bluuebunny/crossref_metadata_2025 huggingface dataset:
DOP84 Risankizumab maintenance therapy results in sustained improvements in endoscopic outcomes in patients with moderate to severe Crohn’s Disease: Post-hoc analysis from the phase 3 study FORTIFY
Authors: Irving P M , Abreu M , Axler J , Gao X , Torres J , Neimark E , Song A , Wallace K , Kligys K , Berg S , Liao X , Panaccione R
Published: January 2022

Background

Data from Phase 3 studies in Crohn’s disease (CD) demonstrated significant improvements in endoscopic outcomes with risankizumab (RZB) versus placebo (PBO) following 12-weeks (wks) induction therapy. Continued maintenance therapy with 360mg RZB SC led to significantly higher rates of endoscopic response and remission at Wk52 compared to withdrawal/placebo. This post-hoc analysis examined the durability of SC RZB maintenance therapy for endoscopic outcomes among patients achieving these endpoints at the end of induction

Methods

Patients achieving clinical response with 12-wks IV RZB induction therapy in ADVANCE or MOTIVATE entered the maintenance study, FORTIFY, and received either RZB SC or had RZB withdrawn and received placebo for 52 wks. For this analysis, endoscopic outcomes in the RZB 360 mg SC (N=141) and withdrawal/placebo (N=164) arms are reported. Maintenance of endoscopic response, endoscopic remission, and/or an SES-CD score of 0–2 were assessed at Wk52 in patients who achieved these endpoints at Wk0 of maintenance (Wk12 of induction). Safety was assessed throughout the study.

Results

Following 12-wks of IV RZB induction therapy (FORTIFY Wk0), 141 patients were randomized to RZB 360 mg (patients achieving endoscopic response, 55/141; endoscopic remission, 39/141; SES-CD score of 0–2, 29/141) and 164 were randomized to withdrawal (PBO SC) (patients achieving endoscopic response, 73/164; endoscopic remission, 46/164; SES-CD 0–2, 32/164). Maintenance of endoscopic response at Wk52 was demonstrated in 70.2% (39/55) of patients receiving RZB 360 mg SC versus 38.4% (28/73) of patients in the withdrawal (PBO SC) arm (P<0.001). Maintenance of endoscopic remission at Wk52 was demonstrated in 74.4% (29/39) of patients receiving RZB 360 mg versus 23.9% (11/46) of patients in the withdrawal (PBO SC) arm (P<0.001). Maintenance of an SES-CD score from 0–2 at Wk52 was demonstrated in 65.5% (19/29) of patients receiving RZB 360 mg versus 21.9% (7/32) of patients in the withdrawal (PBO SC) arm (P<0.001).RZB maintenance treatment was well-tolerated and no new safety signals were observed. The safety profile of RZB has been reported previously.1–5

Conclusion

RZB IV induction followed by SC maintenance therapy led to sustained improvements in endoscopic outcomes, demonstrating the durability of efficacy with continued RZB treatment in patients with moderate to severe CD.

Reference

1. Feagan, B. G. et al. Lancet 389, 1699–1709 (2017) 2 Feagan, B. G. et al. Lancet Gastroenterol Hepatol 3, 671–680 (2018) 3 Ferrante, M. et al. Journal of Crohn’s and Colitis jjab093 (2021) 4 Ferrante, M. et al. in UEGW 2021 5 D’Haens, G. et al. in DDW 2021
P014 Impact of experimental ileitis and Toll-Like Receptor 4 signaling on enteric inhibitory neurotransmission
Authors: Faggin S , Cerantola S , Dal Prà A , Caldana G , Bosi A , Banfi D , Giaroni C , Savarino E , Giron M C
Published: January 2022

Background

Alterations in Toll-like receptor 4 (TLR4) expression and changes in enteric neurotransmissions influence the onset and severity of inflammatory bowel disease (IBD). We aimed to assess the interaction between the enteric inhibitory pathways and TLR4 signaling in a mouse model of dinitrobenzene sulfonic acid (DNBS)-induced small intestine inflammation.

Methods

Male TLR4-/- mice (9±2 weeks old) were intrarectally treated with 2.5% DNBS. Pro-inflammatory cytokines (IL-6 and TNF-α) were measured in ileal samples. Changes in ileal muscle tension were recorded following exposure to: i) 10-Hz electric field stimulation in non-adrenergic-non-cholinergic (NANC) conditions (1 μM guanethidine + 1 μM atropine) with or without 10 µM 1400W (a inducible nitric oxide synthase (iNOS) inhibitor), or 0.1 µM Nω-nitro-L-arginine methyl ester (L-NAME; a pan-NOS inhibitor); ii) 30 μM dopamine or 30 μM SKF38393 (a dopamine 1 receptor (D1R) agonist) or bromocriptine (a D2R agonist). Immunoreactivity of neuronal (HuC/D) and glial (S100β) markers as well as nitrergic chemical coding (i.e. nNOS and iNOS) were determined in longitudinal muscle-myenteric plexus whole-mount preparations (LMMPs) by confocal microscopy.

Results

No changes in IL-6 and TNF-α ileal mRNA transcripts were found after DNBS administration. The development of ileitis did not affect the NANC-inhibitory response, that was partially reduced in presence of 1400W or L-NAME, suggesting that TLR4 signaling influences NO-mediated inhibitory responses. DNBS-treated mice showed a significant increase in dopamine-induced relaxation (+31%) and in D1R- and D2R-mediated inhibitory responses (by +57% and +75%, respectively). A significant reduction of the total number of HuC/D+ neurons (-25%), with a proportional increase in nNOS+ neurons (+11%) was found in LMMPs of DNBS mice, associated with a significant reduction of S100β immunofluorescence (-12%) and no changes in iNOS immunoreactivity, highlighting a potential involvement of TLR4 signaling in the development of neuroplasticity and reactive gliosis.

