play a key role. The complexity of the microbiome has made it difficult to pinpoint whether bacterial species are specifically associated with IBD exacerbations; although select microbes have emerged as compelling candidates. Several groups have identified increased abundance in Fusobacterium in IBD patients. Fusobacterium nucleatum drives inflammation in the oral cavity, but few studies have examined the potential for F. nucleatum to promote intestinal inflammation. We hypothesize that F. nucleatum secretes Outer Membrane Vesicles (OMVs) that activate epithelial Toll-like receptor 4 (TLR4) to drive inflammation.

Methods & Results

Given the prevalence of F. nucleatum in IBD specimens, we sought to determine if this pathobiont could promote pro-inflammatory responses in human epithelial cultures. Using fluorescently tagged F. nucleatum, we demonstrate that F. nucleatum subspecies polymorphum adheres to the mucus layer of human colonic HT29-MTX cells. Application of F. nucleatum metabolites to HT29-MTX cells resulted in upregulation of pro-inflammatory cytokines IL-8 and TNF by qPCR and ELISA. Purified OMVs from F. nucleatum alone were able to stimulate IL-8 and TNF production. This demonstrates the robust response of colonic epithelial cells to F. nucleatum. Additionally, we used human jejunum and colon enteroid monolayers treated with F. nucleatum metabolites in an anti-oxidant free enteroid media and found that F. nucleatum secreted products promoted TNF secretion by ELISA. Using the Luminex Magpix Platform we further queried the enteroid system to assess which pathways were activated. Enteroid monolayers treated with F. nucleatum metabolites exhibited increased phosphorylated ERK and CREB, downstream effectors of TLRs. We next sought to address whether F. nucleatum alone could elicit pro-inflammatory responses in a mouse model. Mice harboring a human microbiota, or humanized mice, were treated for 5 days with a cocktail of antibiotics and treated with F. nucleatum (108 CFU) by oral gavage; a regimen designed to mimic IBD patient treatment. Compared to control mice that received antibiotics and PBS vehicle control, mice treated with F. nucleatum exhibited disruption of the colonic architecture, with increased immune infiltrate and depleted mucus layer, resulting in a closer proximity of luminal contents to the epithelium. Analysis of mucosal gene expression revealed increased levels of epithelial TNF and KC (mouse homolog of IL-8), in addition to immune cell derived IL-6 in F. nucleatum-treated mice compared for controls.

Conclusions

These data provide evidence that F. nucleatum is capable of driving a pro-inflammatory signaling cascade in vitro and in vivo and F. nucleatum may represent a specific target for drug therapy.
P077 A NEW TREATMENT APPROACH FOR INFLAMMATORY BOWEL DISEASE: INTRACOLONIC BIFIDOBACTERIUM AND XYLOGLUCAN APPLICATION
Authors: Bozkurt Hüseyin
Published: January 2020

Background

Inflammatory bowel disease (IBD) pathogenesis includes the altered gut microbiota, environmental factors, human immune responses and genetic. Reduced bifidobacteria level is associated with IBD. Xyloglucan is a plant based prebiotic oligosaccharide. Bifidobacteria level is increased in the presence of xyloglucan.

In this article we aim to share the results of our cases; Ulcerative colitis (UC) patients treated by intracolonic single administration of Bifidobacterium animalis subsp. lactis and Xyloglucan combination.

Methods

Ten UC patients were evaluated; before and after intracolonic single administration of Bifidobacterium animalis subsp. lactis and Xyloglucan combination with colonoscopic laboratory and clinical examination.

Results

Age, sex, diagnosis, disease location, previous medications are summarized in Table 1. All the patients had active ulcerative colitis disease before the administration. The Mayo Score was used to assess the severity of UC. 2 cases had extensive colitis and 8 patients had left-sided colitis. After 6 weeks of the administration mucosal healing and resolution of colonic symptoms were seen. These results are summarized in Table 2. Of the 10 cases, 7 were undertaken 5-ASA +Azathiopurine and three were undertaken vedolizumab treatment. Intracolonic single Bifidobacterium animalis subsp. lactis and xyloglucan administration was found effective in the mucosal healing and resolution of colonic symptoms in ulcerative colitis patients.

