Introduction

The achievement of histological remission (HR) is a key treatment goal in ulcerative colitis (UC), as it is suggestive of better disease management and predicts response to therapy.
The absence of neutrophils in epithelium and lamina is crucial to define HR. However, the role of neutrophil number and localisation remains unclear. We aimed to develop a novel artificial intelligence (AI)-driven system to automate neutrophil detection, localisation, and quantification, supporting assessment of HR and enable the prediction of response to therapy.

Aims & Methods

We developed an AI-driven system by integrating two deep learning models to (1) segment whole slide images (WSIs) into epithelium, crypts and lamina propria and to (2) detect and quantify neutrophils. Outputs from these models were combined to compute neutrophil densities in the lamina propria, epithelium, and overall tissue. The optimal neutrophil density cut-offs to assess disease activity (Geboes score >2B.0) in UC patients were identified in the AMAC phase 2 Mirikizumab trial, and subsequently validated in the multicentre prospective PICaSSO cohort study. Cut-offs to determine treatment response at weeks 12 and 52 (histological improvement [HI; Geboes score ≤3.1] and histological remission [HR; Geboes score ≤2B.0]), were also evaluated.

Results

Table 1 shows the system diagnostic performance in assessing disease activity and predicting response to therapy at W12 and W52 in the Mirikizumab cohort.
303 WSIs from active UC patients from the multicentre, randomised, double-blind, parallel-arm, placebo-controlled phase 2 clinical trial of Mirikizumab were analysed. The model yielded a DICE SØrensen of 0.57 for segmentation, precision of 82.3% and recall of 77.0% for neutrophil detection. The system identified an overall optimal neutrophil density cut-off (cells/mm²) predictive of disease activity of >21.7.0 (>10.1 and >30.4 for epithelium and lamina propria, respectively), with an accuracy of 86% (85% and 85%, respectively). Further validation in the multicenter PICaSSO cohort yielded to similar results.
Moreover, the overall optimal cut-off to predict histological remission at W52 was <20.8 (<10.4 and <27.9 for epithelium and lamina propria, respectively), with an accuracy of 82.0% (81% and 80%, respectively).

Conclusion

Our novel AI-based system demonstrates strong potential as an automated tool to detect, localise, and quantify neutrophils to assess histological activity and predict response to therapy in a clinical trial UC cohort and real-world settings. This framework could be applied in clinical trials and routine clinical practice, offering objective guidance for personalised management in UC patients.

References

[1] Santacroce G, Meseguer P, Zammarchi I, et al. P406 A novel active learning-based digital pathology protocol annotation for histologic assessment in Ulcerative Colitis using PICaSSO Histologic Remission Index (PHRI). Journal of Crohn's and Colitis, Volume 18, Issue Supplement_1, January 2024, Pages i843–i844
[2] Graham S, Vu QD, Jahanifar M, et al. CoNIC Challenge: Pushing the frontiers of nuclear detection, segmentation, classification and counting. Med Image Anal. 2024;92:103047.

Disclosure

MI received research grants and consultant fees from Olympus, Pentax, Eli Lilly, and Janssen. All other authors declare no competing interests.

Introduction

Non-celiac gluten/wheat sensitivity (NCGWS) is characterized by gastrointestinal and extra-intestinal symptoms triggered by gluten/wheat ingestion. Symptoms of NCGWS overlap with those of irritable bowel syndrome (IBS) or functional dyspepsia (FD). Due to diagnostic challenges and symptom overlap, data on the prevalence and predictors of NCGWS among patients with IBS or FD, especially those with refractory symptoms, are limited.

Aims & Methods

This was a prospective, multicentric, double-blind, placebo-controlled, crossover trial conducted from October 2021 to March 2023 in India.This was prospectivly registered with the clinical trials Registry, INDIA (CTRI/2021/10/037323). Adults aged 18–65 years with Rome IV-defined irritable bowel syndrome (IBS) or functional dyspepsia (FD) refractory to standard treatment were enrolled after excluding celiac disease, wheat allergy, and alarm features. Participants underwent a two-step diagnostic protocol. In Step I, patients adhered to a 6-week strict gluten-free diet (GFD) under dietitian supervision. Weekly assessments of gastrointestinal and extra-intestinal symptoms, health-related quality of life (HRQoL), and psychological scores were performed using validated instruments. Gluten responders—defined by ≥30% reduction in one to three primary symptoms—were advanced to Step II: a randomized, double-blind, placebo-controlled gluten challenge with crossover. Subjects received indistinguishable gluten or placebo cookies (8 g/day) for one week, followed by a one-week washout and crossover. A ≥30% symptom difference between gluten and placebo phases confirmed non-celiac gluten/wheat sensitivity (NCGWS). Primary outcome was NCGWS prevalence; secondary outcomes included symptom and HRQoL changes post-GFD and predictors of NCGWS. Statistical analyses included intention-to-treat principles and multivariable regression to identify baseline predictors.

