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Trabalhos Publicados em Agosto / 2017

RECORD 1

Adding Bismuth to Rabeprazole-Based First-Line Triple Therapy Does Not Improve the Eradication of Helicobacter pyloriWu M.-C. Wang Y.-K. Liu C.-J. Yu F.-J. Kuo F.-C. Liu M.-L. Kuo C.-H. Wu D.-C. Huang Y.-K. Wu I.-C.Gastroenterology Research and Practice (2017) 2017 Article Number: 5320180. Date of Publication: 2017This randomized controlled study aimed to evaluate whether adding bismuth to the standard first-line triple therapy could improve the eradication rate of Helicobacter pylori. A total of 162 patients with Helicobacter pylori infection were randomly assigned to either the 7-day triple therapy group (RAK regimen: rabeprazole 20 mg, amoxicillin 1 g, and clarithromycin 500 mg bid; n=81) or the bismuth plus triple therapy group (n=81). In the RBAK group, bismuth subcitrate 360 mg twice daily was added to the RAK regimen. A follow-up endoscopy or urea breath test was performed at least 4 weeks after eradication to confirm the treatment efficacy. Comparable compliance and Helicobacter pylori eradication rates were observed in both groups in either intention-to-treat [RAK 72.8% (59/81) versus RBAK 77.8% (63/81); p=0.47] or per protocol analysis [RAK 74.7% (59/79) versus RBAK 81.8% (63/77); p=0.26]. Adverse effects were commonly reported (50.6% for both groups) although most of these did not cause cessation of treatment. The resistance rate was 27.2% for metronidazole and 12.3% for clarithromycin. Adding bismuth to the standard 7-day triple therapy did not substantially increase the eradication rate. Further study is needed clarifying whether extending the duration of RBAK regimen to 10-14 days can lead to a better result.

 

RECORD 2

Barry James Marshall—Discovery of Helicobacter pylori as a Cause of Peptic UlcerKyle R.A. Steensma D.P. Shampo M.A.Mayo Clinic Proceedings (2016) 91:5 (e67-e68). Date of Publication: 1 May 2016

 

RECORD 3

Higher dietary cholesterol and v-3 fatty acid intakes are associated with a lower success rate of Helicobacter pylori eradication therapy in JapanIkezaki H. Furusyo N. Jacques P.F. Shimizu M. Murata M. Schaefer E.J. Urita Y. Hayashi J.American Journal of Clinical Nutrition (2017) 106:2 (581-588). Date of Publication: 1 Aug 2017Background: Helicobacter pylori infection is a known risk factor for duodenal ulcers, gastritis, and gastric cancer. The eradication of H. pylori is successful in treating these disorders; however, the success rate of eradication therapy is declining. There may be an interaction with nutrient intake to account for this decline. Objective: We investigated the influence of food and nutrient intake on H. pylori eradication therapy. Design: In this study, 4014 subjects underwent endoscopy, were tested for serum antibodies to H. pylori (2046 positive; 51.0%), and had their food intake assessed with the use of a food-frequency questionnaire (FFQ). Of the positive subjects, endoscopies showed that 389 (19.0%) had gastritis and/or duodenal ulcers and were also positive for a (13)C-urea breath test (UBT). These 389 subjects received 1-wk H. pylori eradication therapy with lansoprazole, amoxicillin, and clarithromycin and a second UBT 8 wk after treatment. Complete demographic characteristics, serum lipid, insulin, glycated hemoglobin, C-reactive protein (CRP), and creatinine concentrations as well as complete FFQs were available for 352 subjects. Multivariate logistic regression analyses were performed to determine factors that were associated with successful H. pylori eradication therapy. Results: The success rate of eradication therapy was 60.4% (235 of 389). Factors associated with the failure of eradication therapy included increased age (P = 0.02), higher CRP concentrations (P <0.01), higher dietary cholesterol (P <0.01) or egg intake (P <0.01), higher v-3 (n-3) fatty acid (P = 0.02) or fish intake (P = 0.01), and higher Vitamin D intake (P = 0.02). Moreover, the higher Vitamin D intake was strongly linked to higher fish intake. A limitation of the study is that we did not assess the antibiotic resistance of H. pylori. Conclusions: Our results indicate that higher egg and fish intake may be negatively correlated with successful H. pylori eradication therapy in H. pylori-positive subjects with gastritis and/or duodenal ulcers.

 

RECORD 4

Berberine containing quadruple therapy for initial Helicobacter pylori eradicationZhang D. Ke L. Ni Z. Chen Y. Zhang L.-H. Zhu S.-H. Li C.-J. Shang L. Liang J. Shi Y.-Q.Medicine (United States) (2017) 96:32. Date of Publication: 1 Aug 2017Background: Due to increasing antimicrobial resistance, a bismuth-based quadruple regimen has been recommended as an alternative first-line therapy for Helicobacter pylori (H pylori) eradication. However, different results are varied greatly and the availability of bismuth was limited in some countries. We assessed the efficacy and safety of 14-day berberine-containing quadruple therapy as an alternative regimen for H pylori eradication. Methods: In a randomized, open-label, non-inferiority, phase IV trial between November 25, 2014, and October 15, 2015, 612 treatment-naive patients were randomly assigned to 14-day berberine-containing (n=308) or 14-day bismuth-containing (n=304) quadruple therapy. The primary outcomes were eradication rates determined by the 13 C urea breath test (13 C-UBT) 28 days after the end of treatment. The secondary outcomes were adverse events and compliance. Results: The baseline demographic data including age, gender, body mass index (BMI), general condition and severity score were not statistically different in both groups. The eradication rates in bismuth and berberine groups were 86.4% (266-308) and 90.1% (274-304) in intention-To-Treat (ITT) analysis (P=.149), and 89.6% (266-297) and 91.3% (273-299) in per-protocol (PP) analysis (P=.470), respectively. No statistically significant difference was found in the overall incidence of adverse events between both groups (35.7% vs 28.6%, P=.060). Conclusions: Both regimens achieved the recommended efficacy for H pylori eradication. The berberine-containing quadruple regimen was not inferior to bismuth-containing quadruple regimen and can be recommended as an alternative regimen for H pylori eradication in the local region.

 

RECORD 5

Strategies used by helicobacter pylori to establish persistent infectionAbadi A.T.B.World Journal of Gastroenterology (2017) 23:16 (2870-2882). Date of Publication: 28 Apr 2017Helicobacter pylori (H. pylori) is a Gram-negative and motile bacterium that colonizes the hostile microniche of the human stomach, then persists for the host's entire life, if not effectively treated. Clinically, H. pylori plays a causative role in the development of a wide spectrum of diseases including chronic active gastritis, peptic ulceration, gastric adenocarcinoma, and gastric mucosaassociated lymphoid tissue lymphoma. Due to the global distribution of H. pylori, it is no exaggeration to conclude that smart strategies are contributing to adaptation of the bacterium to its permanent host. Thirty-four years after the discovery of this bacterium, there are still many unanswered questions. For example, which strategies help the bacterium to survive in this inhospitable microniche? This question is slightly easier to answer if we presume the same clinical concept for both persistent infection and disease. Understanding the mechanisms governing H. pylori persistence will improve identification of the increased risk of diseases such as gastric cancer in patients infected with this bacterium. A well-defined and longterm equilibrium between the human host and H. pylori allows bacterial persistence in the gastric microniche; although this coexistence leads to a high risk of severe diseases such as gastric cancer. To escape the bactericidal activity of stomach acid, H. pylori secretes large amounts of surface-associated and cytosolic urease. The potential to avoid acidic conditions and immune evasion are discussed in order to explain the persistence of H. pylori colonization in the gastric mucosa, and data on bacterial genetic diversity are included. Information on the mechanisms related to H. pylori persistence can also provide the direction for future research concerning effective therapy and management of gastroduodenal disorders. The topics presented in the current review are important for elucidating the strategies used by H. pylori to help the bacterium persist in relation to the immune system and the many unfavorable features of living in the gastric microniche.

 

RECORD 6

Helicobacter pylori and gut microbiota in multiple sclerosis versus Alzheimer's disease: 10 pitfalls of microbiome studiesPark A.-M. Omura S. Fujita M. Sato F. Tsunoda I.Clinical and Experimental Neuroimmunology (2017) 8:3 (215-232). Date of Publication: 1 Aug 2017Alteration of microbiota has been associated with intestinal, inflammatory and neurological diseases. An abundance of “good bacteria,” such as Bifidobacterium, or their products has been generally believed to be beneficial for any diseases, whereas “bad bacteria,” such as pathogenic Helicobacter pylori, are assumed to be always detrimental for hosts. However, this is not the case when we compare and contrast the association of the gut microbiota with two neurological diseases, multiple sclerosis and Alzheimer's disease. After H. pylori infection, pro-inflammatory T helper (Th)1 and Th17 immune responses are initially induced to eradicate bacteria. However, H. pylori evades the host immune response by inducing Th2 cells and regulatory T cells that produce anti-inflammatory interleukin-10. Suppression of anti-bacterial Th1/Th17 cells by regulatory T cells might enhance gastric H. pylori propagation, followed by a cascade reaction involving vitamin B(12) and folic acid malabsorption, plasma homocysteine elevation, and reactive oxygen species induction. This can damage the blood-brain barrier, leading to accumulation of amyloid-β in the brain, a hallmark of Alzheimer's disease. In contrast, this suppression of pro-inflammatory Th1/Th17 responses to H. pylori has protective effects on the hosts, as it prevents uncontrolled gastritis as well as suppresses the induction of encephalitogenic Th1/Th17 cells, which can mediate neuroinflammation in multiple sclerosis. The above scenario might explain why chronic H. pylori infection is positively associated with Alzheimer's disease, whereas it is negatively associated with multiple sclerosis. Finally, we list “10 pitfalls of microbiota studies,” which will be useful for evaluating and designing clinical and experimental microbiota studies.

