Empirical rescue treatment of Helicobacter pylori infection in third and subsequent lines: 8-year experience in 2144 patients from the European Registry on H. pylori management (Hp-EuReg).

OBJECTIVE: To evaluate the use, effectiveness and safety of Helicobacter pylori empirical rescue therapy in third and subsequent treatment lines in Europe. DESIGN: International, prospective, non-interventional registry of the clinical practice of European gastroenterologists. Data were collected and quality reviewed until October 2021 at Asociación Española de Gastroenterología-Research Electronic Data Capture. All cases with three or more empirical eradication attempts were assessed for effectiveness by modified intention-to-treat and per-protocol analysis. RESULTS: Overall, 2144 treatments were included: 1519, 439, 145 and 41 cases from third, fourth, fifth and sixth treatment lines, respectively. Sixty different therapies were used; the 15 most frequently prescribed encompassed >90% of cases. Overall effectiveness remained <90% in all therapies. Optimised treatments achieved a higher eradication rate than non-optimised (78% vs 67%, p<0.0001). From 2017 to 2021, only 44% of treatments other than 10-day single-capsule therapy used high proton-pump inhibitor doses and lasted ≥14 days. Quadruple therapy containing metronidazole, tetracycline and bismuth achieved optimal eradication rates only when prescribed as third-line treatment, either as 10-day single-capsule therapy (87%) or as 14-day traditional therapy with tetracycline hydrochloride (95%). Triple amoxicillin-levofloxacin therapy achieved 90% effectiveness in Eastern Europe only or when optimised. The overall incidence of adverse events was 31%. CONCLUSION: Empirical rescue treatment in third and subsequent lines achieved suboptimal effectiveness in most European regions. Only quadruple bismuth-metronidazole-tetracycline (10-day single-capsule or 14-day traditional scheme) and triple amoxicillin-levofloxacin therapies reached acceptable outcomes in some settings. Compliance with empirical therapy optimisation principles is still poor 5 years after clinical practice guidelines update. TRIAL REGISTRATION NUMBER: NCT02328131.

Empirical Second-Line Therapy in 5000 Patients of the European Registry on Helicobacter pylori Management (Hp-EuReg).

BACKGROUND & AIMS: After a first Helicobacter pylori eradication attempt, approximately 20% of patients will remain infected. The aim of the current study was to assess the effectiveness and safety of second-line empiric treatment in Europe. METHODS: This international, multicenter, prospective, non-interventional registry aimed to evaluate the decisions and outcomes of H pylori management by European gastroenterologists. All infected adult cases with a previous eradication treatment attempt were registered with the Spanish Association of Gastroenterology-Research Electronic Data Capture until February 2021. Patients allergic to penicillin and those who received susceptibility-guided therapy were excluded. Data monitoring was performed to ensure data quality. RESULTS: Overall, 5055 patients received empiric second-line treatment. Triple therapy with amoxicillin and levofloxacin was prescribed most commonly (33%). The overall effectiveness was 82% by modified intention-to-treat analysis and 83% in the per-protocol population. After failure of first-line clarithromycin-containing treatment, optimal eradication (>90%) was obtained with moxifloxacin-containing triple therapy or levofloxacin-containing quadruple therapy (with bismuth). In patients receiving triple therapy containing levofloxacin or moxifloxacin, and levofloxacin-bismuth quadruple treatment, cure rates were optimized with 14-day regimens using high doses of proton pump inhibitors. However, 3-in-1 single capsule or levofloxacin-bismuth quadruple therapy produced reliable eradication rates regardless of proton pump inhibitor dose, duration of therapy, or previous first-line treatment. The overall incidence of adverse events was 28%, and most (85%) were mild. Three patients developed serious adverse events (0.3%) requiring hospitalization. CONCLUSIONS: Empiric second-line regimens including 14-day quinolone triple therapies, 14-day levofloxacin-bismuth quadruple therapy, 14-day tetracycline-bismuth classic quadruple therapy, and 10-day bismuth quadruple therapy (as a single capsule) provided optimal effectiveness. However, many other second-line treatments evaluated reported low eradication rates. ClincialTrials.gov number: NCT02328131.

Endoscopic Submucosal Dissection Skills Transfer to Clinical Practice after Hands-On Workshops: An International Survey.

