bluuebunny/crossref_metadata_2025 huggingface dataset:
P155 Evaluation the role of interleukin-22 in inflammation related intestinal fibrosis: its potential influence on gut microbiota or immune system
Authors: Bai X , Runing Z , Hong Y
Published: January 2024

Background

The role of interleukin-22 (IL-22) in inflammation-related intestinal fibrosis remains largely unknown. Previous studies considered it as a double-edged sword between anti-inflammation and fibro-genesis in a tissue-specific manner. Therefore, we aimed to investigate the role of IL-22 in colonic fibrosis formation under inflammation.

Methods

Paraffin-embedded specimens of the colon from patients with CD undergoing surgery were obtained for Masson staining and IL-22 immunohistochemistry. In vivo, male C57B6/J mice aged 8 weeks were divided into the DSS group, DSS+IL-22 group, and control group. The two DSS groups were fed with 2% DSS for 7 days and distilled water for 14 days, repeating three times. Mice were given rIL-22 (200 ng/mouse) or phosphate-buffered saline intraperitoneally at 0, 2, 4, and 6 days after DSS administration. Colonic bacterial 16S rRNA gene sequencing assay and RNA sequencing of colon tissue were performed. In vitro, the DLD-1 cells were stimulated by LPS and treated with different gradients of rIL-22 before the scratch wound-healing migration assay.

Results

A positive correlation between IL-22 expression and Masson staining area was observed in the surgical specimen from CD patients (R2=0.7473) and IL-22 expression was higher in CD patients with intestinal stricture. In animal experiments, the colonic fibrosis model was successfully created and confirmed by Masson’s staining. Notably, the DSS+IL-22 group exhibited a slightly shortened colon length, greater weight reduction, and higher histopathology score than the DSS group at sacrifice. The injection of rIL-22 restored colonic microbiota abundance, notably by reducing Clostridium-sensu-stricto-1 and increasing Lachnospiraceae_NK4A136 and Turicibacter. A total of 278 genes were differentially expressed in the DSS+rIL-22 vs DSS group. We figured out that the 48 upregulated genes were mainly enriched in extracellular function, muscle contraction, and biosynthesis. The 230 downregulated genes were mainly enriched in immune response and pathway response to pathogens. The further immunoinfiltration analysis showed increased aggregation of marginal zone B cells but less infiltrated innate lymphoid cell group 1, natural killer T cell, and effector memory T cell after DSS treatment. In vitro, with longer stimulation time, the higher dose of rIL-22 induced a greater percentage of wound healing under LPS-induced inflammation.

Conclusion

We primarily revealed the potential positive correlation between IL-22 and colonic fibrosis from several aspects. The underlying mechanisms may be related to the influence on microbiota abundance classical pro-inflammatory pathways like TNF pathway and NLR pathway, immune cells or pericytes.
P162 The Biosimilar Switch: IBD nurse's experience in Our Lady of Lourdes Hospital
Authors: McMahon S
Published: January 2024

Background

A biological medication contains an active substance that is produced from a biological source such as living cells, hormones or enzymes. The active substance in a biological medicine is what makes the medicine work. Biological medicines are also called biologics. A biosimilar medicine is a biological medicine that is developed to be highly similar to an existing biologic but they are not identical and so cannot be considered to be generics. Biosimilars were introduced in Ireland in 2014. In 2018, Our Lady of Lourdes Hospital commenced a procurement programme to decide which Infliximab biosimilar to switch our patients to. This process would allow for a huge cost-saving to the hospital budget and also allowed for the allocation of a whole-time clinical nurse specialist to add the IBD nursing team. The infliximab biological switch was then carried out starting in October 2019.

All patients received a letter explaining the switch and a booklet to explain the meaning of biosimilars. The patients were then either phoned or spoken to in person by either the IBD nurse or a GI pharmacist, and any questions or concerns addressed.

Methods

A patient satisfaction survey was sent to each patient 6 months after the switch. Each questionnaire was sent with a prepaid return envelope. The questionnaire consisted of 7 questions with tick box answers.

1. Gender?

2. Age?

3. Did you receive a letter and information booklet in the post prior to the day of your infusion switch.

4. Did you get the opportunity to talk to someone on the phone prior to your infusion?

5. Did you get the opportunity to speak to a nurse or pharmacist on the day of your infusion? If so who?

6. Were you given a named person to contact if you had any issues after our first infusion?

7. Were you happy with the overall experience of the infliximab biosimilar switch?

Results

86 patients were switched from the originator to the biosimilar Flixabi. 22 responses were received.

1. 11 male; 11 female

2. Age 16-19 - 2; 20-29 - 1; 30-39 - 4; 40-49 - 4; 50-59 - 9; 70-79 - 1; preferred not to answer - 1.

3. 20 received the letter and booklet; 2 did not.

4. 15 spoke to someone on the phone; 6 did not and 1 could not remember.

5. 22 - spoke to a nurse; 0 - pharmacist.

6. 20 - yes; 2 - no.

7. 21 - yes; 1 - unsure.

Conclusion

Of the 86 patients who were switched 22 responded to the questionnaire. 21 patients were happy with their overall experience with how the switch was conducted.
P175 HucMSC-Exo ameliorate experimental colitis via modulating gut microbiota and metabolites
Authors: Wang C , Wang D , Luo Y , Guo J , Ma Z , Liang X , Sun D , Li C , Zhang X
Published: January 2024

Background

Gut microbiota and metabolites have been shown to influence the development of inflammatory bowel disease (IBD). Exosomes derived from human umbilical cord mesenchymal stem cells (HucMSC-Exo) have been identified as a promising biological therapy for the treatment of IBD. Previous studies have described that HucMSC-Exo could modulate gut microbiota. However, the mechanism remains unclear. Here, we explored the role of gut microbiota and metabolites in HucMSC-Exo-mediated amelioration of experimental colitis.

