Introduction

Use of Non-steroidal anti-inflammatory drugs (NSAIDS) is associated with gastrointestinal (GI) injury with the degree of damage depending on dose, duration of treatment, concomitant medication, and patient risk profile(Goldstein & Cryer, 2015; Lanza et al., 1999, 2018; Yeomans et al., 2018).

Aims & Methods

Previously, we have reported that the probiotic strain Bifidobacterium breve, Bif195 (DSM 33360) at doses of 50x10⁹ and 100x10⁹ CFU/day alleviated aspirin-induced mucosal injury in the small intestine(Mortensen et al., 2019) and the stomach(Damholt et al., 2021), respectively. Here, we report results from an additional randomized controlled double-blind trial (RCT) of Bif195 in a lower dose on NSAID-induced mucosal injury. Although the trials were not directly comparable in design, they provided an opportunity to evaluate the effect of different doses of Bif195. In this study the NSAID was ibuprofen given in a dose of 800 mg/day for 6 weeks. Video Capsule Endoscopy was used to assess small-intestinal damage and to calculate Lewis score throughout the study(Gralnek et al., 2008).

Results

A total of 160 subjects (63% women) were included in the full analysis set (randomized, consumed at least one dose of trial product and with available efficacy data for the primary endpoint) with mean ± SD body mass index of 26.8 ± 6.1 kg/m² and age of 27.3 ± 5.5 years. There were no effects of the Bif195 intervention on any of the primary and secondary endpoints. Low-dose Bif195 did not reduce ibuprofen-induced damage in the small intestine compared to placebo as evaluated by Lewis score (AUC, mean ± SEM 2358 ± 137 vs 2208 ± 123, p=0.474). It is noteworthy that the degree of damage associated with ibuprofen was markedly lower than that associated with aspirin in an earlier study (AUC, mean ± SEM 4351 ± 574)(Mortensen et al., 2019). Bif195 was well-tolerated, and no treatment-related adverse events were recorded. We conclude that the lower level of damage induced by ibuprofen compared to aspirin in combination with low dose Bif195, might have had an impact on the ability of the trial to identify an effect.

Conclusion

In summary, of three individual RCTs examining the effects of Bif195 on aspirin- and ibuprofen-induced gut mucosal injury, two showed benefits while one employing a lower dose of Bif195 in individuals exposed to ibuprofen failed to show benefit. While these studies suggest that the effects of Bif195 may be dose related this should be interpreted with caution due to the differences in injurious agent and trial design. The trial was registered at Clinicaltrials.gov: NCT04447924.

References

Damholt, A. B. et al. (2021). The probiotic bifidobacterium breve, BIF195, supports the defense against aspirin-induced gastrointestinal mucosal damage. Circulation, 144(SUPPL 1).
Goldstein, J. L., & Cryer, B. (2015). Gastrointestinal injury associated with NSAID use: a case study and review of risk factors and preventative strategies. Drug, Healthcare and Patient Safety, 7, 31–41.
Gralnek, I. M. et al. (2008). Development of a capsule endoscopy scoring index for small bowel mucosal inflammatory change. Alimentary Pharmacology & Therapeutics, 27(2), 146–154.
Lanza, F. L. et al. (2018). Endoscopic comparison of gastroduodenal injury with over-the-counter doses of new fast-dissolving ibuprofen and paracetamol formulations: a randomized, placebo-controlled, 4-way crossover clinical trial. Clinical and Experimental Gastroenterology, Volume 11, 169–177.
Lanza, F. L. et al. (1999). Specific inhibition of cyclooxygenase-2 with MK-0966 is associated with less gastroduodenal damage than either aspirin or ibuprofen. Alimentary Pharmacology and Therapeutics, 13(6), 761–767.
Mortensen, B. et al. (2019). Bifidobacterium breve Bif195 Protects Against Small-Intestinal Damage Caused by Acetylsalicylic Acid in Healthy Volunteers. Gastroenterology, 157(3), 637-646.e4.
Yeomans, N. D. et al. (2018). Randomised clinical trial: gastrointestinal events in arthritis patients treated with celecoxib, ibuprofen or naproxen in the PRECISION trial. Alimentary Pharmacology & Therapeutics, 47(11), 1453–1463.

Disclosure

SE and AD are employed at Chr. Hansen A/S.

Introduction

The extent of gastric atrophy(GA) is closely related to the incidence of Intestinal-type gastric cancer (GC). According to the Kimura-Takemoto classification, determining whether the atrophy extends beyond the cardia is key to assess the extent of GA. However, there is significant difficulty in determining whether the cardia is atrophied under endoscopy.