BACKGROUND: Endoscopic submucosal dissection (ESD) is a complex procedure, requiring enhanced technical skills. Translation into clinical practice of ESD training programs has not been documented. Our aim was to assess ESD training pathways of endoscopists participating in dedicated workshops and its clinical impact on ESD outcomes. METHODS: Participants of live porcine models ESD workshops, from 2013 to 2019, were included. They were invited to complete a survey focusing on human ESD performance after training, prior skills/competencies, complete learning pathway, and clinical outcomes. RESULTS: From 118 invited participants, 40 (34%) completed the questionnaire. Nineteen (47%) endoscopists performed human ESD after the workshop, predominantly male (89%). At the beginning of human ESD, endoscopists had a mean of 7.7 (standard deviation (SD) 4.1) years of endoscopic experience and were all performing endoscopic mucosal resection (and emergency endoscopy. Before ESD practice, 100% of the participants were trained with live animal models and 68% with ex vivo models. The majority started clinical ESD in the lower third of the stomach or rectum (90%), with lesions ≤30 mm (89%). Each endoscopist performed a median of 19 (interquartile range 8-32) cumulative ESDs, over a mean of 3.9 (SD 2.0) years. Total en bloc resection rate was 92%, R0 resection rate 88%, and curative resection rate 86%, whereas adverse events remained <10%. Endoscopists with >10 human ESD procedures achieve clinical competence thresholds. CONCLUSIONS: Participants of ESD workshops are adequately skilled prior to clinical ESD, complying with recommendations for training and properly implementing the technique. Transfer to clinical practice, of prior ESD skills obtained in hands-on training courses, was documented. Structured training programs achieve clinical outcomes exceeding established standards, namely in the very initial clinical phase.

A Steep Early Learning Curve for Endoscopic Submucosal Dissection in the Live Porcine Model.

BACKGROUND: Endoscopic submucosal dissection (ESD) is a demanding procedure requiring high level of expertise. ESD training programs incorporate procedures with live animal models. This study aimed to assess the early learning curve for performing ESD on live porcine models by endoscopists without any or with limited previous ESD experience. METHODS: In a live porcine model ESD workshop, number of resections, completeness of the resections, en bloc resections, adverse events, tutor intervention, type of knife, ESD time and size of resected specimens were recorded. ESD speed was calculated. RESULTS: A total of 70 procedures were carried out by 17 trainees. The percentage of complete resections, en bloc resections and ESD speed increased from the first to the latest procedures (88.2%-100%, 76.5%-100%, 8.6-31.4 mm2/min, respectively). The number of procedures in which a trainee needed tutor intervention and the number of adverse events also decreased throughout the procedures (4 to 0 and 6 to 0, respectively). During the workshop, when participants changed to a different type of knife, ESD speed slightly decreased (18.5 mm2/min to 17.0 mm2/min) and adverse events increased again (0-2). CONCLUSIONS: Through successive procedures, complete resections, en bloc resections, and ESD speed improve whereas adverse events decrease, supporting the role of the live porcine model in the preclinical learning phase. Changing ESD knives has a momentarily negative impact on the learning curve.

Endoscopic submucosal dissection (ESD): how do Western endoscopists value animal models?

INTRODUCTION: Endoscopic Submucosal Dissection (ESD)was introduced in the West later than in the East. Our aim was to assess how Western endoscopists performing ESD have been trained and how they value animal models for training. MATERIAL AND METHODS: An online survey regarding training in ESD was sent to Western endoscopists who published articles on advanced resection techniques. RESULTS: From 279 endoscopists, 58 (21%) completed the questionnaire, of which 50 confirmed performance of clinical ESD. Endoscopists had a median of 15 years of endoscopic experience (IQR 9.75-20.25) and all of them were performing conventional EMR, before starting ESD. Prior to clinical ESD, 74% (n = 37) underwent training with ex vivo models, 84% (n = 42) with live animal models and 92% (n = 46) with at least, one of the two models. After starting clinical ESD, as trainers, 52% (n = 26) were involved with ex vivo and 60% (n = 30) with live animal models. Personal usefulness of ex vivo and live animal models was rated with a median of 9 (IQR 8-10) and 10 (IQR 8-10), out of 10, respectively. Courses with ex vivo and live animal models were considered a prerequisite before clinical practice by 84% (n = 42) and 78% (n = 39), respectively. CONCLUSIONS: Western endoscopists have extensive endoscopic experience before starting ESD. The majority had pre-clinical training with ex vivo and live animal models and more than half are acting as trainers of other endoscopists with these models. Animal models are considered very useful and deemed a prerequisite before clinical practice by the majority of the endoscopists.