 

RECORD 7

“Invasive Helicobacter pylori” should be defined by combination of virulence genes with colonization featuresAbadi A.T.B.Human Pathology (2017) 65 (248). Date of Publication: 1 Jul 2017

 

RECORD 8

Letter: Helicobacter pylori in lean and obese patients with non-alcoholic fatty liver diseaseKountouras J. Polyzos S.A. Katsinelos P. Doulberis M. Zavos C. Kazakos E. Boziki M. Tzivras D. Kotronis G.Alimentary Pharmacology and Therapeutics (2017) 46:6 (637-638). Date of Publication: 1 Sep 2017

 

RECORD 9

Role of LPS-elicited signaling in triggering gastric mucosal inflammatory responses to H. pylori: modulatory effect of ghrelinSlomiany B.L. Slomiany A.Inflammopharmacology (2017) 25:4 (415-429). Date of Publication: 1 Aug 2017Infection with Helicobacter pylori is a primary culprit in the etiology of gastric disease, and its cell-wall lipopolysaccharide (LPS) is recognized as a potent endotoxin responsible for triggering a pattern of the mucosal inflammatory responses. The engagement by the LPS of gastric mucosal Toll-like receptor 4 (TLR4) leads to initiation of signal transduction events characterized by the activation of mitogen-activated protein kinase (MAPK) cascade, induction of phosphoinositide-specific phospholipase C (PLC)/protein kinase C (PKC)/phosphatidylinositol 3-kinase (PI3K) pathway, and up-regulation in Src/Akt. These signaling events in turn exert their influence over H. pylori-elicited excessive generation of NO and PGE2 caused by the disturbances in nitric oxide synthase and cyclooxygenase isozyme systems, increase in epidermal growth factor receptor transactivation, and the induction in matrix metalloproteinase-9 (MMP-9) release. Interestingly, the extent of gastric mucosal inflammatory response to H. pylori is influenced by a peptide hormone, ghrelin, the action of which relays on the growth hormone secretagogue receptor type 1a (GHS-R1a)-mediated mobilization of G-protein dependent transduction pathways. Yet, the signals triggered by TLR-4 activation as well as those arising through GHS-R1a stimulation converge at MAPK and PLC/PKC/PI3K pathways that form a key integration node for proinflammatory signals generated by H. pylori LPS as well as for those involved in modulation of inflammation by ghrelin. Hence, therapeutic targeting these signals’ convergence and integration node could provide a novel and attractive opportunities for developing more effective treatments of H. pylori-related gastric disease.

 

RECORD 10

Helicobacter pylori Induced Phosphatidylinositol-3-OH Kinase/mTOR activation increases hypoxia inducible factor-1α to promote loss of cyclin D1 and G0/G1 cell cycle arrest in human gastric cellsCanales J. Valenzuela M. Bravo J. Cerda-Opazo P. Jorquera C. Toledo H. Bravo D. Quest A.F.G.Frontiers in Cellular and Infection Microbiology (2017) 7:MAR Article Number: 92. Date of Publication: 28 Mar 2017Helicobacter pylori (H. pylori) is a human gastric pathogen that has been linked to the development of several gastric pathologies, such as gastritis, peptic ulcer, and gastric cancer. In the gastric epithelium, the bacterium modifies many signaling pathways, resulting in contradictory responses that favor both proliferation and apoptosis. Consistent with such observations, H. pylori activates routes associated with cell cycle progression and cell cycle arrest. H. pylori infection also induces the hypoxia-induced factor HIF-1α, a transcription factor known to promote expression of genes that permit metabolic adaptation to the hypoxic environment in tumors and angiogenesis. Recently, however, also roles for HIF-1α in the repair of damaged DNA and inhibition of gene expression were described. Here, we investigated signaling pathways induced by H. pylori in gastric cells that favor HIF-1α expression and the consequences thereof in infected cells. Our results revealed that H. pylori promoted PI3K/mTOR-dependent HIF-1α induction, HIF-1α translocation to the nucleus, and activity as a transcription factor as evidenced using a reporter assay. Surprisingly, however, transcription of known HIF-1α effector genes evaluated by qPCR analysis, revealed either no change (LDHA and GAPDH), statistically insignificant increases SLC2A1 (GLUT-1) or greatly enhance transcription (VEGFA), but in an HIF-1α-independent manner, as quantified by PCR analysis in cells with shRNA-mediated silencing of HIF-1α. Instead, HIF-1α knockdown facilitated G1/S progression and increased Cyclin D1 protein half-life, via a post-translational pathway. Taken together, these findings link H. pylori-induced PI3K-mTOR activation to HIF-1α induced G0/G1 cell cycle arrest by a Cyclin D1-dependent mechanism. Thus, HIF-1α is identified here as a mediator between survival and cell cycle arrest signaling activated by H. pylori infection.

 

 

RECORD 11

Helicobacter pylori morbidity in chronic hepatitis B patients: A case-control studyQu H. Sun Y. Zhang J. He X. Ji S.Biomedical Research (India) (2017) 28:13 (5785-5789). Date of Publication: 2017We conducted a case-control study performed in the China-Japan Union Hospital of Jilin University, China from 2010 to 2015 to investigate the seroprevalence of Helicobacter pylori infection in patients with chronic hepatitis B. The cases were 853 patients with chronic hepatitis B who were sex and age matched to 729 healthy controls. All subjects were tested for the presence of serum anti-H. pylori-IgG. H. pylori infection was more prevalent in patients with chronic hepatitis B (59.6%), chronic Hepatitis B virus (HBV)-related cirrhosis (77.3%), and Hepatocellular Carcinoma (HCC) (80.3%) than in healthy controls (43.3%) (χ(2)=35.708, χ(2)=53.175, χ(2)=29.501, respectively; P<0.05). The differences in H. pylori prevalence among the case groups by the serum viral load of HBV DNA were not statistically significant (P>0.05). No significant difference among groups by genotype was detected (P>0.05). H. pylori infection was more highly prevalent in cirrhosis patients with complications such as hepatic encephalopathy (69.6%), peptic ulcers (61.0%), and upper gastrointestinal hemorrhage (78.7%) than in patients without complications (χ(2)=7.713, χ(2)=4.293, χ(2)=16.517, respectively; P<0.05). Whether H. pylori act synergistically with HBV for the progression from chronic hepatitis B to cirrhosis and HCC requires further research.

 

RECORD 12

Prevalence of Helicobacter pylori infection and its association with lipid profilesSun Y. Fu D. Wang Y.K. Liu M. Liu X.D.Bratislavske lekarske listy (2016) 117:9 (521-524). Date of Publication: 2016OBJECTIVE: To evaluate the prevalence of Helicobacter pylori (H. pylori, HP) infection in subjects receiving routine physical examination and its associations with age, sex, body mass index (BMI) and lipid profiles.MATERIALS AND METHODS: Clinical information of 22,103 individuals who took routine physical examinations, including that on age, gender, height, weight, triglyceride, total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol and data of HP infection were collected and analyzed.RESULTS: H. pylori infection rate in 22,103 subjects taking routine physical examination was 44.5 %. More men tended to be infected with H. pylori than women (45.9 % vs 42.8 %; p < 0.01). The highest positive rate group was in the age group of 30-39 years (46.8 %) and the lowest rate was in the age group younger than 30 years (40.5 %). The obese had higher infection rate than the non-obese (p < 0.01). Mann-Whitney U test was used to explore the relationships between lipid profiles and H. pylori infection. There were significant associations among HDL, triglyceride and HP infection (p < 0.01). However, significant differences were not confirmed between cholesterol, LDL and H. pylori infection.CONCLUSION: H. pylori infection was common among subjects receiving physical examination in Shanghai and it was most significantly associated with HDL and triglyceride, indicating that H. pylori might be a new cardiovascular risk factor (Tab. 3, Ref. 23).

