Introduction

Helicobacter pylori (H. pylori) infection remains a major public health problem. Given the high resistance to antibiotics worldwide, quadruple therapies have emerged as a major therapeutic option with unclear long-term consequences.

Aims & Methods

To evaluate if quadruple therapies determine major changes in the immunological profile of patients submitted to H. pylori eradication.
All patients were submitted to eradication treatment with five quadruple therapies (A-Concomitant with metronidazole 500mg tid, 14 days; B-Concomitant with metronidazole 500mg bid, 14 days; C-Quadruple with bismuth, 10 days; D-Sequential, 14 days; E-Hybrid, 14 days)) in a blind, randomized trial. Esomeprazole was the proton-pump inhibitor of choice. Efficacy and safety rates after 2 and 12 months of treatment were evaluated. Analysis of immunological changes included cell populations study by flow cytometry (CD4+, CD8+, B-cell, T-cell, natural killer cells and CD4+/CD8+-cells ratio).

Results

One-hundred-twenty-six patients (42.9% males; mean age: 57.4±16.7 years) completed the protocol. Overall efficacy and adverse events rates were 98.4% and 47.6%, respectively. After treatment, 36 patients (28.6%) developed other infectious diseases (mean time: 9.5±5.7 months), being severe (need for hospitalization) in 3 patients (8.3%). Comparing the post-treatment infection/non-infection groups, there was a significant decrease in the B-cell count (Z(2,52)=3.5;p=0.037). Regarding severe infections, there was a decrease in the CD4+/CD8+-cells ratio, CD4+ and B-cell counts (Z(2,52)=59.9,p<0.001; Z(2,52)=5.9,p=0.005 and Z(2,52)=12.0,p<0.001, respectively) and an increase in the CD8+ count (Z(2,52)=5.6;p=0.006). Considering the different regimens used, a significant decrease in the CD4+/CD8+-cells ratio was verified for regimen C compared to other non-bismuth quadruple therapies (Z(1.4,35.2)=5.2,p=0.019).

Conclusion

Quadruple therapies are highly effective in eradicating H. pylori gastric infection. However, these therapies are associated with adverse events, with infections occurring in ~1/4 of patients. There is a significant decrease in the CD4+/CD8+-cells ratio and B-cell count for all treatments, most significantly in the CD4+/CD8+-cells ratio for bismuth-containing regimen.

References

1. Zamani, M., Ebrahimtabar, F., Zamani, V., et al. (2018) Systematic review with meta-analysis: the worldwide prevalence of Helicobacter pylori infection. Aliment Pharmacol Ther 47(7), 868-876.
2. Malfertheiner, P., Megraud, F., O’Morain, C.A., et al. (2017) Management of Helicobacter pylori infection – the Maastricht V/Florence Consensus Report. Gut 66(1), 6-30.
3. Savoldi, A., Carrara, E., Graham, D.Y., et al. (2018) Prevalence of antibiotic resistance in Helicobacter pylori: a systematic review and meta-analysis in World Health Organization Regions. Gastroenterology 155(5), 1372-1382.
4. Lopo, I., Libânio, D., Pita, I., et al. (2018) Helicobacter pylori antibiotic resistance in Portugal: Systematic review and metaanalysis. Helicobacter 23(4), e12493.
5. Zhang, X., Arnold, I.C., Müller, A. Mechanisms of persistence, innate immune activation and immunomodulation by the gastric pathogen Helicobacter pylori. Curr Opin Microbiol. 2020;54:1-10.
6. Lee, S.K., Josenhans, C. Helicobacter pylori and the innate immune system. Int J Med Microbiol. 2005;295(5):325-34.
7. Pachathundikandi, S.K., Müller, A., Backert, S. Inflammasome Activation by Helicobacter pylori and Its Implications for Persistence and Immunity. Curr Top Microbiol Immunol. 2016;397:117-31.

Disclosure

None of the authors have anything to declare with regard to personal or financial interests in carrying out this work.

Introduction

Delayed perforation (DP) is a serious complication after colorectal endoscopic submucosal dissection (CESD), often requiring emergent surgery. Traditionally, DP has been managed conservatively or surgically. Recently, successful endoscopic closures have been reported. Since 2021, we have attempted endoscopic closure in patients meeting the following: (1) localized symptoms with stable condition, (2) no or minimal oral intake, and (3) endoscopic accessibility and feasibility of closure.