Conclusions

Herein we reported the importance of Bifidobacterium and xylooligosaccharide combination in IBD. Colonoscopic single Bifidobacterium animalis subsp. lactis and xyloglucan administration is a new method that has no side effect and easy to apply for treatment of IBD.This application might provide enhancement of non-stimulatory status and higher biodiversity in colonic mucosa so mucosal healing may be improved rapidly. However, it would be necessary to develop diagnostic strategies in order to discriminate which patients would benefit from this strategy.
P167 ADULT CROHN’S DISEASE TREATED WITH THE SPECIFIC CARBOHYDRATE DIET (SCD): A CASE REPORT USING OBJECTIVE MARKERS OF RESPONSE
Authors: Arjomand Ali
Published: January 2020

The specific carbohydrate diet (SCD) has been shown to resolve symptoms in pediatric IBD patients, inducing clinical remission and normalizing or significantly reducing inflammatory markers. Demonstration of similar effects, including changes to objective disease markers, are lacking in the adult IBD patient. Presented here are clinical, biomarker, microbiome, imaging and histologic observations after successful implementation of the SCD in an adult with moderate-to-severe Crohn’s disease. HISTORY: A 50-year-old male patient, diagnosed with Crohn’s disease in 2001, implemented the SCD in 2017 according to the published protocol. Prior to diet intervention, medical management consisted of mesalamine (1 g orally 4x/day for 6 mo.); infliximab (300 mg IV/8 wks for 5 yrs), natalizumab (300 mg IV/4 wks for 6 mo.), adalimumab (40 mg sc/14 d for 7 yrs; every 7 d for 1 yr) and vedolizumab (300 mg IV/8 wks for 1 yr). Corticosteroids were administered with adalimumab and vedolizumab over a continuous span of 8 yrs (prednisone 15–20 mg/d or budesonide 9 mg/d). Two resections of the terminal ileum were performed in 2003 and 2015. History included annual ER or hospital admissions and severe malnutrition (albumin 1 g/dL). TPN was provided in 2008 and 2015. DIETARY INTERVENTION: The patient was advised to switch to ustekinumab after LOR to vedolizumab and return of active inflammation. The patient refused further biologic treatment and proceeded with the SCD intervention. Prednisone (40 mg/d) was initiated during diet transition. The patient adhered to a strict SCD protocol, eliminating sugar, grains, starch and all forms of processed foods while adding home-fermented yogurt.

Results: By day 10, the patient reported loss of abdominal and lower back pain along with a 5 lb weight drop. Cooked, non-starchy vegetables, nut flours and other foods were then introduced according to the SCD protocol and as tolerated. At month 3, the patient reported 1–2 formed BM/d, increased energy and mobility, loss of joint pain and a stable weight. The patient initiated yoga 3x/wk. Advanced SCD foods continued to be introduced one at a time. Stool was well-formed and of large mass. Prednisone was tapered to 20 mg/d at month 3 and 0 mg/d by month 8. At month 12, MRE and colonoscopy showed resolution of inflammation and normal mucus in the terminal ileum assessed by biopsy. At month 24, FCP and CRP remained in the normal range. Microbiome analysis of fecal samples showed poor diversity at all times with minor phyla-level changes at month 12. International travel resulted in genus-level increase in diversity. The patient has completed 3 years with the SCD and plans to maintain the diet as part of a lifestyle change. Prospective studies are needed in adult IBD patients, including moderate-to-severe cases, to assess the long-term efficacy of the SCD using objective markers of response.
P163 DYSREGULATED MICROBIAL METABOLISM IN ULCERATIVE COLITIS INCREASES THE RISK OF CLOSTRIDIODES DIFFICILE INFECTION
Authors: Kitamoto Hiroko , Higgins Peter , Young Vincent , Kamada Nobuhiko
Published: January 2020