Results

Of the 252 patients screened, 177 were enrolled for 6-week GFD (step I), and 154 patients completed this phase (mean age 41.9±14.2 years, 53.2% males). Eighty two (52.3%) patients responded to GFD, of whom 77 entered step 2 (DBPCGC). Thirty one (20.1%) patients had significant symptom worsening on blinded gluten ingestion, suggesting the presence of NCGWS. Independent predictors of NCGWS were female gender, FD-IBS overlap, headache, fatigue, and anxiety. Significant improvements in gastrointestinal symptoms, health-related quality of life, and psychological scores were observed after GFD in responders. No significant impact of diet sequence was noted.

Conclusion

Introduction

Subjectively reported sleep disturbances are common in IBS¹, as are psychological comorbidities². Whilst sleep and psychological disorders are clearly linked, it has been demonstrated that sleep disturbances amongst IBS patients appear to exist independently of psychological factors³, raising the potential for sleep as a novel intervention target in IBS. Developing our understanding of the role and associations of sleep within the disease experience of IBS patients could lead to better treatment.

Aims & Methods

We aimed to compare the characteristics of patients with IBS according to the quality of their sleep. Participants were recruited from the NIHR research register ContactME-IBS. We collected data for demographics, gastrointestinal symptoms^4,5,6, psychological health⁷, quality of life^8,9, and impact on work and daily activities¹⁰using validated questionnaires among adults with Rome IV IBS. We dichotomised the cohort according to whether they were good or poor sleepers, defined by a Pittsburgh sleep index score >5¹¹. We compared the characteristics of the two groups to explore significant associations.

Results

Of 341 respondents with Rome IV IBS, 287 (84.16%) were poor sleepers. A significantly higher proportion of poor sleepers had been diagnosed with IBS for 5 years or more (82.2% vs 66.7% p=0.009). A greater proportion of good sleepers had a university or postgraduate level of education (59.3% vs 41.1% p=0.014), though this did not meet our threshold for statistical significance. Poor sleepers had a significantly higher burden of severe somatisation, nearly fivefold that of good sleepers (60.3% vs 13% p=<0.001). Poor sleepers reported higher levels of anxiety and depression symptoms. Amongst the good sleepers, none had abnormal depression scores. Poor sleepers experienced greater impairment of their work activities, and were more adversely affected in their home and social activities (p=<0.001 across all analyses). Though not statistically significant, poor sleepers reported higher IBS symptom severity. There was no statistically significant difference between poor and good sleepers in relation to their IBS subtype.

Table 1. Characteristics of Individuals with Rome IV IBS according to the quality of their sleep.

Conclusion

Individuals with Rome IV IBS who report poor sleep have significantly higher levels of somatisation and psychological comorbidity and are more adversely affected in both their work and personal lives, compared with those who report good sleep. Our findings could support the potential of sleep as an intervention target in the management of IBS.

References

1. Tu Q et al. Neurogastroenterol Motil. 2017;29(3).
2. Zamani M et al. Alimentary pharmacology & therapeutics. 2019;50(2):132-43.
3. Koloski NA et al. Alimentary pharmacology & therapeutics. 2021;54(5):627-36.
4. Palsson OS et al. Gastroenterology. 2016:S0016-5085 (16) 00180.
5. Whitehead W et al. Rome III: The functional gastrointestinal disorders, 3rd editionVirginia: Degnon Associates Inc. 2006:835-53.
6. Labus JS et al. Alimentary pharmacology & therapeutics. 2004;20(1):89-97.
7. Spiller R et al. Alimentary pharmacology & therapeutics. 2010;32(6):811-20.
8. Patrick DL et al. Digestive diseases and sciences. 1998;43:400-11.
9. Drossman DA et al. Official journal of the American College of Gastroenterology| ACG. 2000;95(4):999-1007.
10. Reilly M et al. Alimentary pharmacology & therapeutics. 2004;20(4):459-67.
11. Buysse DJ et al. Psychiatry research. 1989;28(2):193-213