Conclusion

The present data suggest that the severity of small intestine ileitis and neuronal dysfunction depend on the interplay occurring between TLR4 signaling and enteric inhibitory pathways. This evidence further strengthens the importance of characterizing neuroimmune interactions to identify potential molecular mechanism(s) representing putative pharmacological targets for the development of efficacious IBD therapies.
P027 Effects of anti-TNF and anti-α4β7 drugs on circulating monocytes migratory capacity in inflammatory bowel disease
Authors: Soleto I , Fernández-Tomé S , Mora-Gutiérrez I , Baldan-Martin M , Ramirez C , Santander C , Moreno-Monteagudo J A , Casanova M J , Casals F , Casabona S , Becerro I , Chaparro M , Bernardo D , Gisbert J P
Published: January 2022

Background

Inflammatory bowel disease (IBD) is an idiopathic and chronic disorder that include ulcerative colitis (UC) and Crohn’s disease (CD). Both diseases are different but show an uncontrolled intestinal immune response that generate tissue inflammation. Monocytes (Φ) play a key role in the tolerogenic maintenance in the gastrointestinal mucosa. These cells are antigen presenting cells highly specialized to control immune response against gut microbiota and food antigens. It has been previously reported that circulating Φ are recruited by intestinal mucosa in a CCR2 dependent manner. Also, in IBD patients this Φ recruitment is more prominent than in healthy controls (HC) but the specific migration mechanism is still unknown.

Methods

This is a cross-sectional observational postmarketing study where the modulatory effect of different biologic treatments on samples from patients with endoscopic diagnosis of IBD and HC was studied ex vivo. Peripheral blood mononuclear cells (PBMC) were obtained from 15 patients per group, and were cultured in presence of anti-TNF or vedolizumab. Following culture, surface markers expression was determined hence assessing the differential effect of biological drugs (if any) over the Φ subset in the different groups. After that, the migratory capacity of circulating Φ toward CCL2, CCL25 and MadCam1 from the different study groups was determined. Finally, we evaluated the Φ migratory capacities in presence of biological drugs or with culture media alone.

Results

Our data showed that within CD14+ population, CD patients presented a higher percentage of CCR5+ and CCR9+ and the surface expression level of CCR2 and CCR9 was increased. In addition, anti-TNF reduced the number of CCR9+ Φ subset in HC. In HC an UC patients vedolizumab reduced the percentage of β7+ Φ (Figure 1). According to the circulating Φ migratory capacity as expected, the migration towards CCL2 was higher than toward culture media (Figure 2). When the effect of biological drugs was evaluated, surprisingly anti-TNF increased the Φ migration. Also, vedolizumab showed a clear tendency to decrease the Φ migration towards CCL2 and MadCam1 in HC and in UC (Figures 3 and 4).

Conclusion

Circulating Φ from IBD patients express a different migration pattern than HC, being the expression of these molecules modulated by anti-TNF drugs. The capacity of circulating Φ to migrate towards CCL2 is higher than towards culture media. Unexpectedly, anti-TNF increases the migratory capacity of Φ. On other hand, treatment of Φ from HC and UC patients with vedolizumab, induces a clear downward trend of their migratory capacity towards CCL2 and MadCam1
P043 3-oxo-C12:2, a Quorum Sensing molecule from the gut, exerts anti-inflammatory effects through a bitter taste receptor
Authors: Coquant G , Aguanno D , Brot L , Belloir C , Briand L , Grill J P , De Sordi L , Thenet S , Seksik P
Published: January 2022

Background

Acyl-Homoserine Lactones (AHLs) are Quorum Sensing molecules involved in the communication network of bacteria and can also have an impact on the host’s cells. We recently showed, in the human gut ecosystem, the presence of AHLs. Among them, we identified one that has never been described: 3-oxo-C12:2. This molecule was decreased in Inflammatory Bowel Disease (IBD) patients, and its presence was correlated to normobiosis. Interestingly, 3-oxo-C12:2 is structurally close to an AHL well described and synthesized by P. aeruginosa, 3-oxo-C12. We intent to describe 3-oxo-C12:2 effects on gut inflammation and to identified which signalling pathways are involved. Given its analogous structure to 3-oxo-C12, we hypothesized that 3-oxo-C12:2 can interact with the same cellular partners, in particular a bitter taste receptor (BTR), called T2R138, which is a GPCR expressed by immune and epithelial gut cells.

Methods

To test our hypothesis, we used murine macrophages cell line RAW264.7, stimulated by interferon-γ (IFN-γ, 20U/mL) and lipopolysaccharide (LPS, 10ng/mL). Inflammatory response was monitored by measuring cytokine secretion via ELISA We performed a transcriptome analysis to identify inflammatory pathways involved in the effects and analyse pathways by capillary Western blot. Probenecid, a known allosteric inhibitor for T2R138, was used to study T2R138 role in AHL signalling. BTR screening assay was performed to extend search for 3-oxo-C12:2 receptors.

Results

After LPS/IFN-γ activation, we observed a decrease of secreted TNFα when cells were exposed to 3-oxo-C12:2, in a dose dependent manner: 15μM (-30%, p<0.05), 25μM (-50%, p<0.001) et 50μM (-65%, p<0.0001) while no change were observed in steady state. This reflects an anti-inflammatory effect, in absence of cytotoxicity. By transcriptomic analysis, we identified the JAK-STAT pathway as differentially down-regulated. Exposing cells to 3-oxo-C12:2 prevented JAK1 and STAT1 protein phosphorylation. In addition, the observed anti-inflammatory effects were lost in presence of Probenecid, a T2R138 inhibitor. In a BTR screening assay, we confirmed that 3-oxo-C12:2 activates T2R38, but also five other BTR (T2R13, T2R8, T2R14, T2R1, T2R10).

