bluuebunny/crossref_metadata_2025 huggingface dataset:
P157 Serial daily recording of patient-reported outcomes (PRO2) might predict treatment change in the patients with Ulcerative Colitis.
Authors: Tsuchiya K , Nagahori M , Hanazawa R , Sasaki M , Sato H , Hirakawa A , Anzai T , Takahashi K , Kobayashi Y , Hibiya S , Takenaka K , Watanabe M
Published: January 2023

Background

Patient-reported outcome (PRO2) score composed solely of the stool frequency and bleeding components from partial Mayo (pMayo) score are used for the evaluation of clinical symptom in the patients with Ulcerative Colitis (UC). Although pMayo and PRO2 score also perform as well as the full Mayo score to identify the disease activity and clinical response, it is unclear whether serial daily PRO2 score are relevant in clinical practice. Moreover, its clinical significance for long-term outcome has not been established. The aim of this study istherefore to clarify the relationship between daily PRO2 records using a smart device application and prognosis.

Methods

This study was approved by the ethics committee in Tokyo Medical and Dental University (TMDU). The application was originally developed by the cooperation with TMDU and Hitachi ltd. Patients with UC input their symptoms by themselves in accordance with PRO2 once a day using the application on their smart device. The alert for their symptom exacerbation is set according to our logic. Patient's condition including alert status is confirmed by the doctor once a week using doctor’s PC. Medical information such as therapeutics and blood examination, was extracted from the electronic medical chart in the hospital. The application data was combined with medical information on a daily basis. We defined a start or change of the treatment with prednisone or biologics as treatment change for the outcome of this study. The difference of PRO2 score before the date of treatment change is calculated for each patient and the odds ratio (OR) and AUC of the ROC curve are estimated by univariate logistic regression analysis.

Results

From July 2020 to March 2022, 183 UC patients participated in this study. Mean age was 46.6 years. Male to female ratio was 81:102. Mean observation period was 346 days. The number of the patients with alert of symptom exacerbation averaged 5.79/week. There were 27 patients with treatment change during the period. PRO2 score in the patients with treatment change was significantly increased compared with the patients with no change in treatment. The OR [95%CI] of the PRO2 change from 90 days to 5 days before treatment change was 7.708 [2.713-21.902], the AUC [95%CI] was 0.872 [0.772-0.973], the OR [95%CI] of the PRO2 change from 10 days to 5 days was 3.309 [1.601-6. 841] and AUC [95%CI] was 0.679 [0.569-0.789].

Conclusion

PRO2 variation over 90 days was highly reliable for predicting treatment change. Further analysis will clarify the clinical significance of serial daily PRO2 score recording.
P166 Calprotectin in patients with perianal fistula: the CANALS study
Authors: Becker drs. M , Stevens T , de Voogd F , Wildenberg M , Gecse K , Buskens C
Published: January 2023

Background

Previous studies suggest that faecal calprotectin can be used to discriminate Crohn’s disease (CD) perianal fistulas from cryptoglandular (CG) perianal fistulas. The aim of this research was to prospectively validate these findings and further investigate local calprotectin production inside fistula tracts. The aim of the current study was to prospectively analyse the clinical value of calprotectin levels in both the faeces and the fistula tract.

Methods

In this prospective study, all consecutive patients with an active perianal fistula undergoing examination under anesthetics were included. Faecal and scraping calprotectin levels collected during surgery were measured. The primary objective was to differentiate between active CD perianal fistulas and CG perianal fistulas based on faecal calprotectin. Secondary outcome parameters were the levels of local calprotectin in fistula tracts and the correlation with fistula characteristics and clinical prognostic parameters like the Geldof Classification system.

Results

Sixty-three fistula patients were included in this study (CD n=45; CG n=18). Faecal calprotectin values were significantly higher in CD patients compared to CG patients (396.8 [61.9-1136.8] vs. 47.3 [14.6-233.6] ug/g, p=0.004). The Area Under the Curve (AUC) was 0.733 (95% CI [0.644 to 0.903] with an optimal FC cut-off value of 344ug/g. Faecal calprotectin was not related to calprotectin levels in fistula scrapings which was not significantly different in CD and cryptoglandular fistulas (p=0.893). Calprotectin in fistula scrapings was also not related to fistula characteristics like number of tracts, duration of disease or (previous) seton drainage. However, a significant correlation was found between scraping calprotectin and fistula disease severity and prognosis as defined by a new Geldof classification system: Patients in group 2a (amenable for fistula repair) had significantly lower calprotectin levels (140 [31.0-149.0])ug/g) when compared to class 2b (symptom control) (706 [198.5 – 1936]ug/g, p=0.054) and class 2c (gradually debilitating disease) (3464.0 [328.5-5692.0]ug/g, p=0.008). Patients in class 3 (exhausted perineum) had the highest calprotectin levels highest (5928.0 [2605.0-6000]ug/g).

Conclusion

CD and CG perianal fistulas can be distinguished by measuring faecal calprotectin levels. The difference can not be explained by local fistula calprotectin production as calprotectin in fistula scrapings is not predictive of CD. However, the results of this study suggest that scraping calprotectin levels may be used to classify fistula patients and predict outcome of fistula treatment.
P176 Clinical features of acute severe ulcerative colitis according to steroid dependency: A KASID multicenter study
Authors: Kim D H , Kim H S , Kim E S , Park S H , Kim S J , Kim K O , Lee Y J , Song E M , Kim D S ,   IBD Research Group in Korean Association for the Study of the Intestinal Diseases (KASID)
Published: January 2023

Background

Intravenous steroid therapy is the main initial treatment for acute severe ulcerative colitis (ASUC). However, steroid dependence in patients who were treated with intravenous steroid therapy for ASUC is not fully evaluated. We aimed to determine the prevalence and risk factors of corticosteroid dependence after treatment of ASUC.

