Gastric Atrophy Research Articles

Combination of artificial intelligence endoscopic diagnosis and Kimura-Takemoto classification determined by endoscopic experts may effectively evaluate the stratification of gastric atrophy in post-eradication status.

Since it is difficult for expert endoscopists to diagnose early gastric cancer in post-eradication status, it may be critical to evaluate the stratification of high-risk groups using the advance of gastric atrophy or intestinal metaplasia. We tried to determine whether the combination of endoscopic artificial intelligence (AI) diagnosis for the evaluation of gastric atrophy could be a useful tool in both pre- and post-eradication status. 270 Helicobacter pylori-positive outpatients (Study I) were enrolled and Study II was planned to compare patients (n=72) with pre-eradication therapy with post-eradication therapy. Assessment of endoscopic appearance was evaluated by the Kyoto classification and Kimura-Takemoto classification. The trained neural network generated a continuous number between 0 and 1 for gastric atrophy. There were significant associations between the severity of gastric atrophy determined by AI endoscopic diagnosis and not having a regular arrangement of collecting venules in angle, visibility of vascular pattern, and mucus using Kyoto classification in H. pylori-positive gastritis. There were significant differences (p=0.037 and p=0.014) in the severity of gastric atrophy between the high-risk group and low-risk group based on the combination of Kimura-Takemoto classification and endoscopic AI diagnosis in pre- and post-eradication status. The area under the curve values of the severity of gastric atrophy (0.674) determined by the combination of Kimura-Takemoto classification and gastric atrophy determined by AI diagnosis was higher than that determined by Kimura-Takemoto classification alone in post-eradication status. A combination of gastric atrophy determined by AI endoscopic diagnosis and Kimura-Takemoto classification may be a useful tool for the prediction of high-risk groups in post-eradication status.

Incidence of Gastric Adenocarcinoma in Those With Gastric Atrophy: A Systematic Review.

Gastric atrophy (GA), or atrophic gastritis, is a pre-neoplastic lesion of gastric cancer (GC). It is part of the Correa cascade, which culminates in intestinal-type gastric adenocarcinoma. The cascade posits that intestinal-type gastric adenocarcinoma develops along a defined pathway of pre-neoplastic stages. The cascade begins with chronic gastritis, most commonly caused by Helicobacter pylori (H. pylori) infection, and proceeds through GA, gastric intestinal metaplasia (GIM), both complete and incomplete, dysplasia, both low and high-grade, and culminating in intestinal-type gastric adenocarcinoma. Attempts in Europe have been made to identify patients at risk of developing GC and target them with surveillance oesophagogastroduodenoscopy (OGD). However, there remains uncertainty about GA's risk of developing into GC. This poses issues in terms of guiding the need for and determining intervals for surveillance OGDs, which are a costly form of surveillance. As such, we attempted to gather all available studies assessing the risk of GC developing from GA, which is the first step in the Correa cascade.This study was a comprehensive systematic review of published papers, reported per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. This systematic review, which included a substantial 25,455 patients across 18 studies, found that the relative risk (RR) of GC in those with GA, using standardised incidence ratios as a measure of RR, was 15.1, with a 95% confidence interval ranging from 13.5 to 16.9. We conclude thatGA does increase the risk of developing GC, and this risk may be higher than previously appreciated. Further large-scale studies are needed in Western cohorts of patients to precisely define this risk and guide the need for surveillance programs. These future studies must be standardised to account for H. pylori status, the topographical distribution of the GA, and the methods for assessing the degree of GA.

Association of miR-499 rs3746444, miR-149 rs2292832 polymorphisms and their expression levels with helicobacter pylori-related gastric diseases and Traditional Chinese Medicine syndromes.

