bluuebunny/crossref_metadata_2025 huggingface dataset:
P196 Major variance in scoring of endoscopic recurrence after ileocolic resection for Crohns Disease – a systematic review and meta-analysis
Authors: Van Der Does De Willebois E , Bellato V , van Dieren S , Duijvestein M , Buskens C , Vignali A , Bemelman W
Published: January 2023

Background

Adequate scoring of endoscopic recurrence in Crohn’s disease patients is of utmost importance, as it is used to diagnose recurrent disease, to predict disease outcomes, to (re-)initiate or change therapy and to monitor its effect. This study aims to assess the variance in endoscopic recurrence in patients after ileocolic resection for Crohn's disease using the most common classification systems, the Rutgeerts (RS) and modified Rutgeerts (mRS) classification.

Methods

A systematic literature search using MEDLINE, Embase and the Cochrane Library was performed. All RCTs and cohort studies describing endoscopic recurrence after an ileocolic resection for Crohn's disease were included. Main outcome was the range of endoscopic recurrence rates within twelve months postoperatively, defined as RS≥i2 and/or mRS≥i2b. A proportional meta-analysis was performed.

Results

Seventy-six studies comprising 7751 patients were included. The weighted mean of the endoscopic recurrence rates, defined as either RS≥i2 and/or mRS≥i2b, was 43.99% (95 per cent CI 43.56 – 44.43), ranging from 5.0% – 93.0%, fig 1. For studies reporting endoscopic recurrence defined as ≥i2 and for studies reporting recurrence defined as ≥i2b the weighted means were 44.0% (range 5.0% – 93.0%) and 41.1% (range 19.8% – 62.9%) respectively. Within studies reporting both RS and mRS the weighted means for endoscopic recurrence were 61.3% (range 39.1% – 84.7%) and 40.6% (range 19.8% – 62.0%) respectively.

Conclusion

This study demonstrates a major variance in scoring endoscopic recurrence after ileocolic resection for Crohn's disease, with the greatest variance when using the original Rutgeerts classification. This suggests a high likelihood of inadequate diagnosis of disease recurrence, with major implications for quality of life and health care consumption. Therefore, there is an important need to improve endoscopic scoring of recurrent disease.
P197 A biomarker of early mucosal destruction: Neutrophil-mediated type IV collagen degradation is elevated in patients with Crohn’s Disease and Ulcerative Colitis
Authors: Sorokina Alexdóttir M , Pehrsson M , Karsdal M A , Godskesen L E , Krag A , Kjeldsen J , Mortensen J H
Published: January 2023

Background

Inflammatory bowel disease (IBD) is characterized by chronic inflammation due to an uncontrolled immune response orchestrated through, i.e. neutrophils. The basement membrane acts as a front-line defense promoting tissue integrity, where the α-3 chain of type IV collagen is solely expressed on the outermost layer of the mucosa. Detection of subclinical ulceration is crucial since early-stage IBD presents a unique window of opportunity for intervention, as the disease might become a self-sustaining process once deep inflammation becomes established. We therefore, wanted to develop a biomarker reflecting early tissue injury, aiding in the implementation of prompt treatment.

Methods

A competitive enzyme-linked immunosorbent assay quantifying a human neutrophil elastase (HNE) degraded fragment of type IV collagen α-3 chain was developed (C4A3-HNE). Dilution- and spiking recovery, inter- and intra-variability, and interference were evaluated. Acceptance criteria for technical validation were a recovery of 100% ±25 and an inter-intra variability of <15%. Commercial serum samples were purchased from ProteoGenex. Biological relevance was validated in an observational study from Odense University Hospital (OUH) and healthy controls. Groups were compared using Kruskal Wallis (Dunn‘s corrected).

Results

The technical validation of the C4A3-HNE assay demonstrated acceptable results for recovery, variation, and interference (table 1). Biological relevance was assessed in commercial IBD samples and healthy donors. C4A3-HNE was elevated in both CD and UC compared to healthy (p=0.001 and <0.0001)(AUC [95% CI]: 0.820 [0.669-0.971]; 0.875 [0.775-1.000]). The results were validated in a cohort of IBD patients (both p<0.0001)(fig.1). For UC, analysis showed that compared to patients in endoscopic remission, C4A3-HNE is elevated in patients with mild endoscopic activity, decreasing dose-dependently for moderate and severe disease. Fecal calprotectin and CRP levels were also lower in IBD patients with high levels of C4A3-HNE (fig.2). With a cut-off value of 54.1 ng/ml, C4A3-HNE could significantly discriminate between mild and severe endoscopic disease (table 2).

Conclusion

Our study demonstrates the biological and possible clinical relevance of the novel C4A3-HNE biomarker. The biomarker is elevated in patients with IBD compared with healthy, and high levels may reflect early mucosal damage in patients with UC. Furthermore, inflammatory markers were lower in IBD patients with high levels of C4A3-HNE, pointing towards high levels being indicative of early disease. C4A3-HNE may provide early detection of mucosal damage; however, further studies are required to assess the clinical validity of this biomarker.
P198 Sonographic features of colonic pseudopolyposis in inflammatory bowel diseases
Authors: Silva Mendes S , Lepore F , Hussey M , Cataletti G , Maconi G
Published: January 2023

Background

Colonic pseudopolyps are a frequent finding in inflammatory bowel disease (IBD). Yet there are no published data describing the characteristics of pseudopolyposis in intestinal ultrasound (IUS). This study aimed at identifying the key features of pseudopolyposis in IUS.