Methods

Adult patients who were admitted for the treatment of ASUC satisfying Truelove-Witts criteria from January 2015 to December 2020 were included in the study. Steroid dependence was defined as a failure to taper steroids below 10 mg within 3 months from initiating intravenous therapy or relapse within 3 months after steroid discontinuation.

Results

Among a total of 140 patients who received intravenous steroids as initial treatment for ASUC, 105 (75.0%) showed a response while 35 (25.0%) were refractory to steroids. Of 105 patients who responded to intravenous steroid therapy, 21 (20.0%) showed steroid dependence during the follow-period. Demographic and clinical variables were not significantly different between steroid-dependent and steroid response groups. However, initial C-reactive protein (CRP) levels in steroid-dependent groups were numerically lower compared with those in the steroid response group with statistical significance (4.4 ± 4.6 mg/dL versus 7.0 ± 6.4 mg/dL, p = 0.04).

Conclusion

A total of 20.0% of responders to intravenous steroid treatment for ASUC had a steroid dependency during follow-up. The demographic and clinical features of ASUC according to the presence or absence of steroid dependency were similar. Initial CRP levels were low in patients with steroid dependence.
P179 Comparative benefit-risk profile of induction and maintenance therapy with upadacitinib versus placebo in patients with moderately to severely active ulcerative colitis
Authors: Blumenstein I , Xuan S , Panaccione R , Baert F , Barreiro-de Acosta M , Ye B D , Klaff J , Vladea R , Levy G , Holweg C T J , Sanchez Gonzalez Y , Dubinsky M C
Published: January 2023

Background

Upadacitinib (UPA) demonstrated efficacy and safety as induction and maintenance therapy for ulcerative colitis (UC) in Phase 3 trials U-ACHIEVE (NCT02819635) and U-ACCOMPLISH (NCT03653026). This post-hoc analysis aims to characterise the benefit-risk profile of UPA induction and maintenance therapy vs placebo (PBO) in patients (pts) with moderately to severely active UC based on a number needed to treat/harm (NNT/NNH) analysis.

Methods

Efficacy and safety data from the pooled intention-to-treat population of U-ACHIEVE and U-ACCOMPLISH trials were included. Pts received UPA 45 mg (UPA45) once daily (QD) or PBO for 8 weeks (induction trials). Clinical responders (per Adapted Mayo score) at Week 8 of induction were re-randomised to receive UPA 15 mg (UPA15) or 30 mg (UPA30) QD, or PBO in the 52-week maintenance study. The primary efficacy endpoint was clinical remission per Adapted Mayo score. Secondary outcomes are listed in Table 1 and safety outcomes are listed in Table 2. N, percentages, and outcome differences compared by Z test were reported. NNT/NNH was calculated as the inverse of the difference in proportions achieving efficacy/safety outcomes for UPA vs PBO. Positive NNT values indicate greater efficacy and negative NNH values imply lower safety risk for UPA vs PBO.

Results

A significantly greater proportion of pts achieved clinical remission at induction (UPA45 29.9% vs PBO 4.4%) and maintenance (UPA15 40.4%, UPA30 53.6% vs PBO 10.8%) with UPA vs PBO, as well as all secondary endpoints (all p<0.001; Table 1). The NNT for clinical remission at Week 8 was 4.0, ranging from 2.1 to 9.6 for secondary endpoints. At Week 52, the NNT for clinical remission was 2.4; NNTs for secondary endpoints ranged from 1.8 to 5.9 (Table 1). At Week 8, adverse events (AEs) were lower for worsening of UC for UPA45 vs PBO-treated pts and greater for creatine phosphokinase (CPK) elevation, acne, neutropenia, and lymphopenia (p≤0.01). At Week 52, AEs were lower for UPA15 and UPA30 vs PBO for worsening of UC, AEs leading to discontinuation (UPA15 only), and arthralgia (UPA30 only), and greater for CPK elevation, herpes zoster, hepatic disorder (UPA15 only), and neutropenia (UPA30 only) (p≤0.05; Table 2). All other AEs were similar between UPA and PBO. Among the safety outcomes significantly different between UPA and PBO, the NNH for UPA vs PBO ranged from –16.1 to 25.6 (Table 2).

Conclusion

This post-hoc Phase 3 analysis demonstrates greater efficacy and generally comparable safety of UPA vs PBO, indicating a favourable benefit-risk profile for UPA in pts with moderately to severely active UC.
P185 Global perception of normal life by healthcare professionals and IBD patients: mind the gap
Authors: Van Oostrom J , Anjie S , Braad M , Horrigan J , Karimi N , Adi B , Ganesh G , Yang S K , Lasa J , Broër C , de Kruif A , Olivera Sendra P , Ye B D , Banerjee R , Connor S , Siegel C , Peyrin-Biroulet L , Gecse K , D’Haens G
Published: January 2023

Background

For patients living with inflammatory bowel diseases (IBD), the ultimate treatment goal is “normal life”. However, no patient-reported outcome measurement (PROM) exists to measure the level of life normality in IBD. We previously asked patients across the world (5 continents) to identify and rank-order items important to their “normal life”. The top-25 ranked items are being used for subsequent PROM development. In this study, we aimed to compare the perception of healthcare professionals (HCP) and patients with IBD on normal life.

