bluuebunny/crossref_metadata_2025 huggingface dataset:
DOP15 Clinical relevance of endoscopic peri-appendiceal red patch in Ulcerative Colitis patients
Authors: Reijntjes M , Heuthorst L , Gecse K , Mookhoek A , Bemelman W , Buskens C
Published: May 2021

Background

Recently, increasing evidence is suggesting appendectomy as an alternative treatment approach for ulcerative colitis (UC), especially in case of pathological inflammation of the appendix. Therefore, pre-operative identification of appendiceal inflammation could be of clinical importance to predict efficacy of therapeutic appendectomy. This study assessed the incidence of peri-appendiceal red patch (PARP) on colonoscopy, with the aim to correlate PARP to patient and disease characteristics. In addition, the prognostic relevance of PARP on course of disease, and more specifically, histopathological findings of inflammation in resection specimens of the appendix were assessed, to analyze if PARP could potentially be used to identify patients eligible for appendectomy.

Methods

All consecutive patients with UC undergoing colonoscopy in 2014 or 2015 were included to determine the incidence of PARP in a cross-sectional study. Findings were correlated to patient and disease characteristics, upscaling of treatment during disease course and colectomy rates. Degree of inflammation of the appendix in case of subsequent appendectomy/colectomy was determined and results were compared between patients with and without PARP. Histological inflammation was scored by an independent pathologist using the Robarts histopathology index (RHI).

Results

In total, 249 patients with an eligible endoscopy report were included. The incidence of PARP was 17.7% (44/249). Patients with PARP were significantly younger and had a shorter disease course. PARP patients with active disease had proctitis more frequently, although not significant (29.4% vs 11.4%, p= 0.19). Out of 44 PARP patients, 27 (61.4%) were found in colonoscopies showing endoscopic Mayo score 0 or 1. Patients with PARP required significantly more upscaling of medical therapy (81.8% vs 58.0%, p= 0.03), and during the median follow up of 71 months the PARP patient group underwent colectomy more frequently (13.6% vs 4.9%, p=0.04). Eighteen appendices were available for histological analysis, of which 8 showed a PARP pre-operatively. Patients with PARP had a higher median Robarts Histology Index (RHI) score compared to patients without a PARP (13.5 vs 6.5 p< 0.01).

Conclusion

PARP was predominantly found in UC patients with younger age and shorter disease duration and were demonstrated to have a more severe course of UC. Patients with PARP had a higher histopathological inflammation score. Since pathological inflammation of the appendix has been associated with improved efficacy of therapeutic appendectomy, it could be attractive to analyze if the presence of PARP might help in selecting patients more likely to respond to therapeutic appendectomy.
DOP24 Crohn’s Disease fistula show skewed lymphoid/myeloid balance, altered myeloid cell profiles and high TNF-α expression
Authors: Becker M , de Krijger M , Bemelman W , de Jonge W , Buskens C , Wildenberg M
Published: May 2021

Background

A fistula is an abnormal tract connecting two epithelialized surfaces, for example the intestine and the skin. Perianal fistula are a common complication of patients suffering Crohn’s Disease (CD), but also occur in non-IBD patients in the form of cryptoglandular fistula. Around one third of all CD patients develop fistula at some point during their disease course. Fistula are often refractory to therapy, due to poor wound healing responses. In contrast, cryptoglandular fistula often respond to standard therapy. The biological background of this difference is unknown, and comparative studies between the two groups are lacking. The aim of this study was to characterize the cellular composition in fistula tracts of CD and cryptoglandular patients.

Methods

Curettage material of perianal fistula tracts was obtained during surgical intervention from patients with CD (n=15) and cryptoglandular fistulas (n=5). Single-cell suspensions were stained with a 35-antibody panel, focusing on myeloid and T-cell markers and were analyzed using mass cytometry (CyTOF). To visualize macrophages in the fistula tract we performed in situ hybridization with CD68 and TNF-α.

Results

The main cellular component of both fistula tracts consisted of CD66a+ granulocytes (64 +/- 24%). However, the remaining mononuclear compartment differed significantly between Crohn and cryptoglandular fistula. In CD, the majority was of lymphoid nature (CD3+ T cells 57 +/-21%, CD19+ B cells 14 +/-15%), while in cryptoglandular tracts, the majority consisted of myeloid origin (61+/- 15%). Within the T cell compartment, the majority of cells was CD45RO+, indicating activation. Presence of a seton increased the proportion of CD45RO+ T cells, in particular in CD4+ cells. In the myeloid compartment, CD14high/HLA-int monocytes, CD14int/HLA-high inflammatory macrophages and CD14high/CD163+ resident macrophages were identified. Interestingly, CD patient samples contained less monocyte-like cells, and substantially more resident macrophages compared to cryptoglandular samples. This feature tended to be even more enhanced in the presence of a seton, although this did not reach statistical significance. In situ hybridization showed a high production of TNF-α in epithelial-like cells in fistula tract of Crohn’s disease patients, but not in macrophages.

Conclusion

Despite granulocytes being the main contributor to the cellular composition of fistula tracts, striking differences were found between Crohns and cryptoglandular fistula, both in lymphoid/myeloid balance, and in the presence of resident macrophages. We also showed that epithelial-like cells in Crohns’s disease fistula tracts produce high amounts of TNF-α. These differences may contribute to the lack of response to therapy in CD.
DOP42 Disease course and clinical outcomes in Taiwan Crohn’s Disease patients with perianal fistula: A nationwide-based study
Authors: Weng M T , Lin K L , Chan K A , Wei S C
Published: May 2021

Background

Perianal fistula (PAF) is a disabling complication of Crohn’s disease (CD) and there are few reports about the disease course in Asian population in a population based nationwide scale. We aimed to evaluate the prevalence, clinical course and outcomes of PAF in Taiwanese CD population.

