Introduction

The Maastricht VI consensus recognizes the ¹³C-urease breath test (¹³C-UBT) as the “gold standard” in the diagnosis of H. pylori infection, including in patients with dyspepsia, in which this infection is detected quite often [1, 2]. Atrophic gastritis of the body of the stomach can cause both false-positive (due to the increased activity of urease producers other than H. pylori) and false-negative ¹³C-UBT result (due to a decrease in the microbial load of H. pylori associated with severe atrophy and metaplasia of the gastric mucosa and deterioration of habitual living conditions bacteria) [3]. Serological tests for the detection of H. pylori IgG are the primary screening method for H. pylori infection, recommended by the Maastricht VI consensus [1]. However, negative ¹³C-UBT and H. pylori antigen in stool with positive antibodies in patients with CAG, it often causes difficulties in assessing the H. pylori status, which emphasizes the relevance of searching for new diagnostic predictors.

Aims & Methods

Aim: evaluate the role of ferritin in determining the presence of H. pylori infection. 143 patients aged from 20 to 79 years were examined. The mean age was 59 (49–66) years. All participants underwent serum determination of pepsinogen-I (P-I), pepsinogen-II (P-II), gastrin-17 and antibodies to H. pylori; esophagogastroduodenoscopy with biopsy according to the OLGA system. Confirmation of H. pylori infection was performed by assessing the presence of antigen in stool using immunochromatography. To confirm autoimmune gastritis (AIG), the level of antibodies to parietal cells and intrinsic factor was determined in the blood. The indicators of clinical and biochemical blood analysis of patients (iron levels, ferritin) were assessed. When not normally distributed, quantitative data were described using the median (Me) and lower and upper quartiles (Q1–Q3). Comparison of two groups according to a quantitative indicator, the distribution of which differed from normal, was carried out using the Mann–Whitney U test. Comparisons of percentages in the analysis of multifield contingency tables were performed using the Pearson chi-square test.

Results

In 69.2% of cases, when verifying the etiology of CAG, AIH was identified, in 21.7% H. pylori-associated gastritis was identified, in 9.1% - CAG of mixed etiology. There was a weak positive correlation between P-I and iron levels (ρ=0.220, p=0.01), as well as between P-I and ferritin levels (ρ=0.229, p=0.007), the ratio P-I/ P-II and ferritin ρ=0.286, p<0.001), P-I/P-II and iron level (ρ=0.229, p=0.007). There was no relationship between P-II and iron content in the blood (ρ=0.025, p=0.775), as well as no association of P-II with ferritin levels (ρ=-0.085, p=0.323). When analyzing the concentrations of iron and ferritin, no statistically significant differences were revealed in these indicators depending on the stage of atrophy in CAG. When comparing groups of patients with IDA and iron deficiency, no statistically significant differences in the etiology of CAG could be found (p=0.167). When comparing ferritin values depending on the presence/absence of H. pylori antigen in stool, statistically significant differences were noted in this parameter (negative – Me = 43.0, 19.8–59.0, positive – Me = 67.0, 51, 7–80.5, p<0.001).

Conclusion

The presence of iron deficiency does not depend on the etiology of chronic atrophic gastritis. A positive correlation was revealed between P-I, P-I/P-II and iron deficiency. Ferritin levels may be a promising diagnostic predictor of H. pylori infection in patients with CAG.

References

1. Malfertheiner, Peter, et al. "Management of Helicobacter pylori infection: the Maastricht VI/Florence consensus report." Gut 71.9 (2022): 1724-1762.
2. Zakharova, N. V., et al. "Prevalence of helicobacter pylori infection in gastroenterological patients in Saint Petersburg." Pharmateca 5S (2016): 33-39.
3. Best, Lawrence MJ, et al. "Non‐invasive diagnostic tests for Helicobacter pylori infection." Cochrane Database of Systematic Reviews 3 (2018).