Conclusion

3-oxo-C12:2 exerts a dose dependent anti-inflammatory effect on murine immune cells by preventing the activation of the JAK-STAT pathway. This response is partly mediated by the bitter taste receptor T2R138. This receptor is a potential target of our AHL of interest. Studying the signalling between the receptor and the anti-inflammatory response would allow us to better understand the inter-kingdom dialogue between microbiota involving AHL in IBD.
P090 Unraveling the rewiring of cytokine signalling in Inflammatory Bowel Disease using a novel network biology approach
Authors: Olbei M , Thomas J , Hautefort I , Treveil A , Bohar B , Madgwick M , Gul L , Csabai L , Modos D , Korcsmaros T
Published: January 2022

Background

Intercellular communication mediated by cytokines is critical to the development of immune responses, particularly in the context of chronic immune-mediated disorders such as inflammatory bowel disease (IBD). By releasing these small molecular weight peptides, the source cells can influence numerous intracellular processes in the target cells, including the secretion of other cytokines downstream. However, there are no readily available resources and studies modelling cytokine-cytokine interactions that would be important for better understanding the dysregulation of cytokine signalling in IBD, and revealing potential new therapeutic targets for patients.

Methods

Based on the workflow of a cytokine signalling resource, CytokineLink, we developed previously, in this effort we built novel interaction networks using single-cell expression data from patients with ulcerative colitis (UC) and Crohn’s disease (CD). We defined two meta-networks for each disease: a cell–cell communication network connected by cytokines; and a cytokine–cytokine interaction network depicting the potential ways in which cytokines can affect the activity of each other.

Results

The rewiring of cell–cell and cytokine–cytokine interaction networks between healthy, non-inflamed and inflamed intestinal tissues in IBD was measured using the generated meta-networks. Cytokine-cytokine interaction networks revealed that in active UC, the Th1 cytokine IFNg and the chemokines CCL28 and CCL14 were central to cytokine-mediated communication networks. In CD, IL12B and IL13 formed the central cytokines in inflamed ileal tissues. Cell–cell interaction networks identified likely main cell types mediating the signalling of these key cytokines in non-inflamed and inflamed intestinal tissues: mast cells being the main source of IL13 in both IBD patients and healthy individuals.

Conclusion

We generated interaction networks aimed at capturing the most prevalent cell–cell and cytokine–cytokine interactions using disease specific single-cell expression data. Using the generated interaction networks we identified the condition-specific rewiring of cytokine mediated signalling in IBD, and key cytokines that could be targeted for ameliorating inflammatory responses. The data can be used by the community as a platform for hypothesis-generation. Potential use cases are deconvoluting the complexities of cytokine signalling in IBD to reveal potential cytokine drug targets, or predicting the downstream effects of drugs on cytokine responses.
P114 SARS-CoV-2 infection in IBD: pandemic waves and predictors of severe or persistent COVID-19
Authors: Taxonera Samso C , Olivares D , Blanco I , Velasco E , Molina S , López G , López-García O N , Alba C , Rey E
Published: January 2022

Background

This study aimed to compare the risk of COVID-19 in patients with IBD versus the general population, and to evaluate predictors of infection acquisition, progression to severe forms, and risk of developing persistent COVID-19. We also assess the differences between cases across the different COVID-19 pandemic waves in our target population.

Methods

This single-centre prospective, cohort study included consecutive IBD patients diagnosed of COVID-19 either by a positive polymerase chain reaction test and/or antigen test in nasopharyngeal swabs, or by anti-SARS-CoV-2 antibodies, and that they had a follow-up of at least 4 months. Using logistic regression, we evaluated cases versus IBD controls included in the IBD Unit database for predictors of COVID-19 acquisition. COVID-19 cases were distributed according to pandemic waves. Cox regression analysis was used for predictors of severe and persistent COVID-19.

Results

By May 31, 2021, 160 out of 1911 IBD patients (8.3%) were diagnosed with COVID-19. IBD patients had a similar adjusted incidence of COVID-19 (OR 0.94; 95% CI 0.86–1.02; P=0.42), and a similar associated mortality ratio (OR 0.83; 95% CI 0.6–1.06; P=0.48), compared to the general population. In multivariable analysis, treatment with biologics was associated with a higher risk (OR 2.22, P<0.001), and treatment with salicylates with a lower risk (OR 0.71, P=0.048) of contracting COVID-19.(Table 1) 62 COVID-19 cases were diagnosed during the first wave of pandemic (until the end of June 2020), and 54 and 44 cases during the second and third waves (until the end of December 2020 and May 2021, respectively).(Figure 1) In multivariate analysis, first wave cases were associated with a higher risk of progression to severe forms of infection (OR 4.76, 95% CI 1.83–12.37, P=0.001), and development of persistent COVID-19 (OR 2.4, 95% CI 1.16–4.95, P=0.018). 29 patients (18.1%) required hospitalisation and were classified as severe COVID-19, which was associated in multivariable analysis with age>48 (HR 3.68, P=0.007), cases diagnosed in the first wave (HR 6.04, P<0.001), and comorbidities (evaluated with Duke Severity of Illness Checklist [DUSOI], P<0.001).(Table 2) During a median follow-up of 8.4 months, 68 patients (42.5%) were diagnosed with persistent COVID-19. Multivariable analysis identified UC (P=0.053), comorbidities (P=0.090), and being diagnosed during the first wave (P=0.011) as risk factors for persistent COVID-19.(Table 3)