Methods

By using data from the National Health Insurance, we defined the CD patients and PAF by the ICD coding and filtered by the medication and surgery history. The prevalence, the fistula disease course was analyzed and the outcomes were compared to the CD patients without PAF.

Results

In this nationwide cohort study, from 2000 to 2017, PAF was diagnosed in 358 (14.6 %) of 2444 CD patients. The majority of CD patients with PAF were men (79.3%). The age of diagnosis for CD was younger in PAF patients (33.7 ± 14.9 years) than those without PAF (45 ± 21.8 years). Approximately half of the PAF occurred before (47.5%) the diagnosis of CD. 33.8% (121/358) patients had recurrent fistula with a median recurrent interval of 239 days (IQR 68–902 days). For CD patients with PAF, they received more often medical treatment including 5-ASA (93.9 vs 67.7 %, p < 0.0001), steroid (94.4 vs 89 %, p < 0.0018), azathioprine (61.7 vs 31.2 %, p < 0.0001) and anti-TNF alpha (44.4 vs 15.1 %, p < 0.0001) and had higher risk of operation (1.4 vs 1.2, p < 0.0032), hospitalization (6.4 vs 3.8, p < 0.0001), Out Patient Clinic (22 vs 6.7, p < 0.0001) and emergency visits (9.7 vs 4.5, p < 0.0001), compared to those without PAF. Although the PAF group needs higher health care utility, the mortality rate is lower than those without PAF (6.7% vs 18.7%, p < 0.0001). Those PAF diagnosed earlier than CD had lower risk of hospitalization (5.1 vs 7.5, p =0.0005) and ER visit (6.3 vs 12.3, p = 0.0056) than PAF diagnosed at the same time or after CD diagnosis. With early use of biologics, patient is associated with lower risk of hospitalization (4.7 vs 9.1, p <0.0001) and ER visit (4.9 vs 13.6, p =0.0116).

Conclusion

By using the nationwide population database, the prevalence of PAF in Taiwanese CD patients is 14.6 %. The fistula recurrence rate was 33.8%. Patients with PAF required more intensive care and consume more medical resources but they did not have poorer survival status compared to those who do not have PAF. Approximately half of PAF patients presented with perianal symptoms before the diagnosis of CD. Early use of biologics can decrease hospitalization and emergency visit.
N10 Experience with telemedicine during the COVID-19 pandemic and preferences for future e-health in a large IBD cohort
Authors: Breiteneicher S , Le Thi T G , Klucker E , Schwerd T , Csollarova K , Neuhaus L , Koletzko S , Török H , Koletzko L
Published: May 2021

Background

The COVID-19 pandemic affects clinical care, daily life and wellbeing of patients with IBD. During the contact restrictions, we realized anxiety among our IBD patients and unmet needs for healthcare. We investigated patient’s experience with telemedicine (TM) during the pandemic, their interest in future TM use, and their preference regarding a qualified IBD Nurse-led or a Medical Doctor-led (MD-led) teleconsultation at a large German IBD center.

Methods

Pediatric and adult patients who attended the IBD unit at least once between 7/2018 and 6/2020) were invited to a prospective survey (KoCo19-CED-1). Questions included items on IBD (phenotype, treatment and disease activity), comorbidities, healthcare utilization, demographic and socioeconomic factors, psychological burden and IBD-related quality of life during the COVID-19 pandemic. This sub-analysis presents patient’s experience with TM and their preference for a contact with an IBD Nurse.

Results

Of 820 identified IBD cases, 504 (62%) patients and/or their parents completed the survey between mid-July to mid-October 2020; 86 were children (aged 6 to 18 years) and 418 were adults (up to 85 years); 58.7% had Crohn’s disease and 35.7% Ulcerative Colitis. Current treatment with any immunosuppressive medication (mono- or combo-therapy with immunomodulators, biologics, JAK-inhibitors and/or corticosteroids) were reported by 79.6% (401/504) of patients. During the pandemic, an in-person visit was substituted with TM by an IBD Nurse or a medical doctor (MD) in 58 (11.6%) and 29 (5.8%) of the patients, with high satisfaction (88.5% vs 92.1 %, respectively, n.s.). Half of the patients (n=246) showed interest in future TM, thereof 60.2% preferred consultation with a MD, 1,6% with an IBD Nurse and 38.2% expressed no preference. Of patients with prior experience with an IBD Nurse-led TM (n=38), 96% are interested to use TM in the future. Rejection of future TM was related to no TM experience (p=0.001), having Crohn’s disease (p=0.032), receiving biologics (p=0.004), and self- or non-employment status (p=0.003), but not to gender, age, self-reported disease activity or disease duration.

Conclusion

Patient acceptance of TM is high, particular in those with previous TM experience, regardless of performed by MD or IBD Nurse. Our data support the statement on e-health in the N-ECCO 2018 Consensus giving an advanced IBD Nurse alongside with MD a key role to improve IBD care.
OP05 Association of ultra-processed food intake with risk of Inflammatory Bowel Disease from the prospective urban rural epidemiology (PURE) study: A prospective cohort study
Authors: Narula N , Wong E , Dehghan M , Mente A , Rangarajan S , Marshall J , Moayyedi P , Reinisch W , Yusuf S
Published: May 2021

Background

Dietary factors may influence the risk of developing inflammatory bowel disease (IBD), but evidence from large, prospective studies is scarce. This study aimed to evaluate the relationship between ultra-processed food intake and the risk of developing IBD in the Prospective Urban Rural Epidemiology (PURE) cohort study.