Disclosure

The authors declare that there is no conflict of interest

Introduction

The therapeutic landscape for ulcerative colitis (UC) is rapidly evolving, with an increasing number of biologic agents available.

Aims & Methods

This systematic review and meta-analysis synthesised randomised controlled trials (RCTs) data on biologic therapies for achieving key endoscopic and histologic endpoints in moderate to severe UC. A systematic search of MEDLINE, EMBASE, Cochrane Library, Web of Science and grey literature was conducted through November 2024. Separate meta-analyses were performed for induction and maintenance. A random-effects model was used to estimate relative risks (RR), with 95% confidence intervals (CI) and confidence in estimates was evaluated with the GRADE approach (Grading of Recommendation Assessment, Development and Evaluation).

Results

We included 40 RCTs (13 therapies , 14,369 patients). Thirty-two trials provided data in induction phase and twenty-eight in maintenance phase. During induction phase, all biologic therapies except for mirikizumab and filgotinib 100 mg demonstrated superiority over placebo (RR 2.02, 95% CI:1.76–2.31, I²=72%) for endoscopic improvement. Upadacitinib showed the highest efficacy (RR 5.53, 95% CI: 3.78-8.09). In biologic-naive patients and in patients with no previous biologic failure status upadacitinib 30mg had the highest efficacy (RR 4.07, 95% CI:2.69-6.16). In biologic-exposed patients or those with previous biologic failure, upadacitinib 30mg also showed the greatest benefit (RR 10.52, 95% CI:4.55-24.34). For induction of mucosal healing, all interventions were superior to placebo (RR 2.95, 95% CI:2.11–4.13,I²=61%), except for filgotinib 100 mg. Risankizumab showed the highest efficacy (RR 10.25, 95% CI:2.49-42.11). In maintenance phase, all therapies showed superiority over placebo for endoscopic improvement. Upadacitinib showed the highest efficacy (RR 4.18, 95% CI: 2.79–6.27). In biologic-naïve patients or those without prior biologic failure, all interventions—except filgotinib 100 mg and vedolizumab—were significantly superior to placebo, with etrasimod showing the highest efficacy (RR 3.12, 95% CI: 1.79–5.43). Among biologic-exposed patients or those with prior biologic failure, upadacitinib, mirikizumab, ustekinumab, etrasimod, tofacitinib, and risankizumab 180 mg were significantly superior to placebo. Upadacitinib showed the highest efficacy (RR 7.58, 95% CI: 3.42–16.8). For mucosal healing all therapies were superior to placebo, except for risankizumab. Upadacitinib showed the highest efficacy (RR 4.01 ,95% CI: 1.81–8.87). In biologic-naïve patients or those without prior biologic failure, only etrasimod, mirikizumab, upadacitinib 30 mg and subcutaneous infliximab were significantly superior to placebo, with upadacitinib showing the highest efficacy (RR 3.02, 95% CI: 1.18–7.71). Among biologic-exposed patients or those with prior biologic failure, only etrasimod, mirikizumab, and upadacitinib were significantly superior to placebo, with etrasimod demonstrating the highest efficacy (RR 9.45, 95% CI: 1.31–68.36).

Conclusion

Biologic and small-molecule therapies demonstrated substantial efficacy in achieving key endoscopic and histologic endpoints in moderate to severe UC. Upadacitinib consistently showed the highest efficacy across both induction and maintenance phases. Stratified analyses revealed enhanced response rates in biologic-naïve patients, supporting early initiation of advanced therapies. Our findings highlight the importance of individualised treatment strategies and the urgent need for standardised endpoint definitions to enhance comparability across future trials.

Introduction

Fecal Microbiota Transplantation (FMT) delivered through capsules is an effective therapy against recurrent Clostrdioides difficile infections (rCDI). Studies suggests that the viral part (mainly represented by bacteriophages) of donor stool plays an important role in FMT treatment effect[1]. Through filtration steps the viral fraction of donor stool can be separated from the bacterial part to produce material that can be capsulized and delivered as fecal virome transplantation (FVT) through capsules[2].
The goal of this study was to compare the effect of FVT capsules against FMT capsules as treatment of rCDI in a randomized controlled pilot trial.