 

RECORD 13

The Helicobacter pylori type IV secretion system promotes IL-8 synthesis in a model of pediatric airway epithelium via p38 MAP kinaseDela Pena-Ponce M.G. Jimenez M.T. Hansen L.M. Solnick J.V. Miller L.A.PLoS ONE (2017) 12:8 Article Number: e0183324. Date of Publication: 1 Aug 2017Epidemiologic studies have reported an inverse relationship between childhood Helicobacter pylori infection and development of allergic asthma. Because lung epithelium plays an important role in allergic asthma pathogenesis, we hypothesized that H. pylori may directly influence airway epithelial cell innate immune function, particularly in early childhood. To test our hypothesis, we established an in vitro H. pylori infection model using primary tracheobronchial epithelial cell cultures derived from infant, juvenile and adult rhesus monkeys. Airway epithelial cell cultures were infected with wild-type or cag pathogenicity island mutant H. pylori strains, followed by evaluation of IL-8 and IL-6 protein synthesis. We found that H. pylori primarily increased IL-8 synthesis in a MOI and age-dependent fashion, with a greater than 4-fold induction in infant versus adult cultures. H. pylori-induced IL-8 synthesis in infant and juvenile cultures was significantly reduced by cag pathogenicity island mutants, indicating a requirement for the type IV secretion system. Although peptidoglycan recognition of nucleotide binding oligomerization domain-containing protein 1 (NOD1) and NF-kappaB have been implicated as key cytokine signaling molecules for H. pylori infection in gastric epithelium, NOD1 (ML130) or NF-kappaB (JSH-23) inhibitors minimally affected IL-8 synthesis in airway epithelial cell cultures following H. pylori infection. In contrast, inhibition of the p38 MAP kinase pathway (SB203580) resulted in almost complete suppression of H. pylori-induced IL-8 synthesis. Collectively, these results indicate that H. pylori can preferentially elicit IL-8 synthesis in a model of pediatric airway epithelium using the type IV secretion system via p38 MAP kinase.

 

RECORD 14

Helicobacter pylori modulates host cell responses by CagT4SS-dependent translocation of an intermediate metabolite of LPS inner core heptose biosynthesisStein S.C. Faber E. Bats S.H. Murillo T. Speidel Y. Coombs N. Josenhans C.PLoS Pathogens (2017) 13:7 Article Number: e1006514. Date of Publication: 1 Jul 2017Highly virulent Helicobacter pylori cause proinflammatory signaling inducing the transcriptional activation and secretion of cytokines such as IL-8 in epithelial cells. Responsible in part for this signaling is the cag pathogenicity island (cagPAI) that codetermines the risk for pathological sequelae of an H. pylori infection such as gastric cancer. The Cag type IV secretion system (CagT4SS), encoded on the cagPAI, can translocate various molecules into cells, the effector protein CagA, peptidoglycan metabolites and DNA. Although these transported molecules are known to contribute to cellular responses to some extent, a major part of the cagPAI-induced signaling leading to IL-8 secretion remains unexplained. We report here that biosynthesis of heptose-1,7-bisphosphate (HBP), an important intermediate metabolite of LPS inner heptose core, contributes in a major way to the H. pylori cagPAI-dependent induction of proinflammatory signaling and IL-8 secretion in human epithelial cells. Mutants defective in the genes required for synthesis of HBP exhibited a more than 95% reduction of IL-8 induction and impaired CagT4SS-dependent cellular signaling. The loss of HBP biosynthesis did not abolish the ability to translocate CagA. The human cellular adaptor TIFA, which was described before to mediate HBP-dependent activity in other Gram-negative bacteria, was crucial in the cagPAI- and HBP pathway-induced responses by H. pylori in different cell types. The active metabolite was present in H. pylori lysates but not enriched in bacterial supernatants. These novel results advance our mechanistic understanding of H. pylori cagPAI-dependent signaling mediated by intracellular pattern recognition receptors. They will also allow to better dissect immunomodulatory activities by H. pylori and to improve the possibilities of intervention in cagPAI- and inflammation-driven cancerogenesis.

 

RECORD 15

ATP-Dependent Lon Protease Contributes to Helicobacter pylori-Induced Gastric CarcinogenesisLuo B. Wang M. Hou N. Hu X. Jia G. Qin X. Zuo X. Liu Y. Luo K. Song W. Wang K. Pang M.Neoplasia (United States) (2016) 18:4 (242-252). Date of Publication: 1 Apr 2016Helicobacter pylori infection is the strongest risk factor for development of gastric cancer. Host cellular stress responses, including inflammatory and immune responses, have been reported highly linked to H. pylori-induced carcinogenesis. However, whether mitochondrial regulation and metabolic reprogramming, which are potently associated with various cancers, play a role in H. pylori-induced gastric carcinogenesis is largely unknown. Here we revealed that Lon protease (Lonp1), which is a key inductive of mitochondrial unfolded protein response (UPR(mt)) and is required to maintain the mitochondrial quality, was greatly induced in H. pylori infected gastric epithelial cells. Importantly, we uncovered that knockdown of Lonp1 expression significantly diminished the metabolic switch to glycolysis and gastric cell proliferation associated with low multiplicity of H. pylori infection. In addition, Lonp1 overexpression in gastric epithelial cells also promoted glycolytic switch and cell overgrowth, suggesting H. pylori effect is Lonp1 dependent. We further demonstrated that H. pylori induced Lonp1 expression and cell overgrowth, at least partially, via HIF-1α regulation. Collectively, our results concluded the relevance of Lonp1 for cell proliferation and identified Lonp1 as a key regulator of metabolic reprogramming in H. pylori-induced gastric carcinogenesis.

 

RECORD 16

Two populations of less-virulent Helicobacter pylori genotypes in BangladeshAftab H. Miftahussurur M. Subsomwong P. Ahmed F. Khan A.K.A. Matsumoto T. Suzuki R. Yamaoka Y.PLoS ONE (2017) 12:8 Article Number: e0182947. Date of Publication: 1 Aug 2017Bangladesh has a population with a low gastric cancer risk but high prevalence of Helicobacter pylori infection. Several studies have examined virulence genes in H. pylori from Bangladesh. We analyzed cagA and vacA subtypes and their association with severe histology phenotypes, and analyzed population types among Bangladeshi strains. We included patients who underwent endoscopy in Dhaka. Sequences of virulence genes and seven housekeeping genes were obtained by next generation sequencing and confirmed by Sanger sequencing. We isolated 56 H. pylori strains from 133 patients, of which 73.2% carried cagA, and all were considered Western-type. Patients infected with cagA-positive strains had more severe histological scores than patients infected with cagA-negative strains. Among vacA s1 and m1 genotypes, the s1a (97.8%, 43/44) and m1c (28/30, 93.3%) genotypes were predominant. All strains containing s1 and m1 (30/56, 53.6%) also had i1, d1, and c1. In contrast, all strains containing the less-virulent genotypes s2 and m2 (12/56, 21.4%) also possessed i2, d2, and c2. Multivariate analysis indicated that subjects infected with vacA m1-genotype strains only had a significantly higher risk of antrum atrophy than patients infected with m2-genotype strains. Of the two main H. pylori populations in this study, hpAsia2 strains were associated with higher activity and inflammation in the antrum compared to hpEurope strains; however, only vacA s1m1i1d1c1 strains, independent of population type, were significantly associated with inflammation in the antrum, unlike the s2m2i2d2c2 genotype. In conclusion, Bangladeshi strains were divided into two main populations of different genotypes. The low incidence of gastric cancer in Bangladesh might be attributable to the high proportion of less-virulent genotypes, which may be a better predictor of gastric cancer risk than the ancestral origin of the H. pylori strains. Finally, the vacA m region may be a better virulence marker than other regions.

 

RECORD 17

Secondary antibiotic resistance of Helicobacter pylori isolates in Israeli children and adultsKhoury J. Geffen Y. Shaul R. Sholy H. Chowers Y. Saadi T.Journal of Global Antimicrobial Resistance (2017) 10 (182-185). Date of Publication: 1 Sep 2017Background Failure of standard therapy for Helicobacter pylori infections results primarily from increasing antibiotic resistance. Patients in Israel are referred for H. pylori culture after failure of at least two therapeutic regimens. Objectives To estimate the prevalence of secondary antimicrobial resistance of H. pylori in Israel. Methods We retrospectively collected results of H. pylori cultures performed by gastric biopsies at Rambam Health Care Campus, Haifa, Israel, between the years 2012-2015. Antimicrobial susceptibility to five drugs was tested by gradient-diffusion. Results 107 patients, 46 adults and 61 children, were referred for performance of H. pylori cultures. Cultures were positive in 64 samples (63.7%). In adults, 23 (50%) patients had positive H. pylori cultures; 8.69% showed resistance to amoxicillin (AM), 39.1% to clarithromycin (CH), 61.9% to metronidazole (MZ), 8.69% to tetracycline (TC), and 21.7% to levofloxacin (LEV). In children, 41 (67%) patients had positive H. pylori cultures; 5.1% showed resistance to AM, 42.5% to CH, 46.66% to MZ, 2.5% to TC and 0% to LEV. In children, 94.9% of H. pylori strains were susceptible to both AM and LEV. In adults, 82.6% of the strains were susceptible to both AM and TC. 28.6% of adults and 24.1% children were resistant to both MZ and CH. Conclusions The sensitivity of H. pylori culture was low. Resistance of H. pylori to MZ and CH was very high after failure of two therapeutic regimens in both adults and children. No LEV resistance was detected in children. AM resistance was higher in adults than in children.