Methods

This was a prospective cohort study among 21 low, middle, and high income countries across seven geographic regions of 116,087 individuals between the ages of 35–70 with at least one cycle of follow-up and complete baseline food frequency questionnaire (FFQ) data. Country-specific validated FFQs were used to document baseline dietary intake. Participants were followed prospectively at least every 3 years. The main clinical outcome for this study was development of IBD, including Crohn’s disease (CD) or ulcerative colitis (UC). Cox proportional hazard multivariable models were used to assess associations between ultra-processed food intake and risk of IBD. Results are presented as hazard ratios (HR) with 95% confidence intervals (CI).

Results

Participants were enrolled in the study between 2003 and 2016. During the median follow-up of 9.7 years (IQR 8.9–11.2), we recorded 467 incident cases of IBD (90 with CD and 377 with UC). Higher ultra-processed food intake was associated with a higher risk of incident IBD (HR 1.82, 95% CI 1.22 to 2.72 for ≥5 servings/day and HR 1.67, 95% CI 1.18 to 2.37, for 1–4 servings/day as compared to <1 serving/day, ptrend=0.006), after adjustment for potential confounding factors. Different subgroups of ultra-processed food including soft drinks, sweets, salty snacks, and processed meat each were associated with higher HR for IBD. Results were consistent in UC and CD with low heterogeneity. White meat, red meat, dairy, starch, fruits, vegetables, and legumes intake were not associated with incident IBD.

Conclusion

Higher ultra-processed food consumption was positively associated with development of IBD. Further studies are needed to identify the potential culprits within ultra-processed foods.
OP08 Automatic detection of enteric ulcers and erosions in capsule endoscopy using a convolutional neural network
Authors: Saraiva M , Afonso J , Ribeiro T , Cardoso H , Ferreira J , Andrade P , Jorge R , Lopes S , Macedo G
Published: May 2021

Background

Capsule endoscopy (CE) is recommended for the diagnosis and assessment of disease extension in patients with suspected or known inflammatory bowel disease, particularly Crohn’s disease. Ulcers and erosions of the enteric mucosa are prevalent findings in these patients. They frequently occur together, and their identification in CE is crucial for an accurate evaluation of disease severity. Nevertheless, reviewing CE images is a time-consuming task, and the risk of overlooking lesions is significant.

Over the last decade, artificial intelligence (AI) has emerged as a mean for overcoming these pitfalls. Of all AI methods, convolutional neural networks (CNN), due to their complex multilayer architecture present the best results in image analysis.

We aimed to develop a CNN for the automatic identification of ulcers and erosions in the small bowel mucosa.

Methods

A total of 1483 CE exams (PillCam SB3®) performed at a single centre between 2015–2020 were analyzed. From these exams, a sum of 11588 frames of the enteric mucosa were obtained, 3163 containing enteric ulcers and erosions, and the remaining containing normal mucosa or other findings. Ulcers and erosions were stratified according to the Saurin’s classification for bleeding potential: P1E – erosions with intermediate bleeding risk; P1U – ulcers with intermediate bleeding risk; P2U – ulcers with high bleeding risk. For automatic identification of these lesions, these images were inserted into an CNN model with transfer learning. Subsequently, the performance of the network assessed using an independent set of images. The output provided by the CNN was compared to the classification provided by a consensus of specialists (Figure 1).

Results

After optimizing the neural architecture of the algorithm, our model was able to automatically detect and distinguish ulcers and erosions (any bleeding potential) in the small intestine mucosa with an accuracy of 96.7%, precision of 95.9%, sensitivity of 91.7% and a specificity of 97.8% (Figure 1). The mean processing time for the validation dataset was 23 seconds (approximately 101 frames/second).

Conclusion

We developed and tested a deep learning model based on a CNN for the automatic detection of enteric ulcers and erosions in CE images. Our system revealed extraordinary performance marks. We believe that our study lays the foundation for the development and application of effective AI tools to clinical practice. These techniques should improve diagnostic accuracy and reading efficiency.
OP26 Risankizumab induces early clinical remission and response in patients with Moderate-to-Severe Crohn’s Disease: Results from the phase 3 ADVANCE and MOTIVATE studies
Authors: Schreiber S W , Ferrante M , Panaccione R , Colombel J F , Hisamatsu T , Lim A , Lindsay J O , Rubin D T , Sandborn W J , Neimark E , Song A P , Liao X , Feng T , Berg S , Wallace K , D’Haens G R
Published: May 2021

Background

Present therapies leave an unmet need for early and effective treatment for patients with Crohn’s disease (CD). Risankizumab (RZB), a humanized immunoglobulin G1 monoclonal antibody against the p19 subunit of interleukin-23, was evaluated as an induction therapy to induce early clinical remission and response in patients with moderate-to-severe CD in two double-blind, randomized, placebo (PBO)-controlled studies (ADVANCE [NCT03104413] and MOTIVATE [NCT03105128]).

Methods

Patients with moderate-to-severe CD (CD Activity Index [CDAI] of 220–450, Simple Endoscopic Score for CD [SES-CD] ≥ 6 [≥ 4 for isolated ileal disease] excluding the narrowing component, and average daily [liquid/very soft] stool frequency [SF] ≥ 4 and/or average daily abdominal pain [AP] score ≥ 2) who had inadequate response or intolerance to conventional and/or biologic treatment (ADVANCE), or biologic treatment only (MOTIVATE) were randomised 2:2:1 (ADVANCE) or 1:1:1 (MOTIVATE) to receive intravenous RZB 600 mg, RZB 1200 mg, or PBO as induction therapy at weeks 0, 4, and 8. Clinical remission (per either CDAI or a composite of SF and AP criteria), clinical response (per CDAI criterion), and enhanced clinical response (per a composite of SF and AP criteria) were evaluated at weeks 4, 8, and 12 (endpoints defined in Figure 1 footnotes). Safety was assessed throughout the studies.

