bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of Next-Generation Assays for Fecal Calprotectin vs the PhiCal Assay
Authors: Lin Leo , Wyness Sara P , Jensen Ryan , Bird Joseph , Norgyal Tenzin , Jensen Gabrielle , Johnson Lisa M
Published: May 2021

Objectives

To compare the PhiCal assay (CALPRO), the first US Food and Drug Administration–approved assay for fecal calprotectin, to 4 next-generation assays.

Methods

Stool samples from 50 patients were selected, and relevant clinical information was collected. Comparisons were performed using the PhiCal, fCAL turbo (BÜHLMANN), LIAISON Calprotectin (DiaSorin), QUANTA Lite Calprotectin ELISA (Inova Diagnostics), and Calprotectin Chemiluminescence ELISA (ALPCO) assays.

Results

All 4 assays had acceptable agreement with PhiCal when qualitatively categorizing results. Within the PhiCal reportable range of 16 to 1,250 μg/g, the DiaSorin, Inova Diagnostics, and ALPCO assays had Spearman correlation coefficients of 0.98, 0.97, and 0.95 and positive biases of 17%, 20%, and 15%, respectively. The BÜHLMANN assay ran approximately 2-fold higher than the PhiCal assay but had a correlation coefficient of 0.98, with similar result categorization.

Conclusions

Our results demonstrate good comparison between PhiCal and 4 next-generation assays. Laboratories performing fecal calprotectin assays may have compelling reasons to adopt next-generation fecal calprotectin testing, such as greater automation, a decreased number of replicates needed per test, and the use of stool-extraction devices. These benefits could decrease turnaround times and lower costs. Although the results of the assays correlated, they are not standardized. Laboratories adopting the newer assays will need to further investigate their performance through validation studies.
Deficits of hierarchical predictive coding in left spatial neglect
Authors: Doricchi Fabrizio , Pinto Mario , Pellegrino Michele , Marson Fabio , Aiello Marilena , Campana Serena , Tomaiuolo Francesco , Lasaponara Stefano
Published: May 2021

Right brain-damaged patients with unilateral spatial neglect fail to explore the left side of space. Recent EEG and clinical evidence suggests that neglect patients might suffer deficits in predictive coding, i.e. in identifying and exploiting probabilistic associations among sensory stimuli in the environment. To gain direct insights on this issue, we focussed on the hierarchical components of predictive coding. We recorded EEG responses evoked by central, left-side or right-side tones that were presented at the end of sequences of four central tones. Left-side and right-side deviant tones produce a pre-attentive Mismatch Negativity that reflects a lower-order prediction error for the ‘Local’ deviation of the tone at the end of the sequence. Higher-order prediction errors for the frequency of these deviations in the acoustic environment, i.e. ‘Global’ deviation, are marked by the P3 response. We show that when neglect patients are immersed in an acoustic environment characterized by frequent left-side deviant tones, they display no pre-attentive Mismatch Negativity both for left-side deviant tones and infrequent omissions of the last tone, while they have Mismatch Negativity for infrequent right-side deviant tones. In the same condition, neglect patients show no P300 response to ‘Global’ prediction errors for deviant tones, including those in the non-neglected right-side, and omissions. In contrast to this, when right-side deviant tones are predominant in the acoustic environment, neglect patients have pre-attentive Mismatch Negativity both for right-side deviant tones and infrequent omissions, while they display no Mismatch Negativity for infrequent left-side deviant tones. Most importantly, in the same condition neglect patients show enhanced P300 response to infrequent left-side deviant tones, notwithstanding that these tones evoked no pre-attentive Mismatch Negativity. This latter finding indicates that ‘Global’ predictions are independent of ‘Local’ error signals provided by the Mismatch Negativity. These results qualify deficits of predictive coding in the spatial neglect syndrome and show that neglect patients base their predictive behaviour only on statistical regularities that are related to the frequent occurrence of sensory events on the right side of space.
DOP05 Target engagement and pharmacodynamic biomarker analysis following treatment with the oral gut-targeted HIF-1α stabilizer GB004 in a Phase 1b trial in Active Ulcerative Colitis
Authors: Sandborn W , Ding Z , Osterhout R , Feagan B , Danese S , Jucov A , Bhandari B R , Raghupathi K , Olson A , Van Biene C , Ford J , Aranda R , Levesque B G , Bruey J M
Published: May 2021

Background

Ulcerative colitis (UC) is characterized by the loss of epithelial barrier function and chronic mucosal inflammation. GB004 is an oral, gut-targeted, small molecule stabilizer of hypoxia inducible factor (HIF-1α) that promotes epithelial repair and function. A phase 1b study was conducted in patients with active UC where trends in clinical efficacy favoring GB004 were observed. Here we report the target engagement (TE) and pharmacodynamic (PD) biomarker analysis of colon biopsies and stool samples from the phase 1b study.

Methods

Subjects with active UC despite 5-ASA treatment were randomized 2:1 to GB004 120 mg solution or placebo (PBO) once daily for 28 days. Colon biopsies (sigmoid and rectum) and stool samples were collected at baseline and Day 28. HIF-1a and myeloperoxidase (MPO) immunohistochemistry was performed on formalin-fixed paraffin-embedded colon biopsies. Gene expression profiling (Affymetrix HTA 2.0) was performed on mRNA extracted from colon biopsies. Fecal calprotectin (FC) and secretory IgA (sIgA) were measured from stool samples. Results presented are overall means for baseline characteristics and differences in mean (HIF-1a, MPO) and median (FC, sIgA) percent change from baseline to Day 28 for GB004 vs PBO.

