Efficacy of quadruple therapy with clarithromycin based on faecal molecular antimicrobial susceptibility tests as first-line treatment for Helicobacter pylori infection: a protocol of a single-centre, single-blind, randomised clinical trial in China

Introduction
Helicobacter pylori is the most well-known risk factor for gastric cancer. Antibiotic resistance is the main reason for the failure of H. pylori eradication, and understanding the antibiotic resistance before treatment may be the main determinant of successful eradication of H. pylori. This study aims to evaluate the efficacy and safety of quadruple therapy based on faecal molecular antimicrobial susceptibility tests for the first-line eradication of H. pylori infection.

Methods and analysis
This is a single-centre, single-blind, randomised controlled trial, enrolling 855 patients with H. pylori infection. Patients are randomised to three groups for a 14-day treatment: group A: amoxicillin- and clarithromycin-based bismuth-containing quadruple therapy (BQT) (rabeprazole 10 mg, amoxicillin 1 g, clarithromycin 500 mg and colloidal bismuth 200 mg two times per day); group B: clarithromycin medication history-based BQT (rabeprazole 10 mg, amoxicillin 1 g, furazolidone 100 mg (with clarithromycin medication history)/clarithromycin 500 mg (without clarithromycin medication history) and colloidal bismuth 200 mg two times per day); group C: antimicrobial susceptibility test-based BQT (rabeprazole 10 mg, amoxicillin 1 g, clarithromycin 500 mg (clarithromycin-sensitive)/furazolidone 100 mg (clarithromycin resistant) and colloidal bismuth 200 mg two times per day). The primary end point is the eradication rate. The secondary end points are the incidence of adverse events and compliance.

Ethics and dissemination
This study was approved by the Ethics Committee of Second Affiliated Hospital, School of Medicine, Zhejiang University (Number 20230103). The results will be published in the appropriate peer-reviewed journal.

Trial registration number
NCT05718609.

Leggi
Luglio 2023

Helicobacter pylori promotes colorectal carcinogenesis by deregulating intestinal immunity and inducing a mucus-degrading microbiota signature

Objective
Helicobacter pylori infection is the most prevalent bacterial infection worldwide. Besides being the most important risk factor for gastric cancer development, epidemiological data show that infected individuals harbour a nearly twofold increased risk to develop colorectal cancer (CRC). However, a direct causal and functional connection between H. pylori infection and colon cancer is lacking.

Design
We infected two Apc-mutant mouse models and C57BL/6 mice with H. pylori and conducted a comprehensive analysis of H. pylori-induced changes in intestinal immune responses and epithelial signatures via flow cytometry, chip cytometry, immunohistochemistry and single cell RNA sequencing. Microbial signatures were characterised and evaluated in germ-free mice and via stool transfer experiments.

Results
H. pylori infection accelerated tumour development in Apc-mutant mice. We identified a unique H. pylori-driven immune alteration signature characterised by a reduction in regulatory T cells and pro-inflammatory T cells. Furthermore, in the intestinal and colonic epithelium, H. pylori induced pro-carcinogenic STAT3 signalling and a loss of goblet cells, changes that have been shown to contribute—in combination with pro-inflammatory and mucus degrading microbial signatures—to tumour development. Similar immune and epithelial alterations were found in human colon biopsies from H. pylori-infected patients. Housing of Apc-mutant mice under germ-free conditions ameliorated, and early antibiotic eradication of H. pylori infection normalised the tumour incidence to the level of uninfected controls.

Conclusions
Our studies provide evidence that H. pylori infection is a strong causal promoter of colorectal carcinogenesis. Therefore, implementation of H. pylori status into preventive measures of CRC should be considered.