Methods

IBD patients without an ostomy, pouch or significant comorbidities were interviewed in their mother tongue in 5 continents about “normal life” using a semi-structured interview guide. All items indicated as important were extracted from translated transcripts using directed content analysis (1) until saturation of items occurred. Categorisation was guided by the Wilson’s & Cleary’s Quality of Life model. (2) Second, in an online Delphi procedure, interviewed patients and HCP from each participating centre scored importance of each item on a 0-10 scale. Items scored 7 or higher by >75% were considered important to the respective group. Patient-ranked items were then presented to a patient focus group to clarify wording and merge similar items. Items merged in the patient focus group were merged similarly in HCP rankings. Third, HCP- and patient-rankings were compared. We compared top-25 items selected for PROM development and top-3 items per category.

Results

45 CD and 40 UC patients spread over 6 countries were interviewed (median age 36, 56% male, 68% employed, median disease duration 7 years [IQR 4-15]) (table 1). Saturation occurred after 33 CD and 36 UC interviews, yielding 156 unique items. In the Delphi procedure, 54 patients considered 31 items important for normal life with IBD of which 25 remained after focus group discussion. 34 HCP (12 IBD nurses, 16 IBD gastroenterologists, 6 colorectal surgeons) considered 72 items important.

Top-25 rankings overlapped in 15 items between patients and HCP, being 5 of 12 physical, 1 of 4 activities, 2 of 3 social, 4 of 11 psychological items and 3 of 5 circumstances (table 2). Top-3 rankings per category overlapped in 2 physical, 1 activities, 2 social, 1 psychological items and 2 circumstances (table 3).

Conclusion

We identified discrepancies in the perception of normal life with IBD between patients living with IBD and healthcare professionals (HCP). Of top-25 selected items for PROM development, 15 items overlapped between patients and HCP. Of top-3 items per category, the least overlap was seen in activities and psychological items. PROM development and international validation is ongoing.
P187 Intestinal ultrasound is accurate for detecting intra-abdominal complications in Crohn’s disease: a meta-analysis
Authors: Pruijt M , de Voogd F , Montazeri N , Jamaludin F , D’Haens G , Gecse K
Published: January 2023

Background

The clinical course of Crohn’s disease (CD) is associated with development of complications including strictures and penetrating lesions such as fistulas and abscesses. Close disease monitoring and optimizing therapy can prevent these complications. Intestinal ultrasound (IUS) is a non-invasive cross-sectional imaging method ideal for frequent assessment of disease activity and intra-abdominal complications. In this meta-analysis we provide an updated assessment of the diagnostic accuracy of IUS and its advanced modalities in the detection of intra-abdominal complications in CD compared to endoscopy, MRI/CT, surgery and pathology.

Methods

We conducted a literature search in Pubmed/MEDLINE and EMBASE databases from 01-01-1970 up to and including 17-10-2022 for studies describing diagnostic accuracy of IUS in adult patients with CD related intra-abdominal complications. Quality of the included studies was assessed with the QUADAS-2 tool. A univariate random-effects model was used to calculate the diagnostic test accuracy variables, including the log diagnostic odds ratio and area under the pooled ROC (AUC for SROC). All data were calculated with 95% confidence intervals (CIs). Chi-squared (χ²) test was used to assess study heterogeneity with p < 0.05 indicating significant heterogeneity. Funnel plots were created to assess publication bias. All meta-analysis were performed using the R-package mada. We calculated pooled sensitivity and specificity in Meta-DiSc.

Results

We identified 1506 studies of which 68 were used for the systematic review. Twenty-three studies with 3863 patients were included in this meta-analysis with an overall moderate to high risk of bias. In total 6 meta-analyses were performed, both for conventional IUS (B-mode) and oral contrast IUS (SICUS) for diagnosing CD-related complications. Pooled overall log diagnostic odds ratio for strictures, fistulas and inflammatory masses by B-mode IUS were 3.56 (2,90-4.21), 3.84 (3.28-4.41) and 3.97 (3.30-4.64) and the AUC were 0.926, 0.896 and 0.960 respectively. Pooled overall diagnostic odds ratio for the diagnosis of strictures, fistulas and inflammatory masses by SICUS were 4.51 (3.28-5.73), 4.80 (3.46-6.14) and 5.46 (3.61-7.30) and the AUC were 0.955, 0.982 and 0.985, respectively. Significant heterogeneity was seen between studies reporting data on diagnosing strictures by B-mode IUS.

Conclusion

These results indicate that IUS is an accurate tool for the diagnosis of intra-abdominal complications related to CD. IUS as a non-invasive, point-of-care modality is recommended as the first-line imaging tool if there is a suspicion of CD-related intra-abdominal complications.
P189 Prospective Validation Study Regarding Disease Complications of the Toronto IBD Global Endoscopic Reporting (TIGER) Score in Ulcerative Colitis and Crohn’s Disease Patients
Authors: Zittan E , Levy M , Saban L , Vered S , Steinhart A H , Milgrom R , Gralnek I M , Silverberg M S , Zelber-Sagi S
Published: January 2023

Background

The recently developed TIGER endoscopy score was established to reliably describe disease severity as it can be utilized for both Ulcerative Colitis (UC) and Crohn’s disease (CD) patients.1 The aim of this study was to assess the TIGER score’s ability to predict outcomes regarding complications such as surgeries, hospitalizations, and drug or disease-related side effects in a sample of both UC and CD patients.

Methods

A cohort of 78 patients with UC (n=40) and CD (n=38) were included in a 52-week multiple visit prospective study. Each visit included patient interviews, IBD disk questionnaire, blood draws for C-reactive protein (CRP), and fecal calprotectin (FC). Endoscopy was performed at baseline. Baseline total TIGER scores were dichotomized as <100 (remission-mild activity) or ≥100 (moderate-severe activity) as a predictor of complications such as surgeries, hospitalizations, and side effects.

