Search

Background: The noninvasive serum markers pepsinogen I (PGI), pepsinogen II (PGII), gastrin-17 (G17), and PGI:PGII ratio (PGR) have recently been proposed as a new tool for predicting various gastric pathologies., Methods: A total of 83 gastritis patients confirmed by gastroscopy were enrolled, with 78 undergoing concurrent colonoscopies. The control group included 99 healthy subjects. Enzyme-linked immunosorbent assay was used to detect PGI, PGII, G17, and PGR. The performance of serological analysis for detecting gastritis pathology was evaluated using receiver operating characteristic (ROC) curves., Results: The G17 and PGII levels increased significantly (P < .001), whereas PGR levels decreased (P = .001) in the gastritis group. The ROC analysis revealed that PGR had a sensitivity and specificity of 70.83% and 86.67%, respectively, in predicting Helicobacter pylori-infected gastritis and a sensitivity and specificity of 88% and 65.52%, respectively, in predicting active gastritis. The G17 levels were significantly elevated in gastritis patients undergoing concurrent colonoscopies (P < .05)., Conclusion: Pepsinogen I:pepsinogen II ratio was found to be a useful predictor of active gastritis and H pylori-infected gastritis. Furthermore, G17 was found to be closely related to pathological conditions found by colonoscopy and may provide recommendations for whether gastritis patients should undergo a concurrent colonoscopy., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: T-helper 17 plays a novel role in inflammation in gastritis by producing IL-17A, IL-17A gene polymorphisms that might be responsible for disease susceptibility and development of different gastric lesions., Objective: The aims of study was to determine the association of IL-17A (G197A) genotype and allele frequency with disease phenotype and risk with different gastric lesions., Methods: Case controlled study involved 30 gastroduodenal ulcer, 30 chronic gastritis and 30 subjects as a control group with negative endoscopic findings. After genomic DNA extraction, IL-17A (G197A)ARMS-PCR genotyping were done for all cases. Serum IL-17A was measured using ELISA method and tissue expression was visualized using immunohistochemistry staining method., Results: The results showed that allele A was significantly frequent in gastroduodenal ulcer more than that in healthy control odd ratio= 4 (1.42-10.46), and none significantly with chronic gastritis p=0.071. Serum IL-17A was significantly higher in gastroduodenal ulcer (116.45±48.09 pg/ml), chronic gastritis (78.02±30.17pg/ml) and healthy control 19.36±9.28 pg/ml).However, the serum IL-17A level is not related to the allele pattern of each group. The tissue expression was expressed as dense granular cytoplasmic and membranous of inflammatory cells. Interestingly, the percentage of IL-17A protein expression was significantly higher in gastroduodenal ulcer (38.2±16.55%), chronic gastritis (30.89±14.02%) and normal mucosa (2.8±3.02%). Furthermore, patients with strong intensity of IL-17A stained mucosa were frequently carrier for mutant allele (68%)., Conclusion: IL-17A might predispose for aggressive inflammation of advanced lesions in stomach like ulcer., Competing Interests: Authors declares that there is no conflict of interest., (© 2021 Haider F. Ghazi, Manar Mustafa, Hayfaa M. Fahad.)

The CagA protein one of the key virulence factors of Helicobacter pylori plays an important role in the pathogenesis of peptic ulcer diseases. Unfortunately the cagA gene status can only be determined by PCR while serology is an alternative approach to detect antigens or antibodies. Our aim is to detect the CagA antigen in sera of infected subjects by the development of an in-house capture ELISA test. Gastric antral biopsies and serum samples were collected from 63 patients. PCR was used to determine the cagA status. Our previously developed recombinant CagA protein and monoclonal antibody were used for setting up the capture ELISA test. H. pylori positive [(38 gastritis, 14 duodenal ulcers (DU), 11 gastric ulcer (GU)] patients were determined by PCR. The cagA gene was detected in 21 (55%) of gastritis, 11 (78%) of DU and 7 (60%) of GU patients. The reagents used in setting up the capture ELISA test following optimization displayed high performance. This study showed that our developed in-house capture ELISA has the potential to detect the CagA antigen at very low concentrations even though not detected in our H. pylori infected patients sera but we are also intended to use it in saliva and stool samples., (Copyright © 2020. Published by Elsevier B.V.)

Objectives: In the diagnostic work up of autoimmune gastritis several immunological methods are available for the detection of antibodies against Intrinsic Factor (IF) and Parietal Cells (PC). However, there are no recent reports directly comparing all the available assays and methods. The objective of this study was to compare the performance of several commercially available anti-IF and anti-PC antibody assays from different manufacturers in a multi-center multi-cohort setting., Methods: Sera were used from 5 different cohorts consisting of samples from 25 healthy elderly, 20 HCV or HIV positive patients and 150 patients positive for anti-IF or anti-PC antibodies or in whom these antibodies were requested. These cohorts were tested for anti-IF antibodies with 6 different assays (IIF, ELISA, DIA and EliA) and for anti-PC antibodies with 7 different assays (IIF, ELISA, DIA and EliA). Performance was evaluated by calculating the concordance and relative sensitivity and specificity., Results: Good concordance was found between the assays for both antibody specificities, ranging from 81 to 100% and 91-100% for anti-IF and anti-PC antibodies, respectively. Highest relative sensitivity was found with the (automated) ELISA based methods. However, all assays had a relative sensitivity between 85 and 100% for anti-IF antibodies and between 95 and 100% for anti-PC antibodies. The relative specificity ranged between 76 and 100% for anti-IF antibodies and between 96 and 100% for anti-PC antibodies., Conclusions: We conclude that most assays perform well and are concordant to each other, despite the methodological differences and the different sources of antigen used. However, the method used affects the sensitivity and specificity. The (automated) ELISA based assays have the highest relative sensitivity and relative specificity. Care should be taken in the interpretation of positive results by IIF and negative results by the Blue Diver when testing for anti-IF antibodies., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objective: Controversy exists regarding an association between Helicobacter pylori infection and asthma in children. We examined the hypotheses of inverse associations of H. pylori seroprevalence and pepsinogen (PG) levels, as markers of gastric inflammation, with asthma in children., Methods: A hospital-based case-control study was conducted among children aged 4.8 to 17.3 years in Israel. Confirmed asthma cases (n = 75) were recruited through a pulmonary clinic, and controls (n = 160) without asthma were enrolled. Using enzyme-linked immunosorbent assays we measured the presence of H. pylori immunoglobulin G (IgG) antibodies, IgG antibodies to cytotoxin-associated gene A antigen (CagA) (virulent factor), serum PG levels and exposure to other enteric pathogens (Shigella flexneri). Multivariable logistic regression models were applied., Results: H. pylori IgG seropositivity was 25% and 40% among cases and controls, respectively (P = .03). H. pylori CagA IgG seropositivity was associated with reduced risk of asthma (adjusted odds ratio [OR], 0.33 [95% CI, 0.11-0.95] but not for the CagA negative serology (adjusted OR, 0.70 [95% CI, 0.32-1.54]). Children who were H. pylori seropositive with a PGI:PGII of ≤6.78 (severe gastric inflammation) had a lower likelihood of asthma (adjusted OR, 0.31 [95% CI, 0.10-0.89]) than did seronegative children. Exposure to Shigella flexneri did not differ between cases and controls, nor according to H. pylori seropositivity. Among the asthmatic children, pulmonary function did not differ according to H. pylori seropositivity., Conclusions: H. pylori infection and its related gastric inflammation may have a protective role in the risk of pediatric asthma and further research into a potential causal pathway is required., (© 2020 Wiley Periodicals LLC.)

Non-invasive biomarkers, such as neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios, may predict inflammation in various disorders, including gastritis, according to recent data. Nevertheless, various studies reported an association between Helicobacter pylori (H pylori) and immune thrombocytopenia in both adults and pediatric patients. The objective of our study was to evaluate the impact of pediatric gastritis, caused or not by H pylori infection on erythrocytes, their parameters, thrombocytes, mean platelet volume, neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR).We performed a prospective, case-control study on 151 patients aged between 1 and 17 years who presented with chronic dyspeptic symptoms. An upper digestive endoscopy with gastric biopsies and a complete blood count was performed in each case.Control group consisted of 67 patients with normal histological findings, while the two study groups were divided into group 1-H pylori-induced gastritis (31 patients) and group 2-non-H pylori-induced gastritis (53 patients). Children from the rural area were more likely to develop both types of gastritis (P < .01). No significant difference was found between either of the study groups and control group in terms of platelets, mean platelet volume, NLR and PLR (P > .05). However, significantly higher values of lymphocytes were associated with non-H pylori-induced gastritis (P < .01). Comparison of the two study groups did not reflect any significant differences in terms of hematological parameters. When assessing these constants in relation to gastritis severity, severe gastritis led to a compelling decrease in hemoglobin (Hb) and hematocrit (Htc) levels. The comparison of parameters between severe, moderate, and mild gastritis did not reveal any significant results.Childhood and adolescent gastritis does not produce a significant effect upon platelet counts, their mean volume, PLR or NLR, according to our study. An important increase in lymphocyte count might predict non-H pylori pediatric gastritis. Moreover, severe gastritis might result in an important decrease in Hb and Htc levels.

