bluuebunny/crossref_metadata_2025_split huggingface dataset:
P061 VALUE OF US AND MRE IMAGES IN THE DIAGNOSTICS OF ACTIVE CROHN’S DISEASE IN CHILDREN
Authors: Zbroja Monika , Cyranka Weronika , Kuczynska Maryla , Piekarska Monika , Siejka Karolina , Nowakowska Malgorzata , Grzegorczyk Magdalena , Brodzisz Agnieszka , Wozniak Magdalena Maria 
Published: January 2020

Abstract

Introduction
Crohn’s disease is classified as chronic inflammatory bowel disease.
The incidence of it in Europe ranges from 1 to almost 11.4 per 100,000 population per year. Ultrasound and magnetic resonance enterography examinations play an important role in imaging diagnostics of inflammatory bowel lesions. They allow for recognising and monitoring changes during therapy as well as assessing complications such as fistula or abscess.

Materials and Methods
36 children were included in the study: 16 boys and 20 girls with an active phase of Crohn’s disease. Each patient underwent intestinal ultrasound examination with a high frequency 7–12 Mhz linear probe and MRE with intravenous administration of a contrast agent.

Results
All patients showed a significant correlation between ultrasound and MRE. In the US examination all children had thickened, low echogenic wall showing varying degrees of vascular flow signals. Additionally, in 8 patients Bauhin’ valve edema was visible. In 16 children, inflammatory infiltration of the periintestinal fat around the affected segment of the intestine was found. In all patients a mesenteric lymphadenopathy in the short axis of 10-15mm was visible. MRE confirmed the presence of the confirmed ideal lesions and Bauhin’ valve edema in all 36 children. In addition, in 4 patients small intestine fistulas were found whereas abscess was observed in another 4 patients. In contrast-enhanced images, a vivid enhancement of the affected bowel section was revealed and in 10 children inflammatory reactions of peri-intestinal fat was demonstrated.

Conclusion
US and MRE are reliable tools in diagnosis of enteric inflammatory disease of the small intestine, evaluation of disease activity and assessment of potential complications. They are complementary elements in diagnostics of Crohn’s disease.
P125 COMPLICATIONS FOLLOWING OUTPATIENT COLONOSCOPY IN INFLAMMATORY BOWEL DISEASE (IBD) PATIENTS
Authors: Chu Daniel , Chen Po-Hung , Brant Steven , Miller Steven , Turner Natasha , Hutfless Susan 
Published: January 2020

Abstract
Inflammatory Bowel Disease (IBD) patients have frequent complications after surgical procedures. Inflammation, immunosuppression and other factors that are more common in Crohn’s disease (CD) and ulcerative colitis (UC) may play a role in increasing their complication risk profile. IBD patients also undergo colonoscopy procedures more frequently than the general population. We aimed to identify risks of complications during or within 7 days of colonoscopy in IBD patients.
Methods: Colonoscopy procedures performed between January 2016 through March 2019 in an outpatient setting (hospital or ambulatory surgical center) were identified from the United States Medicare fee-for-service claims. All Medicare beneficiaries were eligible. Colonoscopy was identified using the Healthcare Common Procedure Coding System (HCPCS) codes (‘45378’ through ‘45393’ and ‘45398’). A patient was considered to have Crohn’s disease (CD) if ICD-10-CM code K50.x was recorded; Ulcerative Colitis (UC) if ICD-10-CM code K51.x was recorded; and IBD if either was recorded on the date of the procedure. Complications recorded during the procedure included intestinal perforation (K63.1), gastrointestinal hemorrhage (K92.2), and “other post-procedural complications of the digestive system” (K91), including, but not limited to, post-gastrectomy syndrome, malabsorption, and intestinal obstruction. We examined these complications in procedures performed on IBD patients compared to the general population using logistic regression. We accounted for age, sex, race, year of colonoscopy, comorbidity score, and procedure discontinuation (identified by HCPCS modifier) in the analysis. A random effect for patient was included in the model to account for multiple procedures performed in the same patient during the study period, restricting patients from contributing multiple procedures.
Results: There were 3,181,759 eligible procedures. There were 26,583 (0.84%) colonoscopy procedures in CD patients and 50,708 (1.59%) in UC patients. After accounting for other risk factors, CD and UC were more likely to have intestinal perforation than the non-IBD population (CD OR=2.7, 95% CI: 1.1–6.5; UC=OR 1.9, 95% CI 0.9–4.1), with CD having a statistically significant increase. Women were at greater risk for perforations (OR=1.3; 95% CI: 1.0–1.7). Conversely, IBD patients were less likely than non-IBD patients to have a complication recorded as “other” (CD OR=0.5; 95% CI: 0.2–0.9; UC OR=0.5; 95% CI:0.3–0.8). Older age at colonoscopy (OR=1.02, 95% CI 1.01–1.03), six or more comorbidities (OR=1.9, 95% CI: 1.5–2.3) and procedure discontinuation (OR=2.0, 95% CI 1.2–3.4) were associated with complications regardless of IBD status.
Conclusion: IBD was associated with higher risk of perforation, and lower risk of other postprocedural complications in outpatient colonoscopy procedures.
4 TOTAL ABDOMINAL COLECTOMIES WITH PROCTECTOMY ARE ASSOCIATED WITH HIGHER 30-DAY READMISSION RATES IN CHILDREN WITH ULCERATIVE COLITIS
Authors: Egberg Matthew , Phillips Michael , Kappelman Michael 
Published: January 2020