Results

At baseline, compared to patients with TIGER scores <100, UC patients with TIGER scores ≥100 had significantly higher CRP, FC, and IBD disk. In CD patients, at baseline, compared to patients with TIGER scores <100, patients with TIGER scores ≥100 had significantly higher CRP, FC, and IBD disk. In terms of hospitalizations, at 52-weeks, compared to patients with baseline TIGER scores <100, UC and CD patients with baseline TIGER scores ≥100 had a significantly increased likelihood of being hospitalized (p<0.02). More specifically, at 52-weeks, 38.5% and 34.5% of UC and CD patients with baseline TIGER scores ≥100 experienced at least one disease-related hospitalization, respectively. Comparatively, there were zero hospitalizations in UC or CD patients with baseline TIGER scores <100. In terms of surgeries, at 52-weeks, 0% and 11.1% of UC and CD patients with baseline TIGER scores <100 had surgery compared to 3.9% and 24.1% of UC and CD patients with baseline TIGER scores ≥100, respectively. In terms of side effects, at 52-weeks, compared to patients with baseline TIGER scores <100, UC and CD patients with baseline TIGER scores ≥100 had a significantly increased likelihood of reporting a side effect from both medications and the disease (p<0.006). More specifically, 0% and 11.1% of UC and CD patients with baseline TIGER scores <100 reported medication and disease side effects compared to 11.5% and 19.2% of UC and CD patients with baseline TIGER scores ≥100, respectively.

Conclusion

The TIGER endoscopic score demonstrates significant association with CRP, FC and IBD disk in both UC and CD patients. Moreover, the TIGER score can be utilized as a measure to predict the likelihood of UC and CD patients with moderate-to-severe disease burden experiencing a disease complications.

1. Zittan E, et al. J Crohns Colitis 2022;16:544-553.
P192 Comparison of Endoscopic Scoring System and Simplified Magnetic Resonance Index of Activity in Patients with Small Bowel Crohn’s Disease: Basis for Therapeutic Plan?
Authors: Na J E , Sung Noh H , Young-Ho K , Tae-Oh K , Sang-Bum K , Sung Hoon J
Published: January 2023

Background

The newly derived simplified magnetic resonance index of activity (MARIAs) has not been verified in comparison with balloon-assisted enteroscopy (BAE) for patients with small-bowel Crohn’s disease (CD). We studied the correlation of MARIAs with simple endoscopic score for Crohn's disease (SES-CD) of ileum based on magnetic resonance enterography (MRE) and BAE, respectively, in patients with small-bowel CD. In addition, we determined the impact of these tools on clinical decision-making.

Methods

Fifty patients with small-bowel CD who underwent BAE and MRE concurrently within three months from September 2020 to June 2021, followed by the reference date of December 2021, were enrolled. The primary outcome was correlation between the active score of ileal SES-CD (ileal SES-CDa)/ileal SES-CD and MARIAs based on BAE and MRE in segmented ileum. The active/severe disease index was set as ileal SES-CDa/ileal SES-CD of 5/7 and MARIAs of 1/2. The secondary outcome was the basis for step-up treatment.

Results

The ileal SES-CDa/ileal SES-CD and MARIAs showed strong associations (R=0.76, p<0.001/R=0.78, p<0.001). The AUROC of MARIAs for ileal SES-CDa ≥ 5 was 0.92 (95% CI: 0.88-0.97). The AUROC of the MARIAs for ileal SES-CD ≥ 7 was 0.92 (95% CI: 0.87-0.97). Among the 26 patients who experienced step-up treatment after BAE and MRE, 23 patients showed active disease on both BAE and MRE.

Conclusion

We validated the applicability of MARIAs compared to the BAE-based ileal SES-CDa/SES-CD. Assessment of disease activity based on both BAE and MRE could optimize the management of small-bowel CD patients.
P215 Deep immune phenotyping of unconventional T cells reveals a depletion in Mucosa Associated T Cells (MAIT) in IBD patients with extraintestinal manifestations
Authors: Catalàn-Serra x I , Xu W , Bruland T , Larbi A , Sandvik A K
Published: January 2023

Background

Extraintestinal manifestations (EIM) are common in IBD and they affect importantly the quality of life of patients. Although the pathogenesis of EIM is still poorly understood, an altered immune response involving T cells has been proposed. In addition, the presence of EIM during disease course will impact the therapeutic choices with new biologics.

In the present work we aim to characterize T cell populations -with focus on Uncoventional T cells- in IBD patients presenting EIM using advance flow cytometry and proteomics.

Methods

A total of 184 individuals (106 F/78 M) and were prospectively included: 149 IBD patients (84 UC/65 CD) and 25 healthy matched controls. Biologic samples including Peripheral Blood Mononuclear Cells (PBMC) and plasma were consecutively stored and classified in an established cross sectional IBD biobank at the Norwegian University of Science and Technology. Patient characteristics including age, sex, smoking status, current medication, Montreal Classification phenotype and inflammation biomarkers (CRP) and fecal Calprotectin were recorded.

PBMC were stained with antibodies and acquired using BD FACS Symphony flow cytometer using automatic compensations and Multiplex ELISA for 65 proteins was performed using Immune Monitoring 65-Plex Human ProcartaPlex™ Panel at Singapore Immunology Network (SIgN), as previously described.

Statistical analysis was performed using GraphPad Prism (San Diego, CA). p≤ 0.05 was considered statistically significant.