Context: The glycoprotein chromogranin A (CgA) is expressed by endocrine and neuroendocrine cells. High levels of serum CgA serve as markers of neuroendocrine tumors (NET), but its role in autoimmunity has not been assessed., Objective: To investigate CgA utility as a marker of endocrine autoimmunity., Methods: CgA serum levels were evaluated in 807 consecutive unselected participants (cross-sectional study) with the time-resolved amplified cryptate emission technology., Results: Serum CgA concentrations were increased in 66%, 39%, 38%, and 24% of patients with NET, type 1 diabetes (T1D), autoimmune gastritis (AG) and autoimmune polyendocrinopathy (AP), respectively. Compared with healthy participant controls (C), the odds of positive CgA measurement were up to 28 times higher in the disease groups. In detail, the odds ratios (ORs) for positive CgA levels were 27.98, 15.22, 7.32 (all P < 0.0001) and 3.89 (P = 0.0073) in patients with NET, T1D, AG, and AP, respectively. In AG, CgA and serum gastrin correlated positively (r = 0.55; P < 0.0001). The area under the receiver operating characteristic curve to predict AG was higher for parietal cell antibody (PCA) positivity than for CgA (0.84 vs 0.67; P < 0.0001). However, in combination with PCA and intrinsic factor autoantibodies, CgA independently improved prediction of AG (OR 6.5; P = 0.031). An impact of age on CgA positivity and on CgA value was detected (P < 0.0001) while current smoking significantly increased CgA serum levels by 25% (P = 0.0080)., Conclusion: CgA qualifies as a novel biomarker for T1D, AP, and AG., (© Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Collagenous gastritis (CG), a rare disorder of unknown etiology, has been postulated to have immune-mediated mechanisms. We investigated (i) the incidence and prevalence of CG in a pediatric population; (ii) the clinical, endoscopic, and histologic characteristics of childhood-onset CG; and (iii) the evidence for autoimmunity and/or inflammatory activity in these patients., Methods: Clinical, endoscopic, and histologic data were reviewed longitudinally in a population-based Swedish cohort of 15 patients with childhood-onset CG diagnosed in the period 2008-2019. A set of 11 autoantibodies, 4 blood inflammatory biomarkers, and the human leukocyte antigen DQ2/DQ8 genotype was analyzed cross-sectionally., Results: The incidence rate of childhood-onset CG was 0.25/100,000 person-years, with an incidence rate ratio of girls to boys of 4.2 (95% confidence interval, 1.2-15). The prevalence of CG was 2.1/100,000 in children aged younger than 18 years. The endoscopic and histologic findings remained pathologic in all the examined patients during a median follow-up of 4.4 years. Many patients had heredity for autoimmune disorders (47%) and/or tested positive for autoantibodies (40%) or human leukocyte antigen DQ2/DQ8 (53%). No associated autoimmune comorbidities were observed. The serum levels of calprotectin and amyloid A were increased in 10/15 (67%) and 5/15 (33%) of the patients, respectively, whereas plasma C-reactive protein levels were normal in all, but 1 patient., Discussion: The results indicate that childhood-onset CG is rare and has a chronic disease course. Although signs of autoimmune predisposition are frequent, early development of autoimmune comorbidities seems seldom. Serum calprotectin and amyloid A represent novel candidate biomarkers of inflammatory activity in CG (see Visual Abstract, Supplementary Digital Content 4, http://links.lww.com/CTG/A349).

Objectives: To assess the concordance and performance characteristics of Helicobacter pylori laboratory tests compared with histopathology and to propose algorithms for the diagnosis of H pylori that minimize diagnostic error., Methods: H pylori diagnostics were reviewed from a 12-year period within a health system (2,560 cases). Analyses were performed to adjust diagnostic performance based on treatment and consensus histopathologic diagnoses among pathologists. Markers of access to care, including test cancellation frequency and turnaround time, were assessed. Costs and performance of candidate noninvasive testing algorithms were modeled as a function of disease prevalence., Results: Serum H pylori IgG demonstrated a higher sensitivity (0.94) than urea breath and stool antigen tests (0.64 and 0.61, respectively). Evidence of an advantage in access to care for serology included a lower cancellation rate. Interobserver variability was higher (κ = 0.34) among pathologists for cases with a discordant laboratory test than concordant cases (κ = 0.56). A model testing algorithm utilizing serology for first-time diagnoses minimizes diagnostic error., Conclusions: Although H pylori serology has modestly lower specificity than other noninvasive tests, the superior sensitivity and negative predictive value in our population support its use as a noninvasive test to rule out H pylori infection. Reflexive testing with positive serology followed by either stool antigen or urea breath test may optimize diagnostic accuracy in low-prevalence populations., (© American Society for Clinical Pathology, 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aims/introduction: The relationship of chromogranin A (CgA) levels above the normal range with various outcomes, such as glycated hemoglobin levels, enterochromaffin-like cell hyperplasia and autoimmune gastritis, was investigated in type 1 diabetes patients with special regard to the progression of comorbidities., Materials and Methods: A cohort study on 153 type 1 diabetes patients was carried out with a prospective branch on clinical and laboratory data, and a retrospective branch on histological data obtained by gastroscopy., Results: Patients with CgA levels above the upper limit of the normal range (n = 28) had significantly higher glycated hemoglobin levels (P = 0.0160) than those with CgA in the normal range (n = 125). The correlation between CgA and glycated hemoglobin was significant (P < 0.0001), but weak (R = +0.32). A slight, but steady elevation (P = 0.0410) in CgA level was observed to co-vary with the duration of type 1 diabetes. Enterochromaffin-like cell hyperplasia and autoimmune gastritis was significantly more frequent (P = 0.0087 for both) in the high CgA group. Detailed analyses on gastric tissue samples confirmed a progression of enterochromaffin-like cell hyperplasia (P = 0.0192) accompanied by CgA elevation (P = 0.0316)., Conclusions: The early detection and follow up of the later progression of enterochromaffin-like cell hyperplasia and autoimmune gastritis into gastric neuroendocrine tumors, which have ~100-fold greater incidence in type 1 diabetes patients, can be achieved by assessment of CgA levels. Therefore, the use of CgA could be considered as a novel auxiliary biomarker in the care of these type 1 diabetes complications., (© 2019 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Background: CD19 + IL-10 + B cells are considered as a particular subset of immunosuppressive cells by producing interleukin 10 (IL-10), which plays an important role in infectious and autoimmune diseases. The aim of this study was to determine the number of CD19 + IL-10 + B cells in Helicobacter pylori (H. pylori) positive patients in comparison with H. pylori negative patients, and to determine the association with different clinical outcomes, such as gastritis and peptic ulcer disease (PUD), in infected patients., Methods and Materials: We studied 25 infected patients with gastritis, 25 infected patients with PUD, and 25 patients negative for H. pylori. The number of CD19 + IL-10 + B cells was determined by immunofluorescence., Results: The number of CD19 + IL-10 + B cells in patients infected with H. pylori was significantly 2.5-fold higher than uninfected patients (P < 0.0001). Also, the number of CD19 + IL-10 + B cells in infected patients with gastritis was significantly 1.45-fold elevated compared to infected patients with PUD (P = 0.001)., Conclusions: These results demonstrate that the increased number of CD19 + IL-10 + B cells in infected patients and its association with other cells may play an important role in the pathogenesis of H. pylori infection., (Copyright © 2020 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Serum pepsinogens have been widely acknowledged as gastric mucosal biomarkers; however, a multicountry report on the benefits of pepsinogens as biomarkers has not yet been published. We analyzed 1,206 sera and gastric mucosal samples collected from Bangladesh, Bhutan, Indonesia, Myanmar, Nepal and Thailand then assessed the association between gastric mucosal changes and Helicobacter pylori infection. The new cutoff values for serum pepsinogen values were evaluated using a receiver operating characteristic analysis. The participants with H. pylori infection had significantly lower pepsinogen I and higher pepsinogen II values, but a lower pepsinogen I/II ratio than participants without the infection (all P < .001). The pepsinogen I and pepsinogen I/II values were significantly higher and lower, respectively, in individuals with atrophic gastritis than in those without (both P < .001). Among uninfected individuals, only the pepsinogen I/II ratio was significantly lower in atrophic individuals. Pepsinogen I/II ratio also were significantly different between disease among H. pylori-positive and H. pylori-negative individuals, suggesting the pepsinogen I/II ratio is a robust biomarker for determining both chronic and atrophic gastritis. The cutoffs for detecting chronic and atrophic gastritis for the pepsinogen I/II ratio were 4.65 and 4.95, respectively. In conclusion, pepsinogen levels are useful biomarker for both chronic gastritis and atrophic gastritis, but they should be used with caution. Population-based validation is necessary to determine the best cutoff values. Among all pepsinogen values, the pepsinogen I/II ratio was the most reliable gastric mucosal-change biomarker., Competing Interests: The authors have declared that no competing interests exist.