Abstract

Background
Hospital readmissions are frequent and expensive. Thirty-day readmission rates for adult patients undergoing colectomy are as high as 25%, with inflammatory bowel disease (IBD) being a major risk factor for readmission. We sought to 1) determine the 30-day readmission rate for pediatric patients with ulcerative colitis (UC) undergoing total abdominal colectomy (TAC) between 2012 and 2017 using a national pediatric surgical database and 2) identify risk factors for unplanned readmission in this population.

Methods
We used the National Surgical Quality Improvement Program-Pediatrics (NSQIP-P) to identify pediatric UC patients undergoing a TAC between 2012 and 2017. The NSQIP-P is a national, multi-center effort by the American College of Surgeons to improve surgical care through standardized collection of patient-level data and longitudinal 30-day monitoring of patients following surgery. We identified patient and procedural data from the index hospitalization and used logistic regression to identify risk factors for 30-day readmission rates, adjusting for confounding factors.

Results
We identified 489 pediatric UC TAC hospitalizations between 2012 and 2017. Among these, 19% were readmitted unexpectedly to the hospital within 30-days of discharge. Patient demographics and preoperative lab values (hematocrit, albumin) were not associated with risk of readmission. However, TAC procedures that included a proctectomy were at a 2-fold (95% CI, 1.2–3.8) higher risk of 30-day readmission than staged procedures after adjusting for patient demographics, index admission length of stay, operative time, pediatric surgeon, and laparoscopic versus open approach.

Conclusion
Nearly 20% of annual pediatric UC hospitalizations involving a colectomy result in an unplanned readmission within 30 days of hospital discharge. Notably, TAC procedures that included a proctectomy had significantly higher rates of readmission than those not including a proctectomy. These results can inform risk management strategies aimed at reducing morbidity and hospital readmissions for children with UC.
P150 ENHANCING EPITHELIAL BARRIER FUNCTION WITH NOVEL E-CADHERIN ACTIVATING MONOCLONAL ANTIBODIES REDUCES INFLAMMATORY BOWEL DISEASE PROGRESSION IN MOUSE MODELS
Authors: Bandyopadhyay Chirosree , Schecterson Leslayann , Gumbiner Barry 
Published: January 2020

