bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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 &lt;250 mg/kg without steroid at month 12; undetectable levels of basal ethyl butanoate correlated with calprotectin &lt;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

Abstract

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 &lt;0.001), CD (aHR with 95% CI, 1.58 [1.237–2.013], p &lt;0.001) and UC (aHR with 95% CI, 1.26 [1.106–1.424], p &lt;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

Abstract

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

Abstract

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) &gt;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) &gt;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

Abstract

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

Abstract

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 &lt; 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

Abstract

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&lt;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&lt;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&lt;0.01) and (RR= 3.14, 95% CI 1.53-6.45, p&lt;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

Abstract

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

Abstract

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.