Results

Thirty-four subjects (age 45.4 years, Mayo score 7.5, sigmoid colon Mayo endoscopic subscore 2.2, sigmoid colon Robarts Histopathology Index 14.1) were randomized to a GB004 120 mg solution (n=23) or PBO (n=11) group. GB004 demonstrated evidence of TE, with an increase in the percent of HIF-1α positive cells (+11.4%) in sigmoid colon segment sections. Tissue and stool-based PD biomarkers of intestinal inflammation associated with lamina propria neutrophil infiltration and cytotoxicity measured by the MPO+ cell count per mm2 (-7.3%) and FC (-30.4%) levels decreased. Lastly, GB004 resulted in an increase in sIgA levels (+87.16%) and transcriptional changes consistent with enhanced epithelial integrity, such as increases in ITGA6 and TJP1.

Conclusion

In this phase 1b study, GB004, an oral gut-targeted HIF-1α stabilizer, demonstrated TE in the sigmoid colon and histologic, fecal biomarker, and transcriptional PD effects consistent with a reduction in inflammation and mucosal healing. These observations are consistent with the role of HIF-1α stabilization in improving barrier function in UC patients and support the trends in clinical effects observed, including histologic endpoints. A Phase 2 study of GB004 in patients with mild-to-moderate UC (SHIFT-UC, NCT04556383) is currently ongoing. Sponsored by GB004, Inc., a wholly owned subsidiary of Gossamer Bio, Inc.
DOP77 Effect of Inflammatory Bowel Disease and Related Medications on COVID-19 Incidence, Disease Severity, and Outcome -The Israeli Experience
Authors: Richter V , Bermont A , Cohen D L , Broide E , Shirin H
Published: May 2021

Background

The COVID-19 pandemic raised concerns among IBD patients fearing an increased risk of infection and poor outcomes. We aimed to evaluate the incidence of COVID-19 among IBD patients; its influence on disease severity and outcome; its relationship to medication use; and how the pandemic affected IBD management.

Methods

An anonymous questionnaire was posted online to members of the Israel Crohn’s Disease and Ulcerative Colitis Foundation (November 2020- January 2021). The questionnaire addressed the course of IBD disease and COVID-19 infection over the past year.

Results

2152 IBD patients completed the questionnaire. 104 (4.8%) had been infected with COVID-19, significantly lower than the “expected” infected cases among the Israeli population (p=0.033). The median age of participants was 39; 60.5% were female. Most patients (75.6%) had no comorbidities other than IBD.

No correlation was found between IBD type or disease severity and COVID-19 infection. Most IBD patients reported mild COVID-19 disease, regardless of the type of IBD medications. Multivariable logistic regression analysis revealed that younger age, elevated BMI, and diabetes were independent risk factors for COVID-19 infection. IBD treatment including 5-aminosalicylic acid, smoking, and hypertension were protective factors. 25.2% of COVID-19 patients discontinued their IBD treatment, compared to 8.5% of non-COVID-19 infected patients. IBD flares were significantly higher in those who discontinued treatment (p<0.001).

Conclusion

IBD patients do not have an increased risk for COVID-19, regardless of IBD activity or treatment. Patients should be encouraged to continue effective IBD therapy, including biologics and steroids, to minimize active IBD.
N05 A Systematic Review of Self-Management Intervention Study for Patients with Inflammatory Bowel Disease
Authors: Iizawa M , Hirose L , Tairaka A , Maya N
Published: May 2021

Background

Patients with inflammatory bowel disease (IBD) have to deal with abdominal symptoms for a long time because the disease often develops at a young age, and radical treatment has not been established. To prevent worsening of symptoms associated with IBD and delay the progression of the disease, and lead a better daily life, patients must self-manage in their daily lives. At this moment, it is not clear which kinds of self-management are effective for IBD patients. Therefore, we conducted a systematic literature review (SLR) to clarify the present status and efficacy of self-management for IBD patients and find out the effective methods of self-management intervention.

Methods

The SLR was conducted in accordance with the methods recommended by the Cochrane Collaboration Handbook7, to reduce the risk of bias and errors. The searches were performed in Embase, Medline, and Cochrane databases. Additionally, the PsychInfo and the cumulative index of nursing and allied health literature (CINAHL) databases were searched, and relevant articles were included as other sources. Abstracts and full texts were screened to select relevant articles based on the inclusion criteria. A quality assessment was undertaken by using the Cochrane risk of bias tool checklist.

Results

Fifty studies met the inclusion criteria and were finally included in this review. In 31 studies, the overall population of IBD patients was included. Fourteen studies included only UC patients, 5 studies included only CD patients. Among 50 studies, 33 studies have statistically significant differences in the outcomes. We categorized the interventions and outcomes of all the studies based on Barlow’s study in 2002 and analyzed the efficacy of the intervention on the outcomes. The most common intervention was informational, subsequently management of psychological effects. The most common outcome was Inflammatory Bowel Disease Questionnaire (IBDQ). We found that psychological management and interventions related to problem-solving, goal setting, action plan, and coping skills had a positive effect on the body and psychology of IBD patients. There were six studies that investigated the effects of intervention by online medical care. Half of the online intervention showed an improvement in the use of medical services.