Metabolic control of T cell immune response through glycans in inflammatory bowel disease.

Mucosal T lymphocytes from patients with ulcerative colitis (UC) were previously shown to display a deficiency in branched N-glycosylation associated with disease severity. However, whether this glycosylation pathway shapes the course of the T cell response constituting a targeted-specific mechanism in UC remains largely unknown. In this study, we demonstrated that metabolic supplementation of ex vivo mucosal T cells from patients with active UC with N-acetylglucosamine (GlcNAc) resulted in enhancement of branched N-glycosylation in the T cell receptor (TCR), leading to suppression of T cell growth, inhibition of the T helper 1 (Th1)/Th17 immune response, and controlled T cell activity. We further demonstrated that mouse models displaying a deficiency in the branched N-glycosylation pathway (MGAT5-/-, MGAT5+/-) exhibited increased susceptibility to severe forms of colitis and early-onset disease. Importantly, the treatment of these mice with GlcNAc reduced disease severity and suppressed disease progression due to a controlled T cell-mediated immune response at the intestinal mucosa. In conclusion, our human ex vivo and preclinical results demonstrate the targeted-specific immunomodulatory properties of this simple glycan, proposing a therapeutic approach for patients with UC.

Helicobacter pylori first-line and rescue treatments in patients allergic to penicillin: Experience from the European Registry on H pylori management (Hp-EuReg).

BACKGROUND: Experience in Helicobacter pylori eradication treatment of patients allergic to penicillin is very scarce. A triple combination with a PPI, clarithromycin (C), and metronidazole (M) is often prescribed as the first option, although more recently the use of a quadruple therapy with PPI, bismuth (B), tetracycline (T), and M has been recommended. AIM: To evaluate the efficacy and safety of first-line and rescue treatments in patients allergic to penicillin in the "European Registry of H pylori management" (Hp-EuReg). METHODS: A systematic prospective registry of the clinical practice of European gastroenterologists (27 countries, 300 investigators) on the management of H pylori infection. An e-CRF was created on AEG-REDCap. Patients with penicillin allergy were analyzed until June 2019. RESULTS: One-thousand eighty-four patients allergic to penicillin were analyzed. The most frequently prescribed first-line treatments were as follows: PPI + C + M (n = 285) and PPI + B + T + M (classic or Pylera® ; n = 250). In first line, the efficacy of PPI + C + M was 69%, while PPI + B + T + M reached 91% (P < .001). In second line, after the failure of PPI + C + M, two rescue options showed similar efficacy: PPI + B + T + M (78%) and PPI + C + levofloxacin (L) (71%) (P > .05). In third line, after the failure of PPI + C + M and PPI + C + L, PPI + B + T + M was successful in 75% of cases. CONCLUSION: In patients allergic to penicillin, a triple combination with PPI + C + M should not be generally recommended as a first-line treatment, while a quadruple regimen with PPI + B + T + M seems to be a better option. As a rescue treatment, this quadruple regimen (if not previously prescribed) or a triple regimen with PPI + C + L could be used but achieved suboptimal (<80%) results.

Management of epithelial precancerous conditions and lesions in the stomach (MAPS II): European Society of Gastrointestinal Endoscopy (ESGE), European Helicobacter and Microbiota Study Group (EHMSG), European Society of Pathology (ESP), and Sociedade Portuguesa de Endoscopia Digestiva (SPED) guideline update 2019.

Patients with chronic atrophic gastritis or intestinal metaplasia (IM) are at risk for gastric adenocarcinoma. This underscores the importance of diagnosis and risk stratification for these patients. High definition endoscopy with chromoendoscopy (CE) is better than high definition white-light endoscopy alone for this purpose. Virtual CE can guide biopsies for staging atrophic and metaplastic changes and can target neoplastic lesions. Biopsies should be taken from at least two topographic sites (antrum and corpus) and labelled in two separate vials. For patients with mild to moderate atrophy restricted to the antrum there is no evidence to recommend surveillance. In patients with IM at a single location but with a family history of gastric cancer, incomplete IM, or persistent Helicobacter pylori gastritis, endoscopic surveillance with CE and guided biopsies may be considered in 3 years. Patients with advanced stages of atrophic gastritis should be followed up with a high quality endoscopy every 3 years. In patients with dysplasia, in the absence of an endoscopically defined lesion, immediate high quality endoscopic reassessment with CE is recommended. Patients with an endoscopically visible lesion harboring low or high grade dysplasia or carcinoma should undergo staging and treatment. H. pylori eradication heals nonatrophic chronic gastritis, may lead to regression of atrophic gastritis, and reduces the risk of gastric cancer in patients with these conditions, and it is recommended. H. pylori eradication is also recommended for patients with neoplasia after endoscopic therapy. In intermediate to high risk regions, identification and surveillance of patients with precancerous gastric conditions is cost-effective.