Abstract
Deficits in gastrointestinal (GI) epithelial barrier function play important roles in the pathogenesis of Inflammatory Bowel Disease (IBD). The CDH1 gene encoding E-cadherin, a key component of the epithelial junctional complex, is associated with Ulcerative Colitis (UC), and perhaps Crohn’s disease (CD). E-cadherin is the principle adhesive component of the adherens junction, and it regulates paracellular permeability by facilitating the formation of tight junctions and organizing the entire epithelial junction complex. We have identified monoclonal antibodies (mAbs) that bind to E-cadherin and activate adhesion in a variety of epithelial cells. In this study, we aim to test the hypothesis that strengthening E-cadherin adhesion with activating mAbs will enhance barrier function and decrease progression of IBD while maintaining mucosal health and homeostasis. Mouse mAbs to E-cadherin have been tested in vivo using the IL10-knock out mouse and adoptive T cell transfer model of colitis with similar histological evaluation. Transfer of CD4+CD45Rb high T cells from donor to immunocompromised mice produced typical histologic lesions for the adoptive transfer model including inflammation of the mucosa/submucosa, crypt damage, erosions, edema, and epithelial hyperplasia. E-Cadherin activating mAb (r56.4) treatment reduced total colitis score, mucosal hyperplasia, inflammation, gland loss scores, and neutrophilic infiltration in CD45Rb high T cell recipient mice compared to control E-cad mAb (r19.1–10) treatment. In IL10 KO BL6 mouse model of colitis, average lesion severity scores were lower in the r56.4 treatment group in comparison to the r19.1–10 treatment group for all the histological hallmarks of colitis. Further studies are in progress to investigate the therapeutic potential of E-Cadherin mAbs in the rescue of inflammation in pre-clinical mouse models of colitis.
P158 LOSS OF AUTOTAXIN ALTERS INNATE AND ADAPTIVE IMMUNE MECHANISM AND PROMOTES SPONTANEOUS COLITIS IN IL10-KO MICE
Authors: Kim Su Jin , Howe Cody , Mitchell Jonathon , Im Eunok , Rhee Sang 
Published: January 2020

Abstract

Background & Aims
Autotaxin (Atx) is a secreted enzyme converting lysophosphatidylcholine (LPC) and sphingosyl-phosphorylcholine into lysophosphatidic acid and sphingosine 1-phosphate, respectively. Given the high affinity of LPC to cholesterol and the enrichment of cholesterol and sphingolipids in lipid rafts wherein LPS sensor Toll-like receptor 4 (TLR4) and its co-receptor CD14 reside, we hypothesized that Atx deficiency inhibits TLR4-mediated innate and adaptive immunity; thereby, accelerating the susceptibility to microbe-induced intestinal inflammation.

Method
We generated myeloid cell lineage-restricted Atx-knockout (ko) mice (AtxdME/dME) to study TLR4-mediated immune and inflammatory responses and investigated LPS-receptor complex formation through fluorescence resonance energy transfer technique, confocal microscopy, and flow cytometry. Lamina propria CD4+ T cells and bacterial load in the intestinal mucosa were examined. An impact of Atx deficiency in inflammatory bowel diseases (IBD) was investigated using AtxdME/dME;Il10-/- mice that have both Atx-deletion in myeloid cells and a global Il10 deletion. We examined the serum samples from IBD patients.

Results
With peritoneal macrophages from AtxdME/dME mice, we identified that Atx-ko disrupted the integrity of lipid rafts at the plasma membrane, resulting in the inhibition of TLR4 complex formation. Accordingly, the recruitment of adaptor molecules to TLR4 was suppressed, and TLR4-mediated responses were substantially reduced in Atx-ko macrophages. TLR4-induced innate immunity such as phagocytosis was attenuated in Atx-ko macrophages. The activation of CD4+ effector T cells and regulatory T cells was diminished in the lamina propria lymphocytes of AtxdME/dME mice compared to that of Atx+/+ littermates. Consequently, AtxdME/dME mice had a higher bacterial prevalence in the intestinal mucosa compared to controls. Just like the notion that commensal microbes translocated from the lumen into the intestinal mucosa can elicit spontaneous colitis in Il10-/- mice, combining AtxdME/dME with Il10-/- mice (AtxdME/dME; Il10-/-) did accelerate spontaneous colitis development. AtxdME/dME; Il10-/- mice had gross inflammation occurring throughout the colon, massive neutrophil infiltration and necrosis in the colonic mucosa, and increased mortality (Log-rank P=0.0046), while Atx+/+;Il10-/- littermates are normal. Notably, ATX serum protein level was lower in UC (n=26) and CD (n=34) patients compared to the level in normal subjects (n=26) (P&lt;0.001), indicating an association of reduced ATX levels with the intestinal inflammation.