To provide an objective experimental basis for the gastric mucosa pathological evolution and the transformation of different Traditional Chinese Medicine (TCM) syndromes in helicobacter pylori (H. pylori)-related gastric diseases (HPGD) patients, based on the combination of TCM syndrome differentiation, molecular biology and histopathology. A total of 203 participants were enrolled in this study. The expressions of miR-499/miR-149 and H. pylori infection in the gastric tissues from all participants were detected. The genotyping for miR-499 rs3746444 and miR-149 rs2292832 was performed. In H. pylori positive subjects, the proportion of precancerous gastric lesions (PGL) in liver-stomach disharmony syndrome (LSDS) group was higher than in spleen Qi deficiency syndrome (SQDS) group (P <0.001); The proportion of gastric cancer (GC) in SQDS group was higher than in spleen-stomach damp-heat syndrome (SSDHS) group and LSDS group (all P <0.001). We also found C allele of miR-149 rs2292832 was linked to lower risk of gastric atrophy [miR-149 rs2292832 C vs T: adjusted odds ratio = 0.207; 95% confidence interval (0.043-0.989); P = 0.048]. Compared with healthy control (HC) group, the expression of miR-499 was significantly increased in GC group, while the expression of miR-149 was significantly decreased in chronic inflammation group, PGL group and GC group (all P < 0.05). Test for trend showed that GC risk was on a rising trend with the increasing expression of miR-499 and decreasing expression of miR-149 (both P for trend < 0.05). The C allele of miR-149 rs2292832 may be a protective factor for gastric mucosal atrophy. H. pylori may participate in the evolution of benign to malignant gastric mucosa lesions by inducing the overexpression of miR-499 and down regulation of miR-149. In addition, patients with H. pylori infection combined SQDS or LSDS may have higher risk of gastric mucosal malignant lesions.

Routine Histopathology in Laparoscopic Sleeve Gastrectomy Over 10 Years.

Laparoscopic sleeve gastrectomy (LSG) is one of the world's most commonly performed types of bariatric surgery. Routine histopathology of the surgical specimen is undertaken at most institutions, regardless of the lack of clinical suspicion of any sinister pathology. We evaluated the histopathology reports of LSG cases done for morbid obesity at our hospital over 10 years to determine the distribution of gastric changes and the prevalence of Helicobacter pylori infection in these specimens. A retrospective study was conducted. All LSGs performed at Shifa International Hospital, Islamabad,Pakistan, from July 1, 2014, to June 30, 2024, were assessed. A total of 538 cases were included. Histopathology reports were reviewed for all these patients, and the histopathological diagnosis and the presence or absence of H. pylori infection were recorded. The mean age was 36.9 ± 11.4 years. There were 201 (37.4%) males. No abnormality was found in 105 (19.5%) cases. Gastritis was present in 433 (80.5%) cases. Intestinal metaplasia was present in eight (1.5%) cases in a background of gastritis. There were no cases of gastric atrophy or dysplasia. There was one case of submucosal lipoma (0.2%) and one case of gastrointestinal stromal tumor (GIST) (0.2%). Both cases were associated with gastritis. H. pylori infection was present in 140 (26.0%) cases. All of these were associated with gastritis. Among the gastritis cases, 319 (73.7%) had chronic gastritis, while 114 (26.3%) had both active and chronic gastritis. The severity of gastritis, as designated by the histopathologist in their report, was minimal in 24 (4.5%) cases, mild in 228 (42.4%), moderate in 176 (32.7%), and severe in five (0.9%). There was one case of granulomatous gastritis (non-caseating) (0.2%). There was no difference in the prevalence of gastritis or H. pylori infection based on age or gender. Histopathological examination of the LSG specimen revealed a very high prevalence of gastritis, with normal findings in less than a fifth of all cases. The prevalence of H. pylori infection (26.0%) is much higher in comparison to other studies. Routine histopathology of LSG specimens should continue to be performed in every case.

Impact of a machine learning–based prediction model on annual surveillance endoscopy costs for detecting gastric cancer

Background and AimsIn this study, we assessed our machine learning (ML)-based model's impact on reducing annual surveillance endoscopy costs for detecting gastric cancer (GC). MethodsAnalyzing 1099 patients with chronic gastritis undergoing annual esophagogastroduodenoscopy (EGD), we randomly divided them into training and test sets (4:1). Using gradient boosting decision trees and incorporating patient characteristics, the ML model was developed. In the test sets, we compared the EGD number needed to screen (NNS) one GC, the cost, and the GC detection rate across different risk stratification strategies. ResultsThe ML-selected high-risk cohort demonstrated low NNS values, low total cost, low cost per one GC, and high GC detection rates compared to alternative risk stratification approaches including operative link for gastric atrophy assessment, and operative link for gastric intestinal metaplasia assessment. ConclusionOur ML model holds promise in reducing endoscopy surveillance costs while maintaining a robust gastric cancer detection rate.

