Introduction

Functional dyspepsia (FD) is one of the most common diseases of the digestive system, which comprises two subtypes, postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS). Acid suppression therapy has been recognized as the first-line treatment for H.pylori-negative FD patients. Potassium-competitive acid blocker (PCAB), a novel acid suppressant, has the characteristics of faster onset of effect and more stable acid suppression compared with traditional proton pump inhibitor (PPI). However, there has been no prospective study of PCAB for FD treatment.

Aims & Methods

This study was therefore conducted to investigate the efficacy and safety of PCAB in FD patients, and initially explore the effects of PCAB on gut microbiota. Patients diagnosed with FD were included prospectively. Eligible subjects were randomly assigned to the trial group and placebo group by 2:1, respectively, to receive Tegoprazan or placebo treatment with 50mg once a day for 2 weeks. 7-point global overall symptom scale (GOSS) was used to evaluate the relief of dyspepsia symptoms (primary endpoint) before the trial and at 1 and 2 weeks after randomization. Quality of life was assessed using the short form Nepean dyspepsia index (SFNDI). The generalized anxiety disorder-7 (GAD-7) and patient health questionnaire -9 (PHQ-9) were used to evaluate anxiety and depression, respectively. Stool samples were collected for 16SrRNA sequencing to evaluate gut microbiota alterations. Blood samples were collected to detect blood routine and blood biochemistry, and drug-related adverse events reported by subjects were collected to evaluate the safety of Tegoprazan.

Results

A total of 84 subjects were randomized, including 55 in the trial group and 29 in the placebo group. Among the subjects, 58.3% (49/84) were females, the median age was 51.00 (38.75, 55.00) years, and the mean BMI was 21.21 ± 3.06kg/m². For FD subtypes, EPS accounted for 44.0% (37/84), and no significant difference between the two groups was evident. In addition, there were no significant differences in the GOSS score, GAD-7 score and PHQ-9 score between the two groups at baseline. In the ITT analysis, the overall response rate was 25.5% (14/55) in the trial group and 17.2% (5/29) in the placebo group at 1 week, with no significant difference between the two groups (P =0.392). The 2-week response rate was 38.2% (21/55) in the trial group and 27.6% (8/29) in the placebo group, with no significant difference between the two groups (P =0.331). The results of PP analysis were consistent with ITT analysis. In the analysis of FD subtype, the response rate of EPS receiving Tegoprazan for 1 week was 45.8% (11/24), and that of the placebo group was 7.7% (1/13), with significant difference between the two groups (P =0.027).The response rate at 2 weeks of treatment with Tegoprazan was 50.0% (12/24), and the response rate after 2 weeks of placebo treatment was 15.4% (2/13), with no significant difference between the two groups (P =0.074). No significant difference was found between Tegoprazan and placebo on PDS (P > 0.05). In terms of gut microbiota, after 2 weeks of Tegoprazan treatment, the abundance of fecal genus streptococcus increased significantly (P < 0.001), especially streptococcus salivarius. There were no significant differences in the incidence of adverse events between the trial group and the placebo group (P > 0.05). No severe adverse events occurred in this study.

Conclusion

Tegoprazan is suitable for short course treatment of EPS. For patients requiring long-term treatment with Tegoprazan, the benefits of acid suppression should be weighed against the risk of intestinal microbiota dysbiosis. Tegoprazan had a similar safety profile to placebo.

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

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

Irritable bowel syndrome (IBS) and functional dyspepsia (FD) are common disorders of gut-brain interaction (DGBI), and bloating and visible abdominal distension are common symptoms among individuals with IBS and/or FD. Bloating refers to a subjective sensation of tension or pressure in the abdomen, which may or may not be reported together with visible abdominal distension. The underlying pathophysiological mechanisms may differ, with bloating suggested to be more related to hypersensitivity and visible abdominal distension to altered motility. The prevalence of these two symptoms in IBS and FD, especially as distinct symptoms, is not well known.

Aims & Methods

The aim was to investigate the link between bloating and distension with IBS and FD. Therefore, we performed a population-based internet survey of adults in the US, UK, and Mexico, including Rome IV IBS and FD diagnostic questions, somatization (PHQ-12), and psychological distress (PHQ-4). Four groups were created: those meeting the Rome IV criteria for IBS only, FD only, both IBS+FD, and a reference group including individuals without IBS, FD and organic diagnoses that could result in IBS- or FD-like symptoms. Within each group, we identified individuals who reported ≥weekly bloating alone (B), ≥weekly visible abdominal distension alone (D), ≥weekly combined B+D, or neither of both. The relationship between B, D and B+D in those with IBS and/or FD vs. the reference group was investigated using logistic regression models.

Results

The analysis included 5,448 participants (49.7% female; mean age 46.5 years, range 18-99), with 131 meeting criteria for IBS only, 360 for FD only, 217 for IBS+FD and 4,740 for the reference group. A larger proportion of individuals with IBS only (64.9%), FD only (50.6%), and especially those with IBS+FD (88.5%) reported bloating and/or visible abdominal distension compared to the reference group (13.7%). In the IBS only group, 16.0% reported bloating alone, 8.4% visible abdominal distension alone, and 40.5% combined bloating and visible abdominal distension. In the FD only group this was 12.8% (B), 8.9% (D), and 28.9% (B+D), and in the IBS+FD group 18.9% (B), 8.3% (D), and 61.3% (B+D), respectively. Reporting bloating alone or combined bloating and visible abdominal distension was strongly linked to fulfilling criteria for IBS only, FD only, and concomitant IBS+FD vs. the reference group, with weaker links for visible abdominal distension in the absence of bloating (Table). After adjusting for age, sex, BMI, psychological distress and somatization, the links persisted. The strongest association was observed between combined bloating and visible abdominal distension (vs. neither) and concomitant IBS+FD (vs. the reference group); adjusted odds ratio 28.6 [95%CI 17.6-46.6].

Conclusion

Bloating and visible abdominal distension as distinct and overlapping symptoms are strongly linked to IBS, FD, and concomitant IBS+FD in the general population. Assessing bloating and visible abdominal distension as separate symptoms may be important to enable individualized treatment for individuals with IBS and FD.