Aims & Methods

In the VISION study treatment with FVT capsules was compared to the standard treatment of FMT capsules in 40 patients with first or second recurrence of C. difficile infection.
Participants were randomized 1:1 to receive either one dose of FMT or FVT capsule treatment preceded by approximately 10 days of Vancomycin 125 mg x 4 daily or Fidaxomycin 200 mg x 2 daily. The same four fecal donors were used to produce FMT and FVT material. The primary endpoint was clinical resolution defined as resolution of diarrhea with ≤ 3 daily bowel movements or persistent diarrhea with a negative C. difficile test result, eight weeks following treatment. Patients receiving antibiotics as treatment of other infections were treated with concurrent Vancomycin and were defined as treatment failures in the Intention-to-treat analysis but were excluded from the per-protocol analysis.

Results

Forty patients were randomized and received FMT or FVT capsule treatment with no significant difference between groups in baseline characteristics (Table 1). The primary outcome was achieved by 70 % (14/20) in the FVT group and 75% (15/20) in the FMT group with no significant difference between groups (p = 1). Three patients were omitted from the per-protocol analysis. Here the primary outcome was achieved by 73.7 % (14/19) in the FVT group and 83.3 % (15/18) in the FMT group with no significant difference between groups (p = 0.69).

Table 1. Baseline characteristics

Conclusion

FVT capsules were effective as treatment of rCDI and were non-inferior to FMT capsules. Larger trials are needed to further explore the efficacy of FVT capsules as treatment of rCDI.

References

[1] Liu Q, Xu Z, Dai M, Su Q, Leung Chan FK, Ng SC. Faecal microbiota transplantations and the role of bacteriophages. Clinical Microbiology and Infection 2023;29:689–94. https://doi.org/10.1016/j.cmi.2022.11.012.
[2] Rasmussen TS, Mao X, Forster S, Larsen SB, Von Münchow A, Tranæs KD, et al. Overcoming donor variability and risks associated with fecal microbiota transplants through bacteriophage-mediated treatments. Microbiome 2024;12:119. https://doi.org/10.1186/s40168-024-01820-1.

Disclosure

Frederik Cold declares support for attending meeting and/or travel from AbbVie and Orion Pharma, Andreas Munk Petersen declares support for attending meeting and/or travel from AbbVie, grants or contracts from Chr. Hansen A/S part of Novonesis and consulting fee from Genfit, Hengameh Chloe Mirsepasi-Lauridsen, Torben Sølbeck Rasmussen, Lars Hestbjerg Hansen, Sofie Ingdam Halkjær, Dennis Sandris Nielsen and Morten Helms declares no conflicts of interest.

Clinical Case Summary

A 64-year-old woman with a prior diagnosis of type I achalasia underwent Heller myotomy with Dor fundoplication in 2015, which resulted in the resolution of dysphagia and regurgitation. However, she kept experiencing chest pain, which partially improved with nitro-glycerine. In 2018, due to worsening pain, she underwent high-resolution oesophageal manometry (HROM), which demonstrated absent peristalsis without oesophageal pressurization. Also, upper endoscopy was unremarkable, and timed barium swallow (TBS) revealed some tertiary contractions. By 2019, the patient received botulinum toxin injections with partial improvement. Another TBS performed in 2023 showed tertiary contractions in the distal third of the oesophagus, contributing to mild oesophageal emptying delay but without stasis. In 2024, repeat HROM revealed pan-oesophageal pressurization, except in the distal-most centimetres of the oesophagus. During rapid drink challenge, the patient reported pain. Given these findings, she was proposed for peroral endoscopic myotomy (POEM) to extend the myotomy proximally. In August 2024, she underwent a complete distal oesophageal myotomy, including the lower oesophageal sphincter and cardia. Endoscopic assessment in November showed no evidence of stasis, esophagitis, or resistance at the cardia. Latest clinical evaluation in March 2025 confirmed complete resolution of chest pain.
Conclusion: Non-cardiac chest pain is a less common yet challenging symptom to manage in achalasia. Its persistence after disease-directed treatment has been described in the literature, with its primary risk factor being its presence preoperatively¹. However, comparative data on different therapeutic approaches for achalasia-related chest pain remain limited. To our knowledge, only two similar cases have been reported in which pain persisted after Heller myotomy but improved following POEM, probably linked to the inadequate or incomplete myotomy of the oesophageal muscle layer^2,3.