Methods

Dextran sulfate sodium (DSS) was used to induce colitis. The role of HucMSC-Exo were assessed in colitis mice. Fecal microbiota transplantation (FMT) and sterile fecal filtrate gavage were employed to evaluate the effect of gut microbiota and metabolites. Gut microbiota and metabolites were analyzed through 16S rRNA sequencing and metabolomic profiling. The proportion of CD4+ T cells were phenotyped by multicolour flow cytometry.

Results

HucMSC-Exo treatment alleviated colon inflammation by regulating flora composition, significantly up-regulated the levels of bacteria such as Bacteroides, Parabacteroides distasonis, and Tannerellaceae. Meanwhile, HucMSC-Exo transformed metabolite short-chain fatty acid (SCFA) profiles, particularly increased butyrate level. Additionally, HucMSC-Exo selectively up-regulated the frequencies of regulatory T (Treg) cells as well as down-regulated the ratio of T helper type 17 (Th17) cells in colonic lamina propria to maintain intestinal immune homeostasis and repaired the colonic mucus barrier. FMT and sterile fecal filtrate gavage were conducted to confirm the above mechanism. Microbiota from HucMSC-Exo-treated mice alleviated the colitis over microbiota from DSS-treated mice. Sterile fecal filtrate from HucMSC-Exo-treated mice and butyrate induced similar beneficial outcomes, such as improved the Th17/Treg balance and repaired the colonic mucus barrier. Collectively, HucMSC-Exo ameliorate colitis by directly modulating gut microbiota and metabolites.

Conclusion

HucMSC-Exo ameliorated experimental colitis via directly modulating gut microbiota and metabolite butyrate, which could regulate CD4+T cells homeostasis and repair colonic mucus barrier. The findings demonstrated the HucMSC-Exo as a potential gut microbiota and metabolites modulator to treat IBD.
P177 Beta-CGRP in inflammatory bowel disease: a protective neuropeptide of the gut
Authors: Pascual M , Gárate G , Serrano M S , González-Quintanilla V , García M J , Castro Senosiain B , Crespo J , Pascual J , Rivero Tirado M
Published: January 2024

Background

Experimental models indicate that beta calcitonin gene-related peptide (beta CGRP), libertated by enteric neurons, has a potential role on gastrointestinal mucosa homeostasis, but its real role is not well profiled. We measured beta-CGRP circulating levels in a cohort of subjects with a recent diagnosis of inflammatory bowel disease (IBD), to assess the potential role of this neuropeptide in its pathogenesis.

Methods

Morning serum beta-CGRP levels were measured by ELISA (CUSABIO, China) in 96 consecutive patients recently diagnosed of IBD patients (< 1 year) and compared with those belonging to 50 matched healthy controls (HC) and 50 chronic migraine (CM) patients matched by age and sex. We only allowed treatment with either steroids or mesalazine, and registered cardiovascular comorbidities, autoimmune concomitant diseases or extraintestinal manifestations. Statistical analysis was made using SPSS®.

Results

Beta CGRP concentrations were lower in IBD patients (3.1±1.9 pg/mL; 2.9 [2.4-3.4] pg/mL) when comparted to HC (4.7±2.6; 4.9 [4.0-5.8] pg/mL; p<0.001) and CM patients (4.6±2.6; 4.7 [3.3-6.2] pg/mL; p<0.001). Respecting IBD subtypes, beta-CGRP levels were lower in ulcerative colitis patients (3.0±1.9pg/mL; 2.5 [2.1-3.4] pg/mL) as well as Crohn’s disease patients (3.3±2.0 pg/mL; 3.2 [2.4-3.9] pg/mL) to those of HC (p<0.01 and p<0.05, respectively) and CM (p<0.01 and p<0.05, respectively). Beta-CGRP levels in CM did not differ to those with HC (p=0.92).

There were no significant differences when patients were classified by presence/absence of cardiovascular risk factors (yes: 3.1±1.7 pg/mL; no: 3.2±2.1 pg/mL; p=0.93); autoimmune comorbidities (yes: 3.4±1.4 pg/mL; no: 3.1±2.0 pg/mL; p=0.24); mesalazine treatment (yes: 3.1±1.9 pg/mL; no: 3.2±1.9 pg/mL; p=0.91); or steroid treatment (yes: 3.0±1.9 pg/mL; 3.2±1.9 pg/mL; p=0.52). Main characteristics and main results are exposed in table 1 and figure 1.

Conclusion

The reduction in serum beta-CGRP concentrations y patients with recent diagnosis of IBD, compared to two control groups, strongly supports a role for this neuropeptide in the pathophysiology of the disease since its early stages. This decrease was found in both IBD subtypes. Our data indicate a protective role of beta-CGRP in the homeostasis of the gastrointestinal tract.

This study has been co-funded by Instituto de Salud Carlos III (ISCIII) through the project PI20/01358 and by Fondos Europeos de Desarrollo Regional (FEDER), "Una manera de hacer Europa".
P194 Health-related quality of life and fatigue in newly-diagnosed inflammatory bowel diseases: findings from a prospective population-based inception cohort, IBD Prognosis Study
Authors: Attauabi M , Roager Madsen G , Bendtsen F , Seidelin J , Burisch J
Published: January 2024

Background

Patients with inflammatory bowel diseases (IBD) often experience impaired quality of life (QoL) and fatigue. In the current study, we aimed to investigate QoL and fatigue at the time of IBD diagnosis and determine their association with the disease presentation.

