Triple-drug combination therapy versus six-month proton pump inhibitor monotherapy in non-Helicobacter pylori Helicobacter eradication, and hyperacid environment preference of Helicobacter suis: a clinical study.

BACKGROUND: At present, eradication regimens for non-Helicobacter pylori Helicobacter (NHPH) have not been established yet. We investigated effectiveness of the standard triple-drug combination therapy for Helicobacter pylori eradication and of a proton pump inhibitor (PPI) monotherapy in eradication of NHPH. METHODS: Subjects were the patients who were diagnosed with NHPH-infected gastritis based on microscopic findings, helical-shaped organisms obviously larger than Helicobacter pylori, in the gastric mucosal specimens using Giemsa staining at Kenwakai Hospital between November 2010 and September 2021, whose NHPH species were identified by polymerase chain reaction (PCR) analysis of urease genes in endoscopically-biopsied samples, and who consented to NHPH eradication with either the triple-drug combination therapy for one week or a PPI monotherapy for six months. Six months after the completion of eradication, its result was determined with esophagogastroduodenoscopy, microscopic examination, and PCR analysis. In cases of unsuccessful eradication, a second eradication with the other therapy was suggested to the patient. RESULTS: PCR analysis detected NHPH in 38 patients: 36 as Helicobacter suis and two as Helicobacter heilmannii/Helicobacter ailurogastricus. Fourteen Helicobacter suis-infected and one Helicobacter heilmannii/Helicobacter ailurogastricus-infected patients requested eradication therapy. The triple-drug combination therapy succeeded in four of five patients, while the PPI monotherapy succeeded in five of 10 patients. Three of five patients who had been unsuccessful with the latter therapy requested the triple-drug combination therapy as the second eradication and all three were successful. In total, the triple-drug combination therapy succeeded in seven out of eight (87.5%) attempted cases, while the PPI monotherapy in five out of 10 (50%) attempted cases. CONCLUSIONS: In NHPH eradication, the triple-drug combination therapy was considered to be effective to some extent and to become the first-line therapy. While, although less successful, PPI monotherapy appeared to be a potentially promising option particularly for patients with allergy or resistance to antibiotics. Effectiveness of PPI monotherapy may be attributed to hyperacid environment preference of Helicobacter suis and PPI's acid-suppressive effect. Additionally, male predominance in NHPH-infected gastritis patients may be explained by gender difference in gastric acid secretory capacity. However, further evidence needs to be accumulated. STUDY REGISTRATION: This study was approved by the Research Ethics Committee of Kenwakai Hospital (No. 2,017,024).

Predicting Helicobacter pylori infection from endoscopic features.

BACKGROUND: Helicobacter pylori infection, prevalent in more than half of the global population, is associated with various gastrointestinal diseases, including peptic ulcers and gastric cancer. The effectiveness of early diagnosis and treatment in preventing gastric cancer highlights the need for improved diagnostic methods. This study aimed to develop a simple scoring system based on endoscopic findings to predict H. pylori infection. METHODS: A retrospective analysis was conducted on 1,007 patients who underwent upper gastrointestinal endoscopy at Asan Medical Center from January 2019 to December 2021. Exclusion criteria included prior H. pylori treatment, gastric surgery, or gastric malignancies. Diagnostic techniques included rapid urease and 13C-urea breath tests, H. pylori culture, and assessment of endoscopic features following the Kyoto gastritis classification. A new scoring system based on endoscopic findings including regular arrangement of collecting venules (RAC), nodularity, and diffuse or spotty redness was developed for predicting H. pylori infection, utilizing logistic regression analysis in the development set. RESULTS: The scoring system demonstrated high predictive accuracy for H. pylori infection in the validation set. Scores of 2 and 3 were associated with 96% and 99% infection risk, respectively. Additionally, there was a higher prevalence of diffuse redness and sticky mucus in cases where the initial H. pylori eradication treatment failed. CONCLUSION: Our scoring system showed potential for improving diagnostic accuracy in H. pylori infection. H. pylori testing should be considered upon spotty redness, diffuse redness, nodularity, and RAC absence on endoscopic findings as determined by the predictive scoring system.

Endoscopic and morphological features of chronic gastritis in patients with lumbar spine osteochondrosis.