Glycans as critical regulators of gut immunity in homeostasis and disease.

The diversity of glycans expression within a cell or an organism is enormous and the amount of relevant biological information that each glycan structure encodes is far from being clarified. The importance of glycans in health and life sciences is highlighted by their multiple functional implications in different cellular and molecular biology processes with impact in homeostasis and diseases, such as cancer and inflammatory conditions. Glycans actively participate in the regulatory circuits that govern both innate and adaptive immune response. Changes in the glycans repertoire occur during the transition from normal to inflamed conditions and the aberrant expression of glycans dictates either pro-inflammatory or anti-inflammatory responses. This review summarizes how glycans integrate the regulatory networks of immune response with a focus on gut immunity.

Helicobacter pylori cagA Promoter Region Sequences Influence CagA Expression and Interleukin 8 Secretion.

Heterogeneity at the Helicobacter pylori cagA gene promoter region has been linked to variation in CagA expression and gastric histopathology. Here, we characterized the cagA promoter and expression in 46 H. pylori strains from Portugal. Our results confirm the relationship between cagA promoter region variation and protein expression originally observed in strains from Colombia. We observed that individuals with intestinal metaplasia were all infected with H. pylori strains containing a specific cagA motif. Additionally, we provided novel functional evidence that strain-specific sequences in the cagA promoter region and CagA expression levels influence interleukin 8 secretion by the host gastric epithelial cells.

Helicobacter pylori chronic infection and mucosal inflammation switches the human gastric glycosylation pathways.

Helicobacter pylori exploits host glycoconjugates to colonize the gastric niche. Infection can persist for decades promoting chronic inflammation, and in a subset of individuals lesions can silently progress to cancer. This study shows that H. pylori chronic infection and gastric tissue inflammation result in a remodeling of the gastric glycophenotype with increased expression of sialyl-Lewis a/x antigens due to transcriptional up-regulation of the B3GNT5, B3GALT5, and FUT3 genes. We observed that H. pylori infected individuals present a marked gastric local pro-inflammatory signature with significantly higher TNF-α levels and demonstrated that TNF-induced activation of the NF-kappaB pathway results in B3GNT5 transcriptional up-regulation. Furthermore, we show that this gastric glycosylation shift, characterized by increased sialylation patterns, favors SabA-mediated H. pylori attachment to human inflamed gastric mucosa. This study provides novel clinically relevant insights into the regulatory mechanisms underlying H. pylori modulation of host glycosylation machinery, and phenotypic alterations crucial for life-long infection. Moreover, the biosynthetic pathways here identified as responsible for gastric mucosa increased sialylation, in response to H. pylori infection, can be exploited as drug targets for hindering bacteria adhesion and counteract the infection chronicity.

Dysregulation of T cell receptor N-glycosylation: a molecular mechanism involved in ulcerative colitis.

The incidence of inflammatory bowel disease is increasing worldwide and the underlying molecular mechanisms are far from being fully elucidated. Herein, we evaluated the role of N-glycosylation dysregulation in T cells as a key mechanism in the ulcerative colitis (UC) pathogenesis. The evaluation of the branched N-glycosylation levels and profile of intestinal T cell receptor (TCR) were assessed in colonic biopsies from UC patients and healthy controls. Expression alterations of the glycosyltransferase gene MGAT5 were also evaluated. We demonstrated that UC patients exhibit a dysregulation of TCR branched N-glycosylation on lamina propria T lymphocytes. Patients with severe UC showed the most pronounced defect on N-glycan branching in T cells. Moreover, UC patients showed a significant reduction of MGAT5 gene transcription in T lymphocytes. In this study, we disclose for the first time that a deficiency in branched N-glycosylation on TCR due to a reduced MGAT5 gene expression is a new molecular mechanism underlying UC pathogenesis, being a potential novel biomarker with promising clinical and therapeutic applications.