Clostridioides difficile infection (CDI) is recognized as a major clinical complication in patients with ulcerative colitis (UC). However, the mechanism associated with increased susceptibility to C. difficile in UC patients remains poorly understood. Given the evidence that the gut microbiota plays a critical role in the prevention of CDI and that gut microbiota is perturbed in UC patients, we hypothesized that UC-associated gut dysbiosis contributes to the increased susceptibility of patients to CDI. To address this hypothesis, we employed the human microbiota-associated (HMA) mouse model. Germ-free mice were colonized with the gut microbiotas isolated from either UC patients or healthy control (HC) subjects. Utilizing this model, we have found that UC-HMA mice are susceptible to C. difficile, while HC-HMA mice are completely protected. An isogenic mutant C. difficile strain, which lacks the succinate utilization operon, exhibited impaired colonization to UC-HMA mice, indicating that succinate is a key metabolite that promotes the colonization of C. difficile in UC-HMA mice. Restoration of healthy microbiotas by fecal microbiota transplantation (FMT) reduced luminal concentration of succinate in UC-HMA mice, thereby rendering the mice protective against CDI. The abundance of succinate-consuming bacteria likely regulates the availability of luminal succinate. We found that host mucus/epithelial N-glycosylation plays a crucial role in the growth of succinate-consuming bacteria in the gut. The expression of N-glycosylation–related enzymes were reduced in UC patients, which may lead to the gut dysbiosis with decreased succinate-consuming bacteria and increased luminal succinate. Taken together, impaired host N-glycosylation in UC induces gut dysbiosis and subsequent dysregulation of gut microbial metabolism. The impaired microbial metabolic activities - reduced succinate utilization - increases host susceptibility to C. difficile.
P166 MICROBIOME AND EPIGENETIC PREDICTORS OF RESPONSE TO BIOLOGIC THERAPY IN PATIENTS WITH ULCERATIVE COLITIS
Authors: Shah Rajesh , Shen Lanlan
Published: January 2020

Introduction

Current ulcerative colitis (UC) treatments have variable efficacy and may take several weeks to assess improvement. Emerging data suggest the intestinal microbiota may serve as a biomarker and mechanistically may influence immune system activity through epigenetic regulation of host gene expression. The aim of this pilot project was to examine whether the colonic mucosal microbiota and mucosal DNA methylation patterns are associated with a response to treatment in UC.

Methods

We conducted a retrospective cross-sectional study of patients with active UC. Fresh frozen colon biopsy samples were obtained from the Texas Medical Center IBD Tissue Bank. Patients were included if they had a colonoscopy performed to assess disease activity and follow up through 14 weeks to assess response. Disease activity was defined using the Partial Mayo Score and response was defined as a 2 point or greater decrease in the score after 14 weeks of follow up. 16s rRNA gene sequencing and DNA methylation pyrosequencing were used to define the microbiome and quantify DNA methylation. Comparisons were performed of alpha and beta diversity, taxonomy and DNA methylation between responders and non-responders at 14 weeks. Additionally, a random forest machine learning model was developed to identify predictors of response.

Results

We identified 16 patients with tissue samples from the cecum/ascending, transverse and rectum/sigmoid available for analysis. After excluding patients with limited rectal disease, recent antibiotic use and inadequate follow up, 4 patients (2 per group) were included and thus provided 12 tissue samples for analysis. The mean age of responders was 38 and non-responders was 24. 50% of patients were male and all were Caucasian. Responders had a numerically lower alpha diversity, though this did not reach statistical significance (p=0.18). Responders and non-responders separated in unweighted (p=0.001) and weighted (p=0.001) beta diversity analysis. Responders had a greater abundance of Firmicutes and Bacteroidetes and lower abundance of Proteobacteria compared to non-responders. This corresponded to responders having a greater abundance of genera for Bifidobacterium, Faecalibacterium and Roseburia. Additionally, we saw increased methylation in the P16, HOXC5 and B4GALNT1 genes of responders compared to non-responders. Finally, in a random forest machine learning model, predictors of response included left sided disease extent and OTUs for the genus Roseburia.

Discussion

Patients with UC and response to therapy had a significantly different pre-treatment microbiome and methylation of genes related to intestinal barrier function, including B4GALNT1. Larger studies will be needed to validate these findings, but these results suggest the microbiome and DNA methylation changes may be effective biomarkers of response to therapy and warrant further study.
11 ENTERAL NUTRITION THERAPY IS ASSOCIATED WITH FEWER READMISSIONS AND DEATHS AMONG MALNOURISHED INPATIENTS WITH INFLAMMATORY BOWEL DISEASE
Authors: LeBrett Wendi , Sauk Jenny , Limketkai Berkeley
Published: January 2020

Background

Malnutrition is a common complication observed in hospitalized patients with inflammatory bowel disease (IBD). Enteral nutrition therapy can be used to support the nutritional needs of inpatients with IBD. However, evidence on the impact of inpatient enteral nutrition on clinical outcomes is equivocal. This study assesses post-hospitalization outcomes associated with enteral nutrition therapy amongst inpatients with IBD in a large nationwide database.