OBJECTIVE: Aim: of the study is to determine the endoscopic and morphological features of chronic gastritis (CG) in patients with lumbar spinal OC. PATIENTS AND METHODS: Materials and Methods: 102 patients with lumbar spine OC and CG were examined. The patients were diagnosed with Helicobacter pylori (HP) infection, according to which the patients were divided into two groups: the first group included 92 HP-positive patients, the second group consisted of 10 HP-negative patients. RESULTS: Results: Among HP infected patients with lumbar spine OC, erosive gastropathy was most often diagnosed (in 40 (43.5%) of the examined), as well as erosive-papular and erosive-hemorrhagic gastropathy (in 14 (15.2%) and in 16 (17, 4 %) of patients, respectively), while erythematous gastropathy was more often diagnosed among HP-negative patients (in 7 (70.0 %) cases, respectively). CONCLUSION: Conclusions: 1. 90.2% of patients with lumbar spine OC and CG have been diagnosed with HP infection. 2. Endoscopically, the lesion of the stomach MM in patients with lumbar spine OC corresponds mainly to erosive and erosive-hemorrhagic forms of gastropathy. 3. During histological examination of stomach MM, mainly 2nd and 3rd degrees of inflammation were established, especially in patients with erosive, erosive-papular and erosive-hemorrhagic forms of gastropathy.

Safety profile of Helicobacter pylori eradication treatments: literature review and updated data of the European Registry on Helicobacter pylori management (Hp-EuReg).

INTRODUCTION: Helicobacter pylori (H. pylori), the most prevalent chronic infection globally, is the major cause of relevant diseases such as gastric cancer, leading to high morbidity and mortality worldwide. Several studies have focused on optimize H. pylori eradication treatment through combination therapies and antibiotic resistance. However, the adverse events profile and its impact, as a primary outcome, remains underexplored.The aim of this review was to summarize the available data on the safety of the most common regimens for H. pylori eradication and its impact on the compliance. AREAS COVERED: This review encompassed the published evidence from the years 2008 to 2023 regarding both the safety and compliance for most common H. pylori eradication regimens. The main sources for this review comprised MEDLINE, PubMed, and Cochrane electronic databases. Furthermore, it included a safety analysis of unpublished data from the European Registry on H. pylori management (Hp-EuReg). EXPERT OPINION: Poor compliance is correlated with significantly lower cure rates, and this is a unique modifiable source of H. pylori treatment failure. Eradication treatments have become complex, involving multiple drugs and dosing intervals. Thus, patient education is crucial; doctors must explain to the patient about potential temporary and most often harmless side effects.

Clinicopathologic and endoscopic characteristics of ten patients with gastric hamartomatous inverted polyp: a single center case series.

BACKGROUND: Gastric hamartomatous inverted polyps (GHIPs) are not well characterized and remain diagnostically challenging due to rarity. Therefore, this study aims to investigate the clinicopathologic and endoscopic characteristics of patients with GHIP. METHODS: We retrospectively reviewed clinicopathologic and endoscopic features of ten patients with GHIP who were admitted to Beijing Friendship Hospital from March 2013 to July 2022. All patients were treated successfully by endoscopic resection. RESULTS: GHIPs were usually asymptomatic and found incidentally during gastroscopic examination. They may be sessile or pedunculated, with diffuse or local surface redness or erosion. On endoscopic ultrasonography, the sessile submucosal tumor-type GHIP demonstrated a heterogeneous lesion with cystic areas in the third layer of the gastric wall. Histologically, GHIPs were characterized by a submucosal inverted proliferation of cystically dilated hyperplastic gastric glands accompanied by a branching proliferation of smooth muscle bundles. Inflammatory cells infiltration was observed in the stroma, whereas only one patient was complicated with glandular low-grade dysplasia. Assessment of the surrounding mucosa demonstrated that six patients (60%) had atrophic gastritis or Helicobacter pylori-associated gastritis, and four patients (40%) had non-specific gastritis. Endoscopic resection was safe and effective. CONCLUSIONS: GHIPs often arise from the background of abnormal mucosa, such as atrophic or H.pylori-associated gastritis. We make the hypothesis that acquired inflammation might lead to the development of GHIPs. We recommend to make a full assessment of the background mucosa and H. pylori infection status for evaluation of underlying gastric mucosal abnormalities, which may be the preneoplastic condition of the stomach.

