Introduction

Helicobacter pylori (H.pylori) infection is the main risk factor for gastric cancer. Infection leads to chronic inflammation and gastric gland hyperplasia. We found that infection induces alterations in the stromal niche, such as inhibited secretion of BMP ligands and increased expression of BMP inhibitors. BMP signaling is known to be involved in differentiation of base progenitor cells into pit secretory cells. However, whether it plays a role in regulating mucosal antimicrobial defense is still unknown and we now investigate how the downregulation of BMP signaling affects mucosal inflammatory responses.

Aims & Methods

Exploiting in vivo murine models as well as in vitro assays, we aim to investigate how the downregulation of epithelial BMP signaling affects mucosal homeostasis.
3D gastric organoids were used to explore the role of BMP in epithelial responses to microbial proteins (qPCR, Western Blotting). The effects of epithelial BMP downregulation and stromal Il1r1 signaling were investigated by exploiting conditional knockout mice (Axin2CreERT2-Bmpr1afl/fl or Bmpr1a KO; Col1a2CreERT2-Il1r1fl/fl or Il1r1 KO) either uninfected or infected with H.pylori PMSS1. Tissue samples were analyzed via immunofluorescence, RNA-in situ hybridization and gene expression analysis (qPCR, whole transcriptome). 2D primary murine stromal cell culture were exploited to investigate stromal responses to inflammatory triggers.

Results

Exploiting 3D organoids, we demonstrate that epithelial cells activate NF-κB signaling in response to microbe-derived proteins, while this effect is inhibited upon BMP signaling activation. In vivo, inhibition of BMP signaling in the epithelium via knockout of Bmpr1a (Bmpr1a KO) not only causes gland hyperplasia but also strongly enhances inflammation at the pit of gastric glands, where it is absent in mice with functional BMP signaling. We explore the consequences of increased inflammation upon epithelial Bmpr1a KO, demonstrating via whole transcriptome analysis that this is linked to enhanced antimicrobial tissue responses and that KO mice show reduced H.pylori colonization. Moreover, we discover that the influx of IL-1β producing cells observed upon BMP signaling downregulation has an impact on stromal cells, which in turn produce pro-regenerative factors causing epithelial reprogramming into a highly proliferative fetal-like regenerative state. We demonstrate that Il1r1 KO mice, where stromal cells lack the ability to respond to IL-1β, do not show fetal-like reprogramming and are more colonized by H.pylori.

Conclusion

Chronic H.pylori infection causes tissue reprogramming into a fetal-like state via a crosstalk between epithelial, stromal and immune cells. This state is linked to an enhanced proinflammatory response, increased proliferation and boosters antimicrobial defense. We propose that long-term activation of this state may enhance the risk for malignant transformation.

Introduction

The urea breath test (UBT) is the clinic's most popular and accurate non-invasive diagnostic method for H. pylori infection. Yet, it is time-consuming and unavailable to some individuals. The oral rapid urease test (RUT) is an emerging non-invasive convenience method but lacks clinical data support.

Aims & Methods

A double-center, double-blind, methodological comparative design experiment is invited to evaluate the consistency of the oral RUT with UBT. 247 participants were enrolled. Their Dental plaque and tongue coating samples were collected, blind and tested with RUT.

Results

The significant association between the RUT and UBT was analyzed.A total of 247 participants were included in the study. The oral RUT showed a high level of agreement with the UBT. The sensitivity of the test reagent was 98.63% (95% CI: 92.64%, 99.76%), and the specificity was 96.34% (95% CI: 92.25%, 98.31%). The overall conformity rate was 97.05% (95% CI: 94.03%, 98.56%). The positive predictive value was 92.31%, and the negative predictive value was 99.37%. The positive likelihood ratio was 26.96, and the negative likelihood ratio was 0.01. The Kappa value was 0.97.

Conclusion

The efficacy of oral RUT for Helicobacter pylori infection diagnosis is extremely consistent with the UBT.