Polyglandular Syndrome type III in a young patient: case report

Introduction: Autoimmune polyglandular syndromes (APS) are rare diseases defined by the coexistence of at least two autoimmune endocrine diseases. Objective: To describe a case of type III polyglandular syndrome in a young patient. Case report: Female, 37 years old, with hypothyroidism, presented with a weight loss of 9 kg, daily vomiting, asthenia, fatigue, and postprandial fullness for 3 months. He also reported arthritis in his wrists, shoulders, and hips. In laboratory tests, macrocytic and hyperchromic anemia associated with leukopenia, as well as hypovitaminosis B12, was observed. Pernicious anemia was investigated as the cause of this deficiency. Upper digestive endoscopy showed moderate gastritis – histopathological with gastric atrophy, positive anti-intrinsic factor antibody. Due to inflammatory arthralgia, ANA was requested, with an associated positive anti-dsDNA result of 1:80. In the EULAR/2019 diagnostic criteria for Systemic Lupus Erythematosus (SLE), she presented 14 points, thus she was diagnosed with SLE, and hydroxychloroquine (HXC) was started. Conclusion: SPA is rare, mainly in association with non-glandular autoimmunity, following an early diagnosis.

Autoimmune gastritis studies and gastric cancer: True renaissance or bibliometric illusion.

A bibliometric analysis of studies dedicated to autoimmune gastritis (AIG) recently published demonstrated a noteworthy surge in publications over the last three years. This can be explained by numerous publications from different regions of the world reporting the results of several studies that stimulated reassessment of our view of AIG as a precancerous condition. Follow-up studies and retrospective analyses showed that the risk of gastric cancer (GC) in AIG patients is much lower than expected if the patients ever being infected with Helicobacter pylori (H. pylori) were excluded. The low prevalence of precancerous lesions, such as the incomplete type of intestinal metaplasia, may explain the low risk of GC in AIG patients because the spasmolytic polypeptide-expressing metaplasia commonly observed in AIG does not involve clonal reprogramming of the gastric gland and can be considered as an adaptive change rather than a true precancerous lesion. However, changes in gastric secretion due to the progression of gastric atrophy during the course of AIG cause changes in the gastric mic-robiome, stimulating the growth of bacterial species such as streptococci, which may promote the development of precancerous lesions and GC. Thus, Streptococcus anginosus exhibited a robust proinflammatory response and induced the gastritis-atrophy-metaplasia-dysplasia sequence in mice, reproducing the well-established process for carcinogenesis associated with H. pylori. Prospective studies in H. pylori-naïve patients evaluating gastric microbiome changes during the long-term course of AIG might provide an explanation for the enigmatic increase in GC incidence in the last decades in younger cohorts, which has been reported in economically developed countries.

Effectiveness of serological markers of gastric mucosal atrophy in the gastric precancer screening and in cancer prevention.

New markers are needed to improve the effectiveness of serological screening for atrophic gastritis. To develop a cost-effective method for serological screening of atrophic gastritis with a high level of sensitivity. Of the 169 patients with atrophic gastritis, selected by the visual endoscopic Kimura-Takemoto method, 165 showed histological mucosal atrophy using the updated Kimura-Takemoto method. All 169 patients were examined for postprandial levels of gastrin-17 (G17) and pepsinogen-1 (PG1) using GastroPanel® (Biohit Plc, Helsinki, Finland). We used the histological standard of five biopsies of the gastric mucosa, in accordance with the Kimura-Takemoto classification system to assess the sensitivity of G17 in detecting gastric mucosal atrophy. We also compared the morpho-functional relationships between the detected histological degree of gastric mucosal atrophy and the serological levels of G17 and PG1, as the markers of atrophic gastritis. The sensitivity of postprandial G17 was 62.2% for serological levels of G17 (range: 0-4 pmol/L) and 100% for serological G17 (range: 0-10 pmol/L) for the detection of monofocal severe atrophic gastritis. No strong correlation was found between the levels of PG1 and degree of histological atrophy determined by the Kimura-Takemoto classification system to identify the severity of mucosal atrophy of the gastric corpus. In the presented clinical case of a 63-year-old man with multifocal atrophic gastritis, there is a pronounced positive long-term dynamics of the serological marker of atrophy - postprandial G17, after five months of rennet replacement therapy. Serological screening of multifocal atrophic gastritis by assessment of postprandial G17 is a cost-effective method with high sensitivity. Postprandial G17 is an earlier marker of regression of atrophic gastritis than a morphological examination of a gastric biopsy in accordance with the Sydney system. Therefore, postprandial G17 is recommended for dynamic monitoring of atrophic gastritis after treatment.