Rapid and multi-target genotyping of Helicobacter pylori with digital microfluidics.

Helicobacter pylori (H. pylori) infection correlates closely with gastric diseases such as gastritis, ulcers, and cancer, influencing more than half of the world's population. Establishing a rapid, precise, and automated platform for H. pylori diagnosis is an urgent clinical need and would significantly benefit therapeutic intervention. Recombinase polymerase amplification (RPA)-CRISPR recently emerged as a promising molecular diagnostic assay due to its rapid detection capability, high specificity, and mild reaction conditions. In this work, we adapted the RPA-CRISPR assay on a digital microfluidics (DMF) system for automated H. pylori detection and genotyping. The system can achieve multi-target parallel detection of H. pylori nucleotide conservative genes (ureB) and virulence genes (cagA and vacA) across different samples within 30 min, exhibiting a detection limit of 10 copies/rxn and no false positives. We further conducted tests on 80 clinical saliva samples and compared the results with those derived from real-time quantitative polymerase chain reaction, demonstrating 100% diagnostic sensitivity and specificity for the RPA-CRISPR/DMF method. By automating the assay process on a single chip, the DMF system can significantly reduce the usage of reagents and samples, minimize the cross-contamination effect, and shorten the reaction time, with the additional benefit of losing the chance of experiment failure/inconsistency due to manual operations. The DMF system together with the RPA-CRISPR assay can be used for early detection and genotyping of H. pylori with high sensitivity and specificity, and has the potential to become a universal molecular diagnostic platform.

Prevalence of Helicobacter pylori infection among Slovenian children and adolescents: A prospective cohort study.

BACKGROUND: Helicobacter pylori (H. pylori) infection is primarily acquired in childhood and is notably influenced by socioeconomic variances across different geographical regions. The aim of this study is to assess the prevalence of H. pylori infection in Slovenian children and to identify potential risk factors that facilitate the infection. MATERIALS AND METHODS: Between 2019 and 2022, we conducted a multi-center prospective cross-sectional study among healthy children residing in three different administrative regions in Slovenia. H. pylori infection status was determined using a monoclonal antibody-based stool antigen test (SAT). A standardized questionnaire was designed to evaluate the influence of various H. pylori-associated risk factors, including demographics and socioeconomic, housing and sanitation conditions. RESULTS: During the 3-year period, we recruited a total of 421 children and adolescents (age range 2-18 years, mean age 10.29 ± 4.95 years). Overall, 46 (10.9%) were diagnosed with H. pylori infection. No associations were found between H. pylori prevalence rates and increasing age, sex, parental education level, country of birth of the child or their parents, number of household members, household income, having a dishwasher, owning a pet, duration of breastfeeding, fruit intake frequency, drinking tap water, and handwashing practices. The only parameters associated with an increased risk of infection were the location of the school (p < 0.001) and living in an urban area (p = 0.036). The odds of infection were approximately 4.77 times higher if the child attended school in the Central Slovenian compared to other regions (OR = 4.77; 95% CI 0.87-2.34). CONCLUSIONS: This is the first study providing information on the prevalence of H. pylori infection among Slovenian children and adolescents. Using SAT, we have shown that the burden of H. pylori infection in our pediatric population is low; however, it seems to depend on regional rather than socioeconomic factors.

Histopathology Features of H. pylori Gastritis Associated With Altered Lipid Profile: An Observational Study from a Tertiary Healthcare Center in North West Romania.

BACKGROUND/AIM: H. pylori infection can promote a systemic inflammatory syndrome, eventually leading to intestinal metaplasia and gastric cancer. The aim of our study was to investigate the possible association between dyslipidemia and histopathological features of H. pylori gastritis. PATIENTS AND METHODS: An observational, retrospective study was conducted over the period 2017-2022 on symptomatic patients with a positive rapid urease test. A total of 121 patients who underwent upper gastrointestinal endoscopy with stomach biopsy were enrolled in this study. Based on the updated Sydney System, we investigated the association between neutrophils, mononuclear cells, intestinal metaplasia, or gastric atrophy and altered lipid profiles. RESULTS: A high prevalence of H. pylori infection was noticed in the studied group upon the application of the rapid urease test, being associated with dyslipidemia regardless of patient sex. All the endoscopic diagnoses (acute, chronic, or atrophic chronic gastritis, metaplasia) correlated with the histopathological features. Mononuclear cells and metaplasia were more likely to be found in H. pylori-positive patients with dyslipidemia, which is consistent with acute and chronic inflammation caused by H. pylori in the gastric mucosa. CONCLUSION: Although our study was conducted on a small scale, it offers new insights and details regarding H. pylori infection and histopathological features. Mononuclear cells and metaplasia were associated with an altered lipid profile in H. pylori-positive patients. These findings warrant future investigation, such as the evolution of gastric biopsies and lipid profiles before and after eradication.