Methods

Incident adult patients (≥18 years old) with newly diagnosed ulcerative colitis (UC) or Crohn’s disease (CD) according to the Copenhagen IBD Criteria were included in the IBD Prognosis Study, a prospective, population-based, inception cohort representing approximately 20% of the Danish population (1.1 million). QoL was assessed using EQ-5D-5L and Short inflammatory Bowel Disease Questionnaires (SIBDQ), while fatigue was assessed using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scale. A severe disease presentation was defined by the need for glucocorticoids, immunomodulators, biologics, or surgery within three months of disease. Multivariable logistical regression analyses were conducted by adjusting for gender, age, and disease phenotype.

Results

Out of the original cohort, 203 (65.9%) and 116 (57.7%) patients with incident UC and CD, respectively, responded to the questionnaires without differences between responders and non-responders.

The mean EQ-5D-5L index values were significantly lower in patients with UC (0.82, SD 0.17) and CD (0.79, SD 0.23), compared to the Danish background population (both p<0.001). The difference between UC and CD was also statistically significant (p<0.001). Further, more than every third of patients reported severely reduced SIBDQ (UC 29.6%, CD 43.1%, p=0.04).

Severe fatigue was experienced frequently at the diagnosis (UC 26.1%, CD 30.2%, p=0.43), and was more common compared to the control group (means: UC 37.2 (SD 12.0), CD 35.3 (SD 11.5), control group: p<0.001).

Female gender and extensive UC were independently associated with severely impaired SIBDQ and fatigue in patients with UC, while EIMs were associated with both outcomes in UC and CD (Table 1). Finally, severely reduced SIBDQ and severe fatigue were independently associated with a severe disease presentation, as well as IBD-related hospitalization specifically, in both UC and CD (Figure 1).

Conclusion

In this prospective population-based inception cohort of newly diagnosed IBD, we found a high proportion of patients with severely impaired generic QoL, SIBDQ, and fatigue compared to healthy controls. This study emphasizes the importance of addressing these negative symptoms in patients with IBD and their prognostic impact on the disease presentation.

Ref:

1. Jensen MB et al., Scand J Public Health. 2023. doi: 10.1177/14034948211058060.

2. Montan I et al., Value Health. 2018. doi: 10.1016/j.jval.2018.03.013.
P201 Deep learning and minimally invasive inflammatory activity assessment: development and score correlation of a pan endoscopy convolutional network
Authors: Cardoso P , Mascarenhas M , Afonso J , Ribeiro T , Mendes F , Martins M , Andrade P , Cardoso H , Mascarenhas Saraiva M , Ferreira J , Lopes S , Macedo G
Published: January 2024

Background

Capsule endoscopy (CE) is a valuable tool for assessing inflammation in patients with Crohn's disease (CD). The current standard for evaluating inflammation are validated scores like (and clinical laboratory values) like Lewis score (LS), Capsule Endoscopy Crohn's Disease Activity Index (CECDAl) and ELIAKIM. Recent advances in artificial intelligence (Al) have made it possible to automatically select the most relevant frames in capsule endoscopy. In this study, our objective was to develop an automated scoring system using CE images to objectively grade inflammation.

Methods

Pan-enteric CE videos (PillCam Crohn's) performed in CD patients between 09/2020 and 01/2023 were retrospectively reviewed and LS, CECDAl and ELIAKIM scores calculated. We developed a convolutional neural network based automated score consisting in the percentage of positive frames selected by the algorithm (for small bowel and colon separately). We correlated clinical data and the validated scores with the artificial intelligence generated score (AIS).

Results

A total of 61 patients were included. The median LS was 225 [0-6006], CECDAI was 6 [0-33], ELIAKIM was 4 [0-38] and SB_AIS was 0.5659 [0-29.45]. We found a strong correlation between SB_AIS and LS, CECDAl and ELIAKIM scores (Pearson's r= 0.751, r= 0.707, r= 0.655, p =0.001). We found a strong correlation between LS and ELIAKIM (r= 0.768, p = 0.001) and very strong correlation between CECDAl and LS (r= 0.854, p = 0.001) and CECDAl and ELIAKIM scores (r= 0.827, p = 0.001).

Conclusion

Our study showed that the Al-generated score had a strong correlation with validated scores indicating that it could serve as an objective and efficient method for evaluating inflammation in CD patients. As a preliminary study, our findings provide a promising basis for future refining a CE score that can accurately correlate with prognostic factors and aid in the management and treatment of CD patients.
P203 Surveying outcomes of service user experience on the effects of emotional well-being and schooling in paediatric IBD (PIBD) patients in a tertiary PIBD centre
Authors: Lashley C , Buckingham R , Huggett B , Sawney T , Chadokufa S , Kiparissi F , Elzein A
Published: January 2024

Background

We conducted a prospective survey with our PIBD patients and parents seeking outcomes in accordance with our ICN- Improve Care Now participation goals to ‘Improve and optimize the care of children and teens with IBD in underserved and underrepresented populations by addressing healthcare disparities’.

Methods

We sent out a survey to our PIBD patients focusing on their overall satisfaction with the service we deliver in relation to their emotional wellbeing and schooling. We prospectively sent this to our patient cohort of 280 PIBD patients, collecting both quantitative and qualitative data.