Conclusions
Collectively, we found that Atx deficiency suppresses TLR4-mediated innate and adaptive immune mechanisms; thereby accelerating the susceptibility to microbe-induced gut inflammation.
P159 PHENOTYPIC CHARACTERIZATION OF INFLAMMATORY BOWEL DISEASE BIOPSIES REVEAL THAT MAST CELLS ARE SIGNIFICANTLY ELEVATED AND ACTIVATED IN PATIENTS WITH ULCERATIVE COLITIS
Authors: Youngblood Bradford , Davis Tina , Schanin Julia , Butuci Melina , Brock Emily , Singh Bhupinder , Rasmussen Henrik , Holman Amy , Drake Richard , Peterson Kathryn , Flynn Ann 
Published: January 2020

Abstract

Rationale
Accumulation and activation of mast cells and eosinophils have been implicated in the pathogenesis of several chronic inflammatory gastrointestinal (GI) diseases, including eosinophilic gastrointestinal diseases (EGIDs) and inflammatory bowel disease (IBD). Despite the strong association of mast cell and eosinophil numbers and activation with the pathogenesis of IBD, no further characterization of these cells has been performed. Current treatment options for IBD include aminosalicylates, antibiotics, immunomodulators, biologic agents and small molecules. These therapies are only moderately effective. A significant proportion of patients fail to respond, do not fully respond, or lose response over time. Therefore, there is significant need for more selective and effective therapy options. Siglec-8 is an inhibitory receptor selectively expressed on human eosinophils and mast cells and represents a novel target for the treatment of IBD with the anti-Siglec-8 mAb, antolimab (AK002). We aimed to quantify and evaluate the activation state of mast cells and eosinophils in colonic tissue from IBD or non-diseased patients. In addition, we quantified the production of TNFa from human colon tissue mast cells and evaluated the inhibitory activity of antolimab (AK002) on these cells.

Methods
Single-cell suspensions were prepared by enzymatic digestion of fresh colonic biopsies from patients clinically diagnosed with IBD (n=29) or non-diseased control tissues (n=16). Multi-color flow cytometry was performed to identify major immune cell populations and evaluate the activation state of mast cells and eosinophils. Mast cells were FACS-sorted from human colon tissue to evaluate cytokine production and inhibitory activity of antolimab.

Results
The percentage of mast cells and the expression of the mast cell degranulation marker CD107a were significantly increased in ulcerative colitis (UC) patient biopsy tissue compared to Crohn’s disease (CD) and non-diseased colonic tissue (Figure 1A and B). Furthermore, FACS-sorted mast cells from human colon tissue produced significant quantities of TNFa that was reduced after ex vivo antolimab treatment. Colonic tissue eosinophils were also elevated in a subset of UC and CD patient biopsies, and all UC and CD tissue eosinophils displayed increased expression of the activation marker CD11b compared to control colonic tissue.

Conclusions
Mast cells and eosinophils may play a significant role in driving the pathogenesis of ulcerative colitis through the production of inflammatory mediators. The high expression of Siglec-8 and the inhibitory activity against mast cells suggests that antibodies that target this receptor, such as antolimab (AK002) represent a potential novel approach for the treatment of IBD.
P141 GREEN TEA POLYPHENOL EPIGALLOCATECHIN-3-GALLATE DIFFERENTIALLY MODULATES ENDOPLASMIC RETICULUM STRESS-MEDIATED WOUND HEALING PROCESS IN SUBEPITHELIAL MYOFIBROBLASTS
Authors: Li Chao , Kuemmerle John 
Published: January 2020