Antiplatelet agents and/or anticoagulants are not associated with worse outcome following nonvariceal upper gastrointestinal bleeding.

BACKGROUND: Nonvariceal upper gastrointestinal bleeding emerges as a major complication of using antiplatelet agents and/or anticoagulants and represents a clinical challenge in patients undergoing these therapies. AIM: To characterize patients with nonvariceal upper gastrointestinal bleeding related to antithrombotics and their management, and to determine clinical predictors of adverse outcomes. METHODS: Retrospective cohort of adults who underwent upper gastrointestinal endoscopy after nonvariceal upper gastrointestinal bleeding from 2010 to 2012. The outcomes were compared between patients exposed and not exposed to antithrombotics. RESULTS: Five hundred and forty-eight patients with nonvariceal upper gastrointestinal bleeding (67% men; mean age 66.5 ± 16.4 years) were included, of which 43% received antithrombotics. Most patients had comorbidities. Peptic ulcer was the main diagnosis and endoscopic therapy was performed in 46% of cases. The 30-day mortality rate was 7.7% (n = 42), and 36% were bleeding-related. The recurrence rate was 9% and 14% of patients with initial endoscopic treatment needed endoscopic retreatment. There were no significant differences between the exposed and non-exposed groups in most outcomes. Co-morbidities, hemodynamic instability, high Rockall score, low hemoglobin (7.76 ± 2.72 g/dL) and higher international normalized ratio (1.63 ± 1.13) were associated significantly with mortality in a univariate analysis. CONCLUSIONS: Adverse outcomes were not associated with antithrombotic use. The management of nonvariceal upper gastrointestinal bleeding constitutes a challenge to clinical performance optimization and clinical cooperation.

Out-of-hours endoscopy for non-variceal upper gastrointestinal bleeding.

BACKGROUND: Most countries lack a well-coordinated approach to out-of-hours endoscopy. Economic constraints and lack of resources have been identified as important barriers. OBJECTIVE: To assess the performance evaluation of an out-of-hours emergency endoscopy model of care. DESIGN: During a 3 year period (January 2010 to December 2012), data from consecutive outpatients (n = 332) with non-variceal acute upper gastrointestinal bleeding admitted or transferred to a single referral hospital were prospectively collected. RESULTS: 34% (n = 113) were direct admissions whereas 66% (n = 219) were transferred from other hospitals. Median time to upper endoscopy esophagogastroduodenoscopy (EGD) was 6 h and 7.7 h for direct admissions and transferred, respectively. EGD was performed within 24 h in 90% of the patients. Rebleeding, in-hospital mortality, 30 day mortality and need for surgery were respectively 9.8%, 5.8%, 7.4%, and 6.6% and were not significantly different between the two groups. Age, malignancy, and moderate to high clinical Rockall risk score were independent predictors of in-hospital mortality in both groups. Age remained as an important predictor of main outcomes in transferred patients, while comorbidities differed according to admission status and predictable outcomes. CONCLUSION: This gastroenterology emergency model improved access and equity to out-of-hours endoscopy in an effective, safe, and timely way, recognized by the rates and the homogeneity observed in the outcomes, between transferred patients and direct admissions.

Role of compliance in Helicobacter pylori eradication treatment: Results of the European Registry on H. pylori management.

BACKGROUND: Adherence to Helicobacter pylori (H. pylori) eradication treatment is a cornerstone for achieving adequate treatment efficacy. OBJECTIVE: To determine which factors influence compliance with treatment. METHODS: A systematic prospective non-interventional registry (Hp-EuReg) of the clinical practice of European gastroenterologists. Compliance was considered adequate if ≥90% drug intake. Data were collected until September 2021 using the AEG-REDCap e-CRF and were subjected to quality control. Modified intention-to-treat analyses were performed. Multivariate analysis carried out the factors associated with the effectiveness of treatment and compliance. RESULTS: Compliance was inadequate in 646 (1.7%) of 38,698 patients. The non-compliance rate was higher in patients prescribed longer regimens (10-, 14-days) and rescue treatments, patients with uninvestigated dyspepsia/functional dyspepsia, and patients reporting adverse effects. Prevalence of non-adherence was lower for first-line treatment than for rescue treatment (1.5% vs. 2.2%; p < 0.001). Differences in non-adherence in the three most frequent first-line treatments were shown: 1.1% with proton pump inhibitor + clarithromycin + amoxicillin; 2.3% with proton pump inhibitor clarithromycin amoxicillin metronidazole; and 1.8% with bismuth quadruple therapy. These treatments were significantly more effective in compliant than in non-compliant patients: 86% versus 44%, 90% versus 71%, and 93% versus 64%, respectively (p < 0.001). In the multivariate analysis, the variable most significantly associated with higher effectiveness was adequate compliance (odds ratio, 6.3 [95%CI, 5.2-7.7]; p < 0.001). CONCLUSIONS: Compliance with Helicobacter pylori eradication treatment is very good. Factors associated with poor compliance include uninvestigated/functional dyspepsia, rescue-treatment, prolonged treatment regimens, the presence of adverse events, and the use of non-bismuth sequential and concomitant treatment. Adequate treatment compliance was the variable most closely associated with successful eradication.