References

1. Olvera-Prado H, et al. Predictive factors associated with the persistence of chest pain in post-laparoscopic myotomy and fundoplication in patients with achalasia. Front Med (Lausanne). 2022 Oct 14;9:941581.
2. Miftahussurur M, Tandan M, Makmun D, Nabi Z. Peroral Endoscopic Myotomy in a Patient with Achalasia Cardia with Prior Heller's Myotomy. Case Rep Gastroenterol. 2020 Jan 22;14(1):48-55.
3. Sato C, et al. Salvage therapy for postoperative residual chest pain due to esophageal achalasia. SAGES 2017 Annual Meeting in Houston [Abstract], https://www.sages.org/meetings/annual-meeting/abstracts-archive/salvage-therapy-for-postoperative-residual-chest-pain-due-to-esophageal-achalasia/

Introduction

H. pylori eradication therapy induces significant alterations in the gut microbiome. While probiotics have been extensively studied as a potential strategy to mitigate microbiota-related consequences of antibiotics, their efficacy remains a subject of debate.

Aims & Methods

The aim of our study was to evaluate the influence of butyric acid+inulin supplements on gut microbiota changes (including gut microbiota taxonomic composition, functional potential, and gut resistome) induced by H.pylori eradication therapy. A total of 22 H. pylori-positive patients aged 19 to 64 years were enrolled in the study. Patients were randomized into two H. pylori eradication regimens: 1) ECAB-14: esomeprazole 20 mg, clarithromycin 500 mg, amoxicillin 1000 mg, and bismuthate tripotassium dicitrate 240 mg, twice daily, orally, for 14 days. 2) ECAB-Z-14: esomeprazole 20 mg, clarithromycin 500 mg, amoxicillin 1000 mg, and bismuthate tripotassium dicitrate 240 mg, twice daily, along with butyric acid+inulin (Zacofalk) supplementation (two tablets daily, each containing 250 mg of butyric acid and 250 mg of inulin), orally, for 14 days. Stool samples were collected from each subject at three time points: prior to eradication therapy (I), after therapy completion (II), and one month post-therapy (III). Total DNA from fecal samples was isolated for whole genome sequencing using the Illumina NextSeq 500 platform.

Results

Gut Microbiota Alpha Diversity (Shannon Index): Immediately after eradication therapy, both the ECAB-14 and ECAB-Z-14 groups experienced a significant decrease in gut microbiota alpha diversity compared to the initial level: (2.46 ± 1.06) vs. (3.75 ± 0.342), p = 0.0029, and (3.22 ± 0.73) vs. (3.82 ± 0.30), p = 0.037, respectively. After one month, the Shannon index was restored to the baseline level in the ECAB-Z-14 treatment group: no statistically significant differences were identified between time points III and I [(3.71 ± 0.33) vs. (3.82 ± 0.30), p = 0.206]. However, even a month after therapy, the ECAB-14 treatment group still exhibited a lower Shannon index than the baseline level [(3.27 ± 0.39) vs. (3.75 ± 0.342), p = 0.019].
Functional Potential Alterations: In the ECAB-Z-14 treatment group, less pronounced alterations in gut microbiota functional potential were observed. Specifically, 72 metabolic pathways changed immediately after eradication therapy. In contrast, the ECAB-14 group showed impact on 112 signaling pathways.
Butyrate Production Genes: The abundance of genes associated with butyrate production decreased only in the ECAB-14 treatment group. However, in the ECAB-Z-14 treatment group, the abundance of genes responsible for butyrate production remained stable.
Antibiotic Resistance Genes: The prevalence of gut microbiota antibiotic resistance genes increased significantly in both treatment groups immediately after eradication. Notably, more severe alterations were observed in the ECAB-14 treatment group, where the abundance of 73 antibiotic resistance genes significantly increased. Meanwhile, the ECAB-Z-14 group showed an increase in only 50 antibiotic resistance genes immediately after eradication therapy.