Introduction

Gastrointestinal (GI) hemorrhage accounts for 30% of acute decompensations in cirrhotic patients, with 60% originating from variceal bleeding. Each decompensation episode carries an in-hospital mortality rate of 13%, and a 6-week mortality rate of 20%, commonly assed using Child Pugh (CP) and MELD scores. The ALBI (Albumin-Bilirubin) score, which includes only two variables, offers a simplified evaluation of liver function. However, there is limited data on its utility in predicting short-term mortality in cirrhotic patients with GI hemorrhage.

Aims & Methods

This study aimed to evaluate the association between ALBI Score with short-term mortality in cirrhotic patients with GI hemorrhage. We conducted a prospective, cross-sectional study between January and December of 2023 at Hospital Roosevelt, Guatemala, including cirrhotic patients admitted for GI hemorrhage. Informed consent was obtained from all participants. Categorical variables were analyzed using the chi-square test, normally distributed continuous variables with Student’s t-test, and non-normally distributed variables with the Mann-Whitney U test. Logistic binary regression and AUROC analysis were used to assess associations with short-term mortality. Statistical analyses were performed using SPSS.

Results

A total of 187 patients were included: 50.8% female and 49.2% male, with a mean age of 56 among survivors and 58 among non-survivors. Of these, 52.9% had a prior diagnosis of cirrhosis, while 47.1% were newly diagnosed. Cirrhosis etiology was metabolic in 50.2%, alcoholic in 42.7%, autoimmune in 4.3%, HCV in 1.6%, and HBV in 1.1%. At admission, 80.8% had no ascites and 97.3% had no hepatic encephalopathy. he causes of GI hemorrhage were 86.1% esophageal varices, 3.2% gastric varices, 9.1% gastric ulcers, and 1.6% esophagitis.
Non-survivors had significantly lower systolic blood pressure (93.90 ± 16.3 mmHg vs. 107.92 ± 17.4 mmHg; p = 0.002) and mean arterial pressure (69.50 ± 14.5 mmHg vs. 79.67 ± 11.7 mmHg; p = 0.005) compared to survivors. Non-survivors exhibited significantly higher INR (1.79 ± 0.56 vs. 1.52 ± 0.41; p = 0.026) and total bilirubin (5.85 ± 8.73 mg/dL vs. 2.02 ± 2.82 mg/dL; p = 0.031), and lower serum albumin levels (2.40 ± 0.43 g/dL vs. 3.10 ± 0.54 g/dL; p < 0.001).

Prognostic scores were significantly higher among non-survivors: MELD (19.25 ± 10.09 vs. 13.57 ± 5.47; p = 0.002), MELD-Na (20.35 ± 9.76 vs. 14.44 ± 6.42; p = 0.002), Child-Pugh (9.15 ± 2.21 vs. 7.18 ± 1.90; p < 0.001), and ALBI score (-0.96 ± 0.51 vs. -1.76 ± 0.58; p < 0.001). Additionally, the length of hospital stay was significantly shorter among non-survivors (3.90 ± 3.82 days) compared to survivors (6.59 ± 5.58 days; p = 0.001).

Scores	Mortality In-Hospital	Mortality at 4 weeks	Mortality at 6 weeks
ALBI	AUC: 0.850 95% CI (0.780 - 0.921) p: 0.000	AUC: 0.881 95% CI (0.823 - 0.938) p: 0.000	AUC: 0.867 95% CI (0.806 - 0.927) p: 0.000
Child Pugh (CP)	AUC: 0.762 95% CI (0.668 - 0.857) p: 0.000	AUC: 0.819 95% CI (0.739 - 0.900) p: 0.000	AUC: 0.805 95% CI (0.728 - 0.881) p: 0.000
MELD	AUC: 0.714 95% CI (0.606 - 0.822) p: 0.002	AUC: 0.785 95% CI (0.693 - 0.878) p: 0.000	AUC: 0.786 95% CI (0.700 - 0.871) p: 0.000
MELD-Na	AUC: 0.711 95% CI (0.599 - 0.823) p: 0.002	AUC: 0.778 95% CI (0.683 - 0.873) p: 0.000	AUC: 0.783 95% CI (0.696 - 0.870) p: 0.000

Multivariable analysis showed that:

• Higher ALBI score was significantly associated with mortality (Risk Ratio 25.80; 95% CI: 6.75–98.67; p < 0.001),
• Hospital stay <5 days (RR 9.91; 95% CI: 2.07–47.47; p = 0.004),
• Endoscopy performed within 12 hours (RR 7.53; 95% CI: 2.01–28.15; p = 0.003).