Results

76/280 patients and parents (27%) responded, of whom 60/76 (79%) completed the entire survey. Of those responders 45 (75%) were mothers speaking on the behalf of their children aged 5-12 years (n=20 patients). 4 (7%) patients completed the survey themselves, of whom 3 (75%) were aged between 12-18 years. 39 (65%) parents and patients were overall satisfied that the IBD team spoke about getting the right help and support for the child at school. Although 39 (65%) of the patients strongly agreed that we provided information and materials on IBD and support, 21 (35%) of the patients felt that we did not provide the necessary information and education to schools to support them whilst at school.30 (50%) of the overall responders to the survey did not feel that the team had discussed with them the effect IBD has on their feelings and emotions.

Conclusion

Our survey has highlighted the need to provide more education at diagnosis and throughout patient care. This can be achieved by providing physical education packs for schools to be given to every child at diagnosis along with our already established welcome pack. We currently ask patients and families if they would like us to contact their school with information about IBD. This is something we can potentially change, by giving all patients a letter for school at diagnosis for them to give to schools. Caring for the patient’s emotional wellbeing is essential as part of delivering a holistic approach in the care we provide. Although we do offer referral to psychology at diagnosis, this should be followed up regularly and should be included as a standard when patients seen in clinics.
P204 Utility of Rotational Thrombo-Elastometry as an Objective Measure of Hypercoagulability in Patients with Ulcerative Colitis-A Prospective Case Control Study
Authors: Bharadwaj K P , Simon E G , Dave R G , Geevar T , Nair S C , Joseph A J , Dutta A K , Jaleel R , John A , Thomas A , Viswanath A
Published: January 2024

Background

Inflammatory bowel disease (IBD) has an increased risk of venous thromboembolism (VTE) with factors like hospitalization and surgery increasing this risk. Although few recent guidelines recommend anticoagulation thromboprophylaxis for hospitalised IBD patients, there is wide variation in reported practices for VTE prophylaxis. This study was aimed to evaluate Rotational Thrombo-Elastometry (ROTEM) for assessing blood coagulation status in ulcerative colitis (UC) and to evaluate the relationship between ROTEM, disease severity and response to treatment.

Methods

This was a prospective age- and sex-matched study with 60 patients each in UC and irritable bowel syndrome (IBS) groups, latter being controls. Clinical details, blood investigations including ROTEM and D-dimer were collected and analysed after taking informed consent. Hypercoagulable state was defined using Kaufmann’s classification. ROTEM parameters [clotting time (CT), clot formation time (CFT), alpha angle (AA), maximum clot firmness (MCF), maximum lysis (ML)] and D-dimer levels were compared between the two groups.

Results

Of the 60 UC patients (age: 38.6±11.64 years, 44 males); 15(25%) were in remission, 18(30%), 17(28.3%) and 10(16.7%) had mild, moderate, and severe disease respectively. The UC group had significantly more hypercoagulable ROTEM than the control group (66.7% vs. 36.7%, p=0.001). Hypercoagulable ROTEM was found in 9(60%), 8(44.4%), 14(82.3%) and 9(90%) of those in remission, with mild, moderate and severe UC respectively.

Compared to controls; CT [292.36±70.45 vs 337.56±77.89, p=0.001], CFT [103.15±30.31 vs 128.61±40.18, p=0.0001], AA [69.88±5.19 vs 65.36±6.4, p=0.00004], MCF [65.75±5.64 vs 63.25±4.43, p=0.008] and D-dimer levels [329(63-2358) vs 145.5(54-1304), p=0.00001) were significantly abnormal in UC group. Among UC patients with mild, moderate and severe disease; only CFT, AA and D-dimer were significantly different between the groups. There was no significant difference in ROTEM values and D-dimer level in patients with severe UC after one week of treatment.

On univariate analysis; partial Mayo score [OR: 1.49, 95% CI: 1.04-2.12, p=0.028], serum albumin [OR: 0.32, 95% CI: 0.10-0.98, p=0.04], hemoglobin [OR: 0.59, 95% CI: 0.40-0.86, p=0.007], and platelets [OR: 1, 95% CI: 1.01-1.02, p=0.035], were predictors of hypercoagulable state in active UC. On multivariate analysis; only haemoglobin [OR: 0.61, 95% CI: 0.38-0.98, p=0.04] was found to be significant independent predictor.

Conclusion

UC patients had hypercoagulable ROTEM regardless of activity of inflammatory process. The degree of hypercoagulability increased with disease activity. Low haemoglobin was found to predictive of hypercoagulable state in active UC patients.
P206 Metabolomic predictors of response to vedolizumab in Inflammatory Bowel Disease
Authors: Reider S , Watschinger C , Koch R , Tilg H , Moschen A
Published: January 2024

Background

Therapeutic options for patients with IBD have increased substantially over the last decades. Nevertheless, there is still an unmet need for optimization and more targeted allocation of therapies. Treatment with the anti-integrin-a4b7-antibody vedolizumab (VDZ) achieves clinical remission at week 6 in about 50 % of patients with CD and UC . Clinical decision support tools have been developed to help identify patients with a higher likelihood of responding to VDZ. Furthermore, exploratory studies reported associations of response to VDZ with differences in baseline multi-omics measurements. However, personalized selection of biologic therapies in IBD is not yet feasible in clinical practice.

Methods

IBD patients scheduled for therapy with VDZ (n=70, both biologic-naive and -experienced) were recruited and biosamples were obtained before initiating therapy. Response was assessed at week 20 using a multimodal definition incorporating clinical (Harvey-Bradshaw Index < 5 or partial Mayo Score < 2; no need for steroids after week 12) and biochemical criteria (faecal calprotectin < 250 µg/g). Metabolic assessment of baseline plasma samples was performed using a mass-spectrometry-based commercially available technique (Biocrates MxP Quant 500). Differences in absolute concentrations of 630 metabolites were measured and compared between patients responding and not responding to therapy using multivariate statistical approaches accounting for IBD subtype and patient sex.