Conclusion

H. pylori eradication therapy significantly affects gut microbiota composition, functional potential, and increases the abundance of antibiotic resistance genes. However, the addition of butyric acid+inulin supplements to the H. pylori eradication regime may mitigate these effects.

Introduction

Infliximab is used to treat inflammatory bowel disease (IBD) but may be associated with adverse events such as infections. We describe hospitalization and emergency department (ED) visits among IBD patients using infliximab bio-originator (INF-O) or biosimilar (INF-B).

Aims & Methods

We used data from Canadian IBD Research Consortium (CIRC) cohorts contributing to CAN-AIM’s biosimilar registry, a pan-Canadian clinical registry of biosimilar/bio-originator users. We included people diagnosed with IBD who initiated infliximab between 2019-2023. Our outcome was self-reported hospitalization or ED visits, any time from INF initiation until outcome, treatment discontinuation or last information available. Categorical variables are presented as absolute numbers (percentage) and continuous as median (interquartile range, IQR). Kaplan-Meier curves with log-rank test and Cox regression model were used for time to event analyses for first hospitalization or ED - adjusted for sex and age at INF initiation.

Results

Of 158 individuals (78% INF-B), 53% had Crohn’s and 47% ulcerative colitis. Individuals were 54% male, 85% Caucasian, age at INF initiation at 37 years; 28% were using prednisone at enrolment. 16% were hospitalized at least once (first hospitalization within a median follow-up of 17 months (IQR 7-25) and 25% had at least one ED visit (first ED occurred at a median of 13 months, IQR 5-26). A total of 45 hospitalizations and 61 EDs were recorded. Most ED visits were due to IBD flare (n=33), infections (n=9), and other reasons (n=15). Most hospitalizations were for IBD-related surgery (n=19), IBD flare (n=16), and infections (n=7). Time from treatment initiation to first hospitalization or first ED was similar for INF-B and INF-O. Compared to INF-O, aHR for first hospitalization was 0.64 (95%CI 0.27-1.50) and ED was 0.72 (0.36-1.43) for INF-B.

Conclusion

In this real-world dataset, almost one-third of infliximab users for IBD had hospitalization or ED visits, often due to IBD flare, IBD-related surgery, and infections. We noted no clear differences between biosimilars and bio-originators, though limited sample size precluded precision.

Disclosure

Author disclosures (speaker, advisory board and/or grants): WA (Abbvie, Amgen, BMS, Dynacare, Eli-Lilly, Janssen, Merck, Novartis, Pfizer, Prometheus, Sandoz, Sanofi, Takeda); NN (Janssen, Abbvie, Takeda, Pfizer, Merck, Sandoz, Novartis, Fresinius Kabi, Amgen, Celltrion, Viatris, Innomar Strategies, Iterative Health, and Ferring); YL: (BMS; Janssen, Abbvie, Frenius Kabus; Amgen; Takeda, Pfizer, Lily, Pendopharm; BioJamp); HS (Amgen Canada, Roche Canada, Sandoz Canada, Takeda Canada, Pendopharm Inc and Guardant Health, Inc); MGB, LL, AN, LW, SB: nothing to disclose.