Introduction

Genome-wide association studies (GWAS) have identified more than 250 risk variants linked to inflammatory bowel disease (IBD). Most genetic variants increase the risk of disease onset, and their impact on clinical presentation is limited.^1,2,3 Variants in NOD2 and IL23R not only modulate the risk of disease onset, but also influence disease behaviour and localisation. Their role in predicting treatment response remains unclear.^3,4
A variant in an intron of TNRC18 (rs7486781, allele frequency 3.6%) was recently identified as having a strong risk-increasing effect (OR 3.2, p=2.4x10-61) for IBD in the FinnGen biobank study. The same allele was also associated with a risk for ankylosing spondylitis (AS), uveitis and psoriasis.⁵ The functional effect of rs7486781 is not yet fully established.⁶

Aims & Methods

The FinnGen biobank study includes the genotype data of 520 000 individuals and their longitudinal register data from national health registers, including 11 298 individuals with verified diagnosis for IBD. The data also include drug purchases, procedure codes and laboratory measurements of the individuals.
Our aim was to study the impact of the TNRC18-variant on IBD phenotype, particularly disease behavior. We assessed established aspects of disease severity⁷: use of immunosuppressants and advanced therapies, necessity to switch medications, frequent use of corticosteroids and risk of procedures. We also evaluated the presence of extraintestinal manifestations (EIM) and other disease complications.

Results

Regarding disease severity, the use of therapies beyond 5-ASA was more common among variant carriers; the use of thiopurines and other immunosuppressants (OR 1.21-1.27, p-values 1.35x10^-5 - 0.00849), ustekinumab and other IL-inhibitors (OR 1.46-1.48, p-values 0.00324 - 0.00286) and TNF-α-inhibitors (OR 1.26, p=0.00753) was more frequent.
In addition, perianal and anal canal operations were more prevalent with TNRC18 variant carriers (OR 2.44, p=1.41x10^-4), indicating perianal disease.
Assessing EIM, we observed that diagnoses for AS and uveitis (OR 1.62-1.67, p=1.3x10^-5 - 1.55x10^-4) were more frequent within IBD in patients with rs7486781.
Interestingly, a reduced risk of primary sclerosing cholangitis (PSC) was implicated by lower number of cholangitis (K83.0) diagnoses (OR 0.617, p=0.00221) and fewer purchases of ursodeoxycholic acid (OR 0.55, p=2.83x10^-5), in addition to lower levels of ALP (mean 75 vs 82, p=0.00296), IgG4 (mean 0.45 g/l vs 0.81 g/l, p=4.81x10^-5) and IgM (0.12 vs 0.15, p=0.00115) among variant carriers. All events survived the false discovery rate–adjusted p threshold of 0.05.
Our results also suggest that the cumulative risk for IBD related procedures⁸ (patients with procedures n=2209) from diagnosis and birth were elevated in TNRC18 variant carriers (HR=1.12 and HR=1.14, p=0.050 and p=0.023, assuming additive effect) using a Cox regression model.
Finally, our results in ulcerative colitis indicate that TNRC18 variant carriers are at higher risk of transitioning from 5-ASA/immunomodulators to biologics/JAK-inhibitors (HR=1.38, p=0.016). Variant carriers receiving immunomodulators or advanced therapies were not, however, in increased risk of colectomy (HR~0.97-1.34, p~0.86-0.37).

Conclusion

TNRC18 variant was associated with greater risk of operative treatment, the need of more advanced medication and perianal disease. AS and uveitis were more common EIMs, but PSC appeared less infrequent. Our preliminary results indicate that TNRC18 variant carriers might benefit from early intervention with immunomodulators or advanced therapies.

References

1. Chang, J. T. Pathophysiology of Inflammatory Bowel Diseases. N Engl J Med 383, 2652–2664 (2020).

2. Cleynen, I. et al. Inherited determinants of Crohn’s disease and ulcerative colitis phenotypes: a genetic association study. Lancet 387, 156–167 (2016).

3. Atreya, R. & Neurath, M. F. Biomarkers for Personalizing IBD Therapy: The Quest Continues. Clin Gastroenterol Hepatol 22, 1353–1364 (2024).

4. Kayali, S. et al. NOD2 and Crohn’s Disease Clinical Practice: From Epidemiology to Diagnosis and Therapy, Rewired. Inflamm Bowel Dis 31, 552–562 (2025).

5. Kurki, M. I. et al. FinnGen provides genetic insights from a well-phenotyped isolated population. Nature 613, 508–518 (2023).

6. Rahimov, F. et al. A genome-wide CRISPR screen supported by human genetics identifies the TNRC18 gene locus as a novel regulator of inflammatory signaling. bioRxiv 2023.10.04.560902 (2023) doi:10.1101/2023.10.04.560902.