Conclusion

The ALBI score outperforms CP and MELD scores in predicting short-term mortality (in-hospital, 4 weeks, and 6 weeks) in cirrhotic patients with GI hemorrhage. Observed mortality was 10% in-hospital, 13% at 4 weeks, and 16% at 6 weeks.

Introduction

Colorectal cancer (CRC) is the most common cancer in Spain, with an estimated 44,573 new cases in 2025. The standard CRC screening strategy involves the immunological faecal occult blood test (FIT), followed by colonoscopy in positive cases. However, the low specificity of FIT results in a significant number of unnecessary colonoscopies, placing a high burden on healthcare systems. There is a growing need to explore alternative screening strategies that offer better cost-effectiveness ratios. The gut microbiota plays a key role in CRC carcinogenesis, and several bacterial species involved in this process have been identified. A diagnostic tool based on the combination of FIT (cut-off 100 ng/mL – FIT100) and a bacterial signature has been designed to detect CRC and advanced lesions (AL, defined as ≥1 cm and/or high-grade dysplasia and/or a hairy component). This tool uses qPCR to analyse the relative abundance of specific bacteria in the same stool sample used for FIT testing. Previous studies, including a proof-of-concept (N=172), confirmatory study (N=327), and clinical performance study (N=2,481), have validated the tool.

Aims & Methods

This study aims to evaluate the diagnostic performance of the bacterial signature applied to FIT100 positive participants and its potential to reduce unnecessary colonoscopies in the CRC screening program in Catalonia.
A prospective observational study was conducted in a multicentre cohort across five hospitals, including participants from the CRC screening program with a positive FIT100. Blinding was applied to the FIT, bacterial signature, colonoscopy, and biopsy. Colonoscopy-biopsy was used as the reference standard. The study included 1,453 participants, of which 48 were excluded from the analysis mainly because of poor sample conditions, resulting in a final sample of 1,405 participants. Sensitivity was defined as the proportion of true positives detected by the FIT that the bacterial signature also identifies as positive. Specificity was defined as the proportion of false positives of FIT that the bacterial signature correctly identifies as true negatives.

Results

From the 1,405 analysed cases, 44 were CRC, 472 AL, and 889 without AL. For CRC detection, the sensitivity was 95.5%, with a specificity of 18.4%. The reduction in false positives was 18.4%. For AL and CRC combined, the sensitivity was 82.6%, with a specificity of 18.4%.

Conclusion

The bacterial signature applied to FIT100 positive participants demonstrates high sensitivity for CRC detection while reducing unnecessary colonoscopies by minimizing false positives. Its implementation in the CRC screening protocol could improve the overall efficiency of the screening process. Future studies should focus on cost minimization and assess the tool's cost-effectiveness to ensure a favourable risk-benefit ratio for broader implementation.

Introduction

Screening programmes for gastric cancer are currently being researched in Europe as part of the TOwards GAstric Cancer Screening Implementation (TOGAS) project (1). A ‘screen & treat’ approach for Helicobacter pylori (H. pylori), is one such strategy being assessed as part of a primary preventative measure. In order for such a programme to be viable, the availability of an effective treatment is paramount. Given the rising rates of antimicrobial resistance worldwide, careful consideration must be given to prescribing first-line treatment with the highest efficacy. This interim report evaluates key performance measures in the treatment of H. pylori within the Irish arm – representing the Western European cohort - of the TOGAS pilot screening programme.