 

RECORD 18

Frequency of H-pylori stool antigen in patients with perforated duodenal ulcer diseaseAhmad I. Latif U. Iqbal Z. Saeed M.S. Ali F.Medical Forum Monthly (2017) 28:4 (62-65). Date of Publication: 1 Apr 2017Objective: To find the frequency of H-pylori stool antigen in patients with perforated duodenal ulcer disease. Study Design: Descriptive / cross sectional study Place and Duration of Study: This study was conducted at the Department of General Surgery, Nishtar Hospital Multan from March 2016 to January 2017. Materials and Methods: A total number of three hundred and seventy eight patients were enrolled. Data was analyzed with a statistical software SPSS version 23. All numerical variables were calculated as mean ± SD and categorical variables were calculated as frequency and percentages. Chi square test was applied to see the effect modification and p value ≤0.05 was accepted as significant. Results: Total number patients included in this study were three hundred and seventy eight (378) in which 237(62.7%) were male with mean age 44.75 ± 8.46 and 141(37.3%) were females with mean age 44.89 ± 9.93. From these 378 patients,200 (52.9%) patients having H-Pylori antigen and in 178 (47.1%) patients H-Pylori antigen was absent. Conclusion: It is concluded that patient with perforated duodenal ulcer are at high risk of Helicobacter pylori infection, so the case of perforated duodenal ulcer should be investigated more aggressively. Early diagnosis can save the patient from dangerous effects of H-pylori infection.

 

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Digestive disease week 2017Croasdell G.Drugs of the Future (2017) 42:6 (377-380). Date of Publication: 2017Summary The 2017 annual Digestive Disease Week (DDW) conference was held in Chicago, Illinois, and brought together researchers from academia and industry to discuss the latest developments in treatments of disease related to the digestive tract, ranging from cancer, hepatitis, irritable bowel syndrome and Crohn’s disease, among others. The sponsoring societies, American Association for the Study of Liver Disease (AASLD), American Gastroenterology Association (AGA), American Association for Gastrointestinal Endoscopy (AAGE) and The Society for Surgery of the Alimentary Tract (SSAT), also added to these sessions focusing on surgery and investigative procedures to create the world’s leading gastrointestinal conference. This report will highlight some of the presentations focused on treatments under development for the range of diseases.

 

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Immunomodulatory effect of H. Pylori cagA genotype and gastric hormones on gastric versus inflammatory cells fas gene expression in iraqi patients with gastroduodenal disordersAl-Ezzy A.I.A.Open Access Macedonian Journal of Medical Sciences (2016) 4:3 (364-373). Date of Publication: 15 Sep 2016AIM: To evaluate the Immunomodulatory effects of CagA expression; pepsinogen I, II & gastrin-17 on PMNs and lymphocytes Fas expression in inflammatory and gastric cells; demographic distribution of Fas molecule in gastric tissue and inflammatory cells. METHODS: Gastroduodenal biopsies were taken from 80 patients for histopathology and H. pylori diagnosis. Serum samples were used for evaluation of pepsinogen I (PGI); (PGII); gastrin-17 (G-17). RESULTS: Significant difference (p < 0.001) in lymphocytes & PMNs Fas expression; epithelial & lamina propria Fas localization among H. pylori associated gastric disorders. No correlation between grade of lymphocytes & PMNs Fas expression in gastric epithelia; lamina propria and types of gastric disorder. Significant difference (p < 0.001) in total gastric Fas expression, epithelial Fas; lamina propria and gastric gland Fas expression according to CagA, PGI; PGII; PGI/PGII; Gastrin-17. Total gastric Fas expression has significant correlation with CagA, PGII levels. Gastric epithelial and gastric lamina propria Fas expression have significant correlation with CagA, PGI; PGII levels. Significant difference (p < 0.001) was found in lymphocytes & PMNs Fas expression; epithelial & lamina propria localization of lymphocytes & PMNs Fas expression according to CagA, PGI; PGII; PGI/PGII; Gastrin-17. Lymphocytes Fas expression have correlation with PGI, PGII, PGI/PGII. PMNs Fas expression have correlation with PGI, PGII. CONCLUSION: Fas gene expression and localization on gastric and inflammatory cells affected directly by H. pylori CagA and indirectly by gastric hormones. This contributes to progression of various gastric disorders according to severity of CagA induced gastric pathology and gastric hormones disturbance throughout the course of infection and disease.

 

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Comparison of 7 - Day concomitant therapy regimen versus classic triple therapy regimen in Helicobacter pylori eradication: A randomized clinical trialMoradniani M. Mirbeik-Sabzevari Z. Bahmani M. Azadbakht S. Jaferian S. Sherkatolabbasieh H. Shafizadeh S. Roozbahany M.M.International Journal of Pharmaceutical Sciences and Research (2017) 8:8 (3568-3573). Date of Publication: 1 Aug 2017There are various treatment regimens including different antibiotics and antacid medications for eradicating Helicobacter pylori to compare the effectiveness of 7-day concomitant regime with classic triple regimen in eradicating H. pylori. In this randomized clinical trial, 206 dyspeptic patients proven H. pylori infection, attended to a gastrointestinal clinic in Khorramabad (west of Iran) were studied. The patients were randomly divided in two equal groups. Classic group were treated for 14 days with a regimen including omeprazole 20mg, amoxicillin 1g and clarithromycin 500mg, twice daily. In concomitant group, the patients were treated for 7 days with a regimen including omeprazole 20mg, amoxicillin 1g, clarithromycin 500mg and metronidazole 500mg twice daily. During the treatment period and a week after the end of treatment, the patients were evaluated in terms of possible side-effects and medication acceptance and tolerance. For confirmation of eradication, 6 weeks after the end of treatment, urea breath test with carbon 13 (UBT) was done for both the groups. Data were analyzed using descriptive statistics, T-test and chi-square test, logistic regression through SPSS software version 21. The level of significance was considered less than 0.05. H. pylori eradication rate in classic group was 68.9% and in concomitant group was 83.4%. (p - value = 0.03). The incidence of gastrointestinal side-effects was not statistically different between the groups. H. pylori eradication rate in 7-day concomitant treatment regimen is more than 14-day classic regimens. Therefore, it is suggested to use 7-day concomitant regimen as first-line of H. pylori eradication.

 

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ACG and CAG Clinical Guideline: Management of DyspepsiaMoayyedi P.M. Lacy B.E. Andrews C.N. Enns R.A. Howden C.W. Vakil N.American Journal of Gastroenterology (2017) 112:7 (988-1013). Date of Publication: 1 Jul 2017We have updated both the American College of Gastroenterology (ACG) and the Canadian Association of Gastroenterology (CAG) guidelines on dyspepsia in a joint ACG/CAG dyspepsia guideline. We suggest that patients ≥60 years of age presenting with dyspepsia are investigated with upper gastrointestinal endoscopy to exclude organic pathology. This is a conditional recommendation and patients at higher risk of malignancy (such as spending their childhood in a high risk gastric cancer country or having a positive family history) could be offered an endoscopy at a younger age. Alarm features should not automatically precipitate endoscopy in younger patients but this should be considered on a case-by-case basis. We recommend patients <60 years of age have a non-invasive test Helicobacter pylori and treatment if positive. Those that are negative or do not respond to this approach should be given a trial of proton pump inhibitor (PPI) therapy. If these are ineffective tricyclic antidepressants (TCA) or prokinetic therapies can be tried. Patients that have an endoscopy where no pathology is found are defined as having functional dyspepsia (FD). H. pylori eradication should be offered in these patients if they are infected. We recommend PPI, TCA and prokinetic therapy (in that order) in those that fail therapy or are H. pylori negative. We do not recommend routine upper gastrointestinal (GI) motility testing but it may be useful in selected patients.

 

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Introduction to PUD - A reviewSingh N. Rattan P. Kothiyal P.Journal of Pharmacy Research (2017) 11:7 (878-886). Date of Publication: 2017Peptic ulcer disease (PUD) is a infectious disorder. Three major causes of peptic ulcer disease are: peptic ulcers are small sores that form in the lining of the esophagus (swallowing pipe), stomach, or duodenum (the first part of the small intestine). Peptic ulcer disease refers to painful sores or ulcers in the lining of the stomach or first part of the small intestine, called the duodenum. Peptic ulcer disease (PUD), also known as a peptic ulcer or stomach ulcer, is a break in the lining of the stomach, first part of the small intestine, or occasionally the lower esophagus. There are three types of ulcers: peptic ulcers, Apthous ulcers, esophageous ulcer. Causes of peptic ulcer include, administration of NSAID, H.pylori, stress, alcohol habits, Smoke, fasting, radiation. Diagnosis include: endoscopy, x- ray, breath test, urine test, and serological test. Drugs or medication therapy that is used for the treatment of peptic ulcer disease are antibiotics, proton pump inhibitor, histamine antagonist, gastric acid neutralization agent, ulcer protective, antacids etc. new advances that have been came fourth are from the family of cucumber, cucurbitaceous. They act as ulcer protective agents and can treat the ulcer.