Conclusion

It is important for IBD patients and health care providers to work together to share the problem, followed by setting goals and decide on an action plan. To succeed in this process, multidisciplinary collaboration is necessary and continuous support by health care providers will be meaningful for IBD patients.
OP02 Ustekinumab versus adalimumab for induction and maintenance therapy in Moderate-to-Severe Crohn’s Disease: The SEAVUE study
Authors: Irving P M , Sands B E , Hoops T , Izanec J L , Gao L L , Gasink C , Greenspan A , Allez M , Danese S , Hanauer S B , Jairath V , Kuehbacher T , Lewis J D , Loftus E V , Mihaly E , Panaccione R , Scherl E , Shchukina O , Sandborn W J
Published: May 2021

Background

We studied the efficacy and safety of ustekinumab (UST) vs adalimumab (ADA) through 1 year in biologic-naïve patients (pts) with moderate-to-severe Crohn’s disease.

Methods

SEAVUE was a multicenter, randomized, blinded, parallel-group, active-controlled study in adults with CD Activity Index (CDAI) scores ≥220/≤450. Biologic-naïve pts failing/intolerant to conventional therapy with any size ulcer on baseline (BL) ileocolonoscopy were eligible. Pts were randomized 1:1 to UST (⁓6mg/kg IV at BL then 90mg SC every 8 weeks [Ws]) or ADA (160/80mg SC at BL/W2, then 40mg SC every 2 Ws) per US-approved regimens (no dose modifications). Primary endpoint was clinical remission at W52 (CDAI <150). Major secondary endpoints were corticosteroid-free remission, clinical response (≥100-point CDAI decrease from BL), remission in pt-reported CDAI components (PRO-2 symptom remission: abdominal pain mean daily score ≤1 and stool frequency mean daily score ≤3), and endoscopic remission (SES-CD score ≤3/0 for pts with BL score=3) at W52 and clinical remission at W16.

Results

386 pts were randomized to UST or ADA. BL demographics and disease characteristics were balanced between groups and indicative of pts with early, moderate-to-severe CD (median CD duration, 2.58 years; CDAI, 289.5; SES-CD, 8.0). At W52, 65% of UST-treated and 61% of ADA-treated pts achieved clinical remission (Δ=4.0%; 95% CI, -5.5%, 13.5%; p=0.417). Major secondary endpoints, including endoscopic remission, were similar between groups (Table 1), as were remission rates at assessment points through W52. Some other secondary endpoints showed numerical (not statistical) differences between UST and ADA (Table 1). Key safety events are summarized in Table 2. Among UST-treated and ADA-treated pts, 34.0% and 40.5% had infections, 2.6% and 7.2% had serious adverse events (AEs) of worsening CD, and 6.3% and 11.3% had AEs that led to discontinuation (DC) of study drug, respectively. One ADA-treated pt had active pulmonary TB. Injection-site reactions associated with active treatment occurred in 1.0% of UST-treated and 10.3% of ADA-treated pts. Overall, 15.2% of UST-treated and 23.6% of ADA-treated pts DC before W52. Reasons for DC were primarily lack of efficacy (UST, 2.1% vs ADA, 5.1%), AEs (UST, 5.7% vs ADA, 10.7%), and withdrawal of consent (UST, 5.8% vs ADA, 5.1%). Time to treatment DC was longer with UST vs ADA (post hoc analysis).

Conclusion

Both UST and ADA were highly effective in this population of biologic-naïve pts. Rates of clinical remission at W52 were not statistically significantly different between treatment groups. DC rates were numerically lower for UST. Safety results were consistent with prior experience for both treatments.
OP13 Mucosal organoids capture Innate Lymphoid Cells (ILC) tissue-specific development and reveal that Inflammatory Bowel Disease-associated ILC modulate intestinal remodelling
Authors: Jowett G M , Read E , Norman M D , Arevalo P A , Vilà González M , Roberts L , Vallier L , Curtis M , Lord G , Gentleman E , Neves J F
Published: May 2021

Background

Innate Lymphoid Cells (ILC) develop from Common Lymphoid Precursors in the bone marrow, and ILC precursors (ILCP) migrate to mucosa where they mature, promote homeostasis, and provide a potent, antigen-non-specific sources of cytokines. Deciphering what local stimuli drive the final stages of ILCP maturation in these tissues remains a pressing question, as ILC frequencies can become dysregulated during chronic infection and inflammatory diseases. For example, Type-1 innate lymphoid cells (ILC1) are enriched in the mucosa of patients with active inflammatory bowel disease (IBD) and the impact of this accumulation remains elusive.

Methods

Here, we develop and use co-cultures of both murine and human iPSC-derived gut and lung organoids with ILCP and with mature ILC isolated from IBD patients’ intestinal biopsies.

Results

Harnessing these versatile models, we demonstrate that epithelial cells provide a complex niche capable of supporting the final maturation of all helper-like ILC1, ILC2, and ILC3. Notably, organoid identity was sufficient to robustly recapitulate tissue-specific ILC imprints and frequencies, even in the absence of microbial stimuli, other cell types, or cytokine supplementation.

In addition, we show that that ILC1 drive expansion of the epithelial stem cell crypt through p38γ phosphorylation, driving a potentially pathological proliferative feedback loop between β-catenin and Cd44v6. We harnessed this model to elucidate that this phenotype was unexpectedly regulated by ILC1-derived TGFβ1. We further show that human gut ILC1 also secrete TGFβ1, and drive CD44v6 expression in both HIO epithelium and mesenchyme. As TGFβ1 is a master regulator of fibrosis, the leading indicator for surgery in IBD, we next characterised the ability of ILC1 to regulate matrix remodelling using a functionalized, synthetic hydrogel system. We show that ILC1 drive both matrix stiffening and degradation, which we posit occurs through a balance of MMP9 degradation and TGFβ1-induced fibronectin deposition.