History of chronic gastritis: How our perceptions have changed.

Currently, the diagnostic strategy for chronic gastritis (CG) is aimed not just at fixing the presence of gastric mucosal inflammation, but also at gastric cancer (GC) risk stratification in a particular patient. Modern classification approach with the definition of the stage of gastritis determines the need, activities and frequency of dynamic monitoring of a patient. However, this attitude to the patient suffering from CG was far from always. The present publication is a literature review describing the key milestones in the history of CG research, from the description of the first observations of inflammation of the gastric mucosa, assessment of gastritis as a predominantly functional disease, to the advent of endoscopy of the upper digestive tract and diagnostic gastric biopsy, assessment of the role of Helicobacter pylori infection in progression of inflammatory changes to atrophy, intestinal metaplasia, dysplasia and GC.

A rapid and high-throughput Helicobacter pylori RPA-CRISPR/Cas12a-based nucleic acid detection system.

BACKGROUND: Helicobacter pylori lives in the human stomach and causes gastric cancer and other gastric diseases. The development of molecular technology has facilitated low-cost, rapid, and high-throughput detection of H. pylori. MATERIALS AND METHODS: The combination of isothermal recombinase polymerase amplification (RPA) and CRISPR-Cas12a was used for early diagnosis and monitoring of H. pylori in clinical settings. The UreB genes from 242 H. pylori strains were subjected to cluster analysis, and we designed corresponding RPA primers and screened 2 sets of CRISPR-derived RNAs (crRNAs) for accurate H. pylori recognition. We then performed specificity and sensitivity validation of seven strains using this RPA-CRISPR/Cas12a method. In addition, the cut-off values of this RPA-CRISPR/Cas12a method based on fluorescence values (i.e., RPA-CRISPR/Cas12a-FT) were determined by comparison with quantitative PCR (qPCR), and further experiments comparing different methods were performed using clinical samples. RESULTS: We developed a rapid detection system based on the combination of RPA and CRISPR-Cas12a, which was applied to the early diagnosis and monitoring of H. pylori in clinical settings. The RPA-CRISPR/Cas12a system was used to detect the UreB gene. We found that the limit of detection (LOD) for the CRISPR/Cas12a method based on the lateral flow dipstick result (i.e., CRISPR/Cas12a-LFD) was 100 copies, the cut-off value was 1.4; and for CRISPR/Cas12a-FT the LOD was 50 copies. This system was used to assess clinical samples and showed high reproducibility with proof-of-concept sensitivity, and the whole detection process was completed within 40 min. CONCLUSION: As a diagnostic method that can detect the UreB gene of H. pylori in gastric tissue samples rapidly, sensitively, visually, and in a high throughput manner, our method provides a new diagnostic option for clinicians. This system is ideal for hospitals or testing sites with limited medical resources.

New Rapid Helicobacter Pylori Blood Test Based on Dual Detection of FliD and CagA Antibodies for On-Site Testing.

Helicobacter pylori is the most prevalent bacterial infection, affecting half of the world's population, with a high morbidity and mortality rate.1,2 Several invasive and noninvasive testing procedures are available, and their selective use serves the specific needs of diverse clinical scenarios. For gastric cancer prevention, mass screening is necessary and requires a noninvasive, rapid, accurate and cost-effective test. For this purpose H pylori serology currently seems to be the preferred noninvasive diagnostic method. Population-based testing and treatment for H pylori is cost effective in high-risk countries, but less effective in low- and medium-risk countries.3,4 Many serologic tests are available on the market, with inconsistent performance often being observed. Therefore, international guidelines recommend considering only serologic tests with high accuracy that have been validated in the respective local populations. To date, no rapid point-of-care test (POCT) has reached a sufficient degree of accuracy.