Results

A total of 1419 patients from ADVANCE (N = 850) and MOTIVATE (N = 569) respectively, were randomised and included in the intention-to-treat population. In both studies, starting at week 4 (the first prespecified measurement), greater proportions of RZB 600 mg or RZB 1200 mg- vs PBO-treated patients achieved clinical remission per either CDAI (P = .01/P < .05) or SF/AP criteria (P < .01/P < .01), clinical response per CDAI criterion (P = .001/P < .01), and enhanced clinical response per SF/AP criteria (P < .01/P = .14) (Figure 1). For both RZB 600 mg and RZB 1200 mg, the efficacy and treatment effect increased through week 12 (P ≤ .001/P ≤ .001) (Figure 1). Treatment with RZB 600 mg or 1200 mg was well tolerated, and no new safety risks were identified.1,2

Conclusion

Induction therapy with both RZB 600 mg and 1200 mg intravenous resulted in significantly greater clinical remission and response vs PBO as early as week 4 and sustained through week 12 in patients with moderate-to-severe CD who had inadequate response or intolerance to conventional and/or biologic treatment.

References
OP37 Rapidity of symptom improvements during filgotinib induction therapy in patients with Ulcerative Colitis: Post hoc analysis of the phase 2b/3 SELECTION study
Authors: Danese S , Hibi T , Ritter T E , Dinoso J B , Hsieh J , Yun C , Zhang J , Zhao S , Loftus Jr E V , Rogler G
Published: May 2021

Background

Filgotinib (FIL) is a preferential Janus kinase 1 inhibitor in development for the treatment of inflammatory bowel disease. SELECTION was a phase 2b/3 randomized, double-blind, placebo (PBO)-controlled trial to evaluate FIL for the treatment of moderately to severely active ulcerative colitis (UC) (NCT02914522). The aim of this post hoc analysis was to assess the speed of improvement in patient-reported outcomes (PROs) during FIL treatment.

Methods

Eligible patients who were biologic-naïve or -experienced were enrolled in induction study A or induction study B, respectively. In each study, patients were randomized 2:2:1 to receive FIL 100 mg, FIL 200 mg or PBO once daily orally for 10 weeks. In this post hoc analysis, data from daily patient diaries up to day 15 of induction, including Mayo stool frequency subscores (SF; range, 0 [normal] to 3 [≥5 stools/day more than normal]) and rectal bleeding subscores (RB; range, 0 [no blood] to 3 [passing blood alone]), were used to evaluate the proportion of patients achieving predefined subscores or subscore reductions.

Results

Induction studies A and B comprised 659 and 689 patients, respectively. Baseline characteristics were similar across treatment groups within induction study A and within induction study B. In induction study A, more patients treated with FIL 200 mg vs PBO reported a reduction in SF of ≥1 from baseline as early as day 6 (FIL 200 mg, 35.8%; PBO, 20.6%, p<0.01) and every day from day 10 (Figure 1), and a reduction in RB of ≥1 from baseline as early as day 4 (FIL 200 mg, 36.9%; PBO, 23.7%; p<0.01) and every day from day 7 (Figure 2). In induction study B, more patients treated with FIL 200 mg vs PBO reported a reduction in SF of ≥1 from baseline as early as day 2 (FIL 200 mg, 21.6%; PBO, 12.1%; p<0.05) (Figure 3) and a reduction in RB of ≥1 from baseline as early as day 3 (FIL 200 mg, 29.5%; PBO, 17.6%; p<0.01) (Figure 4). More patients receiving FIL 200 mg vs PBO achieved the composite score of RB=0 and SF≤1 as early as day 9 in induction study A (FIL 200 mg, 18.8%; PBO, 9.5%, p<0.05). More patients receiving FIL 200 mg vs PBO achieved the composite score of RB=0 and SF≤1 as early as day 7 in induction study B (FIL 200 mg, 10.7%; PBO, 4.2%, p<0.05).

Conclusion

In this post hoc analysis of induction study data from SELECTION, improvements in SF and RB were observed within the first week of therapy with FIL 200 mg, compared with PBO, in patients with moderately to severely active UC. These data demonstrate that FIL 200 mg has rapid onset of action, as assessed by PROs, in both biologic-naïve and biologic-experienced patients.
P024 Development of a treatment for short bowel syndrome using small intestinal organoids
Authors: Sugimoto S , Kobayashi E , Fujii M , Ohta Y , Ishikawa K , Nanki K , Hakamata Y , Kanai T , Sato T
Published: May 2021

Background

Massive small intestinal resection leads to short bowel syndrome (SBS), which is a severe malabsorption disorder. Crohn’s disease is one of the most frequent cause of surgical removal of the small intestine in adults. Severe SBS patients need to receive permanent parenteral nutrition, which can cause serious complications. Intestinal transplantation currently remains the only curative option for such patients but has not widespread due to its high mortality/rejection rates. Here, we propose a concept to generate a rejection-free small intestinalized colon (SIC) by replacing the native colonic epithelium with small intestinal organoids.