Conclusion

Taken together, our work provides unprecedented insight into in situ ILC maturation, which we show to be driven by epithelial signals, and into ILC function. We also report that intestinal ILC1 modulate epithelial and matrix remodelling, which may drive either wound healing in homeostasis, but may tip toward pathology when enriched in IBD.

Moreover, our work introduces a modular organoid platform, which provides exquisite control over both environmental stimuli and host genetics, making it a powerful tool for dissecting the interactions between complex mucosal tissues and rare cell subtypes in development and disease.
P001 Succinate, a gut microbiota-derived metabolite, modulates the inflammatory status of the creeping fat in Crohn’s disease
Authors: Serena C , Monfort-Ferre D , Bautista M , Menacho M , Martí M , Espin E , Vendrell J , Fernández-Veledo S
Published: May 2021

Background

Crohn’s disease [CD] is characterized by severe transmural inflammation with subsequent destruction of the intestinal barrier. Recent works suggest that bacterial infiltration across this leaky gut facilitates access to the mesenteric fat and the development of a subsequent inflammatory reaction in the surrounding adipose tissue named creeping fat [CF]. Dysbiosis in CD patients has been associated with an increase in succinate-producing bacteria and a decrease in succinate-consuming bacteria. In fact, elevated succinate levels have been found in the intestinal and faeces of CD patients. Succinate has been classically considered as a marker of hypoxia and tissue damage, assisting as a pro-inflammatory signal that triggers immune activation. However, recent observations support potential additional functions of succinate. We and others have shown that succinate plays a key role in fine-tuning of the inflammatory response, acting both as an alarmin and resolving molecule. Our hypothesis is that succinate, a microbiota-derived metabolite, is a new determinant of adipose tissue dysfunction in CD.

Methods

A well-characterized cohort was used to obtained mesenteric adipose tissue biopsies including a) 10 subjects with active CD that require surgery for their underlying pathology b) 10 subjects with inactive CD and c) 10 healthy controls undergoing surgery for non-acute process (herniorrhaphy, cholecystectomy for lithiasis, etc.). The groups were comparable in age, sex, and body mass index. We studied the effect of exogenous succinate in adipose tissue explants, adipose-stem cells (ASC), and adipose tissue macrophages (ATM) isolated from adipose tissue biopsies of CD patients with different clinical activity. Circulating succinate levels and inflammatory variables including hs-CRP and faecal calprotectin were also measured.

Results

We observed an increased expression of SUCNR1 in CF, including ASCs and ATMs, mainly in patients suffering from an active disease (figure 1A). Furthermore, succinate appears to elicit a different response in adipose tissue from CD patients, when activity status is considered. Thus, our results indicate that in an inflammatory local and systemic environment, such as occurs in CD active patients, succinate triggers a pro-inflammatory response in VAT depot, while when subjects are in a remission period, the response of VAT explants to succinate is similar to than the observed in healthy subjects, promoting an anti-inflammatory expression profile (Figure 1B). Interestingly, we found elevated circulating succinate levels in active CD patients but those decrease drastically in patients in remission of the disease (Figure 1C).

Conclusion

Succinate has a relevant role in adipose tissue dysfunction in CD.
P029 Activation of FXR restores expression of genes dysregulated in human IBD and suppresses TNFa and IL-6 signaling pathways in adoptive transfer colitis model
Authors: Liu X , Milik A , O’Connell R , White J , Wagner B
Published: May 2021

Background

Farnesoid X receptor (FXR) is a ligand-activated nuclear hormone receptor highly expressed in the gastrointestinal tract. We have shown that FXR agonists improve disease in multiple chronic IBD models (Adoptive transfer (AT) colitis, Mdr1a-/- colitis, and SAMP1/YitFc ileitis) with efficacy similar to anti-IL-12/23. To explore the mechanisms by which FXR agonists reduce colitis in these models and the relevance to human IBD, we identified the genes and pathways regulated by FXR in the AT colitis mice, and compared them with the gene expression profile in human IBD patients.

Methods

Colitis was induced by transplanting CD4+CD45RBhi T-cells to C.B-17 SCID mice. Mice were treated with vehicle (n=10), an FXR agonist (p.o. daily, n=10) or anti-IL-12p40 (i.p., weekly, n=5) in therapeutic mode (started 21 days post AT) for 4 weeks. Efficacy was assessed by colon histopathology of inflammation, erosion, gland loss and hyperplasia (0–5 each). RNAseq was performed on colon RNAs (n=5–7 samples/group). Genes differentially regulated by the FXR agonist were compared with published FXR ChIPSeq data (Thomas et al 2010 Hepatology) and a IBD patients’ gene expression dataset (GSE73661) to identify FXR target genes associated with human IBD. Gene set enrichment analysis (GSEA) was performed to identify enriched pathways.

Results

Direct FXR target genes were identified by comparing genes upregulated by the FXR agonist in the AT mice with FXR ChIPSeq data. Further comparison with GSE73661 identified FXR target genes relevant to human IBD. The majority of these genes are down-regulated in diseased mice and IBD patients compared to healthy controls. Importantly, in GSE73661 dataset, those genes were upregulated in patients that responded to therapy, while remained down-regulated in refractory patients. The function of those genes includes reducing inflammation, improving gut healing and transporter activities. Further pathway analysis by GSEA identified a number of inflammatory pathways significantly upregulated in AT mice and IBD patients, many of which show reduction with the FXR agonist treatment. Of note, TNFα/NF-κB and IL-6/STAT3 pathways, targeted by approved IBD therapies, were significantly elevated in AT mice but reduced by the FXR agonist or anti-IL-12/23.