 

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Multicentric randomised study of Helicobacter pylori eradication and pepsinogen testing for prevention of gastric cancer mortality: The GISTAR studyLeja M. Park J.Y. Murillo R. Liepniece-Karele I. Isajevs S. Kikuste I. Rudzite D. Krike P. Parshutin S. Polaka I. Kirsners A. Santare D. Folkmanis V. Daugule I. Plummer M. Herrero R.BMJ Open (2017) 7:8 Article Number: e016999. Date of Publication: 1 Aug 2017Introduction Population-based eradication of Helicobacter pylori has been suggested to be cost-effective and is recommended by international guidelines. However, the potential adverse effects of widespread antibiotic use that this would entail have not been sufficiently studied. An alternative way to decrease gastric cancer mortality is by non-invasive search for precancerous lesions, in particular gastric atrophy; pepsinogen tests are the best currently available alternative. The primary objective of GISTAR is to determine whether H pylori eradication combined with pepsinogen testing reduces mortality from gastric cancer among 40-64-year-old individuals. The secondary objectives include evaluation of H pylori eradication effectiveness in gastric cancer prevention in patients with precancerous lesions and evaluation of the potential adverse events, including effects on microbiome. Methods and analysis Individuals are recruited from general population (50% men) in areas with high gastric cancer risk in Europe and undergo detailed lifestyle and medical history questionnaire before being randomly allocated to intervention or control groups. The intervention group undergoes H pylori testing and is offered eradication therapy if positive; in addition, pepsinogen levels are detected in plasma and those with decreased levels are referred for upper endoscopy. All participants are offered faecal occult blood testing as an incentive for study participation. Effectiveness of eradication and the spectrum of adverse events are evaluated in study subpopulations. A 35% difference in gastric cancer mortality between the groups is expected to be detectable at 90% power after 15 years if 30 000 individuals are recruited. Biological materials are biobanked for the main and ancillary studies. The study procedure and assumptions will be tested during the pilot phase. Ethics and dissemination The study was approved by the respective ethics committees. An independent Data Safety and Monitoring Board has been established. The findings will be published in peer-reviewed journals and presented at scientific meetings. Trial registration number NCT02047994

 

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PBX1 attributes as a determinant of connexin 32 downregulation in Helicobacter pylori-related gastric carcinogenesisLiu X.-M. Xu C.-X. Zhang L.-F. Huang L.-H. Hu T.-Z. Li R. Xia X.-J. Xu L.-Y. Luo L. Jiang X.-X. Li M.World Journal of Gastroenterology (2017) 23:29 (5345-5355). Date of Publication: 7 Aug 2017Aim: To clarify the mechanisms of connexin 32 (Cx32) downregulation by potential transcriptional factors (TFs) in Helicobacter pylori (H. pylori)-associated gastric carcinogenesis. Methods: Approximately 25 specimens at each developmental stage of gastric carcinogenesis [non-atrophic gastritis, chronic atrophic gastritis, intestinal metaplasia, dysplasia and gastric carcinoma (GC)] with H. pylori infection [H. pylori (+)] and 25 normal gastric mucosa (NGM) without H. pylori infection [H. pylori (-)] were collected. After transcriptional factor array analysis, the Cx32 and PBX1 expression levels of H. pylori-infected tissues from the developmental stages of GC and NGM with no H. pylori infection were measured by real-time polymerase chain reaction (RT-PCR) and Western blot analysis. Regarding H. pylori -infected animal models, the Cx32 and PBX1 mRNA expression levels and correlation between the gastric mucosa from 10 Mongolian gerbils with long-term H. pylori colonization and 10 controls were analyzed. PBX1 and Cx32 mRNA and protein levels were further studied under the H. pylori -infected condition as well as PBX1 overexpression and knockdown conditions in vitro. Results: Incremental PBX1 was first detected by TF microarray in H. pylori -related gastric carcinogenesis. The identical trend of PBX1 and Cx32 expression was confirmed in the developmental stages of H. pylori -related clinical specimens. The negative correlation of PBX1 and Cx32 was confirmed in H. pylori -infected Mongolian gerbils. Furthermore, decreased PBX1 expression was detected in the normal gastric epithelial cell line GES-1 with H. pylori infection. Enforced overexpression or RNAi-mediated knockdown of PBX1 contributed to the diminished or restored Cx32 expression in GES-1 and the gastric carcinoma cell line BGC823, respectively. Finally, dual-luciferase reporter assay in HEK293T cells showed that Cx32 promoter activity decreased by 30% after PBX1 vector co-transfection, indicating PBX1 as a transcriptional downregulator of Cx32 by directly binding to its promoters. Conclusion: PBX1 is one of the determinants in the Cx32 promoter targeting site, preventing further damage of gap junction protein in H. pylori -associated gastric carcinogenesis.

 

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Antiulcer properties of fruits and vegetables: A mechanism based perspectiveHarsha C. Banik K. Bordoloi D. Kunnumakkara A.B.Food and Chemical Toxicology (2017) 108 (104-119). Date of Publication: 1 Oct 2017Gastric ulcer is the damage caused to mucosal layer of the stomach under the action of various factors like high levels of acid and pepsin, invasion by Helicobacter pylori, etc. Although most cases have been controlled and the rate of ulcer occurrence has reduced over the last few decades, gastric ulcer still holds a prime concern today. A range of palliative medicines comprising proton pump inhibitors, H2 receptor antagonists, COX-2 inhibitors (coxibs) is widely in use and patients have also been administered with acid suppression therapies. But these remedies aggravate the condition of patients causing severe side effects, or rather impart temporary relief. Therefore, it is highly imperative to develop safe and effective therapies for the treatment of gastric ulcer. Nature provides us various fruits and vegetables that can combat gastric ulcer through multiple mechanisms; predominantly via antioxidant, anti-inflammatory, antisecretory, antimicrobial, anticholinergic and cytoprotective activity, inhibition of small intestinal propulsion etc. Various phytochemicals from fruits and vegetables such as phenolics, flavonoids, tannins and saponins play a vital role in the prevention and cure of gastric ulcer. This review is a compendium of all fruits and vegetables known for their profound antiulcer effect and their underlying mechanisms of action.

 

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Novel and effective therapeutic regimens for helicobacter pylori in an era of increasing antibiotic resistanceHu Y. Zhu Y. Lu N.-H.Frontiers in Cellular and Infection Microbiology (2017) 7:MAY Article Number: 168. Date of Publication: 5 May 2017Helicobacter pylori (H. pylori) is a common gastrointestinal bacterial strain closely associated with the incidence of chronic gastritis, peptic ulcers, gastric mucosa-associated lymphoid tissue lymphoma, and gastric cancer. A current research and clinical challenge is the increased rate of antibiotic resistance in H. pylori, which has led to a decreased H. pylori eradication rate. In this article, we review recent H. pylori infection and reinfection rates and H. pylori resistance to antibiotics, and we discuss the pertinent treatments. A PubMed literature search was performed using the following keywords: Helicobacter pylori, infection, reinfection, antibiotic resistance, bismuth, proton pump inhibitors, vonoprazan, susceptibility, quintuple therapy, dual therapy, and probiotic. The prevalence of H. pylori has remained high in some areas despite the decreasing trend of H. pylori prevalence observed over time. Additionally, the H. pylori reinfection rate has varied in different countries due to socioeconomic and hygienic conditions. Helicobacter pylori monoresistance to clarithromycin, metronidazole or levofloxacin was common in most countries. However, the prevalence of amoxicillin and tetracycline resistance has remained low. Because H. pylori infection and reinfection present serious challenges and because H. pylori resistance to clarithromycin, metronidazole or levofloxacin remains high in most countries, the selection of an efficient regimen to eradicate H. pylori is critical. Currently, bismuth-containing quadruple therapies still achieve high eradication rates. Moreover, susceptibility-based therapies are alternatives because they may avoid the use of unnecessary antibiotics. Novel regimens, e.g., vonoprazan-containing triple therapies, quintuple therapies, high-dose dual therapies, and standard triple therapies with probiotics, require further studies concerning their efficiency and safety for treating H. pylori.