Cultivo primario de Helicobacter pylori a partir de biopsias gástricas obtenidas por endoscopia / Primary culture of Helicobacter pylori from endoscopic gastric biopsies

Objetivo: Determinar la viabilidad del cultivo de la bacteria Helicobacter pylori en Costa Rica por medio de la documentación de toma de muestras, la comparación del diagnóstico histopatológico y la descripción de los diagnósticos asociados a los aislamientos obtenidos con los resultados de la ureasa rápida. Métodos: Investigación descriptiva que involucró a pacientes de entre los 35 y 70 años, de ambos sexos, que asistieron al Servicio de Endoscopia Digestiva del Hospital Clínica Bíblica entre febrero y junio del 2019 para estudio gastroscópico. Se obtuvieron biopsias gástricas para diagnóstico histopatológico, prueba de ureasa rápida y cultivo de Helicobacter pylori. Para este último, se transportaron las biopsias en un medio de transporte semisólido, se maceró el tejido y se cultivó enagar Skirrow y agar selectivo para Helicobacter; una placa de cada medio se incubó a 37 °C en microaerofilia entre 48 horas y 10 días. La positividad del cultivo se realizó por observación de la morfología colonial y la bacteria se identificó por análisis microscópico al fresco, tinción de Gram y pruebas bioquímicas (catalasa, ureasa y oxidasa). Resultados: Se incluyó a 44 pacientes (edad: 50.6 ± 10.0, 54.5% masculinos). Se recuperó Helicobacter pylori en biopsias de 27 pacientes (61.4% de éxito). La recuperación de la bacteria fue similar en el medio Skirrow y en el selectivo para Helicobacter. El porcentaje de éxito de recuperación semanal aumentó durante el estudio hasta alcanzar un éxito del 100% en la semana 11. Se comparó el cultivo con la ureasa rápida en 27 pacientes y la concordancia entre ambos métodos fue de un coeficiente kappa de Cohen de 0.48. El cultivo detectó la bacteria en un 56% de los pacientes, la ureasa rápida en un 37% y la combinación de ambas técnicas permitió la detección en un 60%. El diagnóstico endoscópico más frecuente en los pacientes con cultivo positivo fue la gastritis eritematosa y gastritis crónica superficial y el diagnóstico histopatológico predominante fue gastritis crónica con atrofia gástrica. El diagnóstico por cultivo coincidió con la detección por azul de toluidina en un 80.4% de los casos. Conclusiones: Se puede implementar el cultivo de Helicobacter pylori en Costa Rica. Este estudio tuvo un porcentaje de recuperación de la bacteria de 61.4%. La combinación del método de cultivo con la prueba de ureasa rápida y la detección histológica contribuye a un diagnóstico certero y oportuno. Recomendamos que, con base en protocolos descritos en esta investigación, cada laboratorio estandarice las condiciones que le permitan un buen porcentaje de recuperación y una implementación adaptada a sus actividades de rutina.

Aim: To document the recent experiences on the implementation of sampling and culturing Helicobacter pylori in Costa Rica, to compare it with other diagnostic methods: rapid urease test and histopathology and to describe the diagnoses associated with the obtained isolates. Methods: Descriptive research involving patients who visited the digestive endoscopy department of the Clínica Bíblica hospital in San José, Costa Rica between February and July of 2019 for gastroscopy. Gastric biopsies were obtained and histopathological analysis, rapid urease test, and bacteriological culture for Helicobacter pylori were performed. For culture techniques, the sample was transported in an in-house semi-solid medium. Biopsy fragments were macerated and plated on Skirrow agar and Helicobacterselective in-house agar, and incubated in microaerophilic atmosphere for 48 hours to 10 days. Culture positivity was determined by observation of the colonial morphology and microscopic observation; Gram staining and biochemical tests (urease, catalase, and oxidase) were used for bacterial identification. Results: 44 patients (mean aged 50.6 ± 10.0 years old, 54.5% male) were included in the study. Helicobacter pylori was recovered in biopsies from 27 patients (61.4% success rate). Bacterial growth was similar regardless the culture medium, but the physiological state of the bacteria was better in the Helicobacter-selective agar than in Skirrow. The weekly recovery rate increased to reach a 100% recovery plateau on week 11. Culture was compared with the rapid urease test in 27 patients, and the concordance between both methods using Cohen's kappa coefficient was 0.48. Whilst the culture detected Helicobacter pylori in 56% of the patients, and the rapid urease test in 37%, the combination of both allowed a 60% rate. The most frequent endoscopic diagnosis in patients with positive cultures were erythematous gastritis and chronic superficial gastritis, and the predominant histopathological diagnosis was chronic atrophic gastritis. Culture-based diagnosis was consistent with the histopathology detection of Helicobacter pylori in 80.4% of the cases. Conclusions: The implementation of H. pylori culture in Costa Rica is possible. This study had a 61.4% recovery rate. The combination of culture with rapid urease test and histopathology increases the probability of an accurate and timely diagnosis. We recommend that, based on previously described protocols such as ours, each laboratory adjusts the conditions to allow a good recovery rate and implement H. pylori diagnostic methods most suitable to their routine activities.