Conclusion

Activation of FXR directly induces IBD-dysregulated genes that can suppress inflammation, promote gut healing and transporter functions. In addition, FXR activation reduced TNFα/NF-κB and IL-6/STAT3 pathways in AT colitis model. These findings support further development of novel FXR agonists as a potential oral therapy for IBD.
P034 Human primary 2D culture as a tool to explore JAK1 pathway inhibition in the intestinal epithelium using siRNA technology
Authors: Dotti I , Sulpice E , Nougarède A , Jary D , Clément F , Gidrol X , Navarro F , Salas A
Published: May 2021

Background

Oral inhibitors of JAK1 have become promising therapeutic agents for the treatment of inflammatory bowel diseases (IBD); however, concerns have been raised regarding their specificity and safety profiles. Currently, a local therapy based on specific JAK1 siRNA combined with lipid nanoparticle (LNP) technology is under investigation as a safer alternative to JAK inhibitors.The purpose of this study is to explore the inhibition of the JAK1 pathway in the intestinal epithelium mediated by siRNA/LNP technology, using human primary 2D culture.

Methods

Human primary 2D cultures were generated from colonic 3D organoids of non-IBD donors. The efficiency of JAK1 pathway inhibition was tested in IFN-y stimulated cultures using either filgotinib (a JAK1 inhibitor, used as a control) or the novel human JAK1 siRNA. JAK1 siRNA transfection was performed using Lipofectamine or LNPs. qPCR was performed on a panel of JAK1 target genes to evaluate the efficiency of JAK1 pathway inhibition.

Results

Incubation of the 2D culture with IFN-y induced the activation of the JAK1 pathway, as suggested by the significant up-regulation of JAK1-dependent genes (i.e., CXCL10, SOCS1, SOCS3 and PLA2G2A). The addition of filgotinib to the culture efficiently inhibited the JAK1 pathway by suppressing the expression of JAK1-target genes. JAK1 siRNA transfection using Lipofectamine reduced JAK1 mRNA expression by 50%, which was mirrored by the concomitant down-regulation (between 60 and 80%) of JAK1-dependent genes. Importantly, the silencing efficiency of the JAK1-dependent pathway by LNPs was comparable to that observed using Lipofectamine.

Conclusion

Organoid-derived 2D culture is a useful model for investigating the activation of the JAK1 pathway and its pharmacological inhibition in human intestinal epithelium. In particular, siRNA/LNP nanoplexes may be a promising technology for locally delivering highly specific siRNAs to the intestinal mucosa, which could pave the way for the development of more effective treatments for IBD patients.
P048 Intestinal inflammation and microbiome diversity are conserved more in consecutive pregnancies among women with inflammatory bowel disease compared to healthy controls
Authors: Agrawal M , Tarassishin L , Rendon A , Hillenbrand C , Debebe A , White S , Eisele C , Hawkins K , Kim E S , Thjømøe A , Mørk E , Chen C L , Kornbluth A , George J , Legnani P , Maser E , Stone J , Dubinsky M , Sabino J , Torres J , Colombel J F , Peter I , Hu J
Published: May 2021

Background

There are increasing data on changes in intestinal inflammation and microbiome diversity during pregnancy in women with inflammatory bowel disease (IBD) with implications towards individual and offspring immune function. However, differences in intestinal inflammation, as measured by fecal calprotectin (FC) and microbial a-diversity, in consecutive pregnancies are not known.

Methods

We prospectively enrolled a cohort of women, 37 with IBD and 39 without IBD, during two consecutive pregnancies, and their offspring. We collected serial stool samples and clinical data, and measured FC and bacterial abundance during each trimester of each pregnancy. We further performed correlation analysis between FC in consecutive pregnancies and between microbial a-diversity in consecutive pregnancies among women with and without IBD.

Results

Compared to healthy controls, IBD pregnancies had significantly lower gestational age at birth and higher frequency of Cesarean section. Mode of delivery, the status of Group B Streptococcus (GBS) infection and GBS infection prophylaxis were significantly associated with the pregnancy order in both IBD and controls (Table). Furthermore, we observed strong correlations of FC (r=0.56, p-value=0.093) and microbial alpha-diversity assessed as operational taxonomic unit (OTU) richness (r=0.88, p=0.0087) between paired consecutive pregnancies in women with IBD, but not in those without IBD (Figure). There were no differences in microbial alpha-diversity using the Shannon and Simpson indices when comparing consecutive pregnancies of women with and without IBD.

Conclusion

In this study, we demonstrate that intestinal inflammation and microbiome diversity are more conserved in consecutive pregnancies of women with IBD compared to healthy controls. These findings may have implications towards understanding the impact of pregnancy on host-microbiome interactions in IBD as well as the potential impact on offspring health.
P069 Artificial intelligence (AI)-filtered Videos for Accelerated Scoring of Colonoscopy Videos in Ulcerative Colitis Clinical Trials
Authors: Gutierrez Becker B , Giuffrida E , Mangia M , Arcadu F , Whitehill V , Guaraglia D , Schwartz M , Sabouni R , Prunotto M , Oh Y , Daperno M
Published: May 2021

Background

Endoscopic assessment is a critical procedure to assess the improvement of mucosa and response to therapy, and therefore a pivotal component of clinical trial endpoints for IBD. Central scoring of endoscopic videos is challenging and time consuming. We evaluated the feasibility of using an Artificial Intelligence (AI) algorithm to automatically produce filtered videos where the non-readable portions of the video are removed, with the aim of accelerating the scoring of endoscopic videos.