 

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Identification of gastric outlet obstruction using point-of-care ultrasoundGottlieb M. Nakitende D.American Journal of Emergency Medicine (2017) 35:8 (1207.e1-1207.e2). Date of Publication: 1 Aug 2017

 

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Accumulated evidence on Helicobacter pylori infection and the risk of asthma: A meta-analysisChen C. Xun P. Tsinovoi C. He K.Annals of Allergy, Asthma and Immunology (2017) 119:2 (137-145.e2). Date of Publication: 1 Aug 2017Background Helicobacter pylori (H pylori) infection has been suggested to be related to a decreased risk of asthma, but findings in the literature are inconsistent. Objective To quantitatively summarize the existing evidence on the association between H pylori infection and asthma risk. Methods The PubMed database was searched for observational studies of H pylori infection in relation to the risk of asthma published in English through May 2017. Measurements of association were pooled using a meta-analytic approach and expressed as odds ratios (ORs) with 95% confidence intervals (95% CIs). Results Twenty-four studies were identified in this meta-analysis, including 8 case-control studies composed of 1,247 cases and 2,410 controls, and 16 cross-sectional studies composed of 50,290 participants (4,185 cases and 46,105 noncases). The average H pylori infection rates were 40.01% and 48.74% in case-control and cross-sectional studies, respectively. Five studies subcategorized H pylori infection according to CagA status, in which 59.37% of H pylori–infected participants were identified as having CagA positivity. Helicobacter pylori infection was significantly inversely associated with the risk of asthma in case-control studies (OR 0.83, 95% CI 0.71–0.98) but was borderline significant in cross-sectional studies (OR 0.88, 95% CI 0.76–1.02). The observed inverse association persisted for CagA-positive H pylori infection (OR 0.77, 95% CI 0.63–0.93, P for interaction = .03) but not for CagA-negative strains (OR 1.08, 95% CI 0.66–1.78). No significant difference was observed across age or region subgroups. Conclusion The accumulated evidence supports that H pylori infection, especially CagA-positive H pylori infection, is inversely associated with the risk of asthma.

 

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Association of Helicobacter pylori infection with olfactory function using smell identification screening testÜstün Bezgin S. Çakabay T. Irak K. Koçyiğit M. Serin Keskineğe B. Cevizci R. Bayazıt Y.A.European Archives of Oto-Rhino-Laryngology (2017) 274:9 (3403-3405). Date of Publication: 1 Sep 2017The aim of the present study is to investigate the role of Helicobacter pylori in olfactory function. Thirty-six patients (mean age 38.5) aged between 18 and 55 years who were diagnosed with H. pylori by gastric biopsies and age- and sex-matched 30 healthy adults (mean age 33.6) were included in the study. All participants underwent a detailed ear–nose–throat examination including endoscopic examination of the nasal cavity and laryngeal area, and olfactory tests were performed using the Sniffin’ Sticks, a 12-item screening test (Sniffin’Sticks; Burghart, Wedel, Germany) and odor scores were recorded. The mean odor score was 7.9 ± 1.7 (range 2–10) in the patient group and 10.3 ± 1.4 (range 6–12) in the control group. There were significant lower scores in the patient group compared to the control group (p < 0.05). In conclusion, it is apparent that there is an association of H. pylori infection with olfactory dysfunction. H. pylori infection should be considered as possible etiological factors in patients with olfactory dysfunction.

 

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Gastric carcinoma in canines and humans, a reviewHugen S. Thomas R.E. German A.J. Burgener I.A. Mandigers P.J.J.Veterinary and Comparative Oncology (2017) 15:3 (692-705). Date of Publication: 1 Sep 2017Gastric carcinoma (GC) is the most common neoplasm in the stomach of dogs. Although incidence in the general population is reported to be low, breed-specific GC has a high incidence. Median age at presentation ranges from 8 to approximately 10 years. The disease is mostly located in the lesser curvature and antropyloric region of the stomach. Unfortunately, diagnosis is usually made when the disease is at an advanced stage and, therefore, prognosis is poor. Due to similarities in clinical presentation, diagnosis, histology and prognosis, canine GC may serve as a valuable model for human GC. Extensive pedigrees of canine gastric carcinoma cases could reveal insights for human gastric carcinoma. Putative species differences include the role of Helicobacter in pathogenesis, the wide array of genetic data and screening available for humans, and treatment protocols that are available for human GC.

 

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Autoimmune hepatitis-Primary biliary cirrhosis overlap syndromeBairy I. Berwal A. Seshadri S.Journal of Clinical and Diagnostic Research (2017) 11:7 (OD07-OD09). Date of Publication: 1 Jul 2017Autoimmune Hepatitis (AIH) and Primary Biliary Cirrhosis (PBC) are important immune mediated liver diseases. They are usually differentiated based on clinical, biochemical, serological, and histological parameters. The presence of autoantibodies, clinical, and serological findings can sometimes occur in different combinations leading to overlap syndromes, which is rare. Early recognition of such overlap syndromes is clinically significant from treatment point of view. Here, we report a case of AIH-PBC overlap syndrome with a brief review of literature on overlap syndromes.

 

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Can Helicobacter pylori be eradicated with high-dose proton pump inhibitor in extensive metabolizers with the CYP2C19 genotypic polymorphism?Ormeci A. Emrence Z. Baran B. Soyer O.M. Gokturk S. Evirgen S. Akyuz F. Karaca C. Besisik F. Kaymakoglu S. Ustek D. Demir K.European review for medical and pharmacological sciences (2016) 20:9 (1795-1797). Date of Publication: 1 May 2016Proton pump inhibitors (PPI) metabolism and pharmacokinetics are regulated by cytochrome P450 enzymes in the liver. Cytochrome P450 2C19 (CYP2C19) polymorphism plays an import role in the metabolism of PPIs. The three possible genotypes for CYP2C19 each has a distinct effect on the pharmacodynamics of PPIs. Homozygote extensive metabolizers (HomEM) are the most frequent genotype and have two wild-types (non-mutant) (*1/*1) alleles. HomEM is associated with increased enzyme activity, which increases the rate of PPI metabolism. Intragastric pH, which is required for eradication, is lowest in HomEM. In HomEMs, an insufficient increase in intragastric pH results in decreased anti-Helicobacter pylori (HP) efficacy of the antibiotics and, therefore, lower eradication rates. We determined whether the HP eradication rate would increase after high-dose PPI treatment of extensive PPI metabolizers who had been treated unsuccessfully with a standard PPI dose. In our report, increasing the PPI dosage in patients with genotype polymorphisms may be effective on eradication rates. Eradication rates are directly affected by CYP2C19 polymorphisms, and eradication treatments should be planned considering such genotypic polymorphisms. Hence, CYP2C19 genotyping prior to treatment may facilitate determination of the optimum PPI dose to improve the therapeutic outcome. However, further researches are required to confirm this hypothesis.

 

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The gastric acid pocket is attenuated in H. Pylori infected subjectsMitchell D.R. Derakhshan M.H. Wirz A.A. Orange C. Ballantyne S.A. Going J.J. McColl K.E.L.Gut (2017) 66:9 (1555-1562). Date of Publication: 1 Sep 2017Objective Gastric acid secretory capacity in different anatomical regions, including the postprandial acid pocket, was assessed in Helicobacter pylori positive and negative volunteers in a Western population. Design We studied 31 H. pylori positive and 28 H. pylori negative volunteers, matched for age, gender and body mass index. Jumbo biopsies were taken at 11 predetermined locations from the gastro-oesophageal junction and stomach. Combined high-resolution pH metry (12 sensors) and manometry (36 sensors) was performed for 20 min fasted and 90 min postprandially. The squamocolumnar junction was marked with radio-opaque clips and visualised radiologically. Biopsies were scored for inflammation and density of parietal, chief and G cells immunohistochemically. Results Under fasting conditions, the H. pylori positives had less intragastric acidity compared with negatives at all sensors >1.1 cm distal to the peak lower oesophageal sphincter (LES) pressure (p<0.01). Postprandially, intragastric acidity was less in H. pylori positives at sensors 2.2, 3.3 and 4.4 cm distal to the peak LES pressure (p<0.05), but there were no significant differences in more distal sensors. The postprandial acid pocket was thus attenuated in H. pylori positives. The H. pylori positives had a lower density of parietal and chief cells compared with H. pylori negatives in 10 of the 11 gastric locations (p<0.05). 17/31 of the H. pylori positives were CagA-seropositive and showed a more marked reduction in intragastric acidity and increased mucosal inflammation. Conclusions In population volunteers, H. pylori positives have reduced intragastric acidity which most markedly affects the postprandial acid pocket.