Results

Of the 184 IBD patients included, the presence or not of EIM was registered in 149 (mean age 37 +/-7.2; 86 female) of which 84 had UC and 65 CD. Of them, 21 (14.1%) presented EIM at inclusion. We analyzed the differences in all subsets of unconventional T cells: gammadelta T cells (VD1, VD2, VD3), MAIT cells, innate NKT cells and CD4/CD8 positive T cells between IBD patients with or without EIM (Fig1A). MAIT cells were selectively depleted in patients with EIM (p<0.01), while there was no statistically significant change in the ratios of other T cell subpopulations.

We then studied the concentrations of plasma proteins between the two groups. We found a significant increase in IL-2, GM-CSF, IL-6, Eotaxin, Leukemia Inhibitory Factor Protein (LIF), TNF-RII and Monocyte Chemoattractant Protein-1 (MCP), all p<0.05 in patients with EIM (Fig1B).

In order to address the potential use of MAIT as marker of EIM we constructed a ROC curve showing an AUC 0.752 (95% CI 0.639-0.865, p= 0.0002) Fig. 1C

Conclusion

MAIT cell depletion associated strongly with the presence of EIM and could be used as a clinical marker for EIM in IBD. A deeper understanding of its role in the pathogenesis of EIM, as well as an external validation as a marker, deserves further investigation.
P234 Differentiation of histopathological features between sporadic and colitis-associated colorectal cancer in a nationwide large cohort.
Authors: Uchino M , Ikeuchi H , Noiguchi T , Okabayashi K , Futami K , Tanaka S , Ohge H , Watanabe K , Itabashi M , Okamoto K , Okita Y , Mzushima T , Mizuuchi Y , Yamada K , Shimada Y , Sato Y , Kimura H , Takahashi K , Hida K , Kinugasa Y , Okuda J , Daito K , Koyama F , Ueno H , Yamamoto T , Hanai T , Kobayashi H , Kono T , Ajioka Y , Sugihara K , Ishihara S ,   Study Group for Inflammatory Bowel Disease Associated Intestinal Cancers by the Japanese Society for Cancer of the Colon and Rectum
Published: January 2023

Background

Colitis-associated colorectal cancer (CAC) can develop in patients with inflammatory bowel disease, and histological features differ between CAC and sporadic colorectal cancer (CRC). Moreover, advanced CAC has a poorer prognosis than sporadic CRC. Therefore, we compared histopathological findings distinct from cancer stage between CAC and sporadic CRC to evaluate the features of CAC.

Methods

We reviewed the clinical and histopathological data collected from 43 institutions, including surgery and gastroenterology departments, in the Japanese Society for Cancer of the Colon and Rectum between 1983 and 2020. Patient characteristics were compared between ulcerative colitis (UC), Crohn’s disease (CD), and sporadic CRC. Comparisons were performed by using all collected data or propensity score-matched data.

Results

A total of 1,077 patients with UC-CAC, 297 with CD-CAC, and 136,927 with sporadic CRC were included in all collected data. Although the prevalence of well or moderately differentiated adenocarcinoma (G1:well differentiated and G2:moderately differentiated) decreased according to tumor progression in all diseases (p<0.01, figure1), the prevalence of G3,G4, including signet ring cell carcinoma, mucinous carcinoma, poorly differentiated adenocarcinoma, neuroendocrine carcinoma and squamous cell carcinoma, was significantly higher in CAC than in sporadic CRC. Based on propensity score-matched data for 982 patients with UC and 268 with CD, the prevalence of histopathological findings other than G1 and G2 was also significantly higher in CAC (figure2,3). At pT4, mucinous carcinoma occurred at a significantly higher rate in patients with CD (45/86 (52.3%)) than in those with sporadic CRC (13/88 (14.8%)) (p<0.01).

Conclusion

Malignant potential is higher in CAC than in sporadic CRC according to tumor progression, which may lead to the poor prognosis of CAC.
P235 Patients with inflammatory ileal pouch anal anastomosis (IPAA) disorders are characterized by a distinct breath volatile organic compounds (VOC) metabolome profile
Authors: Qazi T , Ottichilo R , Grove D , Rayan C , Cohen B , Bhat S , Regueiro M , Dweik R , Rieder F
Published: January 2023

Background

Following creation of an IPAA in patients with ulcerative colitis (UC), more than 60% of subjects develop inflammatory complications. The current objective assessment for inflammation of the pouch is limited to surrogate stool and blood biomarkers or endoscopy. The development of non-invasive and accurate biomarkers for the assessment of IPAA inflammation is an area of unmet need. Measurement of exhaled breath volatile organic metabolome compounds (VOCs) has shown promise as a biomarker for the diagnosis and monitoring of inflammatory disorders. We here aimed to characterize the pattern of VOCs in the exhaled breath of patients with an IPAA and assess whether VOC analysis is able to discriminate patients with endoscopically active IPAA inflammation from patients without IPAA inflammation.

Methods

This is a cross-sectional study of patients with an IPAA created for the management of UC. Exhaled breath samples were collected at time of endoscopic evaluation of the pouch and 97 VOC metabolites assessed via selective ion flow tube mass spectrometry (SIFT-MS). The IPAA cohort was dichotomized using the endoscopic pouch disease activity index (PDAI) into endoscopic PDAI of >= 4 (severe inflammation), or endoscopic PDAI score <= 1 (mild or no inflammation). Principle component analysis (PCA) was conducted to reveal the VOCs with the strongest discriminatory capability and principle component regression (PCR) was performed to assess the association of exhaled breath VOC analysis in differentiating the groups.