Results

Significant differences between responders and non-responders to VDZ in the baseline concentrations of three metabolites were detected. These included acylcarnitine (HMDB00062) and a ceramide species (HMDB0004950) which were lower in patients who would respond to VDZ. Conversely, N-methylglycine (HMDB00271) was elevated in responders to VDZ. Additionally, dimensionality reduction using partial least-squares discriminant analysis (PLS-DA) revealed associations between the baseline abundance of certain primary and secondary bile acids and response to VDZ.

Conclusion

In this cohort of IBD patients undergoing therapy with VDZ, baseline host metabolomic variation was associated with response to therapy. Differences in metabolomic profiles are linked to established pathophysiologic processes in the intestine and IBD and represent intriguing possibilities for application in the context of a predictive biomarker signature for response to VDZ.
P207 It’s time to include capsule endoscopy to assess mucosal activity as part of the ‘treat-to-target’ strategy in Crohn’s disease: a real-life experience from a reference center in Argentina
Authors: Gómez E J , Gonzalez R A , Navar S M , Marturano M V , Conde Serra B , Smolarczuk A D , Mercado J D C , Baron P E , Pedreira S C
Published: January 2024

Background

The evaluation of the small bowel (SB) in known Crohn’s disease (kCD) has a significant impact on prognosis with potential therapeutic implications. The treat-to-target strategy is widely accepted, emphasizing that endoscopic healing is associated with improved long-term outcomes. Although capsule endoscopy (CE) shows promise in monitoring the small bowel in kCD, there is limited evidence supporting routine use. The aim of this study was to investigate clinical utility of CE to assess activity and extension of kCD and to evaluate whether the results of CE modify the therapeutic decisions.

Methods

We conducted a single center retrospective cohort study. Adult patients submitted to CE for kCD from Nov-2012 to Nov-2023 were included. Data on demography, previous research, medications for IBD and follow-up were analyzed. Univariate analysis was carried out to identify CE features associated with changes in therapeutic management. A p value <0.05 was considered statistically significant.

Results

A total of 572 CE protocols were performed, of which 76 were in kCD adult patients. The mean age was 36 years (range 16–76), 59% were males and median disease duration was 5.4 years. The CE reached the cecum in 97% and retention was observed in only two patients (2.6%) without necessity of surgical removal. Thirty two of 76 CE protocols (42%) had findings consistent with mucosal activity of CD. The lesions identified by CE included ulcers 30 (39%), erythema and villous edema 21 (28%), stenosis 2 (3%) and were distributed mainly in the distal part of the SB (3rd tertile) in 27 (35%), but in 15 (20%) the proximal SB (1st and 2nd tertile) was also affected. The mean Lewis Score (LS) was 576 (135-5392). Normal or clinically insignificant inflammatory changes (LS <135) ruled out SB mucosal activity in 44 (58%) patients. The results of the CE modified therapeutic decisions in 29 (38%) patients as follows: 17 were started new biological therapy and 7 were optimized. CEs consistent with mucosal inflammatory activity (LS ≥135) were more frequently associated with changes in therapeutic management (OR: 11, 95% CI 4-35, p: 0.04). When both magnetic resonance enterography (MRE) and CE were utilized to assess SB mucosal activity, diagnostic yields of MRE and CE were 45% and 42% respectively. But of the 8 patients with proximal SB affected in CE, only 1 showed inflammatory activity in the MRE.

Conclusion

In our cohort, CE in patients with kCD added valuable clinical information and had a great impact on therapeutic decisions. These results suggest that CE could be incorporated into the treat-to-target strategy for patients with CD. However, randomized controlled trials are required to confirm this recommendation.
P215 Mir-135b, an Early Biomarker of Sporadic and IBD-Related Colorectal Carcinogenetic Progression
Authors: Barberio B , Borga C , Giada M , Zingone F , Fassan M , Savarino E
Published: January 2024

Background

Although the rates of IBD-related-CRC are decreasing over time, CRC is still a leading cause of mortality and reason for colectomy in patients with IBD. Among the different cancer biomarkers, microRNAs (miRs) have emerged as noninvasive tools for diagnosis, monitoring, and prognosis in tissues and biofluids of patients with IBD. Therefore, we aimed to investigate the role of miRs in the development and natural course of IBD-related CRC, in order to identify potential early biomarkers for IBD-related CRC screening and progression.

Methods

The cases were retrospectively collected from the archives of the Surgical Pathology and Cytopathology Unit at the University of Padua. We analysed 9 miRs in colonic tissue specimens of IBD patients with adenoma or dysplasia, with IBD related-CRC, other than 2 control groups of patients with sporadic CRC and of healthy subjects (HC). In addition, we included tissue samples from a colonoscopy that patients with IBD with adenoma or dysplasia underwent some years before the development of mucosal lesions (from 2 to 5 years before), therefore without evidence of adenoma or dysplasia. Results were analyzed with ThermoFisher Connected™ Software and a p-value < 0.05 was considered significant.