Leggi
Giugno 2023

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

Leggi
Maggio 2023

Farmaci: semplificare la prescrizione per quelli con piano terapeutico. Il position paper Fnomceo-Fism

Semplificare le procedure prescrittive per i farmaci attualmente sottoposti a registro di monitoraggio e a piano terapeutico. A chiederlo, la Federazione Nazionale degli Ordini dei Medici Chirurghi e degli Odontoiatri (FNOMCeO) e la Federazione Italiana delle Società Medico-Scientifiche (FISM), che hanno siglato oggi a Roma un Documento di posizione condivisa

Leggi
Aprile 2023

Large-scale, national, family-based epidemiological study on Helicobacter pylori infection in China: the time to change practice for related disease prevention

Background and aims
Current practice on Helicobacter pylori infection mostly focuses on individual-based care in the community, but family-based H. pylori management has recently been suggested as a better strategy for infection control. However, the family-based H. pylori infection status, risk factors and transmission pattern remain to be elucidated.

Methods
From September 2021 to December 2021, 10 735 families (31 098 individuals) were enrolled from 29 of 31 provinces in mainland China to examine family-based H. pylori infection, related factors and transmission pattern. All family members were required to answer questionnaires and test for H. pylori infection.

Results
Among all participants, the average individual-based H. pylori infection rate was 40.66%, with 43.45% for adults and 20.55% for children and adolescents. Family-based infection rates ranged from 50.27% to 85.06% among the 29 provinces, with an average rate of 71.21%. In 28.87% (3099/10 735) of enrolled families, there were no infections; the remaining 71.13% (7636/10 735) of families had 1–7 infected members, and in 19.70% (1504/7636), all members were infected. Among 7961 enrolled couples, 33.21% had no infection, but in 22.99%, both were infected. Childhood infection was significantly associated with parental infection. Independent risk factors for household infection were infected family members (eg, five infected members: OR 2.72, 95% CI 1.86 to 4.00), living in highly infected areas (eg, northwest China: OR 1.83, 95% CI 1.57 to 2.13), and large families in a household (eg, family of three: OR 1.97, 95% CI 1.76 to 2.21). However, family members with higher education and income levels (OR 0.85, 95% CI 0.79 to 0.91), using serving spoons or chopsticks, more generations in a household (eg, three generations: OR 0.79, 95% CI 0.68 to 0.92), and who were younger (OR 0.57, 95% CI 0.46 to 0.70) had lower infection rates (p

Leggi
Aprile 2023

Impact of Helicobacter pylori on the gastric microbiome in patients with chronic gastritis: a systematic review and meta-analysis protocol

Introduction
Chronic gastritis is a common disease worldwide. Studies have consistently shown that chronic gastritis is usually associated with gastric microbial dysbiosis, especially the infection of Helicobacter pylori. However, the interaction between H. pylori and non-H. pylori bacteria in patients with chronic gastritis has not been clearly identified yet. Consequently, we designed a protocol for a systematic review and meta-analysis, which focused on identifying the changes in gastrointestinal microbiota composition between patients with H. pylori-infective and non-infective chronic gastritis.

Method and analysis
We will search PubMed, EMBASE and Cochrane Library databases to retrieve observational studies on humans. The eligible studies must include data about the relative abundance of the gastrointestinal microbiome in patients with H. pylori-infective or non-infective chronic gastritis. Only the data of adults aged over 18 years will be analysed. Two researchers will extract the data independently, and Newcastle–Ottawa Scale will be used to assess the risk of bias. Random-effects model will be performed in quantitative analyses. Correlation analysis, bioinformatics analysis and function analysis will be performed.

Discussion
Currently, numerous studies have revealed the role of H. pylori in chronic gastritis. However, the alterations of non-H. pylori bacteria in patients with chronic gastritis remain an open question. The results of our study might provide new insights into future diagnosis and treatments.

Ethics and dissemination
This study is based on published documents, unrelated to personal data, so ethical approval is not in need. The results of this study are expected to be published in journals or conference proceedings.

PROSPERO registration number
CRD42020205260; Pre-results.

Leggi
Marzo 2023