Chronic cigarette smoke exposure masks pathological features of Helicobacter pylori infection while promoting tumor initiation.

Gastric cancer is the fifth most common cancer and the fifth leading cause of cancer deaths worldwide. Chronic infection by the bacterium Helicobacter pylori is the most prominent gastric cancer risk factor, but only 1-3% of infected individuals will develop gastric cancer. Cigarette smoking is another independent gastric cancer risk factor, and H. pylori- infected smokers are at a 2-11-fold increased risk of gastric cancer development, but the direct impacts of cigarette smoke on H. pylori pathogenesis remain unknown. In this study, male C57BL/6 mice were infected with H. pylori and began smoking within one week of infection. The mice were exposed to cigarette smoke (CS) five days/week for 8 weeks. CS exposure had no notable impact on gross gastric morphology or inflammatory status compared to filtered-air (FA) exposed controls in mock-infected mice. However, CS exposure significantly blunted H. pylori- induced gastric inflammatory responses, reducing gastric atrophy and pyloric metaplasia development. Despite blunting these classic pathological features of H. pylori infection, CS exposures increased DNA damage within the gastric epithelial cells and accelerated H. pylori- induced dysplasia onset in the INS-GAS gastric cancer model. These data suggest that cigarette smoking may clinically silence classic clinical symptoms of H. pylori infection but enhance the accumulation of mutations and accelerate gastric cancer initiation.

Factors Influencing the Degree of Gastric Atrophy in Helicobacter pylori Eradication Patients with Drinking Habits.

Chronic gastritis caused by Helicobacter pylori (H. pylori) infection can lead to gastric atrophy. This study aimed to identify the factors associated with gastric atrophy in H. pylori eradication patients with drinking habits. Of the 250 patients who visited Hamamatsu University Hospital for H. pylori eradication and underwent eradication treatment between April 2017 and December 2020, 127 patients with drinking habits were included in this study. The degree of gastric atrophy of the patients was classified based on endoscopy. The relationship between patient attributes (sex, age, alcohol consumption, frequency of drinking, smoking status, and medication use) and a highly atrophic stomach was statistically analyzed. The results showed that gastric atrophy was significantly higher in males and in those aged 60 years or older and that gastric atrophy tended to be higher in those who drank 20 g or more per day and 5 days or more a week. There was also a trend toward higher atrophy in sake drinkers and lower atrophy in wine drinkers. This study provides useful knowledge for patient management and guidance after H. pylori eradication treatment and indicates the importance of comprehensive measures, including alcohol consumption control and lifestyle modification, especially for men and older people.

Reference Ranges and Comparison of Pepsinogen by Chemiluminescence Immunoassay and Enzyme-Linked Immunosorbent Assay in Chinese Population.