7. Swaminathan, A. et al. The Disease Severity Index for Inflammatory Bowel Disease Is a Valid Instrument that Predicts Complicated Disease. Inflamm Bowel Dis 30, 2064–2075 (2024).

Disclosure

Anna Aarni: Speaker fee from Abbvie, Clinic visit: travelling expenses from Tillots Pharma

Pauliina Molander: Speaker, consultancy and advisory board member fees from Abbvie, Johnson & Johnson, Lilly, Pfizer and Takeda. Clinic visit: traveling expenses from Tillots Pharma

Jukka Koskela: Pfizer-FinnGen genetic advisory board, traveling, clinic and congress visits: FinnGen partners, Tillots Pharma, Takeda, consulting: Pfizer

Introduction

Acetic acid chromoendoscopy (AAC) is frequently used in Barrett esophagus (BE) surveillance endoscopies. AAC is believed to be useful as a ‘red flag’ technique, thereby improving the overall neoplasia detection and the diagnostic yield of targeted biopsies. Accurate targeted neoplasia detection with AAC therefore holds the promise of abandoning random four-quadrant biopsies at 2cm intervals of the BE segment. Although some data exist on the use of AAC in expert centers, the added value in a non-dysplastic surveillance population in routine clinical practice is currently unclear.

Aims & Methods

A prospective stepped wedge cluster randomized trial was conducted in 18 Dutch community hospitals. BE patients undergoing surveillance endoscopies were eligible, while those with known or previously treated dysplasia were excluded. Participating hospitals shifted from usual care (no AAC; control group) to the incorporation of AAC (AAC; intervention group) in randomized order. Endoscopists were trained in the use and assessment of AAC immediately prior to its implementation. In both study groups, targeted biopsies were obtained in the presence of visible lesions before the acquisition of random four-quadrant biopsies. Primary endpoint was the overall neoplasia detection rate, defined as the percentage of patients with low-grade dysplasia (LGD), high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC) in both targeted and random biopsies, confirmed by an experienced GI pathologist. Secondary endpoint was the neoplasia detection rate of targeted biopsies. Data were analyzed using an as-treated approach, employing mixed effects regression analyses with a random intercept per hospital and correction for calendar time and BE length.

Results

We included 2,267 patients (1570 males; mean age 66) between June 2020 and November 2023. A total of 1,438/2,267 (63%) patients were allocated to usual care and 829/2,267 (37%) to AAC. In patients allocated to AAC, AAC was applied in 679/829 patients (82%). Overall, 163/2,267 patients (7.2%) were diagnosed with neoplasia, which encompassed LGD in 111/2,267 patients (4.9%), HGD in 30/2,267 patients (1.3%), and EAC in 22/2,267 patients (1.0%). The use of AAC did not result in a significantly higher overall neoplasia detection rate (7.4% with AAC [50/679 patients] versus 7.1% without AAC [113/1,588 patients]; OR 0.97; 95% CI 0.65-1.44). Visible lesions were detected in 95/679 (14.0%) patients receiving AAC versus 101/1,588 (6.4%) patients receiving usual care (p<0.001), yet the targeted neoplasia detection rate was not significantly higher (2.1% [14/679 patients] versus 1.8% [29/1,588 patients]; OR 1.05; 95% CI 0.49-2.24). Neoplasia was detected by random four-quadrant biopsies in the majority of patients: 39/50 patients (78%) receiving AAC and 81/113 patients (72%) receiving usual care.

Conclusion

The use of AAC does not improve the overall or targeted neoplasia detection rate in BE patients undergoing endoscopic surveillance in routine clinical practice. Endoscopic surveillance with AAC-guided targeted biopsies cannot replace the random biopsy protocol.

Disclosure

Pentax Medical, C2 Therapeutics

Introduction

Functional gastrointestinal disorders (FGIDs), such as irritable bowel syndrome (IBS) and functional dyspepsia, are prevalent conditions within the field of Neurogastroenterology. These disorders have a profound impact on patients’ quality of life and demand a comprehensive biopsychosocial approach to care. Despite evidence in favor of integrated care, treatment remains largely pharmacological. To address this gap, our hospital established a dedicated Functional Neurogastroenterology Unit by incorporating a nurse trained in health coaching and Neuro-Linguistic Programming (NLP) supported by a custom GPT-based artificial intelligence (AI) tool aimed at enhancing patient communication and clinical decision-making.