Methods

The AI algorithm was based on a Convolutional Neural Network trained to perform a binary classification task. This task consisted of assigning the frames in a colonoscopy video to one of two classes: “readable” or “unreadable.” The algorithm was trained using annotations performed by two data scientists (BG, FA). The criteria to consider a frame “readable” were: i) the colon walls were within the field of view; ii) contrast and sharpness of the frame were sufficient to visually inspect the mucosa, and iii) no presence of artifacts completely obstructing the visibility of the mucosa. The frames were extracted randomly from 351 colonoscopy videos of the etrolizumab EUCALYPTUS (NCT01336465) Phase II ulcerative colitis clinical trial.

Evaluation of the performance of the AI algorithm was performed on colonoscopy videos obtained as part of the etrolizumab HICKORY (NCT02100696) and LAUREL (NCT02165215) Phase III ulcerative colitis clinical trials. Each video was filtered using the AI algorithm, resulting in a shorter video where the sections considered unreadable by the AI algorithm were removed.

Each of three annotators (EG, MM and MD) was randomly assigned an equal number of AI-filtered videos and raw videos. The gastroenterologist was tasked to score temporal segments of the video according to the Mayo Clinic Endoscopic Subscore (MCES). Annotations were performed by means of an online annotation platform (Virgo Surgical Video Solutions, Inc).

Results

We measured the time it took the annotators to score raw and AI-filtered videos. We observed a statistically significant reduction (Mann Whitney U test p-value=0.039) in the median time spent by the annotators scoring raw videos (10.59∓ 0.94 minutes) with respect to the time spent scoring AI-filtered videos (9.51 ∓ 0.92 minutes), with a substantial intra-rater agreement when evaluating highlight and raw videos (Cohen’s kappa 0.92 and 0.55 for experienced and junior gastroenterologists respectively).

Conclusion

Our analysis shows that AI can be used reliably as an assisting tool to automatically remove non-readable time segments from full colonoscopy videos. The use of our proposed algorithm can lead to reduced annotation times in the task of centrally reading colonoscopy videos.
P088 Neurotuberculosis in a patient with Ulcerative Colitis using adalimumab for a long period in Brazil
Authors: Facanali M , Bortolozzo Graciolli Facanali C , Rodrigues Boarini L , Vaz Safatle Ribeiro A , Sobrado C W
Published: May 2021

Background

Immunobiological antibodies to tumor necrosis factor alpha (TNFα), act by decreasing the proinflammatory cytokine TNFα. In this context, patients using these biologicals may develop an immunocompromised state (1). TNFα is important in the activation, differentiation and recruitment of different immune cells, with an important role in the formation and maintenance of granulomas, in response to intracellular organisms (2), such as tuberculosis (TB), whose reports occur, on average, 12 weeks after onset of the biological (1). Neurotuberculosis (NT) is the most severe form of TB (3), being responsible for 5 to 7% of cases of extra-pulmonary involvement (4,5). Its diagnosis being based on suspicious symptoms, biochemical analysis of the cerebrospinal fluid (CSF) and confirmed by the detection of the TB bacillus in the CSF. TB in the central nervous system (CNS) is usually due to the spread of pulmonary infection, and rarely occurs in isolation as in this case we are reporting.

Methods

This study aims to report a case of NT was described in patient with Ulcerative Colitis (UC), 4 years after the start of therapy with biological, and discuss clinical aspects, diagnosis, management and prognosis.

Results

34-year-old woman with UC since the age of 20, using adalimumab for 4 years, presented with progressive headache for 20 days, associated with daily afternoon fever (38⁰C). She denied any contact or familiar with TB. Analysis of CSF revealed TB culture positive. On brain MRI, there were small cortical lesions in the left frontal lobe and two larger lesions, with post-contrast enhancement, in the left temporal lobe and in the right frontal lobe, both measuring about 10 mm (Figure 1). She was in sustained deep remission with adalimumab for 4 years (Figure 2). She has had a chest X-ray and a tuberculin test every year, all of which are negative for TB. The initial management was discontinuing adalimumab, treatment with rifampicin, isoniazid, ethambutol, pyrazinamide and prednisone. The patient showed clinical and neurological improvement. Currently, 12 months after the diagnosis, she is asymptomatic and without neurological sequelae.

Conclusion

The reported case assumes importance because this patient has isolated TB in the CNSDigitar texto without pulmonary involvement who has UC and was using adalimumab. Screening tests for TB can ignore latent infection, especially in patients undergoing immunosuppression (anti-TNF, steroids and HIV). The possibility of TB should always be considered in the presence of fever of unknown origin in patients on anti-TNFα therapy, even for a long period. Early recognition, suspension and appropriate treatment are important steps towards therapeutic success, avoiding neurological sequelae and mortality.
P099 Evaluation of endoscopic mayo score with an artificial intelligence algorithm
Authors: Kani H T , Ergenc I , Polat G , Ozen Alahdab Y , Temizel A , Atug O
Published: May 2021

Background

Multi-layered convolutional neural networks are artificial intelligence (AI) algorithms that allow to process specific datasets. Endoscopic mayo score (EMS) is an endoscopic scoring tool for ulcerative colitis (UC) that is widely using for evaluating the disease activity to make a further treatment plan. EMS is an endoscopist-depended subjective tool that varies according to the physician’s experience. In this study, our aim was to create a high accuracy EMS diagnostic algorithm to minimize endoscopist-depended inconsistency and standardize the patient care.