Serum pepsinogen (PG) is a good indicator of atrophic changes in the gastric mucosa. Gastric mucosal atrophy is a high-risk factor for gastric cancer. Serological testing for PG combined with endoscopy can help to improve gastric cancer screening. In this study, we established the reference ranges of serum PG-I, PG-II, and the PG-I/II ratio (PGR) in the Chinese population by chemiluminescence immunoassay (CLIA) and enzyme-linked immunosorbent assay (ELISA). Besides, in the real world, doctors are often confused by the results of different testing platforms. Thus, a comparison of methods CLIA and ELISA was performed. 2904 individuals were enrolled from six regions in China as part of the Chinese Adult Digestive Diseases Surveillance (2016) program. The individuals completed questionnaires and volunteered to undergo examinations, including gastroscopy, urea breath test, abdominal ultrasound examination and routine serologic tests. Serum was collected to measure PGs (including PG-I, PG-II and PGR) by CLIA and ELISA. Participants who were found obvious abnormalities or absent from the examinations were excluded. Ultimately, 747 healthy individuals were enrolled in this study. The Kolmogorov-Smirnov test was used to assess the distribution of variables. The Kruskal-Wallis H or Mann-Whitney U-tests were used to compare different sex, age, and geographical groups. The 95% reference ranges of PGs obtained by the two methods were established according to document CLSI-EP28-A3, with covariates of sex, age, and region. Spearman correlation analysis, linear regression analysis and allowable total error (ATE) zone analysis were utilized for comparing the two methods. On overall, the 95% reference ranges of PG-I, PG-II, and PGR measured by CLIA were 23.00-110.64 ng/mL, 2.50-19.13 ng/mL, and 3.87-13.30, respectively. Meanwhile, the reference ranges of PG-I, PG-II, and PGR measured by ELISA were 36.93-205.06 ng/mL, 1.65-17.96 ng/mL, and 7.50-33.60, respectively. Both PG-I and PG-II levels measured by the two platforms were found to be influenced by sex and age. PGR measured by CLIA was influenced by age but not by sex, while PGR measured by ELISA was not affected by either age or sex. Regional factors did not significantly impact the PG results, except for PG-I detected by ELISA. Ultimately, reference ranges for PGs were established based on age and sex stratification. Additionally, the Spearman correlation analysis revealed that the correlation coefficients for PG-I, PG-II, and PGR detected by the two methods were 0.899, 0.887, and 0.777, respectively, indicating a strong correlation between the two methods. The regression equation for the PG levels detected by two methods was obtained through linear regression analysis. The ATE analysis provided a visual depiction of the consistency between the two methods, clearly indicating the poor agreement between them. This study established the reference ranges of PGs by strict and intact enrollment standard. In addition, the results indicated a strong linear relationship between the two methods, yet with a clear bias, which was valuable for laboratory interpretation.

Endoscopic findings and outcomes of gastric mucosal changes relating to potassium-competitive acid blocker and proton pump inhibitor therapy.

Gastric mucosal changes associated with long-term potassium-competitive acid blocker and proton pump inhibitor (PPI) therapy may raise concern. In contrast to that for PPIs, the evidence concerning the safety of long-term potassium-competitive acid blocker use is scant. Vonoprazan (VPZ) is a representative potassium-competitive acid blocker released in Japan in 2015. In order to shed some comparative light regarding the outcomes of gastric mucosal lesions associated with a long-term acid blockade, we have reviewed six representative gastric mucosal lesions: fundic gland polyps, gastric hyperplastic polyps, multiple white and flat elevated lesions, cobblestone-like gastric mucosal changes, gastric black spots, and stardust gastric mucosal changes. For these mucosal lesions, we have evaluated the association with the type of acid blockade, patient gender, Helicobacter pylori infection status, the degree of gastric atrophy, and serum gastrin levels. There is no concrete evidence to support a significant relationship between VPZ/PPI use and the development of neuroendocrine tumors. Current data also shows that the risk of gastric mucosal changes is similar for long-term VPZ and PPI use. Serum hypergastrinemia is not correlated with the development of some gastric mucosal lesions. Therefore, serum gastrin level is unhelpful for risk estimation and for decision-making relating to the cessation of these drugs in routine clinical practice. Given the confounding potential neoplastic risk relating to H. pylori infection, this should be eradicated before VPZ/PPI therapy is commenced. The evidence to date does not support the cessation of clinically appropriate VPZ/PPI therapy solely because of the presence of these associated gastric mucosal lesions.

Iron deposition in gastric black spots: Clinicopathological insights and NanoSuit-correlative light and electron microscopy analysis.