Methods

This case-control study included 8 patients with ulcerative colitis or Crohn’s colitis with extensive left colon pseudopolyposis and 24 matched IBD patients without pseudopolyps at colonoscopy. Luminal (diameters, thickening, stratification, margins, and vascularity) and intraluminal (vascular signals at color Doppler), and extraluminal (mesenteric fat) parameters of the left colon were compared. Anonymized still images and videos of these patients were blindly reviewed to estimate the accuracy in detecting this condition.

Results

Among the IUS parameters assessed, the anteroposterior diameter ≥ 12 mm and the presence of luminal vascular signals were significantly correlated with pseudopolyposis (table 1). The detection of both these findings were able to detect extensive pseudopolyposis with a sensitivity of 62.5% a specificity of 96.8%, a positive predictive value of 83.3% and negative predictive value of 88.46%, and an overall accuracy of 87.5% (table 2).

Conclusion

This is the first study describing the IUS features of pseudopolyposis in IBD. The potential use of IUS to assess pseudopolyposis might have an impact on IUS monitoring and surveillance of IBD patients with condition.
P206 Artificial Intelligence reproduces central reading for automated scoring of colonoscopies from multiple clinical trials in Ulcerative Colitis
Authors: Gutierrez Becker B , Arús-Pous J , Yao H , Luscher J , Richmond D , Fisher E , Bojic D , Bigorgne A , Prunotto M
Published: January 2023

Background

Using Artificial Intelligence (AI) for the automated scoring of colonoscopy videos with Mayo Clinic Endoscopic Subscore (MCES) has been successful in several models [1]. However, no study to date has evaluated the performance of such algorithms on a new cohort obtained from a separate clinical trial. In this study, we aimed to build an AI scoring algorithm able to reproduce central reading from three Phase III clinical trials in Ulcerative Colitis (UC).

Methods

As a training dataset, still frames were automatically extracted from sigmoidoscopy videos of two Etrolizumab clinical trials: Hickory NCT02100696 [2] and Laurel NCT02165215 [3]. A quality control AI algorithm [4] was applied and the resulting dataset (N=1897 videos) was paired with central reading MCES for each colon section. The training was achieved on a multiclass MCES scoring algorithm [4] with the challenging task of assigning a multiclass score (MCES between 0 - 3) instead of a binary score (MCES <=1 or not). The performance was assessed on 2,292 videos from independent cohorts (Hibiscus I NCT02163759, Hibiscus II NCT02171429 [5], Gardenia NCT02136069 [6]). Videos were pre-processed in an identical manner as those from the training dataset (N= 637, 636 and 1019 videos for Hibiscus I, Hibiscus II and Gardenia, respectively). This dataset constitutes the largest cohort to date for the evaluation of a MCES scoring algorithm.

Results

The Area Under the Receiver Operator Characteristic curve (AUROC) was evaluated independently for each trial. Table 1 summarizes AUROC values per MCES for each clinical trial. The resulting mean AUROC values were 0.79 for Hibiscus I and 0.77 for both Hibiscus II and Gardenia. The average Cohen’s kappa between the automatic measurements and the central readings is 0.40, in contrast to 0.41 between central and local readers.

Conclusion

Our automated MCES scoring algorithm efficiently reproduces central reading in three independent clinical trials cohorts. In addition, algorithm evaluation was performed on data from independent trials, different from the ones used for the development of the algorithm. This is the first study evaluating, on such an extended cohort, the use of AI based automated MCES scoring in UC.

References:

1. Stafford,et al. Inflamm. Bowel Dis 28(10), 1573-1583.

2. Peyrin-Biroule et al. Lancet Gastroenterol. Hepatol. 7.2 (2022): 128-140.

3. Vermeire et al. Lancet Gastroenterol. Hepatol. 7.1 (2022): 28-37.

4. Gutierrez et al. Ther Adv Gastro Endoscopy 14 (2021).

5. Rubin, et al. Lancet Gastroenterol. Hepatol. 7.1 (2022): 17-27.

6. Danese et al. Lancet Gastroenterol. Hepatol. 7.2 (2022): 118-127.
P208 Validation of the IBD-Disk in a Portuguese cohort of patients with inflammatory bowel disease
Authors: Garrido I , Lopes S , Dias C , Macedo G
Published: January 2023

Background

Inflammatory Bowel Disease-Disability Index (IBD-DI) is a validated tool that was developed for assessing disability and to help clinicians to guide different therapeutic decisions. However, due to its complexity, it is difficult to apply in daily practice. The IBD-Disk is a new shortened adaptation of the IBD-DI, designed to give an immediate representation of disability. However, further investigation is required to validate this tool in clinical practice. The objective of this study was to evaluate the IBD-Disk for its capacity to assess disability in a Portuguese cohort of patients with IBD.

Methods

In this single-center, cross-sectional observational study, patients with IBD were consecutively recruited between February 2021 to February 2022 from our outpatient department. Both IBD-Disk and IBD-DI were delivered and filled out simultaneously by all included patients. Sociodemographic and clinical data were also collected.