 

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Antibiotic susceptibility, heteroresistance, and updated treatment strategies in helicobacter pylori infectionMascellino M.T. Porowska B. De Angelis M. Oliva A.Drug Design, Development and Therapy (2017) 11 (2209-2220). Date of Publication: 28 Jul 2017In this review, we discuss the problem of antibiotic resistance, heteroresistance, the utility of cultures and antibiotic susceptibility tests in Helicobacter pylori (Hp) eradication, as well as the updated treatment strategies for this infection. The prevalence of antibiotic resistance is increasing all over the world, especially for metronidazole and clarithromycin, because of their heavy use in some geographical areas. Heteroresistance (simultaneous presence of both susceptible and resistant strains in different sites of a single stomach) is another important issue, as an isolate could be mistakenly considered susceptible if a single biopsy is used for antimicrobial tests. We also examined literature data regarding eradication success rates of culture-guided and empiric therapies. The empiric therapy and the one based on susceptibility testing, in Hp eradication, may depend on several factors such as concomitant diseases, the number of previous antibiotic treatments, differences in bacterial virulence in individuals with positive or negative cultures, together with local antibiotic resistance patterns in real-world settings. Updated treatment strategies in Hp infection presented in the guidelines of the Toronto Consensus Group (2016) are reported. These suggest to prolong eradication therapy up to 14 days, replacing the old triple therapy with a quadruple therapy based on proton pump inhibitor (PPI), bismuth, metronidazole, and tetracycline for most of the patients, or as an alternative quadruple therapy without bismuth, based on the use of PPI, amoxicillin, metronidazole, and clarithromycin. The new drug vonoprazan, a first-in-class potassium-competitive acid blocker recently approved in Japan, is also considered to be a promising solution for Hp eradication, even for clarithromycin-resistant strains. Furthermore, there is growing interest in finding new therapeutic strategies, such as the development of vaccines or the use of natural resources, including probiotics, plants, or nutraceuticals.

 

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Helicobacter pylori infection in children: should it be carefully assessed?Ortiz-Princz D. Daoud G. Salgado-Sabel A. Cavazza M.E.European review for medical and pharmacological sciences (2016) 20:9 (1798-1813). Date of Publication: 1 May 2016The prevalence of H. pylori infection, mainly acquired during childhood and may be persisting throughout life, has been found high in developing countries; this high prevalence is related to low socioeconomic status. The persistence of bacterium exposure is related to gastritis and other severe complications including peptic ulcer, lymphoma MALT and gastric cancer, which are rarely present in the pediatric age due to a lower inflammatory and immunological response. Virulence factors, host gastric mucosal factors, and the natural environment of patients are associated with the clinical outcome of H. pylori infection. The main bacterial virulence factors include adhesins (BabA, SabA), vacuolating cytotoxin VacA, and the products of the cag pathogenicity island (cag PAI). There are geographic differences between cagA, vacA status and H. pylori related diseases. The main criteria to evaluate H. pylori infection in children are gastrointestinal and extra gastrointestinal manifestations related to H. pylori infection, familial history of gastric cancer, peptic ulcer, lymphoma MALT, symptomatic children living in high prevalence regions, and immigrant or adopted children in developed countries. Early detection of H. pylori and its virulence factors, in addition to effective methods of eradication associated with prevention programs, may lead to the decrease of H. pylori incidence and gastritis, especially in endemic high-risk regions. The early assessment in children may prevent further severe complications in adulthood.

 

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Novel information on the genetic factors involved in the development of diseasesKotelevets S.M. Galeeva Z.M. Karakotova Z.B. Chekh S.A.European review for medical and pharmacological sciences (2016) 20:17 (3672-3678). Date of Publication: 1 Sep 2016Nowadays full-genome sequencing allows achieving revolutionary progress in the modern medicine. As the result of a huge work on the study of the human genome and based on the results obtained, one can conclude that the single nucleotide polymorphisms are the reasons of the vast majority of non-communicable diseases as well as the diseases other than injuries and poisoning, i.e. the diseases where the cause is not obvious. To clarify the role of single nucleotide polymorphism in the occurrence of atrophic gastritis, it is required to perform full-genome sequencing and human genome scanning with a simultaneous mass serological screening of atrophic gastritis. As a result, it will be possible to establish which single nucleotide polymorphism is responsible for mild, moderate, and severe mucosal atrophy in the antrum and the body of the stomach. Serological screening of mild, moderate, and severe mucosal atrophy in the antrum and the body of the stomach can be made using GastroPanel.

 

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Immunogenetic Profiling for Gastric Cancers Identifies Sulfated Glycosaminoglycans as Major and Functional B Cell Antigens in Human MalignanciesKatoh H. Komura D. Konishi H. Suzuki R. Yamamoto A. Kakiuchi M. Sato R. Ushiku T. Yamamoto S. Tatsuno K. Oshima T. Nomura S. Seto Y. Fukayama M. Aburatani H. Ishikawa S.Cell Reports (2017) 20:5 (1073-1087). Date of Publication: 1 Aug 2017Recent successes in tumor immunotherapies have highlighted the importance of tumor immunity. However, most of the work conducted to date has been on T cell immunity, while the role of B cell immunity in cancer remains more elusive. In this study, immunogenetic repertoire profiling for tumor-infiltrating B and T cells in gastric cancers was carried out to help reveal the architecture of B cell immunity in cancer. Humoral immunity in cancer was shown to involve oligoclonal expansions of tumor-specific and private B cell repertoires. We find that B cell repertoires in cancer are shaped by somatic hypermutation (SHM) either with or without positive selection biases, the latter of which tended to be auto-reactive. Importantly, we identified sulfated glycosaminoglycans (GAGs) as major functional B cell antigens among gastric tumors. Furthermore, natural anti-sulfated GAG antibodies discovered in gastric cancer tissues showed robust growth-suppressive functions against a wide variety of human malignancies of various organs.

 

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Peptic ulcer disease and non-steroidal anti-inflammatory drugsDrini M.Australian Prescriber (2017) 40:3 (91-93). Date of Publication: 2017Non-steroidal anti-inflammatory drugs including low-dose aspirin are some of the most commonly used medicines. They are associated with gastrointestinal mucosal injury. Before prescribing, it is important to assess the patient’s gastrointestinal risk factors such as age and history of peptic ulcers. Patients at high risk may require co-prescription to reduce the risk of peptic ulcers. A daily dose of a proton pump inhibitor is the most effective method of reducing the risk of ulcers induced by non-steroidal anti-inflammatory drugs.

 

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The association of Helicobacter pylori with choroidal and retinal nerve fiber layer thicknessCan M.E. Kaplan F.E. Uzel M.M. Kiziltoprak H. Ergun M.C. Koc M. Simsek G.International Ophthalmology (2017) (1-8). Date of Publication: 5 Aug 2017Purpose: To investigate the effect of Helicobacter pylori (H. pylori) infection on choroidal thickness (CT) and retinal nerve fiber layer thickness (RNFLT). Methods: The study included 25 patients with H. pylori infection and 25 healthy individuals as the control group. Helicobacter pylori patients were classified as the pre-treatment (Group 1; n: 25) and the post-treatment (Group 2; n: 25). RNFLT and CT were measured before and after treatment of H. pylori infection, using enhanced depth imaging (EDI) spectral-domain optical coherence tomography (Spectralis, Heidelberg Engineering, Heidelberg, Germany). The axial length and intraocular pressure were also measured. Results: The mean subfoveal CT was 320.96 ± 29.15 μm in Group 1 and 287.48 ± 49.17 in the control group (p = 0.007), while the mean subfoveal CT did not show any difference between Group 2 and the control group (p > 0.05). No statistically significant difference was determined between the H. pylori patients and the control group in respect of RNFLT values (p > 0.05). Conclusions: CT increases during H. pylori infection and returns to the normal range within 6 weeks of treatment. RNFLT does not show any change during H. pylori infection. The data related to the subfoveal CT may be useful in understanding the pathogenesis of central serous chorioretinopathy developing in H. pylori patients.

 

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Impact of health insurance coverage for Helicobacter pylori gastritis on the trends in eradication therapy in Japan: Retrospective observational study and simulation study based on real-world dataHiroi S. Sugano K. Tanaka S. Kawakami K.BMJ Open (2017) 7:7 Article Number: e015855. Date of Publication: 1 Jul 2017Objectives: To explore the prevalence of Helicobacter pylori infection in Japan and the trends of its eradication therapy before and after the changes of the insurance coverage policy, first started in 2000, and expanded to cover H. pylori-positive gastritis in 2013. The impacts that the changes brought were estimated. Methods: In this retrospective observational study and simulation study based on health insurance claims data, product sales data and relevant studies, individuals who received triple therapy (amoxicillin, clarithromycin, proton-pump inhibitors or potassium-competitive acid blockers) were defined as the first-time patients for H. pylori eradication in two Japanese health insurance claims databases (from approximately 1.6 million and 10.5 million individuals). Each sales data of eradication packages and examination kits were used to estimate the number of H. pylori-eradicated individuals nationwide. The prevalence of H. pylori infection, including the future rate, was predicted using previous studies and the estimated population trend by a national institute. Cases completed prior to the policy change on insurance coverage were simulated to estimate what would have happened had there been no change in the policy. Results: The numbers of patients first received eradication therapy were 81 119 and 170 993 from two databases. The nationwide estimated number of patients successfully eradicated was approximately 650 000 per year between 2001 and 2012, whereas it rapidly rose to 1 380-000 per year in 2013. The estimated prevalence of infection in 2050 is 5%, this rate was estimated to be 28% and 22% if the policy changes had not occurred in 2000 and 2013, respectively. Conclusions: The impact of policy changes for H. pylori eradication therapy on the prevalence of infection was shown. The results suggest that insurance coverage expansion may also reduce the prevalence in other countries with a high prevalence of H. pylori infection if the reinfection is low.