Black spots (BSs) are lentiginous findings observed in the gastric body and fundus during upper gastrointestinal endoscopy and are predominantly seen in patients undergoing Helicobacter pylori eradication treatment. However, the detailed patient background and exact composition are poorly understood. This study aims to clarify the clinicopathological features of BSs, examine patient demographics, and use the NanoSuit-correlative light and electron microscopy (CLEM) method combined with scanning electron microscopy-energy dispersive X-ray spectroscopy for elemental analysis. Patients who underwent upper gastrointestinal endoscopy between 2017 and 2022 were included. Data on age, medications, blood tests, and H. pylori infection status were retrospectively gathered from medical records. Univariate analysis was conducted to examine BS presence, with results then used in a multivariate model to identify associated risk factors. Additionally, pathological specimens from patients with BSs were analyzed for elemental composition using the NanoSuit-CLEM method combined with scanning electronmicroscopy-energy dispersive X-ray spectroscopy. An analysis of 6778 cases identified risk factors for BSs, including older age and using proton pump inhibitors, statins, corticosteroids, and antithrombotic drugs. Endoscopically, BSs correlated with higher gastric atrophy and lower active H. pylori infection. Iron deposition at BS sites was specifically identified using NanoSuit-CLEM. BSs on gastrointestinal endoscopy may indicate an absence of active H. pylori inflammation. The discovery of iron deposition within BSs using the NanoSuit-CLEM method has offered new insights into the possible causative factors and advances our understanding of the etiology of BSs, bringing us closer to unraveling the underlying mechanisms of their formation.

Long-term endoscopic gastric mucosal changes up to 20 years after Helicobacter pylori eradication therapy

Helicobacter pylori eradication therapy reduces the risk of gastric cancer. However, it is unclear whether the severity of risk factors for gastric cancer such as atrophy and intestinal metaplasia are reduced after eradication in the long term. We aimed to study long-term changes in endoscopic risk factors for gastric cancer up to 20 years post-eradication. The endoscopic severity of gastritis according to the Kyoto Classification of Gastritis in 167 patients was retrospectively evaluated over an average follow-up 15.7 years. A significant improvement in mean total gastric cancer risk score (4.36 ± 1.66 to 2.69 ± 1.07, p < 0.001), atrophy (1.73 ± 0.44 to 1.61 ± 0.49, p = 0.004), and diffuse redness (1.22 ± 0.79 to 0.02 ± 0.13, p < 0.001) was observed compared to baseline in the Eradication group. However, there was no change in the never infection and current infection groups. The frequency of map-like redness increased over time until 15 years (3.6% to 18.7%, p = 0.03). The Cancer group had significantly higher risk scores at all time points. Endoscopic atrophy significantly improved in eradicated patients over long-term, suggested that eradication is one of the key elements in gastric cancer prevention. Individualized surveillance strategies based on endoscopic gastritis severity before eradication may be important for those at risk of gastric cancer.

Clinical Characteristics of Patients With Previous Helicobacter pylori Infection-Induced Atrophic Gastritis.

Patients with atrophic gastritis unrelated to autoimmune gastritis (AIG) and without active Helicobacter pylori (H.pylori)infection or previous eradication therapy are considered to have previous Helicobacter pylori infection-induced atrophic gastritis (PHIG). This study aimed to clarify the clinical characteristics of patients with PHIG. Consecutive patients who underwent upper gastrointestinal endoscopy during the study period were enrolled in the study. Pepsinogen and gastrin levels, H. pylori serology, and endoscopic atrophic grade were assessed. Patients were divided into five groups based on their H. pylori status and disease history (PHIG, without H. pylori infection, with active H. pylori infection, with successful H. pylori eradication, and AIG). Their gastric cancer risk status was classified according to the ABC method of serological gastric cancer screening. Of 536 consecutive patients who underwent upper gastrointestinal endoscopy during the study period, 318 were included (31 with PHIG, 77 without H. pylori infection, 101 with active H. pylori infection, 80 with successful H. pylori eradication, and 29 with AIG). Of the 31 patients with PHIG, 21 (68%) were H. pylori-seronegative,and 20 (65%) were classified as group A (normal pepsinogen, H. pylori-seronegative). Patients with PHIG accounted for 90.1% of the patients at high risk for gastric cancer misclassified as group A. The pepsinogen and H. pylori serological profiles of patients with PHIG were similar to those of patients with successful H. pylori eradication more than six years previously. A receiver-operating characteristic curve (ROC) analysis that included 13 patients with AIG and without active H. pylori infection and no previous eradication therapy and 31 patients with PHIG revealed that an endoscopic atrophy grade of O-III or greater according to the Kimura-Takemoto classification can predict AIG. Two-thirds of the patients with PHIG were misclassified as being at low risk (group A) according to the ABC method, suggesting that endoscopy is necessary for group A patients. The results of the serological evaluation of PHIG indicated that patients with PHIG may have experienced spontaneous H. pylori eradication, possibly because of the use of antibiotics for other conditions. Autoimmune gastritis should be considered in the presence of grade 0-III or greater gastric mucosal atrophy in patients with suspected PHIG, even if the autoantibody and histological findings are not available.