Aims: We aimed to explore diagnostic efficiencies of long noncoding RNAs (lncRNAs) adjacent to PGC combining with sPGC and anti- Helicobacter pylori IgG in identifying GC (gastric cancer) and precancerous disease. Patients & methods : A total of 265 patients with different gastric diseases were collected. ELISA was to detect sPGC and anti- H. pylori IgG. LncRNAs was determined by qRT-PCR. Results : The area under receiver operating characteristic curve of lncRNAs in discriminating GC+AG (atrophic gastritis) and superficial gastritis (SG) were 79.0, 68.1 and 75.9%. The diagnostic performance of lncRNAs with sPGC had increasing trends in distinguishing GC from non-GC, SG from GC+AG comparing with lncRNAs, with no statistic difference. Diagnosis efficacies of lncRNAs with anti- H. pylori IgG improved dramatically. Conclusions : Serum lncRNAs could distinguish GC, AG and SG. Diagnosis efficiencies of lncRNAs with sPGC and anti- H. pylori -IgG could be improved.

Objectives: Patients with autoimmune gastritis (AIG) are reported to have an increased risk of developing gastric cancer (GC). In this study, we assess the characteristics and outcomes of GC patients with AIG in a multicenter case-control study., Methods: Between April 2013 and May 2017, patients with GC, including cancers of the esophagogastric junction (EGJ) Siewert type II and III, were recruited. Patients with histological characteristics of AIG were identified and matched in a 1:2 fashion for age and gender to GC patients with no AIG. Presenting symptoms were documented using a self-administered questionnaire., Results: Histological assessment of gastric mucosa was available for 572/759 GC patients. Overall, 28 (4.9%) of GC patients had AIG (67 ± 9 years, female-to-male ratio 1.3:1). In patients with AIG, GC was more likely to be localized in the proximal (i.e. EGJ, fundus, corpus) stomach (odds ratio (OR) 2.7, 95% confidence interval (CI) 1.0-7.1). In GC patients with AIG, pernicious anemia was the leading clinical sign (OR 22.0, 95% CI 2.6-187.2), and the most common indication for esophagogastroduodenoscopy (OR 29.0, 95% CI 7.2-116.4). GC patients with AIG were more likely to present without distant metastases (OR 6.2, 95% CI 1.3-28.8) and to be treated with curative intention (OR 3.0, 95% CI 1.0-9.0). The five-year survival rates with 95% CI in GC patients with and with no AIG were 84.7% (83.8-85.6) and 53.5% (50.9-56.1), respectively (OR 0.25, 95% CI 0.08-0.75, p  = 0.001)., Conclusions: Pernicious anemia leads to earlier diagnosis of GC in AIG patients and contributes significantly to a better clinical outcome.

Background/aim: Autoimmune gastritis is an autoimmune and inflammatory disorder. The aim of this study is to examine dynamic thiol/disulfide homeostasis and ischemia modified albumin levels, and to analyze the association between thiol/disulfide homeostasis and gastric emptying time in autoimmune gastritis., Materials and Methods: Thiol/disulfide homeostasis tests and ischemia modified albumin levels were determined in 50 autoimmune gastritis patients and 53 healthy subjects. Patients with delayed and normal gastric emptying were compared by thiol/disulfide homeostasis tests., Results: The results showed that native thiol (μmol/L), total thiol (μmol/L), and native thiol/total thiol ratio (%) of the patients with autoimmune gastritis decreased compared to the control group (177.7 ± 34.18 vs. 245.25 ± 33.83, P = 0.001, 227.25 ± 36.78 vs. 284.20 ± 27.19, P = 0.03, and 8.84 ± 1.1 vs. 7.74% ± 1.3%, P = 0.001). In addition, native thiol (μmol/L), total thiol (μmol/L), and native thiol/ total thiol ratio (%) were found to be lower in patients with delayed gastric emptying (198.65 ± 24.27 vs. 167.12 ± 20.51, 241.81 ± 27.14 vs. 213.92 ± 26.35, 8.34 ± 1.29 vs. 7.20 ± 1.83, P = 0.001). Disulfide level, disulfide/native thiol, disulfide/total thiol (P = 0.001) ratios, and ischemia modified albumin levels (ABSU, 0.71 ± 0.08 vs. 0.83 ± 0.07) were found to be higher in autoimmune gastritis patients with delayed gastric emptying (P = 0.001)., Conclusion: The results showed that thiol/disulfide homeostasis in patients with autoimmune gastritis caused an increase in ischemia modified albumin and disulfide whereas a decrease in thiols. An altered thiol/disulfide balance was also observed in patients with delayed gastric emptying. These results suggest that the oxidative process is involved in patients with autoimmune gastritis., Competing Interests: None declared, (This work is licensed under a Creative Commons Attribution 4.0 International License.)

Background/aims: The aim of this study was to investigate the specificity and sensitivity of eosinophil cutoff points defining the colonic tissue eosinophilia (TE) and compare the yield of reporting the highest count versus the mean of five high-power fields (HPFs)., Materials and Methods: One hundred and seventy-one cases of colonic TE, including 22 primary eosinophilic colitis (PEC) cases, were compared to one hundred and twenty-one normal controls in the University of Jordan. The highest eosinophil count (EC) and the mean of five HPFs were recorded. The receiver operating characteristic curve (ROC) analysis was used to find the cutoff point with the best sensitivity and specificity., Results: There was no significant advantage of counting five fields over counting the most densely populated HPF. Using 30 eosinophils per HPF achieved 80% sensitivity and 65% specificity. This point is close to the mean in normal controls plus one standard deviation (SD) (29 per HPF). However, there was overlap between normal counts and TE, using 30 as a cutoff point resulted in 35% false-positive rate. There was no reliable cutoff point to differentiate PEC from secondary TE., Conclusion: We recommend reporting the highest EC in colonic biopsies and using 30 as a cutoff point, bearing in mind the overlap with normal and correlating with the clinical team to not treat asymptomatic patients. Clinicopathological correlation is essential to separate PEC from secondary TE., Competing Interests: None

Objective: Patients with autoimmune thyroid disease (ATD) have a higher prevalence of autoimmune gastritis (AIG) compared with the general population. The association between ATD and AIG is poorly characterized in the pediatric age. We reviewed the prevalence of anti-gastric parietal cell antibodies (PCA) in young patients with ATD to evaluate its usefulness as a marker for AIG screening., Methods: We evaluated 220 children and adolescents (11.28 ± 6.37 years) with ATD (186 with autoimmune thyroiditis (AT) and 34 with Graves' disease (GD). At ATD diagnosis and annually thereafter, blood counts and PCA levels were measured. In patients positive for PCA, plasma gastrin, chromogranin A, vitamin B 12 , iron and ferritin levels and H. pylori antigen were measured. PCA-positive patients > 18 years were invited to undergo a gastroscopic exam., Results: PCA positivity was detected in ten (4.5%) subjects (5F/5M; 12.6 ± 3.4 years). The prevalence of PCA positivity was not significantly different in the comparison of GD and AT patients (p = 0.9). PCA positivity was detected after 2.7 ± 2.7 years of follow-up in AT and 4.4 ± 4.0 years in GD (p = 0.4). Autoantibody positivity was more prevalent in female patients, in both AT and GD (p = 0.02 and p = 0.03, respectively). At detection of PCA positivity, five out of ten PCA-positive patients had iron deficiency, four vitamin B 12 deficiency, two anemia, three hypergastrinemia and two elevated chromogranin values. Two patients had H. pylori infection. Gastroscopy was performed in the five ATD patients and in all patients, AIG was confirmed., Conclusion: In the juvenile population, ATD and AIG may also be associated. PCA screening is useful to detect subjects at risk for this condition. Due to the longer life expectancy of the pediatric population and considering the relatively high risk of malignant transformation, early surveillance monitoring is mandatory for children and adolescents with ATD.

Background: Eosinophilic gastritis (EG) is a clinicopathologic disorder with marked gastric eosinophilia and clinical symptoms. There is an unmet need among patients with EG for more precise diagnostic tools., Objective: We aimed to develop tissue- and blood-based diagnostic platforms for EG., Methods: Patients with EG and control subjects without EG were enrolled across 9 Consortium of Eosinophilic Gastrointestinal Disease Researchers-associated sites. An EG Diagnostic Panel (EGDP; gastric transcript subset) and EG blood biomarker panel (protein multiplex array) were analyzed. EGDP 18 scores were derived from the expression of 18 highly dysregulated genes, and blood EG scores were derived from dysregulated cytokine/chemokine levels., Results: Gastric biopsy specimens and blood samples from 185 subjects (patients with EG, n = 74; control subjects without EG, n = 111) were analyzed. The EGDP (1) identified patients with active EG (P < .0001, area under the curve ≥ 0.95), (2) effectively monitored disease activity in longitudinal samples (P = .0078), (3) highly correlated in same-patient samples (antrum vs body, r = 0.85, P < .0001), and (4) inversely correlated with gastric peak eosinophil levels (r = -0.83, P < .0001), periglandular circumferential collars (r = -0.73, P < .0001), and endoscopic nodularity (r = -0.45, P < .0001). For blood-based platforms, eotaxin-3, thymus and activation-regulated chemokine, IL-5, and thymic stromal lymphopoietin levels were significantly increased. Blood EG scores (1) distinguished patients with EG from control subjects without EG (P < .0001, area under the curve ≥ 0.91), (2) correlated with gastric eosinophil levels (plasma: r = 0.72, P = .0002; serum: r = 0.54, P = .0015), and (3) inversely correlated with EGDP 18 scores (plasma: r = -0.64, P = .0015; serum: r = -0.46, P = .0084). Plasma eotaxin-3 levels strongly associated with gastric CCL26 expression (r = 0.81, P < .0001)., Conclusion: We developed tissue- and blood-based platforms for assessment of EG and uncovered robust associations between specific gastric molecular profiles and histologic and endoscopic features, providing insight and clinical readiness tools for this emerging rare disease., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. All rights reserved.)