Results

A total of 258 patients were included, the majority female (51.9%), with a median age of 41 years old (IQR 32-52). There were 184 (71.3%) individuals with Crohn′s disease and 74 (28.7%) with ulcerative colitis (Table 1). The median total score of IBD-Disk was 29.6±24.4 and that of IBD-DI was 23.8±11.2. The item on the IBD-Disk with the highest score was “energy” (4.33±3.5) and the lowest scoring item was interpersonal interactions (1.98±2.8). A significant positive correlation between total scores of IBD-Disk and IBD-DI was identified (r=0.722, p<0.001), with a high Pearson correlation. Regarding the validity per item, there was also a good correlation between both scores. Including all 10 items in the IBD-Disk scale, a value of 0.918 was observed for Cronbach’s alpha, demonstrating a very good homogeneity of IBD-Disk items. Performing the one-at-a-time removal procedure, Cronbach’s alpha varied between 0.905 and 0.915, confirming that all items contribute to the construct. All items showed an item-total correlation coefficient >0.4. Table 2 shows the univariate analysis of clinical factors associated with the IBD-Disk score. Hemoglobin level (p=0.973), serum albumin (p=0.998) and fecal calprotectin (p=0.183) were not associated with the IBD-Disk score. In multivariate analysis, a significant impact of the female sex (β=11.760 [6.117; 17.404], p<0.001), biological therapy (β=9.042 [1.546; 16.539], p=0.018) and perianal surgery (β=12.091 [2.862; 21.320], p=0.010) on the IBD-Disk total score was observed.

Conclusion

IBD-Disk is a valid and reliable tool for quantifying disability for both Crohn’s disease and ulcerative colitis in clinical practice. It should allow gastroenterologists to rapidly assess a patient’s disability at a given time.
P217 Volatile organic metabolites to predict clinical response to biological therapy in inflammatory bowel disease
Authors: Ribaldone D G , Arezzo A , Cardenia V , Caviglia G P , Abate M L , Saracco G M , Astegiano M , Morino M
Published: January 2023

Background

Volatiles organic metabolites (VOMs) are a large group of carbon-bound chemicals elements, gaseous at room temperature that are the products of metabolism. There is increasing evidence that variations in faecal VOMs indicate gastroenterological diseases. No study assessed VOMs in the setting of predicting therapeutic response in inflammatory bowel disease (IBD).

Methods

We conducted a prospective study in which we consecutively recruited IBD patients with indications for treatment with biologics.

The primary outcome of our study was the evaluation of prediction ability of VOMs of clinical response at 12 months of adalimumab or vedolizumab therapy. Secondary outcomes included correlations of VOM with clinical features of IBD.

Results

We recruited 50 patients with IBD whose stools were analysed with gold standard technique mass spectrometer (MS) / gas chromatography (GC). Thirty-one patients were treated with adalimumab (of which 30 Crohn’s disease, and 1 ulcerative colitis, UC), 19 patients with vedolizumab (of which 12 CD and 7 UC).

VOMs were not influenced by age, disease duration, sex, smoking habit. Two VOMs, octenol and, in particular, methyl indole were able to distinguish ulcerative colitis (UC) from Crohn’s disease (CD) (AUC = 0.72 and 0.85, respectively) and correlate with higher inflammation markers (C-reactive protein, CRP and calprotectin, respectively). Methylbutanal, instead, was a marker of CD and, in particular, of ileal location (p = 0.01). These results were confirmed at principal component analysis (PCA). Lower levels of ethanol and methyl butanoate correlated with disease remission. Methyl butanoate was able to distinguish remission from active clinical disease, with an accuracy at least equal to that of calprotectin (AUC = 0.69 and AUC = 0.62, respectively). We furthermore demonstrated pre-biologics methyl butyrate prediction ability of clinical response after 12 months of therapy (AUC = 0.68, 95%CI = 0.53-0.81, p = 0.02). Lower levels of methyl indole or of octenol or higher levels of indole were able to predict calprotectin <250 mg/kg without steroid at month 12; undetectable levels of basal ethyl butanoate correlated with calprotectin <250 mg/kg without steroid at month 12 (p = 0.04) in the subgroup of patients treated with vedolizumab, while higher levels of ethyl butanoate correlate with higher CRP levels. Our finding of a lower piperidone level in patients undergoing previous bowel resection is consistent with literature data that found an association between active CD and higher piperidone levels.

Conclusion

The characterization of the intestinal metabolome, using VOMs technology, seems to be a promising method for better characterizing IBD and better speculating on their etiopathogenesis.
P219 Migraine Is Associated with the Development of Inflammatory Bowel Disease: A Nationwide, Population-Based Study
Authors: Lee C , Han K , Yu H , Kim S , Choi K , Lee H J , Koh S J , Im J P , Kim J S
Published: January 2023

Background

Inflammatory bowel disease (IBD) has been associated with an increased risk of migraine in a nationwide cohort sample analysis, but there is no evidence on the impact of migraine on the development of IBD The aim of this study was to determine the association between migraine and the development of IBD.

Methods

This nationwide population-based cohort study was conducted using the Korean National Health Insurance Service (NHIS) database. A total of 10,628,070 people aged 20 years or older who had undergone a national health examination conducted by the NHIS in 2009 were followed up until 2017. The study population was divided into two groups according to the presence or absence of migraine. We analyzed the incidence of newly developed IBD, Crohn’s disease (CD), or ulcerative colitis (UC) during the follow-up period.