Methods

We collected the endoscopic images of UC patients between December 2011 and July 2019 from electronic database of our gastroenterology institute. Images with insufficient bowel cleaning, artifact, retroflection images, terminal ileum images and pouch patients were excluded. Two blinded gastroenterologists evaluated and tagged the images according to the EMS. Images with a disagreement were excluded for a further evaluation. AI algorithm was performed with Python by using PyTorch library. The dataset was divided into two (85% was used for training and %15 was used for test). ResNet18 model was also used for training.

Results

A total of 19690 images of 572 patients from 1053 colonoscopies were identified for the study. The mean procedure number was 1.8 per patient and the mean image number was 18.7 for per colonoscopy. Four thousand and six hundred images without any disagreement between two gastroenterologists were included to the analysis. Two thousand eight hundred and thirteen (61.65%) images were tagged as EMS 0, 956 (20.66%) were tagged as EMS 1, 406 (8.77%) were tagged as EMS 2 and 413 (8.92%) were tagged as EMS 3. Accuracy was found 73.16% with a sensitivity of 773.2% and specifity of 92.9% in assessment of all EMS groups (Image 1). Also, the accuracy of severe mucosal disease diagnosis (EMS 0 and 1 vs EMS 2 and 3) was 96.3% with a sensitivity of 98.2% and specifity of 86.5% (Image 2) with a perfect reproductivity (к: 1.00). The performance of the remission diagnosis (EMS 0 vs EMS 1,2 and 3) was done with a 92% accuracy.

Conclusion

This is an ongoing study and the preliminary results of our EMS diagnosis algorithm was promising with a high accuracy. The accuracy and sensitivity would be improved by including more images and improving the algorithm. The use of AI in daily IBD practice can eliminate the subjectivity according to the endoscopist in diagnosis and assessing the disease severity for treatment decision.
P115 Chronic pouchitis and Crohn’s disease of the pouch after ileal pouch-anal anastomosis: incidence and risk factors
Authors: Bresteau C , Amiot A , Kirchgesner J , de’Angelis N , Lefevre J H , Bouhnik Y , Panis Y , Beaugerie L , Allez M , Brouquet A , Carbonnel F , Meyer A
Published: May 2021

Background

Restorative proctocolectomy with ileal-pouch anal-anastomosis (IPAA) is the operation of choice for patients with ulcerative colitis (UC) or with inflammatory bowel diseases unclassified (IBDU) who had failed medical treatment or with colon dysplasia. The aim of our study was to assess the incidence and risk factors of chronic pouchitis (CP) and Crohn’s disease of the pouch (CDP).

Methods

We conducted a retrospective study among five tertiary referral hospitals. All patients older than 15 years of age with UC or IBDU who underwent IPAA between January, 2011 and December, 2019, were included. Patients with no ileostomy closure or with a follow-up of less than 2 months after ileostomy closure were excluded. The main outcome was the occurrence of CP or CDP. Patients’ demographic, clinical and endoscopic characteristics were collected from medical records at the time of surgery. We looked for risk factors with multivariable and a least absolute shrinkage and selection operator (LASSO) Cox models.

Results

247 patients were included. The median follow-up was 3.1 years (IQR: 1.1–5.7). The incidence rate of CDP was 7.9% (95%CI: 3.9–11.8) two years after IPAA and 18.3% (95%CI: 11.0–25.0), five years after IPAA. The incidence rate of CP was 7.6% (95%CI: 3.8–11.3) two years after IPAA and 19.5% (95%CI: 12.2–26.2), five years after IPAA. The incidence rate of either CP or CDP was 15.6% (95%CI: 10.2–20.7) two years after IPAA and 35.3% (95%CI: 26.2–43.2), five years after IPAA. In multivariable analysis, diagnosis of IBDU (HR 3.18; 95%CI: 1.77–5.70; p<0.001), age of less than 35 years at surgery (HR 2.03; 95%CI: 1.20–3.43; p=0.008) and extra-intestinal manifestations other than articular and primary sclerosing cholangitis (HR 4.37; 95%CI: 2.12–9.02; p<0.001) were associated with higher incidence of either CP or CDP. The LASSO analysis identified these three prognostic factors and also articular manifestations. In patients with two or more prognostic factors, the 5-year cumulative incidence of CP or CDP, was 65.2% (95%CI: 41.8–79.2). It was 18.6% (95%CI: 7.1–28.6) in patients with none.

Conclusion

Five years after IPAA, approximately one-third of patients had either CP or CDP. Risk factors were IBDU, an age of less than 35 years at surgery, articular manifestations and other extra-intestinal manifestations, excluding primary sclerosing cholangitis. These results suggest that high-risk patients might benefit from scheduled endoscopies of the pouch and/or postoperative medical therapy to limit pouch damages.
P118 External validation of model predicting early-onset surgery in Crohn’s Disease patients
Authors: Yao J , Hu B , Wang H , Zhi M
Published: May 2021

Background

Screening Crohn’s disease (CD) patients with high risk of early-onset surgery is crucial in launching therapeutic strategies. We have already identified disease behavior, smoking, body mass index, C-reactive protein level at diagnosis, previous perianal or intestinal surgery, maximum bowel wall thickness, use of biologics, and exclusive enteral nutrition as independent significant factors associated with 1-year surgery surgeries risk and further established a prognostic model (Fig.1,World J Gastroenterol. 2020;26(5):524–534). We aimed to validate this model using external cohort.