Methods

Human normal intestinal organoids and rat intestinal organoids derived from luciferase-expressing LEW transgenic rats were established and cultured as previously described (Fujii et al. Cell Stem Cell 2018). Human colon or ileum organoids were xenotransplanted onto the EDTA-injured colon of immunodeficient mice via transanal infusion as previously described (Sugimoto et al. Cell Stem Cell 2018). In LEW rats, a 4-cm segment of the ascending and proximal transverse colon was dissected with the preservation of the vasculature. After EDTA-based removal of the colon epithelium, rat colon or ileum organoids were transplanted in a blinded manner. Following organoid transplantation, the colon segment was fixed to the abdominal walls as stoma outlets for a week. Afterwards, organoid-transplanted colon segment was trimmed and interposed between the jejunum beginning and the ileocolic valve following total jejunoileum resection. Overall survival and detailed histological analyses were performed.

Results

Xenotransplanted human ileum organoids reconstituted nascent villus structures reminiscent of the ileum epithelium in mouse colon. Furthermore, ileum xenografts exhibited a formation of Lyve-1+ lacteal-like structure equipped with the absorption-related machinery, but not colon xenografts. In rats, engrafted ileum organoids initially formed crypt-like structures in the colostomy and, after interposition, they developed mature villus structures. The villus formation was small intestine-specific and flow-dependent. The SIC gained small intestinal function along with the remodelling of the underlying lymphovascular networks. Ileum organoid-transplanted rats exhibited milder body weight loss and significantly higher survival rate compared to colon organoid-transplanted rats.

Conclusion

The SIC with villus structure, intact vasculature and innervation, and the lacteal, had absorptive and peristalsis functions. Small intestinal organoid transplantation as cell source of the SIC ameliorated intestinal failure in a rat SBS model.
P061 Immune cell infiltrations of myenteric plexus in IBD – characterization and implications
Authors: Wiese J J , Fascì A , Kühl A A , Siegmund B , Prüß M S , Schumann M
Published: May 2021

Background

IBD frequently causes chronic abdominal pain and visceral hypersensitivity. To understand development of pain in IBD in more detail, we analyzed the inflammatory infiltration of the enteric nervous system (ENS). A crucial signaling point for pain transmission is the myenteric plexus situated in the smooth muscle layer of the colon wall. We investigated (i) the immune cell infiltration within the myenteric plexus, (ii) neuronal cell survival and (iii) expression of neurotransmitters by immunostaining in surgical colonic samples from patients with Crohn′s disease (CD) or ulcerative colitis (UC).

Methods

FFPE material from surgeries (ileocecal resections and colectomies) was collected from 12 UC, nine CD and 11 patients that received surgeries for non-inflammatory reasons (controls). Immune cell composition, neurotransmitter expression and cell survival were analyzed by quantifying immune cell infiltration of the myenteric ganglia in immunohistochemistry sections. Immune cells within the myenteric plexus were defined as intraganglionar cells. The neurotransmitters CGRP and substance P as well as annexin V as a cell death marker were quantified based on their expression within the myenteric ganglia.

Results

CD3+CD4+ intraganglionar T-cells (216 ± 44 cells/mm²) were found to be increased for CD myenteric plexus compared to controls (79 ± 35 cells/mm²) (p=0.04) (see Fig. 1). For CD and UC, the cell counts of CD3+CD8+ lymphocytes infiltrating the myenteric plexus were significantly increased (controls: 39 ± 18 cells/mm², CD: 281 ± 105 cells/mm² (p=0.0004), UC: 177 ± 59 cells/mm² (p=0.04), Intraganglionar Foxp3+ T-cells were not significantly changed. Intraganglionar CD163+ and CD68+ monocytes were increased in CD (CD68+ monocytes: control: 377 ± 50 cells/mm², CD: 1278 ± 264 cells/mm², p=0.002 and CD163+ monocytes: control: 501 ± 97 cells/mm², CD: 963 ± 236 cells/mm², p=0.04). Expression levels of the neurotransmitter CGRP were found to be increased for UC myenteric plexus (control: 1.8 ± 0.2 units of intensity, UC: 2.8 ± 0.2 units of intensity, p=0.005). Substance P was found to be reduced in the myenteric plexus of CD patients if compared to controls (control: 2.1 ± 0.1 units of intensity, CD: 1.5 ± 0.2 units of intensity, p=0.007). UC myenteric plexus showed more annexin V-positive cells than control patients.

Conclusion

The intraganglionar immune cell composition of myenteric plexus in IBD comprises CD3+CD4+, CD3+CD8 T-cells in UC and CD3+CD4+, CD3+CD8+ and CD3+Foxp3+ T-cells as well as CD68+ and CD163+ monocytes in CD. In UC myenteric ganglia levels of the neurotransmitter CGRP are increased whereas substance P expression is reduced in CD. UC-affected myenteric plexus show increased levels of apoptosis in comparison to controls.
P065 Conservation of breast milk cytokine profiles in consecutive pregnancies of women with inflammatory bowel disease
Authors: Agrawal M , Tarassishin L , Rendon A , Debebe A , Hillenbrand C , White S , Eisele C , Hawkins K , 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

Preliminary evidence suggests changes in breast milk cytokines in women with inflammatory bowel disease (IBD) compared to healthy controls, with potential implications toward offspring immunological development. However, changes in breast milk cytokine profiles in consecutive pregnancies are not known.

Methods

In this pilot study, we prospectively enrolled 11 pregnant women with, and 10 without IBD during two consecutive pregnancies and collected clinical data during each pregnancy and post birth. We collected breast milk samples at two weeks post birth and obtained the expression levels of 92 cytokines using the Olink proteomic platform. We further analyzed the correlation of cytokine profiles within each sample, in paired breast milk samples from consecutive pregnancies, and in random two unpaired breast milk samples, of women with and without IBD.