Aims & Methods

To compare clinical outcomes before and after the introduction of endoscopic closure for DP and to examine closure techniques. Among Among 4,848 CESD procedures (April 2008–December 2024), 16 cases (0.3%) of DP were identified. In Analysis 1, patients were divided into Group A (before closure: 2008–2020) and Group B (after closure: 2021–). In Analysis 2, closure techniques were reviewed. DP was defined as a perforation undetected during ESD but confirmed postoperatively by imaging or endoscopy.

Results

Analysis 1: Group A: 9 patients; Group B: 7. Median age: 72 vs. 70 years; male/female: 5/4 vs. 4/3. Lesion locations (cecum/ascending/transverse/sigmoid/rectum): Group A, 3/2/1/1/2; Group B, 1/3/2/1/0. Median specimen size: 48 mm vs. 46 mm.
Ulcer base closure (complete/partial/none): Group A, 2/2/5; Group B, 2/4/1. Histology (adenoma/serrated lesion/carcinoma in situ/adenocarcinoma/others): Group A, 3/4/1/1; Group B, 4/1/1/1. Median time to DP diagnosis: 63 vs. 55 hours.
Treatment in Group A was determined case-by-case; Group B applied defined criteria. Initial treatments (conservative/surgical/endoscopic): Group A, 5/4/0; Group B, 1/0/6. One case in each group initially managed conservatively required surgery later. Of 7 surgical cases, all underwent partial colectomy or drainage without stoma creation. All 6 endoscopic closure cases avoided surgery. Surgical avoidance rate: 33% vs. 86% (p=0.06).
Median time to oral intake: 8 vs. 7 days (p=0.67). Median hospitalization: 16 vs. 11 days (p<0.05).
Analysis2: All 6 closures were performed without bowel preparation. Two patients had resumed oral intake, but endoscopy was performed early.
Perforation diameter: median 10 mm (5–15). Closure methods: over-the-scope clip (OTSC; n=1), hemostatic clips (n=4), clips with polyglycolic acid (PGA) sheet (n=1).

Conclusion

Endoscopic closure for DP was associated with higher surgical avoidance and shorter hospitalization, without worsening outcomes. It may offer an effective treatment option for selected patients.​

Introduction

Delayed bleeding after gastric endoscopic submucosal dissection (ESD) is a serious complication in older adults. The BEST-J score, developed by Hatta et al. (Gut, 2021), is widely used for bleeding risk stratification but does not reflect systemic factors. The Prognostic Nutritional Index (PNI), calculated as [10 × serum albumin (g/dL)] + [0.005 × total lymphocyte count (/μL)], may complement this score. This study evaluated whether combining PNI with the BEST-J score improves risk stratification.

Aims & Methods

We retrospectively analyzed 252 patients who underwent gastric ESD between April 2016 and February 2025, including 127 older (≥75 years) and 125 younger (<75 years) individuals. Patients were classified into low (<40) and high (≥40) PNI groups. The association between delayed bleeding, PNI, and BEST-J score was analyzed using receiver operating characteristic (ROC) analysis. To evaluate internal validity, we conducted 5-fold cross-validation of a logistic regression model that added 1 point for PNI < 40 to the BEST-J score. A cutoff value of PNI < 40 was used, based on previously reported clinical thresholds reflecting impaired nutritional and immune status, including its predictive value for bleeding in various clinical settings (Zhao et al., 2024; Lin et al., 2021).

Results

The delayed bleeding rate was 4.7% in the older group and 0.8% in the younger group. Mean PNI was lower in bleeding cases (44.7) than in non-bleeding cases (48.5). Among older adults, the AUCs for PNI and BEST-J alone were 0.65 and 0.72, respectively. Adding 1 point for PNI < 40 improved the AUC to 0.82. Cross-validation confirmed good model reproducibility, with a mean AUC of 0.861 and standard deviation of 0.147, indicating stable predictive performance without overfitting. The inclusion of PNI < 40 enhanced model sensitivity for identifying bleeding cases without substantially compromising specificity, improving clinical applicability. These associations were most prominent in older patients, supporting age-specific application of the combined model.

Conclusion

The combination of BEST-J and PNI provides an improved and practical approach to risk stratification for delayed bleeding after gastric ESD in older adults. Cross-validation supports the model's internal validity and suggests applicability to broader clinical populations. Given the disproportionately higher bleeding risk in the older cohort, our findings underscore the importance of incorporating host-related factors such as nutrition into stratification strategies specifically in this age group.