Abstract
Epigallocatechin-3-gallate (EGCG) has multifaceted roles in the preclinical treatment of diseases including liver and lung fibrosis. EGCG has also been tested with fewer reported side effects than therapeutic drugs. Previously we showed that increase in endoplasmic reticulum (ER) stress response in subepithelial myofibroblasts (SEMF) contributes to activation of TGF-β1 and resultant intestinal fibrosis in patients with fibrostenotic Crohn’s disease. Moreover, different migratory potential of myofibroblasts isolated from inflamed, fibrostenotic, or fistulized Crohn’s disease mucosa could be an explanation for impaired or excess wound healing and subsequently for fistula or fibrosis in patients with Crohn’s disease. To investigate the effect of EGCG on ER stress-mediated wound healing process, SEMF were isolated from normal ileum and affected ileum in the same patient with Crohn’s disease. Cells were cultured and treated with EGCG (10 μg/ml), AG1024 (a tyrosine kinase inhibitor, 6 μM), U1026 (an ERK inhibitor, 6 μM), LY294002 (a PI3K inhibitor, 10 μM), SB202190 (a p38 inhibitor, 50 nM), 4-PBA (a chemical chaperone, 10 μg/ml), and MG132 (a NF-KB inhibitor, 3 μM) for 2 hours in serum free medium. Cell lysates were obtained for Western blot analysis. An ER stress agonist tunicamycin (5 μg/ml) was incubated with SEMF for different time points. Wound healing assay was used in a cell monolayer, capturing the images at the beginning and at regular intervals during cell migration to close the wound, and comparing the images to quantify the migratory potential of the cells. In vivo effect of EGCG was tested in a murine TNBS colitis model and observed by Storz Coloview standard operating procedures. Here we showed that EGCG further decreased endogenous GRP78 protein expression by 18∼29±1.5% in SEMF compared to that treated with different inhibitors targeting other non-ER stress signals. EGCG prevented tunicamycin-induced migratory potential of SEMF isolated from normal ileum by 40±2.5%, 65±3.3% after 48 and 72 hours, as well as cell proliferation by 85±3.3%, 120±6.1% after 48 and 72 hours, respectively. Moreover, EGCG also further decreased cell migratory potential of SEMF isolated from affected ileum by 15±1.2% and 50±1.8% compared to the control group after 48 and 72 hours, respectively. Coloview showed that EGCG decreased inflammatory activity in the mice colon compared to TNBS colitis group after 8-week treatment. Ongoing study includes methylene blue staining of the colonic mucosa during endoscopy, endoscopic scoring of inflammation activity, and trichrome staining of collagen production in a colonic biopsy. Taken together, EGCG alleviates ER Stress response, leads to greater inhibition of migratory potential of SEMF, and decreases TGF-β1 and collagen productions, which is the major molecular feature of fibrosis.
P076 TRANSFERABLE IMMUNE REACTIVE MICROBIOTA DETERMINE CLINICAL AND IMMUNOLOGIC OUTCOME OF FECAL MICROBIOTA TRANSPLANTATION FOR ULCERATIVE COLITIS
Authors: Lima Svetlana , Gogokhia Lasha , Viladomiu Monica , Crawford Carl , Jacob Vinita , Scherl Ellen , Rosenthal Melissa , Brown Su-Ellen , Hambor John , Longman Randy 
Published: January 2020

Abstract

Background
Biologic therapy has significantly improved treatment for UC, but nearly two-thirds of patients attenuate response. Additional therapeutic modalities are therefore needed to address the underlying pathophysiology of UC. Fecal microbiota transplant (FMT) is an emerging therapy for the treatment of UC, but several randomized controlled trials have shown variable efficacy of FMT, and the microbial mechanisms responsible for clinical response are not well understood. Therefore, using samples from our pilot FMT study (Jacob, V, et al Inflamm. Bowel Dis. 2017), we aim to identify the core transferable microbiota (CTM) in UC patients responsive to FMT therapy and to define the therapeutic mechanism of these strains in pre-clinical models.

Methods
IBD disease activity scores were used to define clinical response. Metagenomic sequencing of donor, recipient, and 4 week post-FMT fecal samples was performed to define the CTM. Strain level transferability was defined using StrainFinder. To define the transferable immune-reactive microbiota (TIM), IgA-seq was performed on donor, recipient, and 4 week post-FMT fecal samples. TIM strains were isolated from fecal samples and gnotobiotic mouse models were used to evaluate their impact on mucosal immunity and mouse models of colitis.

Results
Here, we defined a CTM associated with clinical response to FMT for UC. Strain level tracking of the CTM confirmed that clinical response correlated with strain transferability. In addition, we defined a core TIM by IgA-seq that correlated with clinical response. In humanized mouse models, these TIM were found to induce IgA in a T cell independent manner. Colonization of germ-free mice with a core TIM strain of Odoribacter induced IL-10-dependent, RORgt+/Foxp3+ iTreg cells and reduced the severity of transfer T cell colitis in mono-colonized RAG-/- mice.

Conclusion
Our data highlight an immune-reactive, core transferable microbiota in responders to FMT for UC. Using pre-clinical mouse models of colitis, we define the mechanistic impact of these TIM in shaping mucosal immunity and guiding the response to UC. This work provides a framework for rational selection of TIM for microbial-therapy in IBD.