Results

Compared to HC, all nine analysed miRs were significantly up-regulated in patients with sCRC, with IBD-related CRC and in IBD patients with adenoma. While, only 3 miRs (miR-135b, mir-21, miR-224) were significantly upregulated in IBD patients with dysplasia (and in their own controls) compared to HC (p<0.0001). Notably, no differences in miRs expression levels were found in patients with IBD-related CRC compared to those found in patients with sCRC. Among all miRs analyzed, only miR-135b and miR-21 resulted significantly up-regulated in patients with IBD. Considering the levels of miR-135b in the tissue samples of IBD patients, we observed an evident increasing trend going from tissue specimens without lesions to those with adenoma or dysplasia and then to those with neoplastic lesions. miR-21 was significantly upregulated in patients with IBD-related CRC compared to both IBD patients with adenoma and their own control samples from a previous negative colonoscopy (p=0.003 and p=0.006, respectively). Likewise, a significant difference in miR-21 levels was observed between patients with IBD-related CRC and those with dysplasia (p=0.02).

Conclusion

miR-21 and miR-135b are involved in the carcinogenesis process of patients with IBD. They could be potential candidate biomarkers for diagnostic purpose, prognostic and predictive stratification of patients.
P221 Intestinal ultrasound is predictive of disease relapse in asymptomatic Inflammatory Bowel Disease patients
Authors: Picker E A , Choi N K , Reddy N , Rubin D T , Krugliak Cleveland N
Published: January 2024

Background

Intestinal ultrasound (IUS) is a non-invasive, repeatable, and accurate disease monitoring modality that provides real-time assessment of inflammatory bowel disease (IBD). There are few data on the utility of IUS monitoring of asymptomatic patients. We assessed the ability of IUS to predict disease relapse in asymptomatic patients.

Methods

We maintain a prospectively maintained registry and database of IUS cases at our institution. We used this database to perform a retrospective analysis of IBD patients who were asymptomatic (HBI4, SCCAI2) but who had signs of active inflammation on IUS, defined by bowel wall thickness (BWT) > 3mm and/or colour Doppler signal (CDS) (modified Limberg score (mLimberg) > 0). We assessed the prevalence and time to clinical (symptomatic) relapse (HBI>4, SCCAI>2). IUS parameters and treatment change (defined as addition of steroids, immunomodulators, treatment escalation, therapy cycle or swap) were evaluated as predictors of disease relapse.

Results

40 patients (47 CD, 5 UC, 1 IBD-U; 53 IUS exams) were included. 10 patients (18.9%) relapsed within an average of 107.0 (±108.2) days. The relapsed group had a mean BWT of 4.5 (±0.3) mm vs. 3.9 (±0.5) mm in the non-relapsed group (p = 0.112), and a mean mLimberg of 1.7 (±0.3) vs. 1.3 (±0.1) (p = 0.503). Of the 53 IUS exams included in this study, 40 exams resulted in treatment change after the IUS (28 due to IUS findings alone, 12 due to other indications at a later time including elevated faecal calprotectin (FCP), breakthrough symptoms, drug level, perianal symptoms, psoriasis, allergic reaction, and bowel obstruction). Of the 40 patients who had treatment change (including dose escalation (n=16), dose de-escalation (n=4), therapy cycle or swap (n=14), or addition of steroids (n=5) or immunomodulators (n=1)), 9 (22.5%) experienced a clinical relapse, and of the other 13 patients who did not have a treatment change, 1 (7.7%) experience a clinical relapse (p = 0.257).

Conclusion

Silent inflammation identified by IUS in asymptomatic patients is associated with disease relapse in nearly 20% of patients within an average of 3.5 months. The degree of inflammation by BWT and CDS was numerically higher in the relapse group compared to those who did not relapse, although this was not statistically significant. The treatment changes incorporated in this cohort did not lead to lower rates of disease relapse. However, these findings demonstrate the prognostic value of silent inflammation as detected by IUS and the need for future prospective treat-to-target type studies using IUS.
P225 Mucosal transcriptomic profiles associated with clinical response in patients with Ulcerative Colitis receiving filgotinib
Authors: Magro F , Feagan B G , Rogler G , Peyrin-Biroulet L , Bauer Y , Cougnaud L , Oortwijn A , Randall M , Rudolph C , Reinisch W
Published: January 2024

Background

Filgotinib (FIL) is an oral, once-daily, JAK1 preferential inhibitor approved for the treatment of Ulcerative Colitis (UC). In the phase 2b/3 SELECTION trial (NCT02914522), FIL had a high level of efficacy in inducing and maintaining histological remission and endoscopic response, relative to placebo (PBO). Here, we described the changes in the mucosal transcriptomic profiles associated with histologic and endoscopic responses following FIL or PBO treatment.

Methods

Patients with moderately to severely active UC were enrolled into one of two cohorts (biologic-naive or biologic-experienced) and randomized 2:2:1 to receive FIL 200 mg (FIL200), FIL 100 mg (FIL100) or PBO from baseline to week 10. RNA was extracted from colon biopsies collected at baseline and week 10, and RNA sequencing (RNA-seq) was performed according to standard protocols. Clinical responses of interest included histological remission (assessed by categorical Geboes score) and endoscopic response (both defined in Figure legend) at week 10.

To assess transcriptional variability, RNA-Seq data were analyzed by a spectral map separately for baseline and week 10. Differentially expressed gene (DEG) analysis was used to explore differences in transcriptional expression for multiple comparators: from baseline to week 10 between patients with or without clinical response, separately, by treatment arm and cohort.

Results

RNA-Seq data were available for 1086 patients across treatment arms at baseline and/or week 10. Spectral map analysis showed no visual association between baseline transcriptional variability (principal component [PC]1: 26%) and achieving either histological remission or endoscopic response at week 10, nor with the treatment arm. At week 10, the main source of transcriptional variability (PC1: 32%) was visually associated with achieving histological remission or endoscopic response, but not with the treatment arm. From the DEG analysis, more significant genes were associated with histological remission in the FIL200 arm compared with either the FIL100 or PBO arms, especially for biologic-naive compared with biologic-experienced patients (Figure A). Furthermore, more significant genes were associated with endoscopic response in the FIL arms compared with PBO (Figure B).