Introduction: The diagnosis of Helicobacter pylori infection status with white light imaging (WLI) is difficult. We evaluated the accuracies of using WLI and linked color imaging (LCI) for diagnosing H. pylori-active gastritis in a multicenter prospective study setting., Methods: Patients who underwent esophagogastroduodenoscopy were prospectively included. The image collection process was randomized and anonymous, and the image set included 4 images with WLI or 4 images with LCI in the corpus that 5 reviewers separately evaluated. Active gastritis was defined as positive when there was diffuse redness in WLI and crimson coloring in LCI. The H. pylori infection status was determined by the urea breath test and the serum antibody test. Cases in which both test results were negative but atrophy or intestinal metaplasia was histologically confirmed were defined as past infections. The primary endpoint was the diagnostic accuracies of WLI and LCI, and the secondary endpoint was inter-observer agreement., Results: Data for 127 patients were analyzed. The endoscopic diagnostic accuracy for active gastritis was 79.5 (sensitivity of 84.4 and specificity of 74.6) with WLI and 86.6 (sensitivity of 84.4 and specificity of 88.9) with LCI (p = 0.029). LCI significantly improved the accuracy in patients with past infections over WLI (36.8 in WLI and 78.9 in LCI, p < 0.01). The κ values were 0.59 in WLI and 0.70 in LCI., Conclusions: LCI is useful for endoscopic diagnosis of H. pylori-active or inactive gastritis, and it is advantageous for patients with past infections of inactive gastritis., (© 2019 S. Karger AG, Basel.)

Helicobacter pylori ( H. pylori ) is a common problem and a significant cause of chronic gastric inflammation. H. pylori , ongoing gastric inflammation and its severity are the most critical component of precursors of gastric cancer. Hypothetically, every chronic tissue injury activates platelets, and the mean platelet volume (MPV) reflects this action well. The potential relationship between H. pylori and platelet count has been shown before. However, there are few and conflicting papers about the relationship between MPV and H. pylori related chronic gastric inflammation and its severity. The study aimed to assess any potential relationship between MPV and presence of H. pylori , as well as the severity of chronic gastric inflammation. A total of 6890 endoscopic reports were initially evaluated, and a total of 218 dyspeptic patients having undergone upper endoscopy were included. Of these, 118 (54.2%) were H. pylori positive and 100 (45.8%) were H. pylori negative. At least four gastric biopsies were obtained and evaluated according to Sydney classification. Age, gender, hemoglobin, mean corpuscular volume, ferritin, serum iron and C-reactive protein, as well as endoscopic findings were also recorded. A p<0.05 was accepted as significant. The MPV and platelet count did not differ between H. pylori positive and H. pylori negative groups of patients (p>0.05). There were no differences and correlation between MPV and gastric inflammation severity according to Sydney classification (p>0.05). When stratifying MPV as <9.15 fL and >9.15 fL, there was no difference between H. pylori positive and H. pylori negative groups either (p>0.05). In this study, we found no relationship between MPV and presence of H. pylori or severity of gastric inflammation. Although there are still conflicting publications on this issue, in our opinion and according to the results of this study, MPV is not a suitable marker for evaluation of gastric inflammation severity, being H. pylori either positive or negative.

Background: Extra-gastric manifestation of Helicobacter pylori infection involves systemic inflammation, which results in the production of several cytokines. Only a few clinical trials have investigated the effect of H. pylori eradication therapy on lipid metabolism in the infected patients with chronic gastritis. We aimed to evaluate the effect of H. pylori eradication therapy on lipid metabolism in a Japanese population with chronic gastritis., Methods: One hundred and sixty-three patients with H. pylori-associated chronic gastritis were enrolled in this study between June 2015 and March 2017. They underwent H. pylori eradication therapy; the effects of the therapy were assessed by the urea breath test performed at least 4 weeks after the therapy. After confirming H. pylori eradication, the health screening examination was repeated between May 2016 and August 2018. The clinical parameters were compared before and after the administration of the eradication therapy., Results: The mean age of the enrolled patients was 56.7 years, and the mean follow-up duration was 514.7 days. Weight, body mass index, and obesity index were significantly increased post-eradication therapy compared to those pre-eradication therapy. White blood cell and platelet counts were significantly decreased, and high density lipoprotein cholesterol (HDL) level was significantly increased (P = 0.001), while low density lipoprotein cholesterol (LDL), total cholesterol, and triglycerides levels were not altered significantly. Hence, the LDL/HDL ratio was significantly decreased., Conclusions: This study reported that H. pylori eradication therapy increase the HDL levels in the infected patients with chronic gastritis. Hence, the LDL/HDL ratio, which is used to evaluate the risk of atherosclerosis, was significantly decreased post-eradication therapy compared to that pre-eradication therapy., Competing Interests: The authors have declared that no competing interests exist.

Background and Aim: Helicobacter pylori (H. pylori) is closely associated with pre-neoplastic lesions such as atrophic gastritis (AG) and gastric intestinal metaplasia (GIM). The relationshionship between inflammation, hyperhomocysteinemia and arterial stiffness is of pathophysiological relevance for the development of cardiovascular disease. This study aimed to investigate the relationship between vitamin B12, folic acid, homocysteine (Hcy) and pulse wave velocity (PWV) levels in patients with GIM, AG and non-atrophic non-metaplastic chronic gastritis., Patients and Methods: ninety-seven patients with GIM, 67 patients with AG and 69 patients with chronic gastritis were included in the study. Glucose, creatinine, total cholesterol, triglyceride, low-density lipoprotein, cholesterol, high-density lipoprotein cholesterol, vitamin B12, folic acid and Hcy levels were measured by biochemical methods. PWV and other vascular parameters were measured using the Phsyio-port AS device., Main Results: PWV was higher in patients with GIM and AG than in controls (p < 0.05 and p < 0.05, respectively). Vitamin B12 levels were significantly lower in patients with GIM and AG than in controls (p < 0.01 and p < 0.01, respectively). Folic acid levels were significantly lower in patients with GIM than in controls (p < 0.05). Hcy levels were significantly higher in patients with GIM and AG than in controls (p < 0.001 and p < 0.05, respectively). A logistic regression analysis showed that GIM, AG and vitamin B12 deficiency were predictors for arterial stiffness., Conclusions: PWV values increased in patients with GIM and AG compared to non-atrophic non-metaplastic chronic gastritis, without different conventional cardiovascular risk factors.

Neutrophil to lymphocyte ratio (NLR) is a simple, noninvasive, inexpensive inflammatory marker that can useful in the assessment of inflammatory activity, especially in pediatric ages. The aim of our study was to establish correlations between the presence of Helicobacter pylori (HP) proved histologically and NLR in children.A prospective, case-control study was performed on 137 pediatric patients aged between 1 and 18 years, admitted in a Pediatric Tertiary Hospital from Romania, between April 2016 and January 2018. According to the histologic examination, the children were divided into 2 groups: group 1: 50 children with HP infection, and group 2: 87 children without any pathologic findings.The mean age for the study group was 12.86 ± 3.796 years, whereas for control group, it was 12.10 ± 3.879 years (P = .3001). HP infection was significantly more frequent among children from rural area (P = .0089). Epigastric pain and loss of appetite were significantly associated with HP infection (P = .0350 /P = .0281). We noticed that the leukocyte and neutrophil counts were significantly higher in group 1 (P = .0076/P = .0306). We did not find any significant statistical differences between the 2 groups in terms of lymphocytes, erythrocyte sedimentation rate, and NLR or other assessed laboratory parameters. Regarding the IgA antibodies anti-HP and rapid urease test, they were both significantly associated with histologically confirmed HP infection (P < .0001).Even though, we did not identify significant differences in term of NLR between HP-induced gastritis children and healthy controls, the mean NLR values were higher HP-positive patients.