Conclusion

IBD patients have a similar risk of COVID-19 and associated mortality as the general population. Cases diagnosed during the first wave of the pandemic had severe and persistent forms of COVID-19 more frequently. Age and comorbidity were the main risk factors for severe forms of the disease.
P130 Comparison of the clinical course of Ulcerative Colitis according to the presence or absence of clinical symptoms at the time of diagnosis
Authors: Madarame A , Fukuzawa M , Uchida K , Nemoto D , Shinohara H , Yamanishi F , Matsumoto S , Suzuki Y , Muramatsu T , Kagawa Y , Matsumoto T , Morise T , Yamaguchi H , Sugimoto A , Kono S , Yamauchi Y , Naito S , Kawai T , Itoi T
Published: January 2022

Background

Asymptomatic ulcerative colitis (UC) is increasingly detected by improved screening tests such as the fecal immunochemical test. However, there have been few reports on the difference in the clinical course of UC according to the presence or absence of symptoms at diagnosis. The purpose of this study was to compare the clinical course of UC according to the presence or absence of clinical symptoms at the time of diagnosis.

Methods

Data were obtained from a retrospective chart review of 64 consecutive patients with UC diagnosed at our hospital between 2014 and 2020. Patients were grouped according to the presence or absence of clinical symptoms at the time of UC diagnosis, and clinical characteristics (age, sex, extent of disease, Mayo Score, endoscopic severity, and hematological findings) at the time of diagnosis were subjected to univariate and multivariate analyses. In the clinical characteristics, propensity score matched analysis was performed, and systemic steroids use, hospitalization within 1 year, and the introduction of therapies for refractory UC were evaluated. Patients with a clinical course of less than 1 year after UC diagnosis, patients intolerant to 5-aminosalicylic acid, patients with carcinoma, pregnant women, and patients under 15 years of age were excluded.

Results

Eligible patients were 64 UC patients (19 asymptomatic and 45 symptomatic) diagnosed at our hospital during the period of the study. The symptomatic group included 32 cases of bloody stools, 30 cases of diarrhea, 7 cases of abdominal pain, and 4 cases of fever. Multivariate analysis of clinical features at diagnosis showed significant differences in Mayo Score (p=0.003, odds ratio: 3.650, 95% confidence interval: 1.541–8.647) and serum hemoglobin level (p=0.021, odds ratio: 0.367, 95% confidence interval: 0.157–0.859). As a result of propensity score matched analysis, 24 patients (12 asymptomatic, 12 symptomatic) were selected. There were no significant differences in the rates of systemic steroid use (16.7% vs. 16.7%), hospitalization within 1 year (16.7% vs. 8.3%), and the introduction of therapies for refractory UC (16.7% vs. 8.3%) between the two groups (p=1.000 in all items).

Conclusion

There was no difference in the prognosis of the asymptomatic group compared with the symptomatic group using propensity score matched analysis. The results suggest that asymptomatic UC detected by colonoscopy may be acceptable for follow-up without treatment.
P152 Impact of disease location on burden of illness in patients with moderate-severe Crohn’s disease: A real-world survey in the United States, France, Germany, Italy, Spain, and United Kingdom (5EU)
Authors: Sikirica M , Lynch J , Kershaw J , Lukanova R , Baker S , Milligan G
Published: January 2022

Background

Presentation and risks of progression and complications differ according to Crohn’s disease (CD) location. The objective of this study was to investigate how disease burden differs based on CD location, from physician and patient perspective.

Methods

Data drawn from the Adelphi Inflammatory Bowel Disease (IBD) Disease Specific Programme™, a point-in-time survey of gastroenterologists (GEs) and their IBD patients from two waves (Nov 2014-Mar 2015; Sep 2017-Jan 2018) in the United States, and 5EU. GEs completed physician-reported questionnaires for 5–10 consecutively consulting patients with CD, covering demographics, treatment, symptoms, and CD location. Same patients completed voluntary patient-reported questionnaire including outcome measures such as Short IBD Questionnaire (SIBDQ), EuroQol 5-dimension questionnaire (EQ-5D), and Work Productivity and Activity Impairment questionnaire.

Comparisons were drawn between patients with CD in 3 locations: ileal only (IL), ileocolonic (IC), and colonic only (CO). Outcomes such as patient-reported level of pain, sleep disturbance, and fatigue, were compared between locations using linear regression analyses that included potential confounding variables age, gender, body mass index, comorbidities (using Charlson Comorbidity Index [CCI]) and severity at diagnosis. Least square (LS) means were generated for each location and compared using a p-value generated from Wald tests. Variables such as current treatment and symptoms, were compared using univariate tests (ANOVA, chi2 test). Base sizes varied due to the voluntary nature of patient participation.

Results

686 GEs collected data on 2354 patients with moderate-severe CD, identifying patients with IL (28.3%), IC (45.7%), and CO (26.0%) location. Overall demographic characteristics were similar, mean age 39 years, proportion of male patients 51.4%, mean Body Mass Index 24.0, mean CCI 0.14.

Differences were observed between the 3 groups (Table 1). Patients with ileal involvement (IL and IC) were prescribed biologics more often and had greater symptom burden than CO patients, except for rectal urgency. IL patients tended to have slightly greater burden overall in terms of symptomatology and severity. There was similarity across SIBDQ and EQ-5D scores; however, absenteeism was higher amongst IL and IC patients, compared with CO patients.