Conclusion

The overall transcriptional response associated with histological remission or endoscopic response was greater in FIL treatment arms than the PBO arm. This transcriptional response differed between biologic-naive and experienced patients, suggesting that transcriptional changes associated with clinical response were influenced by both FIL treatment and previous biologic use. Preliminary data suggests these transcriptional changes occur in pathways related to UC pathogenesis.
P227 The learning curve for using intestinal ultrasonography
Authors: Bezzio C , Saibeni S , Vernero M , Furfaro F , Monteleone M , Ribaldone D , Fiorino G , Brinch D , Friedman A B , Scalvini D , Maconi G
Published: January 2024

Background

The use of intestinal ultrasonography (IUS) is recommended for suspected or known inflammatory bowel disease (IBD), but the technique is challenging to learn. This prospective study examined how the accuracy of IUS increases with operator experience (“learning curve”) and if prior abdominal ultrasound experience facilitates the learning process.

Methods

The study included five gastroenterologists: four trainees and one expert sonographer. Two trainees had limited abdominal ultrasound experience (< 50 exams) and two had extensive experience (> 500 exams); none had IUS experience. The trainees received an eight-hour course on IUS and one week of hands-on training with the expert sonographer on approximately 50 IUS exams. Thereafter, over a four-week period, each trainee performed 99 examinations and reported four IUS findings. The expert sonographer repeated the exam, and concordance (k) between the expert and trainees was assessed in three consecutive testing periods of 33 exams each.

Results

A progressive improvement in concordance was observed for all IUS findings from Period 1 to Period 3, overall and for both groups of trainees, although those with experience in abdominal ultrasound had faster learning curves. The minimum number of examinations required to achieve concordance with the expert operator (after the initial 50 exams) for detecting increased bowel wall thickness was 34 and detecting bowel dilatation was 29. However, a minimum of 47 examinations was necessary to achieve concordance for detecting intra-abdominal complications, considered an advanced IUS competence. The number of examinations required to achieve concordance was higher for trainees without than with abdominal ultrasound experience.

Conclusion

Basic competence in IUS can be acquired with relatively few examinations, while advanced competence requires more extensive training, particularly for gastroenterologists without abdominal ultrasound experience. These findings have implications for the development of training programs and the establishment of proficiency levels in IUS.
P228 Predictors of steroid therapy refractoriness in admitted Acute Severe Ulcerative Colitis patients
Authors: Abdelmeguid A , Elbanna A , Ibrahim F A E , Whitehead E , Fitzgerald A , Turnbull J , Robertson H , Elsheikh W , Ellakany A , Sebastian S
Published: January 2024

Background

One third of acute severe ulcerative colitis (ASUC) patients are steroid refractory and require colectomy or rescue therapy. Risk stratifying ASUC patients who are steroid non responders to facilitate early initiation of rescue therapy or consideration of colectomy remains an unmet needs in the management of ASUC.

Methods

Records of admitted patients with ASUC over a 5-year period were included. Clinical (diagnosis history, previous medications, disease extent) laboratory (FBC, CRP and albumin at admission and day 3, CRP/albumin ratio) and endoscopic scores (Mayo and UCEIS) at admission were recorded. The primary outcome was response to IV steroids. Secondary outcomes were the proportion of patients requiring re admission or initiation of advanced therapy (biologics or small molecules) within 1 year.

Results

Our study included 103 ASUC patients (44/103 male, median age: 41 years(Min:18, Max:84, range:66, IQR:27). 53 patients were steroid responders, 50 patients were non responders. Among non responders 48 had rescue therapy and 5 had colectomy at index admission (3 after rescue therapy and 2 without rescue therapy). There was no statistical significant difference between both groups in age, gender, disease extent and duration, haemoglobin level, platelets, CRP level, Mayo score of sigmoid, UCEIS score of rectum and sigmoid. There was statistically significant difference between both groups in being on oral steroids at entry, duration of hospital stay, albumin at admission, day 3 albumin, CRP/Albumin ratio at day 3 and Mayo score of rectum.

On univariate analysis, albumin at admission and at day 3, CRP/Albumin ratio at day 3 and being on oral steroids at entry predicted non response to steroids while on multivariate analysis, being on steroids at admission was the only factor independently associated with steroid non-response(OR= 4.695, 95% CI: 1.79-12.34, P=0.002).

Among steroid responders, 13(24.5%) required readmission within 1 year while only 3(6.7%) of the steroid non responders who received rescue therapy required readmission.

Twenty five(47.2%) of steroid responders required initiation of advanced therapies within 1 year of index admission while 28 didn’t. Patients who required initiation of advanced therapy have statistically significant lower hemoglobin and higher platelets than who didn’t. Hemoglobin was the only factor to predict initiation of advanced therapy in multivariate regression analysis(-0.043, P=0.029)

Conclusion

Being on oral steroids at admission for ASUC can predict non response to IV steroids with majority may benefit from upfront advanced therapies at Day 1 of admission. Nearly half of the admitted ASUC patients who respond to steroids require treatment escalation to advanced therapies at 1 year.
P242 Immune-cell specific biomarker of early intestinal inflammation: Neutrophil elastase degraded fragment of type III collagen is elevated in patients with Inflammatory Bowel Disease
Authors: Tsapanou Katranara T , Pehrsson M , Alexdottir M S , Domislović V , Krznarić Ž , Ainsworth M A , Boye T L , Steenholdt C , Bay-Jensen A C , Karsdal M A , Mortensen J H
Published: January 2024

Background

Inflammatory Bowel Disease (IBD) is characterized by epithelial barrier injury of the gastrointestinal (GI) tract. The disease course encompasses abnormal immune responses and excessive secretion of proteases from immune cells. Neutrophils are the first to migrate into the inflamed interstitial matrix, where type III collagen is significantly deposited. Detection of mucosal inflammation in early stages is crucial to prevent cumulative clinical damage, as a delayed diagnosis can hinder effective treatment. Thus, we aimed to develop a biomarker that reflects early intestinal inflammation prior to it becoming medically evident; allowing us to distinguish patients that would respond to an anti-inflammatory treatment.