Introduction: Helicobacter pylori (H. pylori) is closely related to pre-neoplastic lesions such as gastric atrophy (GA), gastric intestinal metaplasia (GIM) and eventually gastric cancer (GC). The diagnosis of GIM and GA is usually based on endoscopic and histopathological features. Nowadays, there are no recognized good serological markers of GIM and GA. Neopterin is an important marker of cellular inflammation. In this study, we aimed to comparatively evaluate C-reactive protein (CRP) and neopterin levels in patients with GIM, GA and chronic gastritis, and to show the increased serum neopterin levels in GIM and GA according to non-atrophic and non-metaplastic chronic gastritis., Patients and Methods: 98 patients with GIM and 68 patients with GA and 70 patients with non-atrophic non-metaplastic gastritis were included in the study. CRP and neopterin levels were assessed in patients and controls., Results: CRP and neopterin levels were significantly higher in patients with GIM and GA than in controls (p<0.05 and p<0.001, respectively). A multiple logistic regression analysis showed that high levels of serum neopterin were positively correlated with GIM and GA. According to the ROC curve analysis, the best cut-off value to differentiate between patients with GIM and/or GA from controls was ≥10.15nmol/l (p<0.001) for serum neopterin levels and ≥1.95mg/l (p<0.001) for serum CRP levels., Discussion: CRP and neopterin levels are significantly increased in GIM and GA. Neopterin may be a useful biomarker and diagnostic test for detecting GIM and GA in clinical practice. CRP levels may be helpful for this observation., (Publicado por Elsevier España, S.L.U.)

Purpose: To evaluate serum levels of high-sensitivity C-reactive protein (hs-CRP) in chronic gastritis patients to predict Helicobacter pylori (HP) infection, inflammatory activity, and precancerous lesions., Methods: A total of 811 patients with upper gastrointestinal symptoms and histopathological diagnosis of chronic gastritis were enrolled in the study. On endoscopy, five gastric biopsies were taken according to Modified Sydney protocol, which were stained with hematoxylin & eosin and Giemsa., Results: HP infection was found in 28.6% of patients, being significantly more common in specimens with acute and chronic inflammatory activity. Mucosal atrophy, intestinal metaplasia, and dysplasia were found in 20.2%, 18.8% and 2.7% of biopsy specimens. Mean hs-CRP was 1.9±1.6 mg/dl for males and 2.2±1.9 mg/dl for females. hs-CRP average were significantly higher in patients with severe acute inflammation (p:0.049), in patients with severe chronic inflammation (p:0.015) and in those with HP (p: 0.001) . The severity of HP infection increased significantly with the increased degree of acute inflammation, chronic inflammation and hs-CRP level (p=0.001 for both)., Conclusion: Serum hs-CRP level increases in patients with chronic gastritis, it could be an indicator of severity of acute or chronic mucosal inflammation, and presence of HP infection. Therefore, hs-CRP may aid the diagnosis of chronic gastritis, but it is not associated with pre-cancerous lesions.

The effects of comorbidities on systemic inflammation markers in stable asthmatics and the consequences of such effects have not been well evaluated. We aimed to evaluate the effect of comorbidities on clinical manifestations and systemic inflammation in asthmatic patients under control. The study group consisted of asthmatic patients who applied to our pulmonology outpatient clinic and volunteered to participate. 120 clinically stable asthma patients (71 females and 49 males) and 35 healthy controls (19 females and 16 males) with similar age, gender, and body mass index distributions were admitted to the study. The levels of osteopontin, interleukin 6 (IL-6), interleukin 8 (IL-8), interleukin 13 (IL-13), eosinophilic cationic protein, adiponectin, and high-sensitivity C-reactive protein of the individuals were evaluated using commercial ELISA kits by taking venous blood samples. Of 120 asthmatic subjects, 47 (39, 2%) had comorbidities and allergic rhinitis (15%) coexisted most frequently. Other comorbidities associated with asthma were gastroesophageal reflux, sinusitis, hypertension, diabetes, gastritis, and peptic ulcus respectively. There was no physician-diagnosed comorbidity in the control group. The levels of IL-6 and IL-8 were found higher in asthma group with comorbidities when compared to those with no comorbidities (p were 0.032 and 0.046, respectively). Comorbidities interfere with the diagnosis and treatment of asthma, besides affecting the disease control. Our findings suggest the possibility of the impact of comorbidities on systemic inflammation markers, especially IL-6 and IL-8. To evaluate the impact of comorbidities on asthma control and systemic markers, further studies are needed.

Background: Eosinophilic gastroenteritis (EoGE) can be diagnosed on the basis of histologic criteria; however, the pathology is considered to be heterogeneous. There is no consensus on the management of this enigmatic disorder with an unknown etiology., Patients and Methods: Data for patients diagnosed with EoGE and followed up over a 1-year period were analyzed. Their symptoms, patterns of flares, and type of treatment were documented. The shift in peripheral blood eosinophil levels was also examined., Results: A total of 10 (mean age, 44 years; range: 31-70 years; women, 5) patients were diagnosed with EoGE. The most frequent presenting symptom was abdominal pain, and eight patients were classified with mucosal type of EoGE. Chronic disease or multiple flares were observed in seven out of 10 (70.0%) patients, and all of them had a history of allergy. Four were corticosteroid dependent (three relapsed during corticosteroid tapering and one following corticosteroid withdrawal). One of them received anti-IL5 monoclonal antibody that enabled corticosteroid dose tapering. In four patients with highly elevated initial eosinophil levels at diagnosis, the peripheral eosinophil level correlated with the amelioration and deterioration of their symptoms. The remaining three patients had a single flare without relapse. Two had no history of allergy., Conclusion: EoGE is a unique disorder with a variable clinical course. Although further studies are required to confirm our observations, the presence of other allergic disorders is associated with chronicity or multiple flares. Peripheral eosinophil level may be an effective biomarker for recurrence in patients with severe systemic disorders at diagnosis.

OBJECTIVE To identify minimally invasive biomarkers to help differentiate dogs with gastric carcinoma from those with chronic gastritis. DESIGN Prospective study. ANIMALS 15 dogs with gastric carcinoma, 29 dogs with chronic gastritis, and 7 healthy dogs. PROCEDURES Dogs with clinical signs of upper gastrointestinal tract disease for > 14 days that underwent gastroscopy or necropsy for collection of gastric biopsy specimens for histologic evaluation were prospectively enrolled. Gastric carcinoma and chronic gastritis were diagnosed on the basis of histologic findings. Additionally, gastric biopsy specimens were collected endoscopically from 7 healthy (control) dogs while they were anesthetized for a routine neutering procedure. Prior to being anesthetized for gastroscopy or euthanized, all dogs underwent a physical examination, and a blood sample was collected for quantification of select serum biomarker concentrations. Histologic findings, body condition score (BCS), and serum biomarker concentrations were compared among the 3 groups. RESULTS Dogs with gastric carcinoma were significantly older and had a significantly lower BCS, lower serum folate concentration, and greater serum C-reactive protein (CRP) concentration, compared with dogs with chronic gastritis and control dogs. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that age > 8 years, BCS < 4, serum CRP concentration > 25 mg/L, and an abnormally low serum folate concentration might be useful noninvasive biomarkers for identification of dogs with gastric carcinoma. For underweight older dogs with signs of upper gastrointestinal tract disease and high serum CRP and low serum folate concentrations, gastric biopsy specimens should be obtained and evaluated so that a prompt definitive diagnosis can be made and appropriate treatment initiated.

The association between gastroesophageal reflux disease (GERD) prevalence and its risk factors in an area with low Helicobacter pylori prevalence is important to clarify. We analyzed the prevalence of GERD and risk factors in an area of Indonesia with low prevalence of H. pylori infection. We recruited 104 dyspeptic patients who underwent endoscopy in Surabaya. Patients were diagnosed with GERD based on the Los Angeles classification. We evaluated gastric biopsy specimens and measured serum pepsinogen levels. Interleukin polymorphisms were evaluated by polymerase chain reaction-restriction fragment length polymorphism. Of 104 patients, 56 (53.8%) were endoscopically found to have GERD, with most categorized as grade A; 48 (46.2%) were classified as non-GERD. Higher economic status, smoking, and a history of proton-pump inhibitor use significantly increased the risk of GERD. GERD Questionnaire scores showed a positive correlation with GERD (P < 0.001). An association was found between antral atrophic gastritis and GERD (P = 0.030), and patients with GERD more frequently had severe antral atrophy than nonerosive reflux disease (P = 0.018). We found an association between pepsinogen I/II levels and GERD (P = 0.047), but with low accuracy. IL-1β -511 TT and CT were predominant among the IL-1β -511 genotypes, and IL-8-251 AT and TT were predominant among the IL-8-251 genotypes. In conclusion, we found a high prevalence of GERD in an area with low prevalence of H. pylori infection, which could be associated with acid reflux. Smoking, history of proton-pump inhibitor use, and higher economic group significantly increased the risk of GERD., Competing Interests: The authors have declared that no competing interests exist.