Double-balloon enteroscopy in the management of patients with Peutz-Jeghers syndrome: a retrospective cohort multicenter study.

BACKGROUND AND OBJECTIVE: Little is known about the clinical impact of double-balloon enteroscopy (DBE) in patients with Peutz- Jeghers syndrome (PJS).The aim of this study was to assess the efficacy and safety of DBE in the management of small-bowel polyps in PJS patients. PATIENTS AND METHODS: We conducted a multicentre, retrospective cohort study, which included all consecutive patients diagnosed with PJS who underwent DBE for polypectomy between January 2006 and August 2012. In all cases, previous videocapsule enteroscopy had shown at least one polyp ≥ 10 mm in size. RESULTS: Twenty-five patients (13 men; median age 36 years; 14 with prior laparotomy) underwent 46 DBE procedures (1 to 5 per patient, 44 via oral route). Polypectomy was performed in 39/46 DBEs. A total of 214 polyps were removed (median-size 30 mm), with a median number of polypectomies per procedure of 5.0 (range 1-18). The estimated maximum-sizes of resected polyps significantly decreased at each session: 30.0, 25.0, 20.0, 15.0, and 17.5 mm (p = 0.02). In 7 DBEs no polypectomy was performed (4-only minor polyps detected; 3-endoscopic irresecability). Complications occurred in 3/39 of therapeutic procedures (2-minor delayed bleeding; 1-mucosal tear), all of them dealt with conservative or endoscopic therapy. Six patients underwent elective surgery post DBE due to polyps not amenable for endoscopic resection. There were no small-bowel polyp related complications during a median follow-up of 56.5 months. CONCLUSION: DBE showed to be a safe and effective technique in the management of small-bowel polyps in PJS patients, allowing a presymptomatic and non-surgical approach.

Helicobacter pylori Diagnostic Tests Used in Europe: Results of over 34,000 Patients from the European Registry on Helicobacter pylori Management.

BACKGROUND AND AIMS: Several methods are available to diagnose Helicobacter pylori infection. Our objective was to evaluate the tests used for both the initial diagnosis and the confirmation of eradication after treatment in Europe. METHODS: The European Registry on the management of Helicobacter pylori infection is an international, multicentre, prospective, non-interventional registry aiming to evaluate the management of Helicobacter pylori-infected patients in Europe. Countries with at least 100 cases registered from June 2013 to April 2021, and with a validated diagnostic method were analysed. Data were quality reviewed. RESULTS: A total of 34,920 adult patients from 20 countries were included (mean age 51 years; 61% women). To establish the initial diagnosis, invasive tests were performed in 19,801 (71%) patients, non-invasive in 11,369 (41%), and both in 3437 (12%). The most frequent were histology (n = 11,885; 43%), a rapid urease test (n = 10,636; 38%) and an urea breath test (n = 7577; 27%). According to the age, invasive tests were indicated in 11,179 (77%) ≥50 years, and in 8603 (65%) <50 years. Depending on the country, the use of invasive tests ranged from 29-99% in <50 years to 60-99% in ≥50. Most of the tests used to confirm eradication were non-invasive (n = 32,540; 93%), with the urea breath test being the most frequent (n = 32,540; 78%). In 2983 (9%) post-treatment tests, histology (n = 1887; 5%) or a rapid urease test (n = 1223; 4%) were performed. CONCLUSION: A great heterogeneity was observed for the initial diagnosis and confirmation of the eradication. The reasons for the apparent lack of adherence to the clinical guidelines should be further explored.