References

1. Hatta W, Tsuji Y, Yoshio T, et al. Prediction model of bleeding after endoscopic submucosal dissection for early gastric cancer: BEST-J score. Gut. 2021;70(3):476–484. doi:10.1136/gutjnl-2019-319926.
2. Zhao Y, Chen X, Zhang M, et al. Association of Prognostic Nutritional Index with Post-Discharge Bleeding in Acute Coronary Syndrome Patients on Dual Antiplatelet Therapy. Front Cardiovasc Med. 2024;11:11995920.
3. Lin Y, Wang J, Chen Z, et al. Preoperative Prognostic Nutritional Index Predicts Intraoperative Transfusion and Surgical Outcomes in Hepatocellular Carcinoma Patients Undergoing Hepatectomy. Cancers (Basel). 2021;13(11):2508.

Introduction

Swallowed topical steroids are highly effective for treating eosinophilic oesophagitis (EoE). Budesonide Orodispersible Tablet (BOT) is the first on-label drug developed for EoE, whereas Budesonide Viscous Solution (BVS) has been used off-label. We previously showed favourable outcomes with Budesonide once daily in EoE (1). This study aimed to evaluate the feasibility and real-world efficacy of maintenance therapy with BOT after initial therapy with BVS for EoE.

Aims & Methods

A retrospective analysis was conducted of a prospectively collected database of confirmed EoE patients at a tertiary care centre. Patients using BVS 1mg once or twice daily with adequate follow-up (endoscopy and histology) were switched to BOT 1mg once or twice daily. Dysphagia Symptom Questionnaire (DSQ), Eosinophilic Esophagitis symptom Activity Index (EEsAI), Adult Eosinophilic Esophagitis Quality of Life Questionnaire (EoE-QOL-A) were completed at baseline and after switch. The primary endpoint was histological remission, defined as <15 eosinophils per high-power field (eos/HPF). Secondary endpoints included deep histological remission (<6 eos/HPF), peak eosinophil count (PEC), total endoscopic reference scores (EREFS), endoscopic remission (EREFS ≤2) and clinical symptoms. The safety endpoint was the endoscopic suspicion of oropharyngeal or oesophageal candidiasis. Data are presented as proportions or medians with interquartile ranges, using non-parametric paired tests for proportions (McNemar) or other variables (Wilcoxon).

Results

Forty-seven patients (34 males; age 35 (28-41) years and BMI 24.3 (20.9-27.5) kg/m²) were included, with a follow-up period of 225 (164.5-421) days and 161 (90.5-182) days of BOT intake. Histological remission was achieved by 32 out of 47 patients (68.1%) taking BVS, with 28 patients (59.6%) reaching deep histological remission. After switching to BOT, 46 patients (97.9%) achieved both histological (P<.001) and deep histological remission (P<.0001). The PEC significantly improved from 1 (0-21.5) to 0 (0-0) after switch (P<.0001). The EREFS score significantly improved from 1 (0-2) to 0 (0-1) after switch (P<.0001). The number of patients in endoscopic remission significantly increased from 36 (76.6%) taking BVS to 45 (95.7%) after switching to BOT (P<.01). Significant improvements were observed in the EoE-QoL-A score, from 77 (62.5-86.5) to 86.5 (66.8-90) (P<.01), and in the NRS score, from 1 (0-2) to 0.5 (0-1) (P=.04). The DSQ and EEsAI scores remained low after switch. Clinical remission was achieved by 74.1% at baseline and 71.9% after switch (P=1). Three patients (6.4%) taking BVS had an endoscopic suspicion of candidiasis, which numerically increased to nine patients (19.2%) after switching to BOT (P=.1). Results were similar for maintenance treatment with BOT 1mg once (N=31) or twice daily (N=12) and only four patients switched from BVS twice daily to BOT once daily (Table).

Conclusion

Treatment with BOT after switching from BVS is feasible and highly effective in EoE patients. The increase in candidiasis with BOT has been linked to treatment response and adherence in EoE (2). A longer follow-up of maintenance therapy with BOT is ongoing.

References

1. Raymenants K et al. The Effectiveness of Budesonide Once Daily as Maintenance Treatment of Eosinophilic Esophagitis. J Clin Gastroenterol 2025;Online ahead of print.
2. Cameron B et al. Esophageal Candidiasis Is Strongly Associated With Treatment Response to Topical Steroids in Eosinophilic Esophagitis and Could Be a Marker of Adherence. Gastro Hep Adv 2024;3(5):612.