Results

The incidence of IBD was significantly higher in patients with migraine (adjusted hazard ratio [aHR] with 95% confidence interval [CI], 1.31 [1.173–1.468], p <0.001), CD (aHR with 95% CI, 1.58 [1.237–2.013], p <0.001) and UC (aHR with 95% CI, 1.26 [1.106–1.424], p <0.001) than those without migraine. After 5 years of follow-up in those with migraine, the curves implying cumulative incidences of IBD showed a steep increase especially for CD. In subgroup analysis, migraine was associated with the risk of UC in those with male sex (aHR, 1.431 vs. 1.117; interaction p = 0.042)

Conclusion

Migraine is significantly associated with the development of IBD. Patients with migraine would be monitored carefully for the development of IBD.
P229 Comparison of the characteristics of segmental mucosal microbiome according to the extent of inflammation in ulcerative colitis.
Authors: Shin J , Kim S Y , Kwon D , Cha B , Kong S M , Kim J S , Kwon K S , Kim H
Published: January 2023

Background

Ulcerative colitis (UC) is a chronic characterized by recurrent remission and relapse and is a subtype of inflammatory bowel disease. The gut microbiome is one of the major factors in the pathogenesis and exacerbation of UC. Whether there is a difference in the mucosal microbiome profile for each segment of the colon according to the extent of inflammation in UC remains an uninvestigated field. Therefore, we investigated the differences in the mucosal microbiome according to colonic segments in patients with proctitis (P) vs Lt side colitis (L) vs remission (R).

Methods

A total of 28 UC patients who underwent endoscopic evaluation between March 2022 and October 2022 were finally enrolled. The patients were allocated by disease extent to P (n=18, 64.3%) L (n=4, 14.3%), and R (n=6, 21.4%) groups. The microbiomes of the cecum, descending colon, and rectum was evaluated. Total genomic DNA was extracted from the samples, and the character of the microbiome was determined by sequencing the V3-V4 region of the 16s rRNA gene (Miseq).

Results

We found that the relative abundance of the rectum and descending colon were increased compared to the cecum in P and L. In segments with active inflammation, Capilobacterota and fusobacteriota phyla were increased and Proteobacteria decreased compared to the cecum. However, in the R group, the relative abundance was not significantly different according to segments.In beta diversity, the microbiome composition was different depending on the segment in the P group. In the L group, the microbiome composition of the rectum and descending colon were similar but separate from the cecum. In the R group, there was no difference in beta diversity by segments.

Conclusion

In summary, biopsy microbiome in inflammation and suboptimal remission differs from remission. Assessment of segmental biopsy microbiome may be provided clinical perspicacity into UC disease progression and predict the extension of inflammation.
P241 Gastrointestinal ultrasonography diagnostic performance and feasibility in IBD during pregnancy: a systematic review and narrative synthesis.
Authors: Pillet J , Perrin J , Martel M , Kherad O , Restellini S
Published: January 2023

Background

Inflammatory bowel diseases (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC) are associated to poor maternal and foetal outcomes during pregnancy, requiring a strict monitoring of the disease activity, preferably with non-invasive modalities. We aimed to evaluate the diagnostic performance and feasibility of gastrointestinal ultrasonography (GIUS) to monitor IBD activity throughout pregnancy.

Methods

A systematic literature review has been performed identifying studies the use of ultrasound modality in pregnant IBD women from date of inception until October 2022 using MEDLINE, Cochrane library, EMBASE and ISI Web of Science databases, with keywords including 1) ultrasound/ultrasonography2) pregnancy, and 3) IBD (CD and UC). Additional relevant studies were identified from cross-referencing and hand-searches of references of the retrieved articles. We included fully published observational studies and abstracts.

Results

Overall, five studies have been selected from 263 citations. All studies were highly heterogeneous in the definition of disease activity as reference standard, GIUS protocols, and outcomes. Two of them used a cut off value of fecal calprotectin (FCP) >100 [ug/g]. In one of them, clinical scores were used when FCP value was ≥100-249 [ug/g] and FCP ≥ 250 [ug/g] was considered as an active disease independently of clinical scores. Only one study used a single reference standard with a Harvey Bradshaw Index (HBI) >4. Across these 3 studies, results suggest a relatively good specificity (range 83%-98%) but low sensitivity (range 33%-84%) to detect disease’s activity. Only 1 study analysed GIUS performance in detecting remission with a sensitivity of 80% and a specificity of 92% compared to the reference standard. The size of the uterus limits the visualization of the terminal ileum and the sigmoid from the 2nd trimester and the 3rd trimester respectively. Evaluation of the rectum remains limited.

Conclusion

GIUS is a feasible, accessible, and accurate method to monitor disease activity in IBD pregnant women. Evidence is limited though and warrants further studies with standardized reference comparator
P242 Universal exclusion of patients with Permanent Ileostomy in Crohn’s disease clinical trials: A systematic review
Authors: Vuyyuru S , Solitano V , Nguyen T , Rieder F , Jairath V
Published: January 2023

Background

Crohn’s disease (CD) can be progressive leading to complications such as strictures and fistula requiring surgery in up to 50% of patients within 10 years of diagnosis and increased risk of permanent ileostomy (PI) formation. Approximately one third of patients with PI experience clinical recurrence within the small bowel which may need medical therapy and 16% significant recurrence requiring further surgery. Despite the physical and psychological morbidity associated with PI formation, there is a paucity of research in patients with CD and PI. We performed a systematic review to investigate whether patients with CD and PI were eligible to take part in pharmaceutical clinical trials.

Methods

MEDLINE, Embase, and the Cochrane library (CENTRAL) databases were searched from inception to April 2022 for randomized, placebo-controlled induction and maintenance trials of biologics and small molecules in adult patients with active CD. Eligibility criteria of included studies were screened by two authors independently. The primary outcome was to determine the proportion of trials that included patients with CD and a PI. Trial characteristics such as number of participants, mean age, sex, trial phase, class of drug, inclusion, or exclusion of patients with ostomy were collected.