Methods

A competitive enzyme-linked immunosorbent assay targeting a human neutrophil elastase derived fragment of type III collagen was developed (C3-HNE). The validation was conducted by assessing its dilution recovery, matrix spiking, interference, and inter- and intra-assay variation. The biological relevance was evaluated in commercial samples, one preclinical, and two clinical studies. In the preclinical study, C3-HNE was measured in serum samples from a dextran sodium sulfate (DSS)-induced colitis rat model. In the commercial samples and clinical cohorts, C3-HNE was measured in serum from patients with IBD and healthy donors (HD). To compare the biomarker levels between groups, two-way ANOVA with a Fisher's LSD, and Mann-Whitney U-tests or Kruskal-Wallis (Dunn’s corrected) were conducted.

Results

The novel biomarker C3-HNE was successfully validated, resulting in a technically robust assay with acceptable technical parameters (Table 1). In the preclinical study, the analysis revealed significant difference in the C3-HNE levels between the control and DSS groups on day 4 (p=0.01) (Figure 1A). Additionally, C3-HNE was released earlier (day 1) in the timeline than the elevation of the current disease activity (DAI) score (day 7) (Figure 1A-B). In both clinical cohorts and commercial samples, C3-HNE levels were significantly higher in patients with Crohn's disease (CD), ulcerative colitis (UC) and IBD than in HD (p<0.01, p<0.05 and p<0.05) (Figure 1C-E). Based on the ROC analysis, the biomarker can significantly discriminate between HD and CD, UC or IBD (Table 1).

Conclusion

C3-HNE is elevated in patients with CD, UC and IBD compared with HD. Furthermore, C3-HNE reflects early stages of clinically apparent mucosal damage during experimental colitis. This biomarker holds the potential to identify early mucosal damage or acute inflammation in the GI tract; nevertheless, additional studies are needed to evaluate its clinical validity.
P244 The first step to IBD prevention exploring rate of pre-clinical inflammation in subset of asymptomatic subjects at risk of IBD: screening stage of the PIONIR trial
Authors: Kenigsberg S , Turpin W , Lee S H , Ledder O , Shimhlash Y , Griffiths A , Huynh H Q , El-Matary W , Otley A , Avni-Biron I , Jacobson K , Panaccione R , Bitton A , Croitoru K , Turner D
Published: January 2024

Background

With the increasing prevalence of inflammatory bowel diseases (IBD) globally, it is necessary to start focusing efforts on prevention of the diseases. The Genetic, Environmental, Microbial (GEM) study identified biological signatures predictive of developing IBD in first degree relatives (FDR) of patients with Crohn’s disease (CD). The ongoing PIONIR (Preventing IBD ONset in Individuals at Risk) study is a randomized controlled trial aimed to explore whether the Tasty & Healthy diet can change the CD-risk associated biomarkers of healthy FDRs who are particularly high risk of developing CD, originally followed in the GEM cohort. We report here the rate of IBD and pre-IBD inflammation in a subset cohort.

Methods

Subjects, 6-35 years of age from the GEM cohort who were identified by a combination of predictors at recruitment to GEM to have an increased risk for persistently elevated fecal calprotectin (FC) (i.e. Microbiome Risk Score (MRS), increased gut permeability and/or multiplex family of CD) were approached to perform a new FC test. Subjects who had FC>70µg/g, confirmed by a second sample, were offered a panenteric video capsule endoscopy (VCE), but some elected to proceed to ileocolonoscopy instead.

Results

For the PIONIR recruitment, a total of 450 subjects were approached from 7 sites in Israel and Canada, of whom 183 consented and provided a stool sample for FC (Figure). FC was elevated in 57 (31%) subjects, confirmed by re-testing in 36 (20%); 25/36 underwent VCE/ileocolonoscopy (Figure). In total, 8 (4.4% of the screened cohort) had normal-appearing mucosa, in 10 (5.5%) there were non-specific mucosal changes (e.g. several erosions or erythema), 6 (3.3%) had ulcers compatible with CD and 1 (0.6%) was inconclusive. The median FC of those eventually diagnosed with CD (816 [IQR 361-1123) was higher than the remaining 30 without IBD with elevated FC (175 [111-281], p=0.003). FC>275µg/g was highly predictive of CD in the entire cohort (AUROC 0.97 (95%CI 0.93-0.99); sensitivity 83%, specificity 94%).

Conclusion

Preclinical mucosal inflammation in VCE/ileocolonoscopy was found in 18 of 183 (9.8%) screened subjects (i.e. elevated FC with either normal or nonspecific mucosal findings), 134 (73%) had normal FC and 11 (6%) with elevated FC had missing VCE/ileocolonoscopy data. Six had CD (3.3%, or 17% of the 36 with elevated FC). Detecting subjects at risk at their preclinical stages, possibly with FC>275µg/g, is the first necessary step in developing preventive strategies for IBD.