Strong evidence for an association between idiopathic thrombocytopenic purpura (ITP) and Helicobacter pylori (HP) infection has been reported in humans. Chronic ITP is known to be improved by the eradication of HP. The purpose of this study was to reproduce these events by the experimental infection of several strains of mice with HP. BALB/c, C57BL/6, and DBA/2 mice were untreated or orally inoculated with HP. Two months later, platelet counts were compared in samples from HP-infected and noninfected mice. Platelet counts (mean ± SD, × 10 4 cells/µl) in blood samples from HP-infected BALB/c, C57BL/6, and DBA/2 mice were 102.28 ± 14.71, 99.65 ± 17.00, and 111.57 ± 16.20, respectively; the respective counts from noninfected mice were 121.80 ± 13.30, 104.35 ± 18.20, and 107.84 ± 14.33. A significant difference in platelet counts between HP-infected and noninfected mice was observed in BALB/c mice (P≤0.01) but was not observed in DBA/2 mice, even though the histocompatibility (H)-2 type of the DBA/2 was the same as that of BALB/c mice. According to ELISA results, the optical density value for the anti-HP antibody in HP-infected BALB/c mice was not correlated with the number of platelets (P>0.50). These results suggest that the decrease in platelet count caused by HP infection is not related to antibody titer and histocompatibility-2 type. Experimental infection of BALB/c mice with HP can reproduce the relationship between HP and ITP and serves as a good model to investigate the mechanistic basis for the effectiveness of HP eradication therapy for ITP treatment.

Background: Recently, significant attention has been paid to the possible activation of an autoimmune response in the presence of obesity. The aim of this study was to evaluate and compare the frequencies of autoantibodies typical of autoimmune diabetes in obese patients with normal glucose tolerance (NGT), obese patients with type 2 diabetes (T2D) and controls. We also evaluated the presence of immunoreactivity to Hashimoto's thyroiditis and autoimmune gastritis., Materials and Methods: Consecutive sera from obese patients, 444 with NGT, 322 with T2D, and 212 controls were analysed by radioimmunoassay or enzyme-linked immunosorbent assay for glutamic acid decarboxylase, protein tyrosine phosphatase islet antigen-2 (IA-2) IC and IA-2 (256-760) , islet beta-cell zinc cation transporter (ZnT8), thyroid peroxidase, and anti-parietal cell autoantibodies., Results: Altogether the presence of organ-specific autoantibodies was significantly more frequent in obese patients with NGT (128/444, 28.5%) and obese with T2D (79/322, 24.5%) than in controls (36/212, 17%; P = 0.002). Thyroid peroxidase immunoreactivity was prevalent in all groups of subjects investigated. The frequencies of diabetes-specific autoantibodies were slightly higher in obese patients with NGT (20/444, 4.5%) than in obese with T2D (12/322, 3.7%) and controls (4/212, 1.9%). The anti IA-2 (256-760) was the most frequent islet autoantibody in obese subjects with NGT (14/20, 70%)., Conclusions: We observed significant evidence of immunoreactivity specific to diabetes, thyroid, and gastric-parietal cells in obese patients with NGT. The relatively higher frequency of the diabetes-related IA-2 (256-760) autoantibodies in obese patients with NGT may suggest that this autoantibody could be associated with obesity the presence of obesity itself., (© 2018 John Wiley & Sons, Ltd.)

Objectives: Anti-parietal cell antibodies (APCA) are a serologic marker of autoimmune gastritis. Their prevalence in healthy individuals is not well defined., Methods: We evaluated APCA prevalence in 515 healthy blood-donors by rat/primate tissue indirect immunofluorescence (IIF), enzyme-linked immunosorbent assay (ELISA), and immunoblot., Results: Fifty-three of 515 (10.3%) subjects were positive for APCA by at least one method: 18 only by ELISA, 10 by rodent tissue IIF, and one by primate tissue IIF; 18 were positive by ELISA and primate tissue IIF, and one by ELISA and rodent tissue IIF. Two were positive by both IIF methods, and three were triple positive. APCA positivity was confirmed by immunoblot in 100% of ELISA positive, in 95.8% of positive primate tissue IIF, and in 50% of positive rat tissue IIF., Conclusions: A great discrepancy in APCA prevalence detected by different methods in this cohort was apparent. Thus, the results on APCA prevalence in healthy individuals are likely method-dependent.

BACKGROUND The bacterial pathogen Helicobacter pylori (H. pylori) can cause chronic gastritis. CA54/61 is a serum tumor marker that has been shown to be positive in the several types of human malignancy. However, the association of between chronic gastritis due to H. pylori and elevated serum levels of CA54/61 has not been previously reported. This report is of three cases of increased serum levels of CA54/61 associated with H. pylori chronic gastritis. CASE REPORT Case 1 was a 44-year-old Japanese woman with a serum CA54/61 level of 138 U/ml (normal level: 12 U/ml). Following treatment and eradication of H. pylori the serum CA54/61 level decreased to 14 U/ml. Case 2 was a 73-year-old Japanese man with a serum level of less than 2 U/ml before completion of successful eradication therapy of H. pylori with a small peak of 30 U/ml after therapy. Case 3 was a 54-year-old Japanese man who maintained a serum CA54/61 level of approximately 20 U/ml before and until 603 days after eradication therapy. None of the three patients had malignancy, which is usually suggested by this serum marker. CONCLUSIONS These three case reports suggest the possibility of an association between chronic gastritis involving H. pylori infection and an elevated serum level of CA54/61. It is possible that the inflammatory gastric mucosal cells supply CA54/61 to the bloodstream. However, further studies are required to confirm the association between serum levels of CA54/61 and H. pylori chronic gastritis and the underlying mechanisms of this association.

Background: Gastric emptying (GE) of solids is delayed and autonomic dysfunction is detected in autoimmune gastritis (AIG). The goals of this study were to: (1) compare serum levels of ghrelin and motilin in subjects with delayed and normal GE and (2) investigate whether circulating antimyenteric antibodies (CAA), serum ghrelin levels and motilin levels have any effect on autonomic function., Materials and Methods: Noninvasive cardiovascular reflex tests were used in order to evaluate the autonomic function. GE was evaluated by a standard 2-hour scintigraphic test. Serum ghrelin and motilin levels were tested by enzyme-linked immunosorbent assay and CAA were tested by immunofluorescence., Results: The serum ghrelin and motilin levels in the patients with delayed GE (n = 22) were significantly decreased compared to the normal GE patients (n = 19), (67.55 ± 8.81 versus 126.79 ± 25.81pg/mL, P < 0.001 and 279.59 ± 111.12 versus 500.42 ± 155.95pg/mL, respectively, P < 0.001). Whereas, the serum ghrelin and motilin levels in the patients with deranged autonomic function (n = 26) were significantly decreased compared to the patients with normal autonomic function (n = 15), (80.73 ± 28.46 versus 127.79 ± 28.06pg/mL, P < 0.001 and 316.92 ± 160.47 versus 490.20 ± 141.02pg/mL, P < 0.001, respectively).  None of the patients were positive for CAA., Conclusions: Ghrelin and motilin levels in AIG subjects with delayed GE and deranged autonomic function were significantly decreased. The decrease in serum ghrelin and plasma motilin levels in AIG suggest their potential role in the delayed GE observed in these subjects., (Copyright © 2018 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Background: Subacute ruminal acidosis (SARA) is a metabolic disease in high-producing dairy cattle, and is accompanied by rumenitis. However, the mechanism of rumenitis remains unclear. Therefore, the aim of this study was to investigate the molecular mechanism of rumenitis in dairy cows with SARA., Results: The results showed that SARA cows displayed high concentrations of ruminal volatile fatty acids, lactic acid and lipopolysaccharide (LPS). Furthermore, the blood concentrations of LPS and acute phase proteins haptoglobin, serum amyloid-A, and LPS binding protein were significantly higher in SARA cows than in control cows. Importantly, the phosphorylation levels of nuclear factor-kappaB (NF-κB) p65, inhibitor of NF-κB (IκB), c-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase 1/2 (ERK1/2) were significantly higher in the rumen epithelium of SARA cows than those of control cows. The ruminal mRNA and protein levels of NF-κB- and mitogen-activated protein kinase (MAPK)s -regulated inflammatory cytokines, tumor necrosis factor α (TNF-α), interleukin 6 (IL-6) and interleukin 1β (IL-1β), were markedly higher in SARA cows than in control cows. Similarly, serum concentrations of TNF-α and IL-6 were also significantly higher in SARA cows., Conclusions: These results indicate that SARA results in high concentration of ruminal LPS, which over activates the NF-κB and MAPKs inflammatory pathways and then significantly increases the expression and synthesis of pro-inflammation cytokines in the rumen epithelium, thereby partly inducing rumenitis.

