bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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

Abstract

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 &lt;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

Abstract

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

Abstract

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 &lt; .05) or SF/AP criteria (P &lt; .01/P &lt; .01), clinical response per CDAI criterion (P = .001/P &lt; .01), and enhanced clinical response per SF/AP criteria (P &lt; .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

Abstract

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&lt;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&lt;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&lt;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&lt;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&lt;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&lt;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

Abstract

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

Abstract

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

Abstract

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.