Results

Exhaled breath metabolome analysis was performed on 10 subjects with PDAI >=4 and 7 subjects with PDAI <=1. Demographics are provided in Table 1. PCA indicated robust discrimination of the two groups based on breath VOCs (Figure 1). 10 out of 97 VOCs were up-regulated in the PDAI >=4 group compared to control, including ammonia and hydrogen sulfide. Isopropenyltoluene, tetrachloroethylene, and 3-pentanone provided the highest contribution to differentiate between the cohorts (Figure 2). Receiver operative curve (ROC) analysis of the PCR model indicated an area under the curve (AUC) of 0.81 (0.61-99), suggesting a strong association of breath VOCs with inflammation of the pouch (Figure 1).

Conclusion

VOC exhaled breath metabolome analysis shows a strong ability to discriminate patients with severe endoscopic pouch inflammation from patients with minimal to no endoscopic inflammation. The differences in reported VOCs point toward metabolic differences in bacterial fermentation, lipid and carbohydrate metabolism, and an increase in reactive oxygen species in patients with endoscopic pouch inflammation. Validation studies addressing the role of VOC analysis for non-invasive disease assessment patients with IPAA are ongoing.
P238 The ‘Malnutrition Universal Screening Tool’ (MUST) is less effective than an IBD specific Malnutrition Inflammation Risk Tool (MIRT) in identifying malnutrition risk with hospital admissions and surgical complication
Authors: xia Q , Mujiri S , Syme G , Mehta S
Published: January 2023

Background

IBD is associated with altered body composition and micronutrient deficiencies. None of the existing validated nutritional screening tools can correctly identify nutritional deficiencies in IBD. MUST is a widely used malnutrition screening tool in the UK. However, it failed to present relevance to clinical outcomes, while a newly developed IBD-specific tool, MIRT, showed significant correlations in CD patients.

Methods

Two single-centred retrospective projects were conducted in IBD tertiary centre at Royal London Hospital. Study A focused on IBD inpatients during the year 2021 with hospital stays ≥7 days 69 patients (43 males and 26 females), while study B examined 49 who underwent IBD-related surgery admitted between October 2019 and March 2022. They share the same defining criteria in MUST and MIRT. Hospital length of stay (LoS) and Clavien-dindo grade (CDG) were used to assess the clinical outcomes in surgical patients (study B).

Results

Study A: There were significant differences between MIRT and MUST in identifying the risk of malnutrition (Chi-square statistics =1.817, df =1, p =0.178). Fisher’s exact test P=0.239. and accepted alternative hypothesis. MIRT identified a significantly higher proportion of patients with the risk of malnutrition in comparison to MUST (strengths of relationship k=0.165 [95% CI] p =0.178). An independent sample t-test was undertaken to determine the association between malnutrition -MUST ≥2 and LoS. It was found that there was no difference between the means of the two groups and the LoS. t (32) =-0.002 p=0.998 P>0.05. Similarities have been found with MIRT≥3 score and association with LoS t (67) = -0.158 p=0.875 p>0.05Study B: The MUST did not significantly correlate with CDG or LoS (ρ =0.145, P =0.322; ρ = 0.033, P =0.823); however, the MIRT score did (ρ = 0.339, P =0.017; ρ =0.399, P = 0.005). The MIRT is thus a better NST than MUST in correlating with surgical outcomes within the IBD patient population. A higher MIRT score of ≥3 was significantly associated with both CDG (P =0.009) and hospital LoS (P =0.003), while a higher MIRT score ≥2 was not significantly associated with either (P =0.272; P =0.095) shown in Table 1

Conclusion

MIRT identifies a higher proportion of malnutrition in IBD patients 1 week from admission, but there is no direct correlation with complications and LoS. However, the opposite is the case in surgical patients where MIRT is a better pre-indicator for longer stays and complications. Having a disease-specific tool that correctly identifies the risk of malnutrition and predicts disease clinical outcomes in the IBD inpatient setting will improve the quality of healthcare and also will reduce healthcare costs. Further studies are needed ideally prospectively.
P239 Incidence of Long COVID and impact of medications on the risk of developing Long COVID in a nationwide cohort of Inflammatory Bowel Disease patients
Authors: Khan N , Mahmud N , Patel M , Sundararajan R , Reinisch W
Published: January 2023

Background

With the ongoing SARS-CoV-2 pandemic there is concern for development of Long COVID in patients with immune-mediated diseases treated with immunosuppressive agents. We aimed to determine the incidence of Long COVID among Inflammatory Bowel Disease (IBD) patients and to identify associated risk factors. Our study also aimed at studying the differences in risk of Long COVID among different IBD medication exposures.

Methods

We conducted a retrospective cohort study utilizing a nationwide cohort of patients with IBD in the Veteran Affairs Healthcare System (VAHS). Patients diagnosed with SARS-COV-2 between March 10th, 2020, and January 24th, 2021, were included. All charts were reviewed to determine recent IBD hospitalization, hospitalization for SARS-CoV-2 infection, and stability of IBD control pre and post infection. COVID-19 hospitalizations were also reviewed for intensive care unit requirement (ICU). COVID-19 treatments including remdesivir, monoclonal antibody infusions, and corticosteroids were also ascertained. Primary outcome was development of Long COVID. Cox regression analysis was used to identify variables associated with Long COVID.

Results

A total of 677 patients with SARS-CoV-2 infection were included, of which 49 (7.3%) were diagnosed with Long COVID (Table 1). No significant differences in IBD medication class between patients with and without Long COVID diagnoses were noted. In multivariable regression analysis, COVID-19 hospitalization (HR 3.56, 95% CI 1.80-7.09, p<0.001), ICU requirement (HR 2.20, 95% CI 1.18-4.08, p=0.01), and COPD (HR 2.41, 95% CI 1.03-5.64, p=0.04) were significantly associated with Long COVID (Table 2). Adjusted survival curves showed that relative to patients who were not hospitalized, patients hospitalized in the ICU had an 8.61-fold increased hazard of Long COVID (HR 8.61, 95% CI 3.98-18.65, p<0.001) (Figure 1).