Conclusion

Differences were observed between IL, IC, and CO CD location groups. Despite IC patients experiencing the greatest burden overall, there were key distinctions between IL and CO patients, particularly in medication, symptoms, and work productivity impairment, suggesting that disease management with attention to CD location could lead to better patient outcomes.
P160 Pan-enteric mucosal inflammation in CD patients treated with vedolizumab – interim results of a prospective observational study using a panenteric capsule (PiilCam CD)
Authors: Kopylov U , Lipkin M , Ungar B , Haj O , Shachar E , Lahat A , Ben-Horin S , Eliakim R
Published: January 2022

Background

Mucosal healing is associated with improved short- and long-term outcomes in Crohn’s disease (CD). However, the likelihood of reaching mucosal healing differs between segments of the mucosal tract. The prevalence of panenteric mucosal healing is scarcely described. Capsule endoscopy is the prime modality for evaluation of the entire small bowel. Recently, a combined pan-enteric capsule (PillCam Crohn’s capsule (PCCD) that enables evaluation of mucosal inflammation in the entire digestive tract in a single procedure, has been developed.

The main aim of our study was to evaluate the rate of panenteric mucosal healing in Crohn’s disease patients treated with vedolizumab (VDZ) after 52 weeks of therapy. The current interim report focuses on the rates of mucosal improvement after 14 weeks of VDZ treatment.

Methods

This was a prospective open- label observational study. Patients starting vedolizumab (VDZ) for Crohn’s disease underwent a patency capsule (PC) and if it was excreted within 30 hours, enrolled in the study. The patients were evaluated with PCCD at week 0, 14 and 52 of VDZ treatment. Mucosal inflammation was quantified using the Lewis score (LS) and the panenteric Pillcam score (PS). In addition, fecal calprotectin (FC) and CRP levels were measured at each visit. Patients without active mucosal inflammation on week 0 PCCD were excluded from further participation

Results

We enrolled 30 patients; 5/30 failed PC and were dropped out of the study.Twenty five patients underwent PCCD at week 0 and 19/25 (78%)% -at week14 (six patients were dropped out for either absence of active mucosal inflammation at week 0 (1 patient), treatment discontinuation before week 14 (2 patients) endoscopic activity – 1, withdrawal of consent (1 patient) or loss to follow-up (1 patient)).

After 14 weeks of VDZ treatment, there was a significant improvement in LS (median of 900 (interquartile ration (IQR)- 1143)), vs 450 (IQR-750), p=0.013), ES (15 (IQR-18) vs 10 (IQR-11), p=0.012) and FC (996 (IQR-455) vs 742 (IQR -740), p=0.012), while CRP levels were not significantly different.

Conclusion

VDZ induces significant improvement in mucosal inflammation evaluated by panenteric capsule endoscopy, in addition to a significant improvement in FC levels, after 14 weeks of therapy

*The study was supported by IIR grant from Takeda and Medtronic
P165 Characterization and risk of sarcopenia in patients with Ulcerative Colitis, compared with older and younger adults. Cross-sectional study
Authors: Alison S C , Ylse G G , Viridiana M M , Bueno Hernández N
Published: January 2022

Background

Ulcerative colitis (UC) is characterized by being associated with a large number of extraintestinal manifestations that can affect any organ before or during the course of the disease, one of which is sarcopenia. Which is a progressive disorder of the generalized skeletal muscle that causes a decrease in muscle mass, muscle strength, and physical performance. In a patient with UC, it can cause an increased risk of falls and fractures, impaired ability to perform daily activities, and increased mortality. The objective of this study was to characterize and measure the risk of sarcopenia in UC patients compared to elderly people.

Methods

The study included 78 people of both genders and treated in the gastroenterology service of the Hospital General de México “Dr. Eduardo Liceaga ”. This was a cross-sectional study in patients with UC, elderly people, and healthy volunteers. Sarcopenia was diagnosed through measurement of muscle mass (bioelectric impedance), muscle strength (dynamometry), and physical performance (gait speed and Sit to Stand Test). And all the participants were divided into presarcopenia, sarcopenia, and severe sarcopenia.

Results

In this study 26 patients with UC, 22 older adults, and 30 healthy volunteers were included. In the UC group, there was a mean age of 40±10, in the elderly people group had a mean of 68±9.09 and healthy volunteers was 39±9.16. We can see that in the three groups there was a greater presence of women (UC: 57.7%; elderly 68.2% and healthy volunteers: 73.3%). The prevalence of sarcopenia was significantly higher in the UC group (27%) than in the elderly people (14%) and healthy volunteers (3%) group (P<0.05). However, the presence of presarcopenia was higher in elderly people (41%), compared to UC (23%) and healthy volunteers (17%) (P<0.05). The risk of developing sarcopenia was higher in UC patients compared to elderly people (OR=12.8; 95%CI=1.4–11.8; P=0.008). In UC patients there was lower physical performance (m/s=7.52±1.15) compared to the elderly people (m/s=7.72±1.39) and healthy volunteers (m/s=4.66±0.74).

Conclusion

Sarcopenia has a high prevalence in patients with UC. Patients with a diagnosis of UC have a higher risk of presenting sarcopenia compared to older adults. Sarcopenia manifests with physical deterioration in UC patients. A multidisciplinary approach is necessary for the early detection of sarcopenia to avoid the risk of falls, fractures, impaired movement capacity, increased mortality, and poor response to treatment.
P169 Delayed diagnosis of inflammatory bowel disease in women: Characterization and use of health resources
Authors: Sempere Robles L , Bernabeu P , Cameo Lorenzo J I , Laveda R , García M F , Aguas M , Belén O , Zapater P , van-der Hofstadt C , Jover R , Gutiérrez A , Ruiz M T
Published: January 2022

Background

Delayed diagnosis of IBD is associated with increased complications. Female gender is one of the factors most frequently associated with delayed diagnosis. Higher prevalence of functional gastrointestinal disorders in women probably hinders the diagnosis of IBD. The aim of this study is to explore delayed diagnosis of IBD and assess differences between women and men in healthcare access routes.

Methods

This multicentre prospective cohort study included 190 patients with newly diagnosed IBD. Data were collected on clinical and demographic characteristics, IBD activity and systematic reconstruction of the diagnostic process in a semi-structured interview together with a review of their medical record.