Methods

We conducted a retrospective propensity score-matched study among IBD inpatients diagnosed with protein-calorie malnutrition using the Nationwide Readmissions Database from 2010–2015. ICD9 codes associated with each admission were used to identify patients who received enteral nutrition. Using propensity score matching, patients who received inpatient enteral nutrition were matched with patients who did not receive enteral nutrition based on the following variables: age, sex, elective admission, patient income, teaching hospital, and hospital urban or rural locality. Primary endpoints included 30-day readmissions, 90-day readmissions, 30-day mortality and 90-day mortality.

Results

Among the 1,588 IBD patients (822 Crohn’s disease, 755 ulcerative colitis, 11 unclassified IBD) with protein-calorie malnutrition, patients who received enteral nutrition (n=794) had fewer 30-day readmissions (OR 0.73; 95% CI 0.55 – 0.96) and 90-day readmissions (OR 0.77; 95% CI 0.61 – 0.97). None of the patients (0%) in the enteral nutrition group died on a subsequent admission within 30 days of discharge, compared to 6 patients (0.8%) in the control group (p=0.027). Inpatient mortality within 90 days of discharge did not differ significantly between the two groups (0.8%, enteral nutrition vs. 1.6%, control; p=0.086).

Discussion

Enteral nutrition therapy among IBD inpatients with malnutrition was associated with lower odds of readmission and 30-day mortality, but not 90-day mortality. The findings of our study support the use of enteral nutrition in IBD inpatients and motivate the need for prospective studies assessing the impact of enteral nutritional support in IBD inpatients.
P027 TRANSITION OF CARE OF ACTIVE DUTY PATIENTS WITH IBD TO THE VETERANS ADMINISTRATION HEALTHCARE SYSTEM: TOOLKIT FOR SUCCESS
Authors: Patel Anish , Keefer Laurie
Published: January 2020

The shift from being an active duty military patient with inflammatory bowel disease (IBD) seen in a military treatment facility (MTF) to being a veteran receiving chronic illness care within the Veterans Administration (VA) is a time of increased vulnerability and risk for loss of continuity of care, and poor disease outcomes. A transitional care program must prioritize the psychosocial growth, self-efficacy and disease-specific knowledge of active military patients who are transitioning to VA care as well as enhance collaborative management between military and VA providers. The Department of Defense (DoD) has established the Transition Assistance Program (TAP) to assist military members to civilian life, but limit preparedness in skills to navigate/understand medical care. There is currently no available data on transition readiness from active duty military medical care to VA medical care and our objective is to determine the feasibility and acceptability of a self-management intervention.

Methods: We prospectively measured readiness with the use of the IBD Self-Efficacy Scale (IBD-SES) and Transition Readiness Assessment Questionnaire (TRAQ). All enrolled patients (50 active duty servicemembers) were in disease remission and underwent TAP and 50% were further randomized to undergo TRAQ-based educational and behavioral interventions via mobile applications and clinical consults.

Results: Servicemembers who underwent further TRAQ-based interventions compared to those only undergoing TAP demonstrated significant improvement in medication/appointment management, tracking/managing health issues, and talking with providers (p<0.001). Furthermore, these servicemembers also demonstrated significant improvement in self-efficacy and self-management which was maintained up to 3 months post military discharge (p<0.001). Servicemembers had an average VA primary care wait time of 3.5 months and for Gastroenterology specialist of 5.4 months, resulting in >60% of servicemembers having to discontinue therapy due to lapse in care (50% rate of flares) and unnecessary therapy switch.

Conclusion: This is the first and only study to assess transitioning from active duty service to VA medical care for a chronic illness. We demonstrated improved and sustained self-efficacy outcomes with a transition program for IBD along with potential limitations in the VA transition. We have an opportunity to influence the conversation of appropriate DoD transition of medical care and to develop a model of care with wider applicability.
P041 DEVELOPMENT OF PROMIS PEDIATRIC PATIENT-REPORTED OUTCOME SHORT FORMS FOR FATIGUE AND PAIN INTERFERENCE IN CHILDREN WITH CROHN’S DISEASE
Authors: Schuchard Julia , Kappelman Michael , Grossman Andrew , Clegg Jennifer , Forrest Christopher
Published: January 2020

Introduction

There is a need for reliable, valid patient-reported outcome (PRO) measures to assess the health and quality of life in pediatric Crohn’s disease (PCD). The development of PROs for this population may be facilitated by using Patient-Reported Outcomes Measurement Information System (PROMIS) item banks, which were developed using rigorous psychometric methods. We aimed to develop disease-specific PROMIS short forms by conducting qualitative research to identify the items that are most relevant to children with PCD.