Conclusion

Hospitalization and ICU care for COVID-19, as well as pre-existing COPD, were associated with increased risk of developing Long COVID, suggesting that severity of infection with a vulnerable substrate are key drivers of risk. Medications used in the treatment of IBD did not impact the risk of Long COVID. These findings should help reassure and inform IBD patients about the risk of Long COVID.
P251 Level of Interleukin-17 in Inflammatory Bowel Disease and Its relation to disease activity.
Authors: Menesy A , Hammad M , Aref S , Abozeid F
Published: January 2023

Background

Inflammatory bowel disease (IBD) is a chronic relapsing inflammatory disorder of the gastrointestinal tract (GIT).It causes progressive structural and functional damage to the GIT epithelium. Chronic inflammation in IBD is characterized by an imbalance in the production of T helper -1 (Th1),Th2 andTh17 cytokines.This imbalance is important in chronic inflammatory process, since the formation of defective immune response to pathogenic agents promotes the recurrence of the disease.Whether interleukin-17A (IL-17A) has pathogenic and/or protective roles in the gut mucosa is controversial.The aim of this study was to detect serum IL-17 levels in IBD patients and its relation to disease activity.

Methods

This was a single center cross-sectional study, conducted at hepatology & gastroenterology unit, Mansoura specialized Medical Hospital, Egypt.Patients who were aged 18-65 years and diagnosed either UC or CD based on previous colonoscopy were included.55 patients were UC, 24 patients were CD,21 patients were control.Patients who were excluded were <15 y, with history of GIT malignancy or any comorbidities affecting kidney,liver ,etc.All population were subjected to routine history, physical examination& laboratory investigations including serum IL-17 by ELISA besides CBC,CRP,ESR,Stool analysis, fecal calprotectin.

Results

Table (1): Correlation between laboratory findings and IL-17 among studied cases

We found that serum IL-17 level was increased significantly among UC ;median (min-max)= 72(21-502), in CD 54.5(25-260) versus control19(14-35) ng/l, P<0.001.However, it was not correlated to the disease activity either Mayo score of UC or CDAI of CD.

It showed significant correlation to the extent of inflammation in UC affecting the colon (either proctosigmoiditis or left sided colitis or pan colitis), also to the type of CD (either inflammatory or stricturing or fistulizing) by P<0.05.

It was not correlated significantly with any of the IBD activity markers (either CRP, ESR,or fecal calprotectin).Yet there was only negative significant correlation with Hb level (r =-0.28, p=0.005).

AUC was significantly differentiating between IBD and control group =0.993 with the best-detected cut off point from curve is 32 yielding sensitivity of 97.5% and specificity of 95.2%, while for discriminating activity of IBD by IL-17 ;AUC of UC and CD =0.56 & 0.65, with sensitivity 52.6% & 61.5% and specificity 58.3% &63.6 % respectively.

Conclusion

IL-17 increases in colonic inflammation significantly more than in control group, however its increase is not correlated to IBD activity.
P252 Solid organ transplant (with the exception of liver) in patients with inflammatory bowel disease: An ECCO CONFER Multicentre Case Series
Authors: Ribaldone D G , Vieujean S , Julsgaard M , Zingone F , Savarino E , Cañete F , Aratari A , Imperatore N , Ramos L , Plaza R , Pugliese D , Barberio B , Drobne D , Chaparro M
Published: January 2023

Background

There are limited data available on the course of IBD in patients with solid organ transplantation.

The aim of this ECCO CONFER study was to evaluate the trend of IBD before and after solid organ transplantation but liver.

Methods

This was a retrospective observational multicentre study that collected cases through the CONFER project. Patients with an established IBD diagnosis who underwent a solid organ transplantation (with the exception of liver) were eligible candidates.

Results

33 patients with solid organ transplantation (67% male; 55% CD) were collected from 12 referral centres in five different countries.

Mean age was 53 ± 16 years. 34 organs were transplanted in 33 patients. Most of the patients underwent kidney transplantation (n=27, 82%). 4 (12%) received a heart and 1 (3%) underwent lung transplantation; 1 (3%) underwent a combined heart and kidney transplant.

The mean duration of IBD was 18.4 ± 14.7 months. Clinical characteristics are summarized in Table 1.

The median follow-up after transplantation was 4.3 years (IQR 3.25 – 10.7).

7/33 patients (21.2%) experienced organ rejection, with 1 kidney retransplant.

Regarding immunosuppressive therapy, 29/33 patients (88%) were treated with tacrolimus, 25 (76%) with systemic steroids, 22 (67%) with mycophenolate mofetil, 11 (33%) with everolimus, 6 with cyclosporine (18%), 3 (9%) with thiopurines. Regarding biologics, 1 patient was treated with infliximab, 2 with adalimumab, 2 with vedolizumab, 1 with ustekinumab.

Defining a severe IBD course the need for biologic therapy or bowel resection or hospitalization, 4 patients (11.7%) had a severe disease course after transplantation versus 3 patients (9.3%) in the first 51 months of disease before transplantation (p = 0.26). Univariate analysis is reported in Table 2.

1 case of low-grade dysplasia was found 10 years after the transplantation. 1 case of colorectal cancer was found in a patient affected by CD five years after kidney transplantation. The other cases of tumours after transplantation are reported in Table 3.

The first serious infectious episode after transplantation is shown in Table 4: 17 of 33 patients (51.5%) reported at least 1 episode of serious infection.