Differential expression of metallothionein and p21 in gastric cancer and some precursor lesions.

OBJECTIVE: Gastric cancer (GC) is a heterogeneous disease with molecular diversity between and within tumors; therefore, searching for altered genes within this cancer is mandatory to reach the proper individualized targeted therapy. Expressions of Metallothionein (MT) and p21 are not uniform in various types of cancers and their predictive value in GC is controversial. This study aimed to assess the role of MT and p21 in intestinal-type GC and some of its precursor lesions. MATERIALS AND METHODS: Immunohistochemical staining for MT and p21 was applied on paraffin blocks belonging to 30 GCs and 51 benign gastric lesions/precancerous lesions [33 chronic gastritis and 18 chronic gastritis with gastric intestinal metaplasia (GIM)]; 27 of them were associated with H. pylori infection. RESULTS: MT expression was dramatically increased while p21 expression was dramatically decreased from chronic gastritis to GIM to GC. In precancerous lesions, H. pylori-positive cases had significantly higher MT expression and lower p21 expression compared to H. pylori-negative cases. In GCs, decreased expression of both MT and p21 was associated with high-grade and advanced-stage cancers. CONCLUSIONS: Both MT and p21 may have a role in the development and progression of GC, and both proteins may be useful for selecting targeted therapy for GC patients.

Protein-losing gastroenteropathy complicated with asymptomatic primary biliary cholangitis, refractory to immunosuppressant, and improved by Helicobacter pylori eradication: a case report.

BACKGROUND: Protein-losing gastroenteropathy (PLGE) is a syndrome with a chief complaint of hypoalbuminemia, which occurs due to plasma protein leakage in the gastrointestinal tract, leading to general edema, ascites, and pleural effusions. CASE PRESENTATION: A 71-year-old woman visited another hospital for evaluation of hypoalbuminemia and systemic edema. She was hospitalized for a close inspection of hypoalbuminemia and was diagnosed with PLGE. Steroid and azathioprine therapy was prescribed; however, hypoalbuminemia did not improve, and the patient's condition worsened due to anasarca. As hospitalization was prolonged, the patient was transferred to our hospital. She was infected with Helicobacter pylori, and we performed H. pylori eradication. Following H. pylori eradication, her edema improved remarkably. CONCLUSION: We present the first case wherein H. pylori eradication successfully improved protein leakage in the lower gastrointestinal tract in a patient diagnosed with PLGE complicated with refractory to immunosuppressant treatment. H. pylori eradication should be considered in patients with PLGE complicated with H. pylori infection, without specific endoscopic finding or refractory to immunosuppressants.

Targeting Cytotoxin-Associated Antigen A, a Virulent Factor of Helicobacter pylori-Associated Gastric Cancer: Structure-Based In Silico Screening of Natural Compounds.