Results

The baseline characteristics of women with and without IBD were comparable (Table). The cytokine profiles were significantly correlated between paired breast milk samples from consecutive pregnancies compared to unpaired breast milk samples from women with or without IBD. The overall correlations of cytokine profiles in paired IBD pregnancies were significantly higher than the controls (Figure).

Conclusion

Our pilot study results suggest that the breast milk cytokine signatures are more conserved in consecutive pregnancies of women with IBD compared to those without IBD. Future analysis will test if our findings have implications toward familial clustering of immune functions in offspring.
P091 Switching to TNFi versus non-TNFi biologics in Crohn’s Disease patients: Real-world outcomes from a German claims data analysis
Authors: Antolin-Fontes B , Borsi A , Nissinen R , Bravatà I , Barthelmes J N , Le Bars M , Lee J , Maywald U , Bokemeyer B , Wilke T , Ghiani M
Published: May 2021

Background

Determining the best treatment path for Crohn’s Disease (CD) patients following loss of response (LoR) to a tumour necrosis factor inhibitor (TNFi) is challenging for clinicians. This study seeks to provide real-world evidence on treatment failure, treatment discontinuation and corticosteroid-free drug survival in CD patients with LoR to a first TNFi, switching to another TNFi compared to a non-TNFi biologic.

Methods

Adult CD-patients without biologics therapy in the last 6 months who started treatment with adalimumab or infliximab and switched due to LoR to another biologic between 01/10/2014–31/12/2018 were identified from German claims data (AOK PLUS). The identified patients were classified as either within-class switchers (WCS) (if they switched to adalimumab or infliximab) or outside-class switchers (OCS) (if they switched to vedolizumab or ustekinumab). The date of first treatment switch was set as the index date. Patients were followed for at least one year after treatment switch. To compare WCS and OCS, baseline covariate adjustment through inverse probability of treatment weighting (IPTW) of the propensity scores was conducted. Time-to-event analyses were performed using Cox Proportional Hazard regressions adjusted for an indicator of primary non-response and secondary LoR (if the first switch happened within or after 6 months from the initial TNFi).

Results

112 patients (53 WCS and 59 OCS) were identified. Upon IPTW, 43 WCS and 54 OCS satisfying the common support assumption were included for comparative analyses with adjustment for primary non-response and secondary LoR. WCS were significantly more likely to receive corticosteroid therapy, more likely to fail and to discontinue the treatment they had switched to; and more likely to switch again to another biologic compared to OCS (Figure 1). Having switched due to primary non-response or due to secondary LoR was not significantly associated with any outcome.

Figure 1: Kaplan-Meier curves and Cox proportional hazard models adjusted for an indicator variable of primary non-response/secondary loss of response

Abbreviations: CD, Crohn’s disease; CI, confidence interval; HR, hazard ratio

Conclusion

Whilst small sample size is a limitation, these results suggest that following loss of response to a TNFi, patients may benefit from switching to vedolizumab or ustekinumab rather than switching to a different TNFi.
P109 Impact of ethnicity on colorectal cancer incidence in a cohort of colitis-associated dysplasia patients
Authors: Kabir M , Curtius K , Kalia P , Al Bakir I , Choi C H R , Hartono J L , East J E , Lindsay J O , Vega R , Thomas-Gibson S , Graham T A , Hart A , Wilson A
Published: May 2021

Background

Racial disparities in inflammatory bowel disease (IBD) phenotypic presentations and outcomes are recognised. However, there are conflicting data from Western population-based cohort studies as to whether racial differences in colitis-associated colorectal cancer (CRC) incidence exists. To our knowledge this is the first study to investigate the impact of ethnicity on the natural history of dysplasia in ulcerative colitis (UC).

Methods

We performed a retrospective multi-centre cohort study of adult patients with UC whose first low-grade dysplasia (LGD) diagnosis within the extent of colitis was made between 1 January 2001 and 30 December 2018. Only patients with at least one follow-up colonoscopy or colectomy by 30 August 2019 were included. The study end point was time to CRC or end of follow-up. Statistical differences between groups were evaluated using Mann-Whitney U tests and Chi-squared tests. Survival analyses were performed using Kaplan-Meier estimation and multivariate Cox proportional hazards models.

Results

408 patients met the inclusion criteria (see Figure 1 for patient and clinical demographics). More patients from a Black or Asian (BAME) background progressed to CRC [13.4% vs. 6.4%; p=0.036] compared to their White Caucasian counterparts, despite having surveillance follow-up. Figure 2 displays Kaplan-Meier curves demonstrating the probability of remaining CRC-free after LGD diagnosis and categorised by ethnicity. BAME patients were more likely to have moderate-severe inflammatory activity on colonic biopsy within the 5 preceding years [42.0% vs. 28.9%; p=0.023], but no significant differences in medication use and a longer median time interval from LGD diagnosis to colectomy date [32 months vs. 11 months; p=0.021]. After adjusting for sex, age and UC duration at time of LGD diagnosis and presence of moderate-severe histological inflammation, being Black or Asian was a predictive factor for CRC progression on multivariate Cox proportional hazard analysis [HR 2.97 (95% CI 1.22 – 7.20); p = 0.016]. However, ethnicity was no longer predictive of CRC progression on sub-analysis of the 317 patients who did not have a colectomy during the follow-up period.