Results

After excluding duplicates 11693 records from databases and additional sources were selected for screening. In total,144 records were assessed for full text assessment and 81 studies (induction: 58 and maintenance: 23) which enrolled 22000 participants were considered eligible (Table 1). The majority were phase 2 trials (n=41, 50.6%), 86.4% (n=70) evaluated efficacy and safety of biologics and the remaining studies (n=11, 13.6%) evaluated oral small molecules. Amongst the induction trials, 39 (67.2%) specifically stated that they excluded patients with an ostomy and the remaining studies (n=19, 32.8%) did not comment. For maintenance trials, 16 (69.6%) stated that they excluded patients with an ostomy and the remaining seven (30.4%) studies did not comment. Twenty-one induction studies and thirteen maintenance studies reported the proportion of patients with prior intestinal resection which ranged from 2.4% to 51%. No clinical trial included patients with a PI.

Conclusion

Patients with CD and PI have been excluded from pharmaceutical trials of biologics and small molecules to date. This group represents a high-risk patient population that have developed penetrating disease and may require medical therapy to prevent and treat recurrence. There is an urgent need to identify barriers to enrolment and develop eligibility and outcome measures that enable inclusion of patients with CD and PI into clinical trials.
P249 Colonic Explant Lactate Concentration and Disease Progression in Ulcerative Colitis
Authors: McShane C , Corcoran R , O'Connell F , MacDonagh P , O'Sullivan J , Kevans D
Published: January 2023

Background

There is therefore an unmet need for biomarkers of ulcerative colitis (UC) disease behaviour and clinical response. Lactate is known to have immunoregulatory effects. Recent studies have demonstrated that lactate concentrations are decreased in colonic tissue of patients with inflammatory bowel disease. We aimed to investigate if lactate concentration in tissue cultured media (TCM) from UC patient-derived colonic explants is associated with endoscopic disease severity and disease progression.

Methods

UC patients were prospectively recruited in 2 cohorts: discovery (2018 – 2019) and validation (2020 - 2021). Endoscopic biopsies were collected from the sigmoid colon and TCM generated as per previously described methods. Total protein content of biopsies was quantified to allow normalisation of secretions. TCM secreted lactate was quantified using a colorimetric L-Lactate assay (Abcam, UK). Patients demographics, baseline characteristics and disease behaviour were characterised. Endoscopic disease severity was categorised by endoscopic Mayo score. Disease progression was defined as the requirement for corticosteroid therapy, UC-related hospitalisation, UC-related surgery or the introduction of a new immunomodulatory agent in follow-up period. P values < 0.05 were considered significant in analyses.

Results

52 patients were included in the study (discovery cohort n=28, replication cohort n=24), baseline characteristics of each cohort are described in figure 1. No differences in TCM lactate concentration were observed in patients segregated by endoscopic Mayo score, disease duration and biologic exposure status. [Figure 2]. In the discovery cohort, patients in the lowest quartile of TCM lactate concentration had a shorter time to disease progression, p=0.005. This observation was not replicated in the validation cohort, p=0.79 [Figure 3]. Multivariate analysis demonstrated clinical remission was the only variable independently associated with time to disease progression in the discovery cohort (HR 0.17 (95% CI 0.05 – 0.66), p= 0.004). Endoscopic remission was the only variable independently associated with time to disease progression in the validation cohort (HR 0.21 (95% CI 0.06 – 0.81), p = 0.02).

Conclusion

Lactate is produced in high amounts by innate immune cells on inflammatory activation. UC TCM lactate concentration was not associated with endoscopic severity and was not reproducibly associated with disease progression in discovery or replication cohorts.
P253 Histological Remission and Activity as Predictor of Relapse, Hospitalization, and Surgery in Ulcerative Colitis: Systematic Review and Meta-analysis
Authors: Shehab M , Akram S A , Hassan A , Alrashed F , Bessissow T
Published: January 2023

Background

Treatment targets in patients with inflammatory bowel disease (IBD) have evolved over the last two decades. The significance of histological remission as a treatment target in patients with ulcerative colitis (UC) is not well established. The aim of this study is to assess risk of clinical relapse, hospitalizations and need for surgery in patients who achieved histological remission compared to patients with active histology in UC.

Methods

MEDLINE, EMBASE, Cochrane CENTRAL and conference abstracts were searched from inception to October 2022. Inclusion criteria included any randomized controlled trial or observational study that included adult patients with UC who achieved histological remission. The primary outcome was the risk of clinical relapse, hospitalization and need for surgery in patients with UC who achieved histological remission compared to patients with active histology. The outcomes were collected and stratified by 2 time points, 6-12 months and 13 or more months. Random effects model was used to calculate pooled risk ratio (RR) and 95% CIs and I2 statistics were used to assess heterogeneity.

Results

In total 28 studies were included in this meta-analysis. At 6-12 months, the risk of clinical relapse was higher in patients with active histology compared to patients who achieved histological remission (RR= 2.41, 95% confidence interval (CI) 1.69-3.44, p<0.01). There was no difference in risk of hospitalization in patients with histological remission compared to patients with active histology (RR= 4.22, 95% CI 0.91- 19.62, p=0.07). At 13 months or more, the risk of clinical relapse was higher in patients with active histology compared to patients who achieved histological remission (RR= 2.07, 95% CI 1.55-2.76, p<0.01). Risk of hospitalization and need for surgery was also higher in patients with active histology compared to patients who achieved histological remission; (RR= 2.52, 95% CI 1.59-4.00, p<0.01) and (RR= 3.14, 95% CI 1.53-6.45, p<0.01) respectively.