Results

Figure 1 shows clinical and demographic characteristics. In CD, patients’ symptoms were similar between both genders, except for a higher incidence of bowel incontinence, arthralgias, asthenia and other symptoms in women. In UC, there was no gender difference in clinical presentation. Overall, the median time from symptom onset to IBD diagnosis was 4.5(2.1–12.9) months, being significantly longer in women than in men, 7.8(3.3–18.9) vs. 3.8(1.7–7.8) p<0.001. In diagnostic process, the time from symptom onset to initial physician visit was 0.7(0.26–2) months with no statistically significant differences between women and men. While the time from initial physician visit to IBD diagnosis was 3.4(1.1–7.4) months with a longer time in women than in men 4.2(1.9–11.1) vs 2.2(0.82–5.1) p< 0.001. Figure 2 shows the different diagnostic times by sex in CD and UC. Misdiagnosis were reported in 61.6%, women had a higher percentage of misdiagnosis than men, 77.3% vs 48% (OR 3.6; 95% CI 1.9–6.9). These differences between women and men were maintained in CD 83% vs 55.3 (OR 3.9; 95% CI 1.5–9.9) and in UC 68.6% vs 41.8% (OR 3; 95% CI 1.2–7.4). Misdiagnosis were observed in 66/120 (55%) patients evaluated in Emergency Department, 89/166 (53.6%) in Primary Health Care, 25/122 (20.5%) in Gastroenterology Outpatient Clinics, 4/11(36.5) in another medical specialist, and 14/84 (16.7) in Hospital Admission. Women had a higher percentage of misdiagnosis, in Emergency Department 66.1%/44.3% (OR 2.4; 95% CI 1.1–5.1), Primary Health Care 65.1%/42.2% (OR 2.5; 95% CI 1.3–4.7), Gastroenterology Outpatient Clinics 29.5%/11.5% (OR 3.2; 95% CI 1.2–8.4) and Hospital Admission 25.6%/7.3% (OR 4.3; 95% CI 1.1–16.9). Figure 3 shows the distribution of the most frequently misdiagnosed pathologies prior to IBD diagnosis.

Conclusion

Delayed diagnosis of IBD in women affects both CD and CU, due to a longer delay in the diagnostic process since the patient consults for the first time. Gender biases in the misdiagnosis of IBD patients occur at all levels of health care.
P171 PSC/IBD and IBD have similar type and location of colonic lesions, but Dye ChromoEndoscopy (DCE) increases detection rate compared to White Light Endoscopy (WLE)
Authors: Labarile N , Parigi T , Smith S C , Hejmadi R , Nardone O M , Cannatelli R , Shivaji U , Ghosh S , Iacucci M
Published: January 2022

Background

Inflammatory bowel disease (IBD) increases the risk of colorectal cancer proportionally to the extent and duration of the disease. Moreover, up to 5% of IBD patients have concomitant PSC, an additional risk factor, especially for right colon cancer. To mitigate this risk patients with PSC-IBD undergo stricter annual surveillance colonoscopy. We aimed to analyze differences in incidence, location and type of lesions detected during surveillance colonoscopies in PSC/IBD and only IBD. In addition, we assessed the impact of dye spray chromoendoscopy on detection rates.

Methods

In a retrospective single-center study, we collected all surveillance colonoscopies performed at Birmingham University Hospital between January 2014 and August 2019. The procedures were divided for patient diagnosis in PSC-IBD or IBD-only. Demographic, clinical, endoscopic and histologic data were retrieved from electronic medical records. Categorical variables are presented as absolute and relative frequencies and compared using chi-square test and Fisher’s exact test. Continuous variables are presented as mean and compared by Student t-test after testing for normality.

Results

We retrieved 856 colonoscopies from 622 patients, of these 282 colonoscopies were performed in 147 patients with PSC, the remaining 574 in 475 patients with IBD-only. Demographic data are presented in (Table 1).

In 64 (22%) colonoscopies in PSC/IBD and 173 (30%) in PSC/IBD at least one lesion was found (p=0.02). The total number of lesions was 70 for PSC/IBD (0.248 lesions per procedure) and 226 for IBD-only (0.394 per procedure) (p=0.02). While these differences were statistically significant, PSC/IBD patients had 58% (1.2 vs 1.9) more colonoscopies, due to the stricter surveillance regimen, thus likely reducing the rate of lesions per procedure (Table 2 and 3).

There was no statistically significant difference in histologic type and localization of lesions between the two groups (Table 3).

Dye spray chromoendoscopy (DCE) was used in 52% of procedures in the IBD-only group, and 65% of the PSC-IBD. Colonoscopies with DCE were significantly more likely to detect lesions both in PSC-IBD and IBD-only cohorts (both p<0.05). Table 4.

Conclusion

We found a higher detection rate of colonic lesions in colonoscopies of the general IBD population compared to those PSC-IBD patients, though this might be influenced by the frequency of surveillance. The location and type of polyps were similar between groups. DCE increased the rate of detection compared with no DCE regardless of disease phenotype.
P175 Low relapse rates after biologic therapy discontinuation in a large real life cohort of IBD patients with initial severe disease: do biologics alter the natural history of disease?
Authors: Banerjee R , Pal P , Akki Y , Adigopula B , Reddy D N
Published: January 2022

Background

Discontinuation of biologic therapy has been associated with high risk of relapse. However indefinite biologic therapy is often not feasible in low resource settings of the developing countries where tuberculosis (TB) is endemic and cost is prohibitive. There is very limited data on the course of disease after stopping biologics from this region. We analysed the predictors of relapse including the rate and severity post withdrawal of biologics in a large real-world cohort of patients from India.