In total 29 different serious infectious episodes after transplantation were recorded, compared to 28 episodes in the pre-transplantation period.

At the last follow-up visit, 6/33 (18.2%) patients had died: 1 due to cholangiocarcinoma, 1 amyloidosis, 1 heart failure, 1 myocardial infection (2 not available).

Conclusion

Solid organ transplantation appears to have a satisfactory course for both the transplanted organ and IBD, in terms of organ survival and IBD severity; furthermore, the use of biologics in these patients does not appear to be linked to a worse outcome.
P262 Development and validation of a score predicting non-response to intravenous corticosteroids in patients with Acute Severe Ulcerative Colitis on day 3 of admission
Authors: Subhaharan D , Ramaswamy P K , Willmann L , Moattar H , Bhullar M , Ishaq N , Dorrington A , Shukla D , McIvor C , Edwards J , Mohsen W
Published: January 2023

Background

Colectomy rates in acute severe ulcerative colitis (ASUC) patients have declined over the last 25 years. Objective predictors of non-response to IV corticosteroids (IVCS) in ASUC can further improve outcomes. Our aim was to develop and validate predictors of IVCS non-response in ASUC patients in the biologic era.

Methods

Consecutive patients with ASUC satisfying Truelove and Witts’ criteria hospitalised at two tertiary IBD centres in Australia between 2013-2020 were included. Primary outcome was steroid non-response requiring medical or surgical rescue therapy. UCEIS was scored on flexible sigmoidoscopy performed within 24-48 hours of admission. Development cohort comprised 112 episodes of ASUC between 2013 and 2017, and the validation cohort comprised 114 episodes of ASUC between 2018-2020.

Results

In the development cohort, 52 (46.4%) episodes were steroid non-responders and 18 (16%) episodes underwent colectomy during the same admission. On multi-variable analysis, predictors of non-response to IVCS were UCEIS score [OR 2.45 (1.65-3.63, p <0.001)] and serum albumin day 3 after admission [OR 0.83 (0.76-0.90), p <0.001]. A score was developed allocating 1 point to each variable (UCEIS ≥ 7 and day 3 serum albumin ≤ 25 mg/L) For predicting steroid non-response, the score had OR 6.31 (3.11- 12.79), p <0.001, AUROC 0.763 (0.676-0.849), score of 2 points had a sensitivity of 26%, specificity 100%, PPV 100, NPV 59.5%; for same admission colectomy OR 20.58 (6.16-68.6), p <0.001, AUROC 0.905 (0.846-0.964). In the validation cohort, 52 (45.6%) episodes were steroid non-responders and 7 (6.1%) episodes underwent colectomy during the same admission. For predicting steroid non-response, the score had OR 4.26 (2.07-8.76), p <0.001, AUROC 0.684 (0.593-0.776), score of 2 points had sensitivity 13%, specificity 100%, PPV 100%, NPV 57%; for same admission colectomy OR 5.42 (2.44-12.05), p <0.001, AUROC 0.83 (0.753-0.907).

Conclusion

In the biologic era, UCEIS score and serum albumin on day 3 of admission are predictors of steroid non-response in patients with ASUC. We have developed and validated a score comprising UCEIS ≥ 7 and day 3 serum albumin ≤ 25mg/L. A score of 2 has a specificity of 100% and PPV 100% for predicting non-response to IVCS.
P264 Machine learning can accurately predict development of Inflammatory Bowel Disease
Authors: Dyer E , Kliper E , Zamstein N , Hodik G , Kariv R , Cohen N A
Published: January 2023

Background

Prediction of inflammatory bowel disease (IBD) development is the subject of intense study. We have previously shown that significant changes occur in routine laboratory tests in the 5 years preceding IBD diagnosis. Using routinely collected laboratory results, we developed machine learning models to predict development of IBD.

Methods

We extracted data from the electronic medical records of Maccabi Health Services and included patients with IBD ≥ 16 years of age with a minimum of 5 years follow up and an age and sex matched healthy cohort. The outcome measured was entry into the IBD registry. The study population was split into training and validation cohorts and using laboratory values in the 5 years prior to IBD diagnosis as features, we assessed the performance of supervised learning models and performed interpretability analysis with unsupervised dimensionality reduction.

Results

5643 patients with IBD and 17199 healthy people were included in this study. 3039 (53.8%) had Crohn’s disease (CD), 2322 (41.1%) ulcerative colitis (UC) and 282 (5%) indeterminate colitis. The mean age of the IBD and healthy cohorts at study inclusion was 39.3 ± 16.5 and 38.5 ± 15.6 years, respectively. Weighted nearest neighbour imputation was used to correct for data missingness. Unsupervised Uniform Manifold Approximation Projection dimensionality reduction correctly separated the cohort into healthy and IBD clusters (Figure 1A). Furthermore, this algorithm identified two distinct groups correlating to CD or UC diagnosis (Figure 1B). Supervised learning models, namely neural net (AUC 0.95), linear support vector machine (SVM) (AUC 0.93), radial basis function SVM (AUC 0.85) and logistic regression (AUC 0.93) models, accurately predicted IBD diagnosis (Figure 2). These models were repeated without C-reactive protein and the predictive value was not significantly changed. Moreover, we excluded data in the 2 years preceding IBD diagnosis to determine whether model performance was reduced and the predictive value remained the same. Interestingly, using only data from 3-5 years preceding IBD diagnosis, the model could better distinguish between CD and UC (Figure 3).

Conclusion

In this study, machine learning models could accurately predict a diagnosis of IBD using laboratory data from the 5 years preceding IBD diagnosis. Prospective studies are needed to test these models in a real world setting.