Conclusion

Histological remission in ulcerative colitis represents a treatment target that is not yet routinely sought in practice. Our study suggests that patients who achieve histological remission have better outcomes in UC than those with active histology.
P254 Deep Learning Model for Distinguishing MES 0 and MES 1 in Patients with Ulcerative Colitis
Authors: Kim J E , Choi Y H , Lee Y C , Seong G , Song J H , Kim E R , Hong S N , Chang D K , Kim Y H , Shin S Y , Kim T J
Published: January 2023

Background

Endoscopic remission has recently been defined as a Mayo endoscopic sub-score (MES) of 0. Therefore, patients with MES 1 need to step up to achieve an MES of 0 on the endoscopic score. In discriminating between MES 0 and 1, the inter-observer variation was very severe among the endoscopists. This study aimed to narrow the gap in distinguishing between MES 0 and MES1 using a deep learning model.

Methods

From the endoscopic images of 492 ulcerative colitis (UC) patients with MES improvement (MES 0 or MES 1) from January 2018 to December 2019 at this center, two representative images of the colon and rectum were selected, and a total of 984 images were analyzed. Our model was composed of a convolutional neural network (CNN)-based encoder, two auxiliary classifiers for the colon and rectum, and a final MES classifier for the combined image features of the two inputs. The following three experiments were conducted to validate and test the proposed model: 12-fold cross-validation for representative model selection, performance comparison with a novice group through an internal test dataset, and an external test with Hyperkvasir, a public gastrointestinal endoscopic image dataset.

Results

In the internal test, our model showed an F1-score of 0.92. This was, on average, 0.11 higher than each of the seven novices and 0.02 higher than their consensus. Considering MES 1 as positive, the area under the receiver operating characteristic curve (AUROC) was 0.97, and the area under the precision-recall curve (AUPRC) was 0.98. In the external test with Hyperkvasir, our model showed an F1-score of 0.89, AUROC of 0.86, and AUPRC of 0.97.

Conclusion

We found that the proposed CNN-based model that integrates the image features of the colon and rectum has superior performance in discriminating between MES 0 and MES 1 in patients with UC. Further prospective studies are required to prove the clinical utility of our model in clinical practice.
P259 Correlation between the Mayo endoscopic scoring system for Ulcerative Colitis with histological and clinical outcomes
Authors: Gibbons E , Afridi I , Sheehan T , Smyth C , Farrell R , Hall B , Kelly O B
Published: January 2023

Background

There is a growing body of literature demonstrating that persistent histological activity, despite endoscopic remission, is associated with increased risk of relapse in patients with UC. A recent meta-analysis reported a two-fold higher risk of relapse. The primary aim of this study was to examine the correlation of the Mayo endoscopic scoring system with histological outcomes and their association with flare/hospitalisation in the ensuing twelve months.

Methods

We selected 87 random colonoscopies performed for UC surveillance/assessment during between 2017-2019. Adult patients with a complete colonoscopy were included. All reports were reviewed and blindly scored by 2 expert endoscopists using the Mayo scoring system. Histology was classified as normal, mild, moderate and severe by an experienced gastrointestinal histopathologist. Clinical/ IBD demographics, flare episodes and hospitalisations were recorded. Correlation between endoscopic and histologic activity was tested. Comparisons were made between patients in both endoscopic and histologic remission, those in endoscopic remission with histologic activity and those with both endoscopic and histologic activity.

Results

87 patients with UC (median age 50; M:F 46:41) were included. Patient groups were similar (p=ns for demographic variables). All levels of the Mayo scale (median score 1) were represented. 31/87 (36%) were in both endoscopic and histologic remission. Of these, 5/31 (16%) had a flare requiring steroids and change of treatment at 12 months. Only 5/87 (5.7%) were endoscopically in remission with persistent histologic disease. Of these 1/5 (20%) had a flare and required steroids at six months. Endoscopic activity was independently associated with steroid use/ flare at six months (Z= -.3.39, p= -.0006) and change in treatment (Z= -1.9, p= 0.03). Histologic activity was also independently associated with steroid use/ flare (Z= -2.9, p= 0.0038) and change in treatment (Z= -1.96, p= 0.025). Looking at the three groups together there was a significant difference in steroid use and flare, deep remission versus endoscopic remission histologic activity and endoscopic activity (Chi square = 11.6, p= 0.003 for steroids, Chi square = 7.39, p= 0.025 for flare).

Conclusion

The therapeutic target in IBD has evolved over recent years from a focus on clinical remission to endoscopic remission. There is now a growing body of evidence that histological remission is an important endpoint. The extent that histologic remission affects outcomes is unclear to date. Further studies are required incorporating greater numbers of patients and robust histologic scoring systems.
P260 Care pathway modelling and economic analysis of a single NHS IBD Service following introduction of Small bowel ultrasound.
Authors: Radford S , Tench C , Moran G
Published: January 2023

Background

Small bowel ultrasound (SBUS) is an accurate, inexpensive and non-invasive method of diagnosing and monitoring IBD. The service delivery and economic implications of SBUS implementation on NHS IBD services have not previously been explored.