Results & Findings

A descriptive observational study was conducted on nurse-led consultations between September 2024 and April 2025. The intervention integrated coaching sessions, Neuro-Linguistic Programming (NLP), and the use of a customized GPT-based system to support communication and care planning. Data collected included demographic characteristics, presenting symptoms, and referral patterns. Additionally, each patient was invited to write a personal narrative reflecting on their experience throughout the intervention.

Summary & Discussion

Forty-eight patients were attended during the study period (mean age: 38.6 years; 68.7% female). The most common diagnoses were functional dyspepsia, irritable bowel syndrome, and nonspecific digestive disorders. Frequently reported symptoms included bloating, epigastric pain, early satiety and burning. 20.8% of patients were referred to psychology services and 2.1% to psychiatry. Patient narratives revealed improvements in emotional self-regulation, greater sense of empowerment, and high levels of satisfaction. AI reduced administrative burden, improving focus on direct care, interdisciplinary communication, and adherence to treatment.

Conclusion

Coaching, NLP and AI are effective tools to address FGIDs from nursing, promoting personalized care and improving the patient's emotional well-being.

References

1.Alenazi, S. K., et al. (2024). Integrating Artificial Intelligence Technologies into Nursing Practice: Revolutionizing Patient Care and Healthcare Efficiency. Journal of International Crisis & Risk Communication Research (JICRCR), 7.
2.Barr, J. A., & Tsai, L. P. (2021). Health coaching provided by registered nurses described: a systematic review and narrative synthesis. BMC nursing, 20, 1-18.
3.Vitale, E., & Germini, F. (2021). Nurse coaching improves healthy conditions: an integrative review of the literature. Italian Journal of Medicine, 15(3).
4.Thomas, J. (2025). Artificial intelligence in nursing research: A narrative review of transforming clinical practice, enhancing patient outcomes, and shaping future care. decision-making, 1, 3.
5. Feingold JH, Drossman DA. Deconstructing stigma as a barrier to treating DGBI: Lessons for clinicians. Neurogastroenterol Motil. 2021 Feb;33(2):e14080. doi:10.1111/nmo.14080. Epub 2021 Jan 23.
6.Zia JK, Lenhart A, Yang PL, Heitkemper MM, Baker J, Keefer L, et al. Risk factors for abdominal pain-related disorders of gut-brain interaction in adults and children: A systematic review. Gastroenterology. 2022 Oct;163(4):995-1023.e3. doi:10.1053/j.gastro.2022.06.028. Epub 2022 Jun 16.
7.Alonso-Sierra M, Malagelada C, Serra J. Organization of Neurogastroenterology and Motility units with a multidisciplinary, patient-centered perspective. Rev Esp Enferm Dig. 2024 Jun;116(6):302-304. doi:10.17235/reed.2024.10368/2024.

Introduction

Helicobacter pylori (H. pylori) infection is a major cause of gastric diseases, with the virulence factor CagA carried by exosomes playing a crucial role in regulating inflammation. Ferroptosis and M1 polarization are key mechanisms in promoting inflammation, yet the role of CagA in inducing macrophage ferroptosis and M1 polarization to exacerbate gastric mucosal inflammation remains unclear.

Aims & Methods

CagA-positive (CagA+) and CagA-negative (CagA-) H. pylori strains were co-cultured with gastric epithelial cells, and their supernatants were collected. Exosomes were isolated using ultracentrifugation to obtain CagA+Exo and CagA-Exo. Changes in macrophage M1/M2 polarization markers and ferroptosis markers were analyzed under CagA+Exo and CagA-Exo treatment. The activation of the JAK/STAT1 signaling pathway was assessed by Western blot, and STAT1 expression in the nucleus was evaluated using a nuclear protein extraction kit. Chromatin immunoprecipitation (ChIP) was used to identify the binding site of STAT1 on the SLC7A11 promoter. Biopsy samples from the gastric mucosa of gastritis patients infected with CagA+ or CagA- H. pylori were analyzed for macrophage polarization and ferroptosis markers.

Results

Exosomal CagA was found to induce macrophage M1 polarization and ferroptosis, with the ferroptosis inhibitor SLC7A11 playing a key role in CagA-induced ferroptosis. Exosomal CagA activated the JAK/STAT1 signaling pathway, leading to M1 polarization and ferroptosis. Additionally, CagA+Exo increased nuclear STAT1 expression, which subsequently bound to the SLC7A11 promoter to regulate its transcription. In gastric mucosa biopsies from CagA+ H. pylori-infected gastritis patients, increased levels of iNOS (a marker of M1 polarization) and decreased expression of SLC7A11 were observed.

Conclusion

Our findings indicate that exosomal CagA promotes macrophage M1 polarization and ferroptosis through the JAK/STAT1 signaling pathway. This study provides new insights and potential therapeutic targets for H. pylori-associated gastritis.