Aims & Methods

This study developed a novel artificial intelligence (AI)-assisted white light endoscopy system for identifying the cardia part and diagnosing cardia atrophy . In this multicenter study, patients undergoing upper gastrointestinal endoscopy at 5 hospitals in China were prospectively included between November 2022 and December 2024. Among them, a total of 895 patients from 2 units were assigned to the training and validation sets (292 with cardia atrophy and 603 without cardia atrophy) to establish a cardia atrophy diagnostic model. 220 patients from our unit (84 with cardia atrophy and 136 without cardia atrophy) were included in the internal test set. Additionally, a total of 354 patients from 3 other units were included in the external test set (106 with cardia atrophy and 248 without cardia atrophy). In the internal and external test sets, 3 senior and 3 junior endoscopists made online diagnoses, comparing the performance differences between physicians with different levles of experience and the AI-assisted cardia atrophy detection system.

Results

This study established a AI-assisted cardia atrophy diagnostic model and tested its diagnostic performance with multicenter image data in internal and external tests. In the internal test dataset, the accuracy, sensitivity, and specificity of the AI-assisted system were 0.927, 0.941, and 0.919, respectively, with a PPV of 0.878, NPV of 0.962, and AUC of 0.967. In the external test dataset, the accuracy, sensitivity, and specificity were 0.918, 0.894, and 0.931 respectively, with a PPV of 0.874, NPV of 0.943, and AUC of 0.953. Further comparison of the diagnostic efficiency of the AI-assisted system with endoscopists of different levels of experience revealed that both in the internal and external test set, the diagnosis accuracy, sensitivity, specificity, PPV, and NPV of the AI-assisted system were all higher than those of senior endoscopists. TheAI-assisted cardia atrophy diagnostic ROC curve area (AUC) was 0.967 and 0.953 in the internal and external test sets, respectively. Heat map analysis further showed a high consistency between theAI-assisted system and endoscopists in cardia atrophy diagnosis.

Conclusion

Our newly developed AI-assisted cardia atrophy diagnostic system shows superior performance in identifying cardia atrophy compared to senior endoscopists, and can be used to guide white light endoscopic judgment and targeted biopsies for cardia atrophy.

Introduction

Autoimmune-related phenomena appearing after anti-TNFα agent use are increasingly being reported. However, the precise pathogenesis has not been elucidated, and there is little evidence to establish a clear cause-effect relationship. Therefore, we evaluate whether exposure to anti-TNF agents is associated with the development of autoimmune diseases in patients with inflammatory bowel disease (IBD).

Aims & Methods

This population-based case-control study investigated all IBD patients identified from 2004 to 2018 using the Korean National Health Insurance Service (NHIS) database. IBD patients with diagnostic codes for autoimmune disease (central nervous system (CNS) event, psoriasis, interstitial lung disease (ILD), lupus or systemic vasculitis) was included as case in the study. Each case was matched to a control patient with IBD without the presence of autoimmune disease based on index date, age, sex, and subtype and diagnosis year of IBD. Incidence estimates were established by using the earliest claim data with diagnostic codes for autoimmune disease as the index date. Association with TNF inhibitor was evaluated with conditional logistic regression. Subgroup analyses were performed according to the type of autoimmune disease, and we also stratified anti-TNFα agent exposure according to drug type, cumulative frequency, and duration.

Results

During the study period, a total of 515,707 incident IBD patients (ulcerative colitis, 314,824; Crohn’s disease, 180,669) were included. We identified 45,430 cases of autoimmune disease and 470,277 unmatched controls. Of this total, more than two-thirds (68%) were over the age of 40 and median of IBD duration until diagnosis of autoimmune disease was 5.75 years. The proportion of cases with overall autoimmune disease who received treatment with anti-TNFα agents (3.2%) was higher than that of controls (2.4%). Exposure to anti-TNFα agents after IBD diagnosis significantly increased overall autoimmune disease risk by approximately 1.35, and the elevated risk was maintained even after adjusting for multiple confounding factors (adjusted odds ratio [AOR], 1.43; 95% CI, 1.35–1.51). Logistic regression analysis was also performed after matching and revealed that use of anti-TNF agents increases the risk of autoimmune disease compared to never use especially in psoriasis and lupus. In addition, the cumulative effect of anti-TNF agents, which increases the risk of autoimmune disease according to frequency, was confirmed (P_trend <0.0001).

Conclusion

This study found that exposure to anti-TNFα in patients with IBD appeared to be associated with increased risk of autoimmune disease especially psoriasis and lupus. It is presumed that inhibition of inflammatory cascade by anti-TNF agents induces other unexpected immune responses. Therefore, clinicians should be aware of the risks and benefits of theses agents and take appropriate measures to minimize potential adverse effects.