Methods

Prospectively collected data of consecutive patients treated with biologics from the IBD registry of a large tertiary care centre from India was analyzed. Demographic and disease characteristics, reasons for biologic discontinuation and relapse rate and severity post withdrawal including its management were analyzed. Cox proportional hazard analysis was done to identify predictors of relapse.

Results

403 patients (Median age-35 yrs, range 6–75, 62.5% male, 58% Crohn’s disease:CD, 42% Ulcerative colitis:UC) received biologics for moderate-severe disease (steroid dependent or with complications) with a median follow up of 23 months (IQR-7–48 m, range- 3–228 m). 274 patients (68%) discontinued biologics. 77(28 %) were primary or secondary non-responders. 65 (24%) stopped due to financial constraints. 98 (36%) stopped after clinical and/or endoscopic remission. The other reasons included TB reactivation 8 (2.6%), non-TB infection-5 (2%); infusion reactions: 4 (1.5%); non compliance 14 (5%), aggravated psoriasis 2(1%) and death(1).

87/274 (32%) relapsed after stopping biologics. 187/274 (68%) were in remission over a median follow up of 24 months (IQR: 10–51 months). 52/87(60%) relapsed in first year and 67/87(77%) in 2 years. Most relapses were mild and responded to steroids 43 (49.4%) or re-treatment with biologics 34 (39%). 10 patients (11%) needed surgery. On Cox proportional hazard analysis, perianal/fistulizing disease (HR-2.03, 95% CI-1.1–3.8, p=0.027) and steroid dependent/resistant disease (HR-1.79, 95% CI-1.1–2.9, p=0.019) were associated with a higher risk of relapse after withdrawal of therapy. Patients who stopped after clinical and endoscopic remission had lower likelihood of relapse after biologics discontinuation(HR-0.48, 95% CI-0.29–0.80, p=0.005).

Conclusion

The relapse rates on discontinuation of biologic therapy was low in patients with clinical and endoscopic remission particularly in non-fistulizing, disease. Most relapses were mild. Majority of the patients with an initial severe disease had a milder course post withdrawal of biologic therapy suggesting that biologics could alter the natural course of the disease. Further multi-centre and long term studies are warranted.
P228 Appendiceal Orifice Inflammation Is Associated with Lower Rate of Complete Endoscopic Remission in Patients with Ulcerative Colitis
Authors: Oh C K , Lee H H , Kim J S , Lee B I , Cho Y S
Published: January 2022

Background

Appendiceal orifice inflammation (AOI) is commonly considered a skip lesion in ulcerative colitis (UC). However, the clinical significance of AOI in UC patients remains controversial. This study aimed to evaluate the clinical feature and long-term outcomes of AOI by comparing UC patients with and without AOI.

Methods

This study was conducted as a retrospective design of patients who were newly diagnosed or referred within 3 months after diagnosis at Seoul St. Mary’s Hospital from January 1, 2001 to December 31, 2020. All patients underwent index and follow-up colonoscopies. The long-term outcomes involved achieving complete endoscopic remission (ER), use of biologics, hospitalization, and proximal disease extension. Complete ER was defined as Mayo endoscopic subscore 0.

Results

In total, 318 UC patients were included, of which 140 had AOI. The baseline characteristics were not significantly different between AOI and non-AOI groups. The cumulative risk of complete ER was a significant difference between AOI and non-AOI groups (p=0.041). The other cumulative risks of disease outcomes were not significantly different between AOI and non-AOI groups (use of biologics, p=0.542; hospitalization, p=0.795; proximal disease extension, p=0.403). The multivariate Cox regression analysis also revealed that AOI was the only significant factor of complete ER (hazard ratio, 0.636; 95% confidence interval, 0.446–0.906; p=0.012) in UC patients.

Conclusion

AOI shows a significant association with lower rate of complete ER in UC patients. Therefore, a meticulous treatment strategy may be recommended to achieve complete ER in UC patients with AOI.
P245 Dynemics of the Immune-transcriptome and Microbiome in Paediatric Inflammatory Bowel Disease
Authors: Elawad M A , Kumar M , Saadaui M , Elhag D , Akobeng A , Al-Mudahka F , Hendaus M , Al Khodor S
Published: January 2022

Background

Inflammatory Bowel Disease (IBD), including Crohn’s disease (CD), ulcerative colitis (UC) and IBD unclassified (IBDU) is characterized by a chronic relapsing inflammation of the gastrointestinal tract, resulting from the complex interplay between genetic make-up, microbiome, environmental factors, and immune response. The potential role of the immune response and microbiome in the development and progression of IBD has been extensively studied, however, markers that can predict disease relapse remain scarce, especially in children with IBD. Developing non-invasive monitoring tools are also extremely needed in the field.

Methods

Multi-omics analysis provides a global view of changes in immune, microbial, and environmental factors. In this study, we enrolled a total of 85 IBD patients and 57 matching controls living in Qatar and attending Sidra Medicine IBD clinic. Patients were followed- up every 3 months and when they felt unwell. In addition to the phenotypic and clinical data, saliva, blood, and stool samples were collected at each visit. Salivary and gut microbiome analysis was performed using high throughput 16S rRNA gene sequencing. Blood samples were stimulated with a total of 14 ligands before being processed for immune transcriptomics and proteomics. Patients were compared to their matching healthy controls.

Results

Reduced microbial diversity and increased variability in the microbiome composition was observed in both CD and UC patients compared with controls. Our preliminary data show that Bacteroidetes, Firmicutes, Actinobacteria and Proteobacteria are the common phyla present in both patients and controls. Interestingly, the longitudinal microbiome analysis revealed reduced temporal microbial stability in both CD and UC patients, particularly in patients with changes in disease activity. The microbiome composition of patients in remission appeared similar to healthy controls, whereas dysbiosis was mostly observed in patients with increased disease activity. We then characterized the spectrum of transcriptional responses in blood collected from healthy controls and IBD patients stimulated for 6 hours with 14 ligands. Blood transcriptomics analysis separated patients from controls and a clear clustering was observed when the same patient was in relapse or remission. We aim to identify microbial and immune signatures that can classify patients CD, UC and IBD-U and predict onset of both remission and relapse.