Aim: To investigate the clinicopathological features of the patients testing negative for high titer serum anti- Helicobacter pylori ( H. pylori ) antibody., Methods: The antibody titers were measured using antigens derived from Japanese individuals. 13 C-urea breath test-positive individuals were defined as having H. pylori infection. We investigated the demographic characteristics, laboratory data, endoscopic findings including Kyoto classification of gastritis, and histology in negative-high titer patients without H. pylori eradication therapy. Kyoto classification consisted of scores for gastric atrophy, intestinal metaplasia, enlarged folds, nodularity, and redness., Results: Of the 136 subjects enrolled, 23 (17%) had H. pylori infection. Kyoto classification had an excellent area under the receiver operating characteristics curve (0.886, 95% confidence interval: 0.803-0.968, P = 3.7 × 10 -20 ) for predicting H. pylori infection with a cut-off value of 2. Further, Kyoto classification, H. pylori density, and neutrophil activity had high accuracies (89.7%, 96.3%, and 94.1%, respectively). Kyoto classification was independent of the demographic and laboratory parameters in multivariate analysis., Conclusion: Endoscopic Kyoto classification of gastritis is a useful predictor of H. pylori infection in negative-high titer antibody patients., Competing Interests: Conflict-of-interest statement: During the last five years, Toyoshima O received personal fees from Otsuka Pharmaceutical Co., Ltd. and Takeda Pharmaceutical Co., Ltd. outside of the submitted work; Suzuki H received scholarship funds for the research from Astellas Pharma Inc., Astra-Zeneca K.K., Otsuka Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., and Zeria Pharmaceutical Co., Ltd. and received service honoraria from Astellas Pharma, Inc., Astra-Zeneca K.K., Otsuka Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., and Zeria Pharmaceutical Co., Ltd.

Aims: The aim of the study was to evaluate the rationale of blood pepsinogen (PG) testing in population based screening settings., Methods: Participants from a cross-sectional population-based study of cardiovascular risk factors in Latvia were invited to participate in the current study. Pepsinogen I and II were measured in blood samples taken during the initial study and at follow-up; upper gastrointestinal endoscopy was performed. There were three groups of patients: with moderately decreased (PG I< 70 ng/ml and PG I/PG II ratio < 3), with strongly decreased (PG I< 30 ng/ml and PG I/PG II ratio < 2), and with normal PG level. Biopsy with H. pylori detection was performed (updated Sydney system)., Results: Results from 259 patients were analyzed. Pepsinogens were decreased in 133 (51.4%), H. pylori was positive in 177 (66.0%) cases. Mean age was significantly lower in patients with normal compared to strongly decreased PG level group (52.8 vs. 64.1 years, p<0.001). Prevalence of severe corpus atrophy was higher in the strongly decreased compared to the normal PG test group: 7.0% vs. 0%; the same tendency was noted in the distribution of OLGA stages III-IV - 10.5% and 0.0%, OLGIM stages III-IV - 3.5% and 0%, and low-grade dysplasia - 15.8% and 2.4% (p<0.05). Two cases of gastric cancer were found; both presented decreased PG levels. A strong association between H. pylori eradication and PG ratio dynamics was found (p<0.05)., Conclusions: All high-risk lesions were found in the decreased PG test groups; two cancer cases were revealed. However, PG demonstrated low specificity and low value of repeated testing. The value of PG as a sole test for gastric cancer risk is limited.

Background/aims: Autoimmune gastritis patients may have autonomic nerve dysfunction. The goal of our study was to explore the predictive value of two scoring systems in the differentiation of altered autonomic nerve function in autoimmune gastritis patients., Materials and Methods: Seventy-five patients with autoimmune gastritis were evaluated by using cardiovascular reflex tests in order to delineate autonomic nerve function. Data were analyzed by using two laboratory-based scoring systems: "global score" (hemoglobin, mean corpuscular volume, gastrin, vitamin B12, and chromogranin A) and "simple score" (hemoglobin, mean corpuscular volume, gastrin) in order to discriminate deranged and normal autonomic nerve function., Results: Mean "simple" and "global" scores were significantly higher in subjects with altered autonomic dysfunction than in subjects with normal autonomic function (3.55±1.88 vs. 0.908±0.409, p<0.001 and 5.95±2.07 vs 2.46±1.28, p<0.001, respectively). Receiver operatör characteristic (ROC) analysis revealed that the optimum "simple score" cutoff point was 0.75 with a sensitivity of 86.7% and specificity of 92.3% for discriminating autoimmune gastritis patients with autonomic nerve dysfunction from patients with normal autonomic nerve function [area under the curve (AUC): 88.3, positive predictive value (PPV): 97.5% and negative predictive value (NPV): 66.6%; 95% confidence interval (CI), 88.4-99.7]., Conclusion: Simple score and global score have a high predictive value in the assessment of autoimmune gastritis patients with autonomic nerve dysfunction. These scoring systems may help physicians while evaluating autoimmune gastritis patients for the existence of autonomic nerve dysfunction instead of complex cardiovascular reflex tests.

Objective: Introduction: Ghrelin is 28-amino-acid peptide that is produced by X/A-like cells present in the stomach. Gastrin is a hormone that stimulates gastric acid secretion and mucosal cell growth. The aim: to study the interrelation between ghrelin and gastrin levels in patients with combination of chronic gastritis and type 2 diabetes mellitus., Patients and Methods: Materials and methods: 60 Helicobacter pylori positive patients with a combination of chronic gastritis and type 2 diabetes mellitus were examined. The diagnosis of type 2 diabetes mellitus is based on the recommendations of the International Diabetes Federation (IDF, 2005). Gastric acid secretion function was studied by intra-stomach express-pH-metry (method of prof. V.N. Chernobrov). Serum gastrin was determined using ELISA using Gastrin-EIA test kit Cat. No. CS 001 030. Serum ghrelin was determined by immunoassay analysis using the Human Ghrelin ELISA Kit from RayBiotech No. 1.03930005306., Results: Results: The obtained data testify to the existence of a feedback between the level of ghrelin and gastrin in the blood of patients with chronic gastritis and type 2 diabetes mellitus. That is, with increasing levels of gastrin in the blood, the level of ghrelin in the blood decreases and vice versa with a decrease in the level of gastrin in the blood, the level of ghrelin - increases., Conclusion: Conclusions: A significantly higher level of ghrelin was found in patients with type 2 diabetes mellitus and chronic gastritis compared with control group. The reverse association between gastrin and ghrelin levels in patients with combination of chronic gastritis and type 2 diabetes mellitus has been obtained.

Gastrin acts physiologically as a gut hormone to stimulate acid secretion after meal and as a cell-growth factor of oxyntic mucosa. Increase in serum gastrin level happens under various conditions including Zollinger-Ellison syndrome, antral G cell hyperplasia, autoimmune gastritis, atrophic gastritis, renal failure, vagotomy, Helicobacter pylori infection and acid suppressive therapy. As acid suppressive therapy causes hypergastrinemia, the association between acid suppressive therapy and gastric neuroendocrine cell tumor (NET) has been discussed during the past 30 years. In this review article, the definition of hypergastrinemia and the related disorders including acid suppressive therapy and gastric NET are discussed., (© 2018 Japanese Gastroenterological Association Published by S. Karger AG, Basel.)

Background: Endothelial dysfunction is one of the early stages of vascular diseases., Objective: The aim of this study was to investigate the endothelial dysfunction markers in patients with chronic gastritis associated with Helicobacter pylori (H. pylori) infection., Methods: By a cross sectional study, basic and clinical information of 120 participants (40 patients with positive H. pylori infection, 40 patients with negative H. pylori infection and 40 healthy people) were analyzed. Carotid intima media thickness and flow-mediated dilation levels were measured in all patients and controls. Soluble vascular cell adhesion molecule-1 (sVCAM-1) and intercellular adhesion molecule-1 (ICAM-1) were measured with Elisa for all subjects. IgG level was assessed in chronic gastritis patients., Results: The flow-mediated dilation level in patients with positive H. pylori infection (0.17%±0.09) was significantly lower than those with negative H. pylori infection (0.21% ±0.10, P<0.05) and compared to the control group (0.27% ±0.11, P<0.05). Carotid intima media thickness level in patients with positive H. pylori infection (0.58±0.13 mm) was significantly higher than those with negative H. pylori infection (0.48±0.32 mm, P<0.05) and compared to the control group (0.36±0.44mm, P<0.05). The mean level of sICAM-1 in positive H. pylori infection group (352.16±7.54 pg/mL) was higher than negative H. pylori infection group (332.64±8.75 pg/mL =0.75) and compared to the control group (236.32±12.43 pg/mL, P<0.05). A direct relationship was revealed between flow-mediated dilation and carotid intima media thickness changes and between sICAM-1 and sVCAM-1 associated with the level of H. pylori IgG in chronic gastritis., Conclusion: The levels of flow-mediated dilation, carotid intima media thickness and sICAM-1 were higher among patients with positive H. pylori infection. Patients with chronic gastritis associated with H. pylori infection are at risk of endothelial dysfunction due to flow-mediated dilation and carotid intima media thickness abnormalities and increased level of sICAM-1 and sVCAM-1.