Gastric cancer is the fifth most frequent cancer and the third major cause of mortality worldwide. Helicobacter pylori, a bacterial infection linked with GC, injects the cytotoxin-associated antigen A (CagA; an oncoprotein) into host cells. When the phosphorylated CagA protein enters the cell, it attaches to other cellular components, interfering with normal cellular signaling pathways. CagA plays an important role in the progression of GC by interacting with phosphatidylserine of the host cell membrane. Therefore, disrupting the CagA-phosphatidylserine connection using small molecules appears to be a promising therapeutic approach. In this report, we screened the natural compounds from ZINC database against the CagA protein using the bioinformatics tools. Hits were initially chosen based on their physicochemical, absorption, distribution, metabolism, excretion, and toxicity (ADMET) characteristics, as well as other drug-like characteristics. To locate safe and effective hits, the PAINS filter, binding affinities estimation, and interaction analysis were used. Three compounds with high binding affinity and specificity for the CagA binding pocket were discovered. The final hits, ZINC153731, ZINC69482055, and ZINC164387, were found to bind strongly with CagA protein, with binding energies of -11.53, -10.67, and -9.21 kcal/mol, respectively, which were higher than that of the control compound (-7.25 kcal/mol). Further, based on binding affinity and interaction pattern, two leads (ZINC153731, ZINC69482055) were chosen for molecular dynamics (MD) simulation analysis. MD results showed that they displayed stability in their vicinity at 100 ns. This study suggested that these compounds could be used as possible inhibitors of CagA protein in the fight against GC. However, additional benchwork tests are required to validate them as CagA protein inhibitors.

Detection of Helicobacter pylori in virtual slides requires high resolution digitalisation.

To diagnose Helicobacter pylori (HP) infection and its related mucosal injuries requires the histopathological analysis of gastric biopsies. The move from glass slides interpretation towards digital pathology implies technical choices to maintain the performances of histopathological diagnosis. The intra-rater agreement in assessing gastritis diagnostic criteria between glass slides, low resolution and high resolution digital slides in the subject of the present study. One hundred gastric biopsies were re-assessed by a single digestive pathologist on glass slides and digitalised slides at low resolution (ie, x20 magnification and single focus without z-stack) and high resolution (ie, x40 magnification with seven focus levels and z-stack) about the criteria of the updated Sydney system and the detection of HP. Inter-analyses agreement were very good (Kappa values>0.81) for every criteria but slightly inferior (ie, Kappa values<0.9) comparing glass slides interpretations with low resolution digital slides-based ones. Indeed, some HP infections were misdiagnosed using x20 magnification histochemical stained digitalised slides (p<0.05). At the opposite, anti-HP immunohistochemistry slides and/or x40 magnification digitalisation permitted to maintain almost perfect concordance in diagnosis (Kappa value>0.9). As mentioned in current guidelines, a high resolution x40 magnification digitalisation must be favoured in order to avoid some misdetection of microorganisms as HP.

Oral and gastric microbiome in relation to gastric intestinal metaplasia.

Evidence suggests that Helicobacter pylori plays a role in gastric cancer (GC) initiation. However, epidemiologic studies on the specific role of other bacteria in the development of GC are lacking. We conducted a case-control study of 89 cases with gastric intestinal metaplasia (IM) and 89 matched controls who underwent upper gastrointestinal endoscopy at three sites affiliated with NYU Langone Health. We performed shotgun metagenomic sequencing using oral wash samples from 89 case-control pairs and antral mucosal brushing samples from 55 case-control pairs. We examined the associations of relative abundances of bacterial taxa and functional pathways with IM using conditional logistic regression with and without elastic-net penalty. Compared with controls, oral species Peptostreptococcus stomatis, Johnsonella ignava, Neisseria elongata and Neisseria flavescens were enriched in cases (odds ratios [ORs] = 1.29-1.50, P = .004-.01) while Lactobacillus gasseri, Streptococcus mutans, S parasanguinis and S sanguinis were under-represented (ORs = 0.66-0.76, P = .006-.042) in cases. Species J ignava and Filifactor alocis in the gastric microbiota were enriched (ORs = 3.27 and 1.43, P = .005 and .035, respectively), while S mutans, S parasanguinis and S sanguinis were under-represented (ORs = 0.61-0.75, P = .024-.046), in cases compared with controls. The lipopolysaccharide and ubiquinol biosynthesis pathways were more abundant in IM, while the sugar degradation pathways were under-represented in IM. The findings suggest potential roles of certain oral and gastric microbiota, which are correlated with regulation of pathways associated with inflammation, in the development of gastric precancerous lesions.

Lifetime incidence risk for gastric cancer in the Helicobacter pylori-infected and uninfected population in Japan: A Monte Carlo simulation study.