Conclusion

In this UK multi-centre cohort of UC surveillance patients diagnosed with LGD, delays in receiving cancer preventative colectomy may contribute to an increased CRC incidence in certain ethnic groups. Further work is required to elucidate whether these delays are related to institutional factors (e.g. inequity in the content of decision-making support given or access to healthcare) or cultural factors.
P111 Cross-sectional imaging is highly sensitive in detecting endoscopic post-operative recurrence in Crohn’s disease patients
Authors: Bachour S , Shah R S , Lyu R , Nakamura T , Shen M , Li T , Rieder F , Cohen B , Qazi T , Lashner B , Achkar J P , Philpott J , Lightner A , Holubar S , Regueiro M , Dane B , Baker M , Axelrad J , Click B
Published: May 2021

Background

Postoperative Crohn’s disease (CD) surveillance relies on endoscopic monitoring. The role of cross-sectional imaging in post-operative CD surveillance is less clear. We aimed to evaluate radiographic characteristics, endoscopic concordance, and the predictive ability of imaging for postoperative recurrence (POR).

Methods

Multi-institution retrospective cohort study of adult CD patients who underwent ileocolonic resection (ICR) between 2009–2020. Patients with a CT or MR enterography within 90 days of a postoperative surveillance colonoscopy were included. Imaging studies were interpreted by blinded expert CD radiologists. Endoscopic activity was assessed by Rutgeerts’ scoring (POR ≥ i2b). Patients were categorized by presence of endoscopic POR (E+ or E-) or radiographic disease activity (R+ or R-) and grouped by endoscopic and radiographic concordance.

Results

201 CD patients (57.7% female, mean age 31 years, 81.2% stricturing CD, 17.9% >1 prior ICR, 22.5%) with paired colonoscopy and imaging were included. Median time from ICR to paired endoscopy was 23.2 months. Imaging was highly sensitive for detecting POR (84.2%), but poorly specific (32.8%). The plurality (41.8%, N=84) were discordant E-/R+, 32.8% concordant positive (E+/R+), 20.4% concordant negative (E-/R-), and 5% discordant E+/R-. In patients with endoscopic POR, imaging detected intestinal wall thickening (86.8%; p=0.004) and hyper-enhancement (84.2%; p=0.003) at higher rates and corresponded with endoscopic severity (Figure 1). Multiple correspondence analysis showed association between severe endoscopic (i3/i4) disease and advanced radiographic disease. The majority (58.3 %) of E+/R- patients (N=12) had a Rutgeerts’ score of i2b. Majority of E-/R+ (N=84) had minimal/mild radiographic disease (81%). Differences in characteristics between the E-/R+ and E+/R+ was most pronounced in length of disease >10 cm (26.1%, 45.3%). Subsequent colonoscopies were performed in 74 E-/R+ (i0=28, i1=12, i2a=34) and 35 E-/R- (i0=20, i1=9, i2a=6) patients with 18 E-/R+ (24.3%; i0=8, i1=3, i2a=7) and 4 E-/R- (11.4%; i0=1, i1=2, i2a=1) patients developing POR (p=0.09). However, survival analysis between E-/R+ and E-/R- showed no difference to time to subsequent POR (p=0.24) (Figure 2). Imaging features at time of paired negative endoscopy did not predict subsequent endoscopic POR.

Conclusion

Cross-sectional imaging is highly sensitive to detect endoscopic POR; advanced radiographic disease correlates with increased endoscopic severity. Patients with no endoscopic recurrence in the presence of radiographic activity may require increased surveillance, though larger study cohorts are needed. Imaging compliments, but should not supplant, endoscopic POR surveillance paradigms.
P139 Significant Changes In Routine Biochemical Markers Occur Up To 5 Years Prior To Inflammatory Bowel Disease Diagnosis: A Case-Control Study
Authors: Cohen N A , Kliper E , Zamstein N , Ziv-Baran T , Ben Tov A , Kariv R
Published: May 2021

Background

Early diagnosis of inflammatory bowel diseases (IBD) is associated with improved response to treatment and disease outcomes. Predicting patients at risk of developing symptomatic IBD would provide a window of opportunity to treat patients before irreversible bowel damage is caused. Our aim is to determine whether there is a pattern of change in use of health resources, medications and laboratory results in the years prior to diagnosis.

Methods

This is a retrospective study performed using electronic medical records (EMR) of Maccabi Health Services (MHS) which insures 25% of the Israeli population with a nationwide distribution. Data was extracted using MDClone (MDClone Ltd). IBD patients ≥ 16 years of age and minimum of 5 years follow up were identified by entry into the MHS IBD registry and included in the study. Demographic, clinical, medication and laboratory data was collected. Generalized estimating equation (GEE) model was applied to study trends and compare between years.

Results

A total of 5643 IBD patients were included. Of these, 3039 (53.8%) had Crohn’s disease (CD), 2322 (41.1%) had ulcerative colitis (UC) and 282 (5%) had indeterminate colitis (IC). The mean age of the total IBD population at inclusion to the registry was 39.3 ± 16.5 years. Overall, CD patients had significantly increased visits to general practitioners, emergency rooms and admissions compared to UC patients (33.2 vs 30, p<0.0001; 0.2 vs 0.17, p<0.0001 and 0.88 vs 0.71, p<0.0001, respectively). CD and IC patients had similar patterns of medical professional/institution visits. Laboratory parameters such as haemoglobin and mean corpuscular volume showed significant decrease and white blood count, platelets and c-reactive protein showed significant increase in mean values primarily in the 2 years prior to diagnosis with stable values prior to that (p<0.0001 for all parameters). In contrast, parameters such as creatinine, total protein, albumin and calcium showed earlier significant and progressive decreases in mean values starting 5 years prior to diagnosis (p<0.0001 for all parameters) (Figure 1). Use of medications such as nonsteroidal anti-inflammatory drugs, etanercept, steroids, proton pump inhibitors and antibiotics significantly increased in the 2 years prior to IBD registry entry (P<0.0001 for all).