Trained Immunity and Trained Tolerance: The Case of Helicobacter pylori Infection.

Trained immunity is a concept in immunology in which innate immune cells, such as monocytes and macrophages, exhibit enhanced responsiveness and memory-like characteristics following initial contact with a pathogenic stimulus that may promote a more effective immune defense following subsequent contact with the same pathogen. Helicobacter pylori, a bacterium that colonizes the stomach lining, is etiologically associated with various gastrointestinal diseases, including gastritis, peptic ulcer, gastric adenocarcinoma, MALT lymphoma, and extra gastric disorders. It has been demonstrated that repeated exposure to H. pylori can induce trained immunity in the innate immune cells of the gastric mucosa, which become more responsive and better able to respond to subsequent H. pylori infections. However, interactions between H. pylori and trained immunity are intricate and produce both beneficial and detrimental effects. H. pylori infection is characterized histologically as the presence of both an acute and chronic inflammatory response called acute-on-chronic inflammation, or gastritis. The clinical outcomes of ongoing inflammation include intestinal metaplasia, gastric atrophy, and dysplasia. These same mechanisms may also reduce immunotolerance and trigger autoimmune pathologies in the host. This review focuses on the relationship between trained immunity and H. pylori and underscores the dynamic interplay between the immune system and the pathogen in the context of gastric colonization and inflammation.

Chronic autoimmune gastritis and its relation to megaloblastic anemia – Main histopathological and pathophysiological characteristics

Chronic autoimmune gastritis is a sustained inflammation of the stomach, characterized by being immunologically mediated against intrinsic factor-producing parietal cells, leading to nutritional deficiencies that may result in anemia. This study investigates the prevalence and underlying mechanism of anemia in patients with chronic autoimmune gastritis, focusing on iron deficiency anemia and megaloblastic anemia due to vitamin B12 deficiency. A bibliographic review was carried out on the subject, in databases of scientific relevance and verified by peers, whose inclusion criteria allowed only studies relevant to the subject, published in the last five years, which establish a relationship with chronic autoimmune gastritis and anemia. Thus, the exclusion criteria left out studies on chronic gastritis due to other etiologies, those cases not related to anemia, or other studies not relevant to the general objective. In the pathophysiological framework, there is an autoimmune destruction of gastric parietal cells, which leads to a reduction in the secretion of hydrochloric acid and intrinsic factor, essential for the absorption of vitamin B12 and iron, predisposing to iron deficiency and megaloblastic anemia. Histological examination reveals gastric atrophy with loss of glands, lymphocytic infiltration, and presence of plasma cells. Symptoms include dyspepsia, loss of appetite and loss of appetite.