Methods

This study took the form of a service evaluation. Analysis of patient care episodes and flow through the established imaging (MRE and SBUS) and IBD care pathways was undertaken, data relating to patient flow, waiting times, resource use and healthcare engagement of patients were collected from care episodes between 01/01/2021 – 30/03/2022. Costs were calculated per care episode.

Results

Data from a service evaluation relating to 192 imaging referrals from IBD clinics for patients with Small bowel Crohn's disease (SBCD), and patient flow through the pathway were collected. Per scan, MRE was almost 5 times more costly than SBUS examinations (£305 versus £51 respectively). Patients from the SBUS pathway had fewer healthcare interactions across all three categories (Helpline, IBD Nurse or IBD Consultant appointments). Patients from the MRE pathway. Estimated costs per patient in the SBUS pathway were £81.72, and £379.58 per patient in the MRE pathway. Further to this the waiting times for MRE were significantly longer than those for SBUS.

Conclusion

The use of SBUS is a potential cost saving option when compared to MRE for adult patients with SBCD. There was a difference between the SBUS and MRE pathways in the waiting times for both the medical imaging scans, the reports of the scans and the initiation of an appropriate treatment plan. SBUS waiting times were shorter in all aspects except for the time between scanning report and the treatment initiation, indicating that it is the waiting times for the scans and the respective reporting that cause delays in treatment initiation. Future research in this area should attempt to consider the wider impact on cost effectiveness of the use of SBUS through investigation of costs including treatment costs, including the timing and use of biologic and immunomodulator treatments, impact of delays on service use and healthcare interactions of patients, work productivity and quality adjusted life years.
P261 Rate of Community Acquired Pneumonia, related hospitalization, and mortality among younger unvaccinated Inflammatory Bowel Disease patients
Authors: Khan N , Trivedi C , Shah Y , Patel M , Sundararajan R , Xie D , Yang Y X
Published: January 2023

Background

Community Acquired Pneumonia (CAP) is among the most common infections among Inflammatory Bowel Disease (IBD) patients. Current vaccine guidelines recommend vaccination at a younger age in individuals with IBD on immunosuppressive medications. Our aim was to determine the absolute and relative risk of CAP, related hospitalization, and death among unvaccinated IBD patients under the age of 65 years and compare the rates between those exposed and unexposed to immunosuppressive medications. We also sought to determine if exposure to immunosuppressive/immunomodulatory medications was associated with an increased risk of CAP in this group.

Methods

We conducted a retrospective cohort study utilizing a nationwide cohort of IBD patients under the age of 65 in the Veteran Affairs Healthcare System (VAHS) who were pneumococcal vaccine naive. The unexposed group included those patients on 5-ASA medications only. Exposure was administration of any immunosuppressive medication. The primary outcome was the first occurrence of pneumonia. Secondary outcomes were pneumonia related hospitalization and mortality. We reported event rate per 1000 person-years, hazard ratio, and 95% confidence intervals (CIs) for each outcome.

Results

A total of 26,707 patients were included in our study. 513 of these patients developed pneumonia (Table 1). The overall crude incidence rate of CAP was 3.2 per 1000 patient-years (4.04/1000 patient years in the exposed vs 1.45/1000 patient-years in the unexposed). The overall crude incidence rates for pneumonia-related-hospitalization and mortality were 1.12 and 0.09 per 1000 patient-years, respectively (Table 2). In Cox regression, exposed group was associated with an increased risk of pneumonia (AHR 2.85; 95% CI 2.21 – 3.66, p < 0.001) and pneumonia-related-hospitalization (AHR 3.46; 95% CI 2.20 – 5.43, p < 0.001) (Table 3).

Conclusion

Overall incidence of CAP among younger unvaccinated IBD patients was 3.2 per 1000 PY. We observed that while the incidence rates of CAP and CAP-related hospitalization were low overall, they were higher among those who received immunosuppressive therapy compared to those who only received 5-ASA medications. Knowing the exact risk of developing CAP among younger IBD patients will help patients and their physicians make informed decisions during these times of complex vaccine recommendations.
P269 Predicting IBD years before diagnosis using routine blood tests
Authors: Lev Zion R , Dolev A S , Greenfeld S , Kariv R , Ledderman N , Matz E , Dotan I , Kopylov U , Turner D , Lerner B
Published: January 2023

Background

Recent studies such as the GEM project have identified microbial, serological and metabolomic markers that may help predict inflammatory bowel disease (IBD) well in advance of diagnosis, with the ultimate goal of pre-disease prevention. In this population-based study, we used the epi-Israeli IBD Research Nucleus (IIRN) validated cohort to explore the utility of routine blood tests as markers for pre-diagnostic IBD prediction.

Methods

We included all blood tests from all IBD patients diagnosed from 2005-2020 insured in three of the four Israeli health maintenance organizations (HMOs), and individually matched each to two non-IBD controls. Test results were collected and collated by number of months pre-diagnosis, then reported over time until diagnosis. Means were compared using Welch's t-test with false discovery rate correction to account for multiple comparisons. Trends over time were analyzed to detect tests that showed divergence between cases and controls at least one year before diagnosis.

Results

Pre-diagnosis results from 142 different blood tests were collected for 7,630 Crohn’s disease (CD) patients and 6,026 ulcerative colitis (UC) patients (mean age 33.3±17.4 years for CD and 38 ± 17.9 years for UC).

Median duration of pre-diagnosis data collection was 50 (IQR 11-96) months for CD and 48 (IQR11-96) months for UC. Of the 142 tests, 24 (17%) showed significant differences between CD and controls at least one year pre-diagnosis (Figure 1); these included not only inflammation-related tests such as ESR, hemoglobin and albumin, but also seemingly unrelated tests such as bilirubin, cholesterol and creatinine.