Methods

Participants in an initial card sorting study included 42 children with CD (ages 8–17), 70 parents of children with CD, and 26 clinicians with expertise in CD. Using an online program, participants rated the importance of PROMIS items for pediatric CD patients. This exercise indicated that children, parents, and clinicians endorse Fatigue and Pain Interference items as important for PCD. In a separate study, trained research coordinators conducted one-on-one semi-structured interviews with 37 children with CD to further explore their experiences with fatigue and pain. Research coordinators also conducted one-on-one cognitive interviews with 14 children with CD. Each participant completed a questionnaire and then was interviewed about the reasoning for their answers. All interviews were transcribed and coded for meaning units, defined as conceptually distinct statements in the words of the participant.

Results

In semi-structured interviews, highly reported facets of fatigue and its impact included feelings of tiredness, friendships, and sports/exercise. Highly reported facets of pain and its impact included feelings of hurt, friendships, family, attention, and sports/exercise. Participants’ responses revealed the same breadth and types of lived experiences of fatigue and pain as children from the development samples drawn from the general population. Ratings of children’s reasoning and logic in cognitive interviews showed strong understanding of PROMIS items. Final item selection for the PCD-specific PROMIS short forms involved consideration of the concepts that participants identified as important, item understandability, psychometric evaluation of precision and coverage, and balance across different facets of each domain.

Conclusions

Results support the content validity and comprehensibility of PROMIS Pediatric Fatigue and Pain Interference measures in PCD. This work contributed to the development of 8-item short forms that are tailored to assess the lived experiences of fatigue and pain interference in PCD.
P042 FATIGUE AND DISEASE ACTIVITY: A SECONDARY REVIEW OF PATIENT MEDICAL RECORDS
Authors: Kamp Kendra , Clark-Snustad Kindra , Lee Scott D
Published: January 2020

Introduction

Fatigue is often the most prevalent symptom in inflammatory bowel disease (IBD). Previous research has highlighted that patients with active clinical disease activity have greater levels of fatigue compared to those with inactive clinical disease activity. Endoscopic assessment of inflammation is considered the best measure of disease activity; yet, clinical disease activity does not necessarily correlate with endoscopic inflammation. Therefore, there is a need to examine the relationship between endoscopic inflammation and fatigue.

Methods

A retrospective chart review was conducted of adult patients at an academic medical center. Participants were included in the review if they had a diagnosis of ulcerative colitis or Crohn’s disease, a clinic visit between 2018–2019 with completed Short Inflammatory Bowel Disease Questionnaire and clinical disease activity measures (Harvey Bradshaw Index [HBI] or Simple Clinical Colitis Activity Index [SCCAI]), and had a scored endoscopic disease activity score (Mayo Score of Ulcerative Colitis or the Simple Endoscopic Score for Crohn’s Disease) within 6 months of the clinic visit. Fatigue (range 1–7) was reversed scored; a higher number indicated increased fatigue. Descriptive statistics were calculated using STATA 14.

Results

Individuals (N=43) had a mean age of 37.4 (SD=12.3) and 54% were female. Disease location was 9% ileal, 53% ileocolonic, and 37% colonic; 54% were in endoscopic remission. The mean fatigue score was 4.2 (SD=1.7). There was no difference in fatigue between individuals in endoscopic remission (M=4.2, SD=1.6) compared to individuals with active endoscopic disease (M=4.2, SD=1.9; p=0.97). Fatigue was correlated with clinical disease activity measures including the HBI (r=0.61) and the SCCAI (r=0.58). Increased levels of fatigue were associated with abnormal c-reactive protein (p<0.01), erythrocyte sedimentation rate (p<0.01), and albumin (p=0.04) but not hematocrit (p=0.71) or hemoglobin (p=0.60).