Advancing Automatic Gastritis Diagnosis: An Interpretable Multilabel Deep Learning Framework for the Simultaneous Assessment of Multiple Indicators

The evaluation of morphological features such as inflammation, gastric atrophy, and intestinal metaplasia is crucial for diagnosing gastritis. However, artificial intelligence (AI) analysis for nontumor diseases like gastritis is limited. Previous deep learning models have omitted important morphological indicators and cannot simultaneously diagnose gastritis indicators or provide interpretable labels. To address this, an attention-based multi-instance multilabel learning network (AMMNet) was developed to simultaneously achieve the multilabel diagnosis of activity, atrophy, and intestinal metaplasia with only slide-level weak labels. To evaluate AMMNet's real-world performance, a diagnostic test was designed to observe improvements in junior pathologists' diagnostic accuracy and efficiency with and without AMMNet assistance. In this study of 1,096 patients from 7 independent medical centers, AMMNet performed well in assessing activity (area under the curve (AUC): 0.93), atrophy (AUC: 0.97), and intestinal metaplasia (AUC: 0.93). The false-negative rates (FNRs) of these indicators were only 0.04, 0.08, and 0.18, respectively, and junior pathologists had lower FNRs with model assistance (0.15 vs. 0.10). Furthermore, AMMNet reduced the time required per whole-slide image (WSI) from 5.46 minutes to only 2.85 minutes, enhancing diagnostic efficiency. In block-level clustering analysis, AMMNet effectively visualized task-related patches within WSIs, improving interpretability. These findings highlight AMMNet’s effectiveness in accurately evaluating gastritis morphological indicators on multicenter datasets. Using multi-instance multilabel learning strategies to support routine diagnostic pathology deserves further evaluation.

Lower IFN-γ expression causes more severe gastric inflammation in BALB/c infected by Bali 03 Helicobacter pylori isolate that provided by low iron diet

Background: Helicobacter pylori (H. pylori) infection is associated with various gastrointestinal diseases including gastritis, peptic ulcers, gastric carcinoma, and gastric mucosa-associated lymphoid-tissue lymphoma (MALT) lymphoma. Several studies have shown that H. pylori plays a role in iron deficiency that is refractory to iron administration. This study aims to analyze whether the lower IFN-γ expression causes more severe gastric inflammation in BALB/c infected by Bali 03 H. pylori isolate that is provided by a low iron diet. Methods: This research was an experimental study by inoculating the bacterial isolate H. pylori Bali 03 in two groups of BALB/c mice. The treatment group was given a low iron diet at a dose of &lt;3 mg/kgBW of mice, while the control group was given a normal dose of iron diet at a dose of 40 mg/kgBW of mice. The cellular immune response of the two groups of BALB/c mice was measured by comparing the expression of IFN-γ, granzyme B, IFN-γ/IL-10 ratio to the degree of gastric inflammation. Results: The results of the research were that the H. pylori Bali 03 isolate caused inflammation in 36 (100%) gastric of the mice. The degree of gastric inflammation of mice was more severe in the treatment group than in the control group, within 6 weeks precancerous lesions occurred, namely gastric gland atrophy and metaplasia in the treatment group, 1 (2.7%). There is a significant difference between the control group and the treatment group (p=0.019). There was a significant difference in IFN-γ expression between the treatment group and the control group (p=0.034). Conclusion: Iron deficiency affects the degree of gastric inflammation through IFN-γ expression in BALB/c infected with H. pylori isolate Bali 03. Iron deficiency worsens the degree of gastric inflammation in BALB/c mice infected with H. pylori isolate Bali 03.

Statistical Models for High-Risk Intestinal Metaplasia with DNA Methylation Profiling.

We consider the newly developed multinomial mixed-link models for a high-risk intestinal metaplasia (IM) study with DNA methylation data. Different from the traditional multinomial logistic models commonly used for categorical responses, the mixed-link models allow us to select the most appropriate link function for each category. We show that the selected multinomial mixed-link model (Model 1) using the total number of stem cell divisions (TNSC) based on DNA methylation data outperforms the traditional logistic models in terms of cross-entropy loss from ten-fold cross-validations with significant p-values 8.12×10-4 and 6.94×10-5. Based on our selected model, the significance of TNSC's effect in predicting the risk of IM is justified with a p-value less than 10-6. We also select the most appropriate mixed-link models (Models 2 and 3) when an additional covariate, the status of gastric atrophy, is available. When the status is negative, mild, or moderate, we recommend Model 2; otherwise, we prefer Model 3. Both Models 2 and 3 can predict the risk of IM significantly better than Model 1, which justifies that the status of gastric atrophy is informative in predicting the risk of IM.