In UC patients, no tests showed statistically significant differences at least one year pre-diagnosis.

Conclusion

We were able to detect changes in blood tests collected as part of routine care long before CD diagnosis, opening the possibility of detecting early signals of future CD in patients undergoing routine blood tests. These may be used for developing screening and prediction models for prevention strategies.

This research was partially supported by the Israeli Council for Higher Education (CHE) via the Data Science Research Center, Ben-Gurion University of the Negev, Israel. The epi-IIRN project has been funded by an educational grant from the Leona M. and Harry B. Helmsley Charitable Trust.
P272 Reduced delay in diagnosis of Crohn’s disease in patients presenting with perianal disease: results of a retrospective cohort study at a non-academic, IBD-expert centre in the Netherlands
Authors: Munster L , de Groof E J , van Dieren S , Mundt M W , D’Haens G R A M , Bemelman W A , Buskens C J , van der Bilt J D W
Published: January 2023

Background

In up to 10% of patients with Crohn’s disease (CD), a perianal fistula (PAF) or perianal abscess (PAA) is the first presenting symptom. Delay in diagnosis in those patients is common and twice as long as in the general CD population. For the majority of patients (>70%) diagnosis takes >12 months. Delay is associated with more complex fistula formation impairing opportunities for clinical and radiological fistula closure, currently only successful in 65% and 30% respectively (combining anti-TNF and surgery). Moreover, delay in diagnosis is associated with worse outcomes and impaired quality of life (QoL). Since 2017, a low threshold for diagnostic work-up (ileocolonoscopy) for CD in patients presenting with perianal disease was introduced by a dedicated IBD surgeon in order to reduce delay in diagnosis of CD.

Methods

Patient records of all consecutive patients ≥16 years presenting with perianal disease (before diagnosis of CD) were retrospectively assessed. Differences in delay of diagnosis, defined as the time between first presentation with a PAA/PAF and confirmed diagnosis of CD, and differences in outcome measurements between the period 2007-2016 and 2017-2021 were determined in those eventually diagnosed with CD.

Results

A total of 25 patients were included in this study (n=13 in 2007-2016 and n=12 in 2017-2021, 52% male) with median age at presentation of 27 years (IQR 21,5-38,5). In the period 2007-2016, a median delay of 33 months (IQR 23-64) in CD diagnosis was observed and less than 20% of patients were diagnosed within one year after the first perianal surgical procedure. In the period 2017-2021 the median time to diagnosis significantly decreased to only 3 months (IQR 0-5, p=,000) and the proportion of patients diagnosed within one year increased drastically up to 79% (p=,000). Due to the relatively limited number of patients, no significant differences in outcome measurements (e.g. (re)interventions before CD diagnosis, number of successful fistula closure rates (clinical/radiological), and stomas/proctectomies) could be demonstrated between the two periods.

Conclusion

This study showed a significantly reduced delay in diagnosis of CD in patients presenting with perianal disease by introducing a low threshold for diagnostic work-up for CD. The promising results of this study were reason to continue data collection in a larger prospective study (currently ongoing) that forms the basis for the international development of an evidence based clinical decision tool including a perianal Red Flag Index and calprotectin measurement to select those at risk of having CD. Reducing delay in diagnosis by using such a clinical decision tool may improve outcomes and QoL in patients with perianal Crohn de novo.
P274 Clinical manifestations, risk factors and prognostic factors of Cytomegalovirus Colitis in Inflammatory Bowel Disease patients
Authors: Hsieh C R , Le P H , Kuo C J , Yeh P J , Chiu C T
Published: January 2023

Background

CMV colitis is associated with acute flare-up and poor prognosis in inflammatory bowel disease (IBD). However, few studies showed the clinical manifestations, risk factors, prognostic factors and the impact of anti-viral treatment of CMV colitis in IBD inpatients. Therefore, we aimed to comprehensively analyze these issues in this largest cohort study in Asia.

Methods

We retrospectively enrolled 118 IBD patients, including 42 CMV colitis and 76 non-CMV colitis, confirmed by CMV immunohistochemistry (IHC) staining from colonic tissue biopsy, from the pathology database in a 4000-bed tertiary medical center between January 2000 and May 2021. The patient characteristics, clinical manifestations, risk factors, prognostic factors and the impact of anti-viral treatment were analyzed.

Results

Major clinical manifestations in the CMV group included bloody stool (75.6%), diarrhea (68.3%) and abdominal pain (61%). The risk factors of CMV colitis were hypoalbuminemia (p=0.008) and antibiotic exposure (p=0.029) (Table 1). Seventy-nine percent of patients with CMV colitis received anti-viral treatment. In view of overall IBD complications, biological failure (OR 4.034, CI 1.659-9.805, P=0.002) and antiviral agents use (OR 0.08, CI 0.008-0.787, P=0.03) were independent prognostic factors in multivariate analysis (Table 2). In CMV group, the patients receiving adequate anti-viral treatment (≧ 14 days) had significantly lower IBD complications (29.2% vs. 72.2%) than inadequate or no treatment, especially in Crohn’s disease (Table 3).

Conclusion

Hypoalbuminemia and antibiotics use were the risk factors for CMV colitis in IBD patients. CMV colitis and biological failure lead to more overall IBD complications. However, definitive diagnosis and adequate anti-viral therapy can decrease the overall IBD related complications.