Helicobacter pylori (H. pylori) infection is considered the leading cause of gastric cancer. Gastric cancer is currently a common cancer with high incidence and mortality rates, but it is expected that the incidence rate will gradually decrease as the H. pylori infection prevalence decreases in the future. When evaluating the effectiveness of gastric cancer prevention strategies, it is essential to note the differences in long-term cumulative risks between H. pylori-infected and uninfected populations, but this has not yet been precisely evaluated. In our study, we aimed to estimate the cumulative incidence risks of developing gastric cancer from birth to 85 years among H. pylori-infected and uninfected populations by using population-based cancer registry data and birth year-specific H. pylori infection prevalence rates. Death from gastric cancer and other causes of death were considered in the estimations of the adjusted cumulative incidence risks stratified by sex and H. pylori infection status. After performing 5000 Monte Carlo simulations with repeated random sampling using observed cancer incidence in selected three prefectures (Fukui, Nagasaki, Yamagata) of prefectural population-based cancer registry in Japan, the mean adjusted cumulative incidence risk for gastric cancer in the H. pylori-infected population was 17.0% for males and 7.7% for females and 1.0% for males and 0.5% for females in the uninfected population. These results calculated with Japanese cancer registry data may be useful in considering and evaluating future prevention strategies for gastric cancer in Japan.

Prevalence and predictors of colonoscopic findings in patients with autoimmune gastritis.

The clinical spectrum of autoimmune gastritis is silent in the early stages of the disease and no specific symptom is related to this entity. Although gastroscopic findings of this entity are well defined, data regarding colonoscopic findings are limited. The aims of this study were to determine the prevalence of colonoscopic findings and to explore factors that might affect these findings. This is a retrospective chart review of patients with autoimmune gastritis (n=240). Data regarding colonoscopic findings, serum gastrin and chromogranin A (CgA) levels and gastric histopathological results were extracted and compared with 550 patients positive for Helicobacter pylori and gastric atrophy. Control subjects had colonoscopy and gastroscopy with biopsies. Colorectal lesions were observed in 64 (26.6%) of patients with autoimmune gastritis and 36 (6.6%) patients had colorectal lesions in the control group (p<0.001). Serum gastrin (OR: 8.59, 95% CI 1.72 to 25.07, p<0.001) and CgA levels (OR: 6.79, 95% CI 0.41 to 27.26, p<0.001) were found as factors affecting the presence of colorectal carcinoma. Serum gastrin and CgA levels were also found as predictors for the presence of colorectal adenomas. There is a higher prevalence of colorectal neoplastic lesions in patients with autoimmune gastritis. Serum gastrin and CgA levels were found to be determinants of colorectal neoplastic lesions observed in patients. In the workup of these patients, serum gastrin and CgA levels may guide physicians for the demonstration of colorectal neoplastic lesions.

Efficacy and Safety of Antofloxacin-Based Triple Therapy for Helicobacter pylori Eradication Failure in China.

AIMS: Quinolone-containing triple therapy has been considered as the second-line therapy for eradication of Helicobacter pylori (H. pylori). At present, there are no data to show the efficacy and safety of antofloxacin-based rescue therapy for the eradication of H. pylori, and this pilot clinical trial was designed. METHODS: A total of 196 patients who failed H. pylori eradication using the clarithromycin-based or metronidazole-based triple or bismuth quadruple therapy were randomly allocated to one of the following rescue eradication therapy groups: AEA group (antofloxacin 200 mg once daily, esomeprazole 20 mg + amoxicillin 1000 mg twice daily) for 14 days, or LEA group (levofloxacin 500 mg once daily, esomeprazole 20 mg + amoxicillin 1000 mg twice daily) for 14 days. The minimal inhibitory concentrations were tested by the E-test method. The gyrA mutation was analyzed by sequencing. Follow-up 13/14C-urea breath test was examined at 1 month after discontinuation. RESULTS: A total of 178 eligible patients were included in this study. The eradication rate was significantly higher in AEA group than in LEA group according to both ITT (87.6% vs. 68.5%; P = 0.002) and PP analyses (90.7% vs. 70.1%; P = 0.001). ITT analyses indicated that the eradication rate was significantly higher in AEA group than in LEA group with Asn87 mutation (78.9% vs. 31.3%; P = 0.005) and levofloxacin-resistant strains (76.9% vs. 44.2%; P = 0.003). Two groups exhibited similar adverse event rates (AEA 14.6% vs. LEA 20.2%, P = 0.323). CONCLUSIONS: The findings showed that antofloxacin may be a promising candidate in rescue therapy for H. pylori eradication failure in China.