Conclusion

This is the first paediatric data to show that, by integrating various multi-omics datasets collected from CD, UC and IBD-U patients and comparing their profiles with their matching controls, we are able to identify specific non-invasive predictive markers for disease remission and relapse.
P275 New non-invasive biomarkers of intestinal inflammation in pediatric inflammatory bowel diseases and their correlation with fecal calprotectin – pilot study
Authors: Szymanska E , Bierla J , Wierzbicka A , Dadalski M , Konopka E , Cukrowska B , Kierkus J
Published: January 2022

Background

Current data indicates that increased intestinal permeability leading to intestinal damage plays a key role in the pathogenesis of inflammatory bowel diseases (IBD) and correlates with disease flare. Therefore, recently, the role of non-invasive biomarkers in both diagnosis and monitoring IBD is emphasized.

Zonulin is the protein that increases permeability in the epithelial layer of the small intestine by reversibly modulating the intercellular tight junctions.

Fatty acid binding proteins (FABPs) are intracellular proteins expressed in several tissues including intestine. Intestinal FABP (I-FABP) is a plasma and urine marker of intestinal damage.

The aim of this study was to investigate fecal and serum zonulin and I-FABP in pediatric IBD patients and theircorrelation with fecal calprotectin (FCP).

Methods

Seventy-one individuals: 32 Crohn’s disease (CD) patients, 33 ulcerative colitis (UC) patients and 6 controls were examined for fecal and serum zonulin and plasma I-FABP. Values were correlated to FCP and to each other for all children included in the study. A stool specimen and blood samples were collected during check-up visit at hospital. Then fecal and serum zonulin, I-FABP and FCP were tested by ELISA test. Non-parametric statistical tests were used for data analysis.

Results

The level of fecal zonulin and FCP were higher in IBD patients compared to control group (CG): median for CD – 113.6(53.6–150) ng/mL, 46 (7–551) ug/g; UC – 115.3 (50.7–150.4) ng/mL, 40 (16.0–251.2) ug/g; CG – 60.8 (31.8–81.2) ng/mL, 41.5 (31.0–97.7) ug/g, respectively, (P<0.05). No statistically significant difference in concentrations of serum zonulin and I-FABP was reported between patients and CG (P=0.55). The only correlation that has been reported was between fecal zonulin and FCP and the strongest one was in CD: CD – R = 0.73, UC – R = 0.67, All – R=0.67, CG – R=0.65.

Conclusion

Accordnig to our results it seems that only fecal zonulin may serve as another, next to FCP, biomarker of intestinal damage in IBD. However, both fecal and serum zonulin as well as I-FABP need further studies to assess their usefulness in diagnostics and monitoring in IBD.
P284 Prophylactic medication for the prevention of endoscopic recurrence after ileocolonic resection in Crohn’s disease: a prospective study based on clinical risk stratification
Authors: Arkenbosch J H , Beelen E M J , Dijkstra G , Romberg-Camps M , Duijvestein M , Hoentjen F , van der Marel S , Maljaars P W J , Jansen S , de Boer N K , West R , Horjus C , Stassen L P S , van Schaik F , van Ruler O , Jharap B J H , Erler N E , Doukas M , Ooms A H A G , Kats-Ugurlu G , van der Woude J , De Vries A C
Published: January 2022

Background

In patients with Crohn’s disease (CD), postoperative prophylactic medication based on clinical risk stratification is recommended in international guidelines to prevent recurrence after ileocolonic resection (ICR). This study aimed to evaluate the risk of endoscopic recurrence after implementation of a predefined management algorithm after ICR incorporating clinical risk stratification.

Methods

In this multicenter, prospective clinical cohort study, CD patients (≥16 years) were included who were scheduled for ICR and gave informed consent. Endoscopy-guided treatment (no prophylactic medication directly after ICR) was recommended in patients at low risk (LR) of postoperative recurrence, and prophylactic medication (immunosuppressant/biological) in high risk (HR). HR was defined as ≥1 risk factor: smoking, penetrating disease, re-resection. Clinical and histologic risk factors for endoscopic recurrence (Rutgeerts’ score ≥i2) were assessed using logistic regression models and ROC curves based on predicted probabilities.

Results

In total 213 CD patients were included (median age 34.5 years, 65.3% women): 93 (43.7%) at LR and 120 (56.3%) at HR (smoking 45 (21.3%); penetrating disease 51 (23.9%); re-resection 51 (23.9%)). Adherence to the proposed management algorithm was 65%; 76/93 (81.7%) in the LR (no prophylaxis) and 61/120 (50.8%) in the HR population (prophylaxis). Endoscopic recurrence in LR patients was 69% without prophylaxis versus 48% with prophylaxis (p=0.070); in HR 78% without prophylaxis versus 55% with prophylaxis (p=0.019). Clinical risk stratification corresponded with an area under the curve (AUC) of 0.64 (95%CI 0.55–0.73) (Figure 1). Clinical factors combined with histology (active inflammation, granulomas, plexitis in resection margins) increased the AUC to 0.69 (95% CI 0.61–0.88) (Figure 1).

Conclusion

This prophylactic medication algorithm in CD patients based on clinical risk stratification after ICR, results in an absolute risk reduction of endoscopic recurrence of 23% in HR versus 21% increase in LR patients in whom medication is omitted. For this latter population, further refinement of risk stratification is required, and may include histologic assessment.