Conclusions

The majority of the sample reported fatigue; however, fatigue did not correlate with endoscopic disease activity despite previous research suggesting that clinical disease activity correlates with fatigue. Further confounding our understanding of disease activity’s association with fatigue is the fact that clinical disease activity and biochemical abnormalities (CRP, ESR, albumin) did correlate with fatigue. Additional research is clearly needed to characterize the cause of fatigue among individuals with IBD.
P050 SUBSTANCE USE OCCURS FREQUENTLY IN PATIENTS WITH CROHN’S DISEASE
Authors: Chen Po-Hung , Miller Steven , Brant Steven , Hutfless Susan
Published: January 2020

Background

Crohn’s disease (CD) is an inflammatory disease of the gut with multiple psychosocial comorbidities, including lost wages, stress on loved ones, and psychiatric illnesses, all of which are associated with substance use disorders. While approximately 7.5% of individuals aged 12 or older in the United States have a substance use disorder, we know little about this issue among patients with CD. Using a nationally representative dataset, we examined the burden of alcohol, tobacco, and illicit drug use among patients with CD in the United States.

Methods

We queried the national Medicaid claims data from 2010 through 2014 using ICD-9-CM codes for CD and use of alcohol, tobacco, opioids, cocaine, amphetamine, and cannabis. We defined CD as having two or more CD diagnostic codes; all included individuals must have at least one continuous year of Medicaid eligibility. The primary outcomes of interest were the total and the substance-specific prevalence of use in patients with CD.

Results

During our five-year study period, there were 51,091 individuals with CD. Among them, 7.4% had at least one code to suggest substance use, and 1.3% had codes for two or more substance types. Non-users were 65% female, 39-years old at the first CD diagnosis, and had 1.7 years of median follow-up after the said diagnosis. Users were 62% female, 40-years old at the first CD diagnosis, and had 1.8 years of median follow-up after diagnosis. The frequencies of substance use codes by CD patients were tobacco (3.9%), opioids (2.2%), alcohol (1.6%), cannabis (0.4%), cocaine (0.3%) and psychostimulants (0.3%).

Conclusion

At least 1 in 13 patients with CD in the US Medicaid cohort noted substance use from 2010 through 2014. Our finding was comparable to the reported prevalence of substance use disorders in the general US population.
P054 WHAT ARE THEY WORRIED ABOUT?: FINDINGS FROM THE IBD DISTRESS SCALE
Authors: Beard Jacklyn Stellway , Beeson Erynn , MacKay Heather , Paternostro Jennifer , Bassett Mikelle , Lin Henry , Harris Michael
Published: January 2020

Introduction

It is intuitive to expect youth with IBD will have higher rates of depression and anxiety than their otherwise healthy peers, and most research bears this notion. However, existing literature of emotional distress has not consistently addressed the differentiation between general depression and anxiety and normative emotional experiences of IBD. Assessment measures often used for youth with IBD align with the DSM criteria; based on symptoms, without considering etiology or context (e.g., chronic disease). The IBD Distress Scale (IDS) was designed to identify distress/worry in response to extraordinary circumstances of having IBD.

Methods

The IDS is a 27-item measure of distress related to IBD symptoms, treatment, and disease burden. The youth self-report was completed by 108 patients ages 12–19, and 101 parents. The IDS measure was administered with general measures of depression (Patient Health Questionnaire, PHQ8) and anxiety (General Anxiety Disorder, GAD7) to youth with IBD attending their routine gastroenterology appointment. Item responses were classified as “not a problem,” “moderate problem,” or “serious problem.” For some analyses, “not a problem” and “moderate problem” were collapsed. Correlations and frequencies were conducted to compare youth and parent responses.

Results

Results identified top “serious problems” rated by youth and parents, separately. The highest rated problem for youth was worries about not being able to eat what others are eating, with 18% reporting this as a serious problem. The second most highly rated “serious problem” by youth was fear of not having bathroom access (15%). For parents, the highest rated “serious problem” was fear of surgery (24%). Parents also rated worrying about next flare, and feeling there’s no way to avoid a flare, as “serious problems,” both with 16% frequency. Pearson correlations for the top problems identified as “serious” by youth and parents revealed significant agreement for socially-oriented worries; e.g., anxiety about patient not being able to eat what others are eating (r=.33).

Conclusion

The CCF states IBD treatment goals are five-fold: achieve remission; control inflammation; maintain remission; prevent and manage complications; maximize quality of life. Based on research with other diseases, integrating the IDS into current IBD treatment protocols is a logical step for identifying target areas for treatment. Thematically, results revealed youth and parents worry about future-oriented (e.g., worrying about next flare) and socially-oriented issues (e.g., possibility of not having access to a bathroom). The identified themes enlighten current treatment and provide guidance for improved interventions. Future directions should include development and implementation of appropriate interventions specific to the identified serious problems for IBD distress.