Methods

This retrospective study was conducted from Jan, 1, 2017, to Dec, 31, 2019 in three tertiary referral centers including Sixth Affiliated Hospital of Sun Yat-Sen University, Second Affiliated Hospital of Zhejiang University, and Second Affiliated Hospital of Military Medical University. Data of patients with a confirmed diagnosis of CD were collected through hospital electronic system. The published model was validated with calibration using the Hosmer-Lemeshow goodness-of-fit test, and discrimination was assessed using areas under the curve (AUC).

Results

A total of 756 patients were enrolled in our study with 101 (13.4%) excluded for the sake of incomplete data and loss of follow-up. Of the enrolled patients, 74.8% were male (n = 490) at the mean age of 28.4 ± 11.0 years, with the mean follow-up period of 21.8 ± 8.1 months. An ideal predictive ability of this model was confirmed by receiver operating characteristic curves and AUC as high as 94.5%. Besides, acceptable sensitivity of 69.5% and excellent specificity of 97.0% supported further clinical promotion and application of this model.

Conclusion

This model owns ideal ability to predict 1-year surgery risk in CD patients, which definitely help clinical decision-making and acid therapeutic strategies launching.
P119 There is minimal agreement on the recognition of deep ulcers as seen on endoscopy in patients with Inflammatory Bowel Disease: a national survey
Authors: Chavannes M , Hart L , Afif W , Lakatos P , Bitton A , Bressler B , Bessissow T
Published: May 2021

Background

Deep ulcers have been described as a marker of severe disease phenotype in patients with IBD and play a role in choice or escalation of therapy. However, there is no agreed upon characterization of deep ulcers in the literature. We therefore assessed Canadian gastroenterologists’ ability to identify the presence of deep ulcers on endoscopic images.

Methods

We present a post-hoc analysis of a cross-sectional questionnaire from gastroenterologists across Canada (March-October 2017). Three IBD experts independently rated 20 ileocolonoscopy images of single bowel segments. They described the images by selecting descriptors from a list developed a priori. Images described by all 3 experts as having “deep ulcers” were retained for analysis (5 images). Survey participants similarly applied descriptors from the same list to each endoscopy image. We examined the percent agreement between the gastroenterologists and the experts. The percent agreement for each question was summarized using median and IQR. Difference in median scores in physician subgroups was determined using the Mann-Whitney U test. We also assessed the inter-observer agreement on the presence of deep ulcers amongst gastroenterologists using Fleiss Kappa.

Results

131 gastroenterologists participated in the study. The majority (55.7%) were between 36–50 years old. 48% were in practice for less than 10 years. 59.5% practiced in an academic setting. 9.9% of responders were pediatric gastroenterologists. The median agreement between the gastroenterologists and the experts was 30.5% (30.5–76.3), indicating an under-recognition of deep ulcers. As a group, inter-observer agreement on the presence of deep ulcers was minimal (k = 0.39, CI: 0.16–0.65). Inter-observer agreement was lower in the academic setting than the community setting (k= 0.39 vs k= 0.49 respectively) and was fairly similar in those with more experience compared to those with less experience (k= 0.40 for less than 10 years in practice, vs k= 0.36 for those with greater than 10 years in practice). Compared to the experts’ responses, there was no significant difference if the physician practiced in an academic vs community setting (49.24% correct identification vs 54.52%, p = 0.6004) or if the physician had less than 10 years’ experience vs greater than 10 years’ experience (48.26% vs 53.44%, p =0.2948).

Conclusion

Deep ulcers have been described as a critical indicator of disease severity in patients with IBD. However, our study shows that there is poor agreement between physicians in identifying this important feature. This indicates the need for a standardized definition of deep ulcers to prevent undertreatment of patients who require escalated therapy.
P143 Depression and anxiety symptoms among patients with early inflammatory bowel disease during and after COVID-19 lockdown
Authors: Sempere Robles L , Bernabeu P , Cameo J , Gutiérrez A , García G , García M F , Aguas M , Zapater P , Ruiz-Cantero M T , van-der Hofstadt C
Published: May 2021

Background

Patients with inflammatory bowel disease (IBD) are vulnerable to some psychological disorders. Here we describe the psychological impact of a COVID-19 pandemic lockdown in patients with IBD.

Methods

This multicenter prospective cohort study included 145 patients recently diagnosed with IBD. Data on clinical and demographic characteristics, anxiety and depression (Hospital Anxiety and Depression Scale), and IBD activity (the Modified Harvey Bradshaw Index for CD and Simple Clinical Colitis Activity Index for CU) were collected in two telephone surveys, during and after the first COVID-19 lockdown in Spain. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated.

Results

During lockdown, 33.1% and 24.1% scored high on the anxiety and depression scales, respectively. Independent factors related to anxiety (all values ORs; 95% CIs) during lockdown were female sex (2; 1.2–5.4) and IBD activity (4.3; 1.8–10.4). Factors related to depression were comorbidity (3.3; 1.1–9.8), IBD activity (6; 1.9–18.1), use of biologics (2.9; 1.1–7.6), and living alone or with one person (3.1; 1.2–8.2). After lockdown, anxiety and depression symptoms showed significant improvement, with 24.8% and 15.2% having high scores for anxiety and depression, respectively. Factors related to post-lockdown anxiety were female sex (2.5; 1.01–6.3), Crohn’s disease (3.3; 1.3–8.5), and active IBD (4.1; 1.2–13.7). Factors associated with depression were previous history of mood and/or anxiety disorders (6.3; 1.6–24.9), active IBD (7.5; 2.1–26.8), and steroid use (6.4; 1.4–29).

Conclusion

Lockdown during the COVID-19 pandemic had a significant psychological impact in patients with IBD. Disease activity was related to the presence of anxiety and depression symptoms during and after lockdown.