Aims & Methods

This interim data evaluates the efficacy of 10-day treatment with single capsule combination therapy: Bismuth subcitrate 140mg/Metronidazole 125mg/Tetracycline 125mg, three tablets, four times daily (PYLERA, Juvise pharmaceuticals) with a high-dose proton pump inhibitor (Esomeprazole 40mg twice daily).
Secondary outcome measures include;

1. Treatment acceptance rate
2. Side-effect profile
3. Adverse events

3030 individuals aged 30-34 years were invited to undergo screening for H. pylori through their general practitioner or workplace in the period January 24-March 25. Those who tested positive on both serology (BIOHIT H. pylori IgG antibody) and 13-C urea breath test (IR Force 200, Richen Medical) were offered treatment. Treatment consisted of 10-day combination therapy (PYLERA) and a high-dose proton pump inhibitor (PPI). Eradication confirmation with a 13-C UBT was offered a minimum of 6 weeks post-treatment. Demographics, risk factors for infection, treatment effectiveness and side effect profile were recorded. Stata was used for statistical analysis. χ² test was used for comparison of categorical variables (significance level p<0.05).

Results

464 asymptomatic individuals were enrolled. The median age was 32; 48%(n=223) were male. 11%(n=50) tested positive on both serology and 13-C UBT. Those who tested positive were more likely to be male [64%] (p < 0.02), a history of current or previous smoking was found to be nonsignificant (34%, p <0.9). 96%(n=48) of positive participants consented to treatment; 2 were excluded from receiving treatment due to pregnancy. Among those treated, 96% (44/46) reported adherence rates of >90%. In those reporting compliance rates <90 %, side effect profile was the leading cause of non-compliance. Side effects were reported by 24% (11/46) of participants. These were predominantly gastrointestinal side effects and reported as mild-moderate in severity, 6% discontinued treatment on account of them (n=3). All symptoms resolved after cessation. No serious adverse events occurred. Post-treatment, a 13-C UBT was completed in 80% (n=37) of treated individuals. Eradication rates were 97% (36/37) in the per-protocol group and 89% (33/37) in the intention-to-treat group. Treatment discontinuation due to side effects was the leading cause of treatment ‘failure’. In those requiring 2^nd line therapy (n=4), levofloxacin-based quadruple therapy was found to be successful in 66%(2/3) of those who completed eradication follow-up.

Conclusion

Single capsule combination therapy and high-dose PPI achieved eradication rates of >90% in the per-protocol group. No serious adverse events occurred secondary to treatment. These interim results indicate that 10-day combination therapy serves as an effective first-line therapy for future population-based screening programmes in a European population.

References

1. Commission E. TOGAS - Towards Gastric Cancer Screening Implementation in the European Union: European Commission; 2023 [Available from: https://health.ec.europa.eu/non-communicable-diseases/cancer/europes-beating-cancer-plan-eu4health-financed-projects/projects/togas_en.

Disclosure

Dr. Deane reports receipt of research funding support from EU4 Health grant GA number: 101101252. Juvise pharmaceuticals provided PYLERA for this branch of the study.

Introduction

Europe’s Beating Cancer Plan identified the urgent need for a gastric cancer screening strategy. In response, the TOGAS consortium (TOwards GAstric cancer Screening in the European Union) was established to evaluate different methods for gastric cancer prevention and detection within Europe(1). One such approach involves population-based screening of young adults for Helicobacter pylori (H.pylori) as a primary preventative strategy.

Aims & Methods

The pilot study aimed to assess the feasibility of screening asymptomatic 30-34 year olds for H.pylori. Key outcome measures included:
1) Response rate
2) Seropositivity
3) Treatment acceptance rate
4) Treatment effectiveness
Methods: Individuals aged 30-34 years were invited to participate in free screening via GP practices or occupational-based screening programmes in the period January 2024- March 2025. Invitations were distributed through email or text message at the discretion of the recruitment stream. Exclusion criteria included prior history of treatment of H. pylori or gastrectomy. Those who tested positive on serology (BIOHIT H. pylori IgG antibody, antibody titer >30 IU/ml) were offered confirmatory 13-C urea breath testing (Richen IR Force 200). Positive participants were offered treatment with a 10-day regimen of single capsule combination therapy (Bismuth subcitrate 140mg/Metronidazole 125mg/Tetracycline 125mg, three tablets, QDS; PYLERA, Juvise pharmaceuticals) + Esomeprazole 40mg BD. Eradication confirmation was offered a minimum of 6 weeks post-treatment. Demographics, risk factors, and treatment effectiveness were recorded.
The calculated sample size for statistical significance at a 95% confidence interval with a presumed prevalence rate of 30% was 323. The Mann-Whitney U-test was used for comparison of continuous variables, and the Chi² test for categorical variables (significance set at p<0.05).