Conclusion

There are clear changes from baseline in uptake of medical resources, medication usage and laboratory results in the 5 years prior to IBD diagnosis. Parameters such as creatinine and albumin give earlier signal than others. This data may allow the development of an algorithm stratifying patients into those who need more intensive follow-up or investigations to enable earlier disease diagnosis.
P178 Remote monitoring as an effective management strategy in inflammatory bowel disease: the lesson from COVID-19 pandemic
Authors: Busacca A , Sinagra E , Guida L , Carrozza L , Melodia M , Maida M , Battaglia S , Celsa C , Cammà C , Cappello M
Published: May 2021

Background

During the COVID-19 outbreaks many IBD clinics in Italy adopted a remote monitoring approach both to ensure an adequate follow-up of patients with inflammatory bowel disease (IBD) and respect the rules of social distancing, while access to hospital was restricted. Aim of the study was to perform a survey on IBD patients submitted to remote monitoring in our tertiary referral center in order to assess adherence and patients’ perceptions and satisfaction as well as their opinions for future monitoring. Changes in disease activity and Quality of Life were also evaluated.

Methods

Consecutive patients with IBD scheduled for follow-up visits were switched to remote monitoring through e-mail from March 2020 to February 2021, Patients were asked to complete a questionnaire focusing on 3 elements of the intervention: (1) self-assessment questions, (2) action plans, and (3) educational messages. With regards to self-assessment questions, we used the SIBDQ (to evaluate the QoL) and the IBDSI (to evaluate symptoms as patients’ reported outcomes). All patient sent by email results of blood texts: ESR, CRP, CBC, faecal calprotectin, ferritin, serum iron. HBI Index and Mayo UC score were calculated by the treating physicians.

Results

424 subjects, 100% Caucasians, completed the survey. 233 (55,1%) were male, 220 (52.0%) had Crohn’s Disease (CD). Median baseline Mayo Score and Harvey Bradshaw Index were 3 and 4, respectively. 9 (2,1%) patients were referred to emergency department because of disease flares. 2 (1%) UC patients needed to add topical therapy, 9 (4%) CD patients started therapy with systemic steroids and 3 (1,3%) with biologics. 410 (96,9%) patients were satisfied about telemedicine, and 320 (76,5%) patients reported that would maintain this approach also after COVID-19 outbreak. On univariate logistic regression analysis, only a high ferritin value was found to be related to patients’ satisfaction (p=0.001). Lower calprotectin (p=0.012) and need for treatment change (p<0001) were found to be related to QoL, while CD (p=0.052), age (p=0.027), disease duration (p=0.046) and higher calprotectin (p=0.021) were associated to the need for treatment change. None of the variables were significant on multivariate analysis.

Conclusion

Our results confirm in an homogeneous cohort of IBD patients from southern Italy that a telemedicine approach can substitute face-to-face consultations at least for patients in remission or mild clinical activity. Patients’outcomes were not affected as far as concerns referral to emergency services or the use of steroids for disease flares. A high proportion of patients would maintain this management strategy.
P266 The impact of vedolizumab and ustekinumab on arthropathy and arthralgia in IBD patients: a real-life multicentric cohort study
Authors: Truyens M , De Galan C , Peeters H , Mesonero Gismero F , Elorza A , Torres P , Vandermeulen L , Jauregui Amezaga A , Ferreiro-Iglesias R , Holvoet T , Zabana Y , Peries Reverter L , Geldof J , Varkas G , De Vos M , Lobaton T
Published: May 2021

Background

Extra-intestinal manifestations (EIM) are frequently reported in inflammatory bowel diseases (IBD). Although the efficacy of TNF inhibitors is well documented, data regarding the effect of vedolizumab (VDZ) and ustekinumab (UST) are limited. Theoretically, the advantage of VDZ, i.e. gut-selectivity, may reduce the efficacy on EIM while the systemic effect of UST may be of benefit. Therefore, we evaluated the differences in new onset and evolution of EIM during both treatments.

Methods

An international multicentric retrospective study was performed on IBD patients who started VDZ or UST between May 2010 and December 2020. EIM were assessed at baseline and during follow-up. Arthropathy was defined as joint inflammation (arthritis/sacroiliitis) and arthralgia as articular pain without confirmed inflammation. Skin EIM included erythema nodosum (EN), pyoderma gangrenosum (PG) and Sweet syndrome. Ocular EIM included (epi)scleritis and uveitis. Uni- and multivariate analyses were performed.

Results

In total 856 patients were included: 528 treated with VDZ and 328 with UST. At baseline, arthropathy was more prevalent in UST treated patients (12.2% vs 7.2%; p=0.037; Table 1). No differences in rates of new onset (Fig 1) or evolution of pre-existing arthropathies could be identified between VDZ and UST. In multivariate analyses new onset arthropathy was not associated with smoking, IBD type, sex nor studied biological. In 5 out of 48 (10.4%) VDZ patients and 2 of 46 (4.3%) UST patients with either pre-existing or new arthropathy, treatment was stopped due to articular disease (difference not significant).

In contrast, new arthralgia onset within 1 year of follow-up was significantly associated with VDZ treatment (OR 2.1 (1.1–4.0); p=0.022; Fig 1). Arthralgia was the reason to stop treatment in 2 of 87 (2.3%) VDZ patients and never in UST patients.

Beside joint EIM, 2 patients developed EN, 1 PG and 1 episcleritis during VDZ treatment. Under UST treatment 1 patient developed EN. No patients developed new Sweet syndrome, scleritis nor uveitis.

Conclusion

No differences in the rate of new arthropathy onset were observed between VDZ and UST. In contrast, VDZ treatment did increase the risk of new onset arthralgia.