Objective Clinically useful serum biomarkers for the diagnosis and monitoring of eosinophilic gastrointestinal diseases are not available. This study was conducted to examine the possible value of eosinophil-related proteins as serum biomarkers. Methods The serum concentrations of 49 cytokines, chemokines, and other proteins were measured in 29 patients with eosinophilic gastrointestinal diseases and 80 controls. Results The levels of interleukin (IL)-5, IL-33, eotaxin-3, and thymic stromal lymphopoietin (TSLP), previously reported as possible biomarkers of eosinophilic esophagitis, were not significantly elevated in the serum. In contrast, the B cell-attracting chemokine (BCA)-1/chemokine (C-X-C motif) ligand (CXCL) 13 and hemofiltrate C-C chemokine (HCC)-1/CC chemokine ligand (CCL) 14α levels were significantly elevated, while the granulocyte chemotactic protein (GCP)-2/CXCL6 levels were suppressed in patients with eosinophilic esophagitis as well as in those with eosinophilic gastroenteritis. The cutaneus T cell-attracting chemokine (CTACK)/CCL27, stromal cell-derived factor (SDF)-1/CXCL12, macrophage inflammatory protein (MIP)-3β/CCL19, and squamous cell carcinoma antigen (SCCA) 2 levels were elevated only in patients with eosinophilic esophagitis. However, there were large overlaps of data obtained from the patient and control groups, indicating that these serum biomarkers are not adequately sensitive for clinical use with presently available assay systems. Conclusion Of the 49 investigated serum proteins, none were shown to be adequately sensitive for use as biomarkers for the diagnosis or monitoring of eosinophilic gastrointestinal diseases.

Autoantibody detection for autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC) and autoimmune gastritis (AIG) is traditionally performed by IIF on a combination of tissues. Multiplex line/dot blots (LIA/DIA) offer multiple advantages, i.e. automation, objective reading, no interfering reactivities, no coincidental findings. In the current study we evaluated automated DIA (D-Tek) for detecting autoantibodies related to autoimmune diseases of the gastrointestinal tract. We tested samples of the Dutch EQC program and compared the results with the consensus of the participating labs. For the autoimmune liver diseases and AIG, respectively, 64 and 36 samples were tested. For anti-mitochondrial and anti-smooth muscle antibodies a concordance rate of 97% and 88% was observed, respectively. The concordance rate for anti-parietal cell antibodies was 92% when samples without EQC consensus (n=15) were excluded. For antibodies against intrinsic factor a concordance of 96% was observed. For all these antibodies discrepancies were identified that relate to the different test characteristics and the preponderance of IIF utilizing labs in the EQC program. In conclusion, we observed good agreement of the tested DIA blots with the consensus results of the Dutch EQC program. Taken together with the logistic advantages these blots are a good alternative for autoantibody detection in the respective diseases. A large prospective multicenter study is warranted to position these novel tests further in the whole spectrum of assays for the detection of these antibodies in a routine autoimmune laboratory., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Gastric cancer arises, mainly, on an inflammatory background. Helicobacter pylori neutrophil activating (HP-NAP) protein functions as a potent pro-inflammatory mediator. Similarly, IL-4 plays a critical role in the inflammation pathway, the levels of which are altered by C to T transition at position -590 in its promoter region. Here, we have aimed to assess the risk of gastritis and gastric cancer in the co-presence of these two inflammation modulating mediators., Methods: Gastritis (n=58) and gastric cancer (n=31) patients were evaluated and compared with H. pylori-positive asymptomatic controls (n=46), for serum antibodies against recombinant HP-NAP and IL-4 C-590T single nucleotide polymorphism using immunoblotting and PCR-RFLP, respectively. Multivariable logistic regression, adjusting for age, gender and ethnicity, was used for data analysis., Results: In terms of susceptibility to gastritis, seropositivity to HP-NAP projected a risk impact of 4.62 fold (OR=4.62, 95% CI=1.50-14.22), which when present in IL-4 -590 T carriers augmented the risk up to 9.7 fold (OR=9.70, 95% CI=2.06-45.69). A similar pattern, but of a stronger magnitude, occurred for the risk of gastric cancer, which was estimated at 9.07 fold (OR=9.07, 95% CI=1.99-42.0) for HP-NAP-seropositive subjects and was drastically amplified (OR=33.64, 95% CI=2.06-548.68), when double-positive (HP-NAP seropositive/IL-4 -590 T carrier) subjects were examined against double negatives (HP-NAP seronegative/IL-4 -590 CC)., Conclusion: Our preliminary data indicate that serum antibodies against HP-NAP represent a state of risk, which is further exacerbated in IL-4 -590 T carriers. These biomarkers, if validated in larger prospective studies, can be used to screen for gastric cancer susceptibility.

The significance of Helicobacter pylori (H. pylori) infection in pediatric abdominal pain remains poorly recognized. We examined associations of H. pylori infection and serum pepsinogens (PGs), as non-invasive markers of gastritis, with pediatric abdominal pain. A case-control study was conducted among 99 children aged 5-17 years admitted to one hospital for abdominal pain (cases) without an apparent organic reason. Using enzyme-linked immunosorbent assays, sera were tested and compared with 179 controls for anti-H. pylori immunoglobulin G (IgG) antibodies and PGI and PGII levels. Multivariable analysis was performed to adjust for potential confounders. H. pylori IgG sero-positivity was 34.3 and 36.3% in cases and controls, respectively, P = 0.7. H. pylori-infected children had higher median PGI and PGII levels and a lower PGI/PGII ratio than uninfected children. Cases infected with H. pylori had a higher median PGII level (P < 0.001) and lower PGI/PGII ratio (P = 0.036) than controls infected with H. pylori. The percentage of cases with PGII ≥7.5 μg/L, as indication for antral inflammation, was higher than in controls: 58.6 versus 44.7%, P = 0.027. Children with PGII levels ≥7.5 μg/L had increased risk for abdominal pain: adjusted prevalence ratio 1.73 [95% confidence intervals 1.02, 2.93], P = 0.039., Conclusion: Children with increased serum PGII levels, as an indication of gastritis, are more likely to have abdominal pain. Serum PGs can be a useful non-invasive marker for gastritis, in evaluating children with severe abdominal pain with no apparent organic reason. What is Known: • The significance of Helicobacter pylori infection in pediatric abdominal pain remains debated. • Serum pepsinogens (PGs), non-invasive markers of gastric inflammation, were rarely utilized in assessing the association between H. pylori in pediatric abdominal pain of unknown origin. What is New: • High serum PGII level, as an indication of gastritis, rather than H. pylori infection itself, was associated with increased risk for abdominal pain. • Serum PGs can be a useful biomarker for gastritis in evaluating children with severe abdominal pain with no apparent organic reason.

Rationale: The treatment of iron-deficiency anemia with oral iron supplements can present side-effects on the GI tract mucosa including necrosis, ulceration, or ischemia. The particular endoscopic findings and the histopathological exam will establish the diagnosis of erosive gastritis with iron deposits in the gastric mucosa., Patient Concerns: We present the case of a 14-year-old female admitted in our clinic for upper digestive hemorrhage, nausea, melena, and abdominal pain. Her personal history revealed iron deficiency anemia receiving oral iron supplements for approximately 2 weeks., Diagnosis: The laboratory tests at the moment of admission pointed out anemia, increased level of serum iron, increased liver transaminases, a decreased level of ferritin, but with normal levels of both total iron-binding capacity and transferrin., Interventions: The eso-gastro-duodenoscopy revealed multiple brown deposits on the surface of the gastric mucosa and multiple hemorrhagic lesions, under the aspect of erosions all over the gastric mucosa, but more severe in the antral part, and the histopathological exam confirmed the presence of iron deposits at this level., Conclusion: Iron-pill induced gastritis is a rare, under-diagnosed entity that can be present even at pediatric ages with potential severe clinical impact.

Circular RNAs are new type of endogenous RNAs, which play an important role in the regulation of gene expression and indicate a great capacity in clinical diagnosis and treatments of diseases. However, the role of circular RNAs in gastric cancer remains unknown. In this study, we chose hsa&#95;circ&#95;0006633 as the target circular RNA and measured its levels in human gastric cancer tissues, plasma, and gastric cell lines by real-time quantitative reverse transcription polymerase chain reaction. Hsa&#95;circ&#95;0006633 levels at multiple stages of gastric tumorigenesis were then explored, and its relationships with clinicopathological features were analyzed as well. We found that the expression levels of hsa&#95;circ&#95;0006633 in four gastric cancer cell lines, HGC-27, SGC-7901, MGC-803, and AGS, were downregulated than those in normal gastric mucosal epithelial cell line GES-1. Then, we further detected that it was downregulated in 79.2% (76/96) gastric cancer tissues compared with the adjacent non-tumorous tissues. The lower expression of hsa&#95;circ&#95;0006633 was associated with cancer distal metastasis ( p = 0.037) and tissue carcinoembryonic antigen level ( p = 0.041). In addition, hsa&#95;circ&#95;0006633 expression was significantly decreased in gastritis and dysplasia tissues comparing with the healthy control. Moreover, plasma hsa&#95;circ&#95;0006633 levels were significantly increased in gastric cancer compared with healthy control. Our data imply that hsa&#95;circ&#95;0006633 may play an important role in gastric carcinogenesis and is also a potential biomarker for screening gastric cancer.