Results

3030 invites were distributed (80% GP practices, 20% occupation-based). 20%(n=604) of recipients expressed interest in participating. Among these; 5%(n=31) were excluded and 18%(n=109) refused or ceased responding. 464 consented to and completed the study. The median age of participants was 32, 48%(n=223) were male. 15% (n=75) of those who underwent serology testing were seropositive. 97% agreed to have a confirmatory 13-C UBT, of which 50/73 (66%) tested positive. The median titre in this dual positivity group was 109 IU/mL [range 40-142], compared to 37 IU/mL [range 32-148 IU/ml] in the 13-C UT negative group. Overall, the true ‘positivity’ rate among those who agreed to screening was 11%. 96%(48/50) of positive participants agreed to treatment, a further 2 were excluded due to pregnancy. Among those treated, 96% (44/46) reported >90% adherence. 1^st line eradication rates, confirmed by a 13-C UBT, were 97%(36/37) in the per-protocol group and 89%(33/37) in the intention-to-treat group. Side effects were reported by 24%, the majority of which were GI. 4 patients required 2^nd line therapy due to early discontinuation or poor compliance, 1 failed 2^nd line therapy on follow-up eradication confirmation.

Conclusion

These interim results indicate that a population-based H.pylori screening approach is feasible within an Irish population. Despite a decreasing worldwide prevalence, infection remains a persistent issue. Although initial response rates to screening are modest, this is a novel pilot programme and reflects trends seen in the early phases of other national screening programmes, such as the colorectal cancer screening. As public awareness increases, higher engagement rates are anticipated.

References

1. Commission E. TOGAS - Towards Gastric Cancer Screening Implementation in the European Union: European Commission; 2023 [Available from: https://health.ec.europa.eu/non-communicable-diseases/cancer/europes-beating-cancer-plan-eu4health-financed-projects/projects/togas_en.

Disclosure

Dr. Deane reports receipt of research funding support from EU4 Health grant GA number: 101101252

Clinical Case Summary

Introduction: This case describes a rare complication, triggered by SARS-CoV2 infection in a patient with Crohn’s disease (CD) and a long history of gastrointestinal and extraintestinal manifestations but otherwise stable at the infection onset.
Case Presentation: 25-year old male,non smoker, unvaccinated against COVID-19,with fistulizing and stricturing CD diagnosed at age 12 with multiple extraintestinal complications (articular,ocular, thrombotic, malnutrition). Therapeutic history is marked of various failed attempts over the years, ranging from many courses of steroids, anti-TNFalfa drugs, immunosupresives to holistic approaches until the age of 24 when he presented at our clinic and we initiated treatment with ustekinumab with a good response. During his previous visit,he presented with fever and COVID-19 infection. Radiologic image of the lung was normal but a computed tomography scan was performed to rule out a complication of CD. Both clinical and imaging evaluations confirmed a stable condition with colo-cutaneous fistula in partial remission. Four days later he presented with signs of acute abdomen, extremely distressed, hypotensive,tachycardic.
Tests revealed: leukocytosis, rised inflammatory markers, thrombocytopenia, high D-dimer. The scan suggested a perforation and was taken to surgery where the laparotomy confirmed it, at the level of the transverse colon. He suffered a cardiopulmonary arrest during the surgery and died despite resuscitative efforts.
Discussion: SARS-CoV2 virus binds to the human angiotensin-converting enzyme 2 receptors and triggers direct endothelial lesions and activation of prothrombotic factors resulting in a cascade of microvascular injury and ultimately ischemic tissue damage. Ischemia weakens the bowel wall, increasing risk of ulceration, necrosis,and perforation, especially in Crohn’s patients with fragile mucosa.
Conclusion: The case highlights the potential for fatal outcomes and the importance of close observation in CD patients during SARS CoV2 infection.

References

Images with the colo-cutaneous fistula before and after the treatment with ustekinumab
Ragiologic and computed tomography imaging from his previous visit with the first SARS-CoV2 positive test
Radiologic and computed tomography imaging from his last visit when he presented with acute abdomen