 

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Non-organ-specific autoimmunity in patients suffering from gastric ulcer with and without Helicobacter pylori infectionAstegiano M. Touscoz G.A. Caviglia G.P. Ribaldone D.G. De Angelis C. Peyre S. Smedile A. Saracco G.M. Pellicano R.Minerva Biotecnologica (2017) 29:3 (109-113). Date of Publication: 1 Sep 2017BACKGROUND: To evaluate the prevalence of non-organ specific autoantibodies (NOSAs) in patients with gastric ulcer (GU) associated or not with Helicobacter pylori (H. pylori) infection. MetHoDS: We compared 43 patients (26M/17F, median age 63 years) suffering from gU and H. pylori infection to 39 subjects (19M/20F, median age 69 years) affected by GU caused by the assumption of non-steroidal anti-inflammatory drugs (NSAIDs). H. pylori infection was diagnosed by histology and 13c-urea breath test. autoimmunity was assessed by the presence of NoSas in serum. all patients with H. pylori infection were treated with one or more antibiotic regimens to eradicate the bacterium. reSUltS: antinuclear (aNa), anti-smooth muscle (aSMa) and anti-liver/kidney microsomal-1 (lKM-1) antibodies were present respectively in 5 (11.6%), 1 (2.3%) and none out of 43 patients with gU and H. pylori infection. considering the 39 patients with NSaiDs-related gU, aNa was present in 5 (12.8%), ASMA in 3 (7.7%) and anti-LKM-1 in none. The difference was not significant. All but one H. pylori infected subjects (97.7%) eradicated the bacterium with a multistep strategy; in none of them significant changes in terms of prevalence or titer of NOSAs, after 6 months of follow-up were observed. coNclUSioNS: in patients with gU, H. pylori infection is not associated with an increased prevalence of NoSas and the cure of the bacterium does not influence the NOSAs profile. (Cite this article as: astegiano M, touscoz ga, caviglia gP, ribaldone Dg, De angelis c, Peyre S, et al. Non-organ-specific autoimmunity in patients suffering from gastric ulcer with and without Helicobacter pylori infection.

 

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Which Regimens Should Be Used and Which Rejected for the Treatment of Helicobacter pylori?Georgopoulos S.D. Xirouchakis E.American Journal of Gastroenterology (2017) 112:7 (1168-1169). Date of Publication: 1 Jul 2017

 

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Importance of antimicrobial susceptibility testing for the management of eradication in Helicobacter pylori infectionArslan N. Yilmaz O. Demiray-Gürbüz E.World Journal of Gastroenterology (2017) 23:16 (2854-2869). Date of Publication: 28 Apr 2017The management of Helicobacter pylori (H. pylori) infection treatment differs from the common treatment protocol for other infectious diseases. Because culture- or molecular-guided approaches face several practical issues, such as the invasive procedures required to obtain gastric biopsy specimens and the lack of availability of routine laboratory testing in some places, H. pylori treatment includes the administration of two or three empirically selected antibiotics combined with a proton pump inhibitor rather than evidence-based eradication treatment. The efficacy of empirical therapy is decreasing, mostly due to increasing multiple resistance. Multiresistance to levofloxacin, clarithromycin, and metronidazole, which are commonly used in empirical treatments, appears to have increased in many countries. Mutations play a primary role in the antimicrobial resistance of H. pylori, but many different mechanisms can be involved in the development of antibiotic resistance. Determining and understanding these possible mechanisms might allow the development of new methods for the detection of H. pylori and the determination of antimicrobial resistance. A treatment based on the detection of antimicrobial resistance is usually more effective than empirical treatment. Nevertheless, such an approach before treatment is still not recommended in the Maastricht guidelines due to the difficulty associated with the routine application of available cultureor molecular-based susceptibility tests, which are usually administered in cases of treatment failure. The management of first and rescue treatments requires further research due to the steadily increase in antimicrobial resistance.

 

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The study of memory and executive dysfunction in patients infected with Helicobacter pyloriRezvani F. Sayadnasiri M. Rezaei O.Neurological Research (2017) (1-6). Date of Publication: 9 Aug 2017Background: Infectious agents are considered as potential causes of Alzheimer’s disease. Recently, evidence of a high prevalence of Helicobacter pylori (H. pylori) infection in patients with Alzheimer’s disease has been observed. The aim of this study was to investigate memory and executive function in H. pylori positive persons not suffering from Alzheimer’s or other marked cognitive disorders. Methods: This is a cross-sectional study. A total 140 participants were selected using purposive sampling from the patients within the age group of 18–60 years old at Fayyaz Bakhsh Hospital, Tehran in spring 2016. The participants were divided into two groups of H. pylori positive and negative according to results of the serologic tests to measure the levels of specific antibodies of IgA and IgG against H. pylori using ELISA method. They were subsequently assessed using two tests of Trail Making (TMT) part A and B and Wechsler Memory Scale – Third Edition. Data were analyzed using independent t-test and chi-square. The level of significance was considered P-value ≤ 0.05. Results: Out of 140 participants, there were 41 male (29.3%) and 99 female (70.7%) among which 84 patients (60%) suffered from H. pylori infection (seropositive) and 56 patients (40%) were not infected. Comparison of the results using independent t-test showed a significant difference (P = 0.006) between the memory scores of patients (M: 106, SD: 8.12) and healthy ones (M: 112, SD: 1.12). In addition, the executive function showed there is a significant difference in the executive ability of seropositive individuals in the two age groups of 20–50 years old (Part A: M: 1.36, SD: 7.11, and Part B: M: 8.8, SD: 8.25 p = 0.01) and over 50 years old (Part A: M: 55, SD: 8.20, and Part B: M: 106, SD: 7.22, p = 0.009). Conclusion: The results of this study showed that the infected patients have a lower cognitive performance in comparison to healthy individuals. In other words, H. pylori infection increases the prevalence of memory and executive dysfunction.

 

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Serum VEGF levels in Helicobacter pylori infection and correlation with Helicobacter pylori cagA and vacA genesSiregar G. Sari D. Sungkar T.Open Access Macedonian Journal of Medical Sciences (2017) 5:2 (137-141). Date of Publication: 15 Apr 2017BACKGROUND: Helicobacter pylori vacA and cagA genes are associated with higher virulence. Vascular Endothelial Growth Factor (VEGF) is one important marker for neo-angiogenesis. AIM: The purpose of this study was to investigate the relationship between VEGF serum levels with cagA and vacA genes in H. pylori infection. METHODS: A cross-sectional study was done on eighty patients that consecutive admitted to endoscopy unit. The diagnosis of H. pylori infection was based on rapid urease test. Serum samples were obtained to determine circulating VEGF level. Polymerase chain reaction was done to examine H. pylori vacA and cagA genes. Data analysis were carried-out using SPSS version 22. RESULTS: A total of 80 patients were examined. There were 45 (56.3%) patients infected with Helicobacter pylori. There were 33 (73.3%) patients with H. pylori cagA positive. Serum VEGF levels in patients with the H. pylori positive were significantly higher compared to the patients that have no H. pylori. Serum levels of VEGF were significantly higher in cagA positive than negative. CONCLUSION: Serum VEGF level is correlated with H. pylori infection and its virulence status. The more virulence of H. pylori, cagA gene, the higher serum VEGF levels were found.

 

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A one-step immune-chromatographic Helicobacter pylori stool antigen test for children was quick, consistent, reliable and specificKalach N. Gosset P. Dehecq E. Decoster A. Georgel A.-F. Spyckerelle C. Papadopoulos S. Dupont C. Raymond J.Acta Paediatrica, International Journal of Paediatrics (2017). Date of Publication: 2017Aim: This French study assessed a quick, noninvasive, immuno-chromatographic, Helicobacter pylori (H. pylori) stool antigen test for detecting infections in children. Methods: We enrolled 158 children, with a median age of 8.5 years (range eight months to 17 years), with digestive symptoms suggesting upper gastrointestinal tract disease. Upper digestive endoscopy was performed with gastric biopsy specimens for histology, a rapid urease test, culture test and quantitative real-time polymerase chain reaction. The H. pylori stool antigen test was performed twice for each child and the results were compared to the reference method. Results: The reference methods showed that 23 (14.6%) of the 158 children tested were H. pylori positive. The H. pylori stool antigen test showed 91.3% sensitivity, with a 95% confidence interval (95% CI) of 86.9-95.6 and 97% specificity (95% CI 94.3-99.6), 30.84 positive likelihood ratio and 0.09 negative likelihood ratio. The test accuracy was 96.2% (95% CI 93.2-99.1). The two blinded independent observers produced identical H. pylori stool antigen test results and the Kappa coefficient for the H. pylori stool antigen test was one. Conclusion: The H. pylori stool antigen test was found to be a consistent, reliable, quick and specific test for detecting the H. pylori infection in children.

 

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Decrease of Estradiol and Several Lifestyle Factors, but Not Helicobacter pylori Infection, Are Significant Risks for Osteopenia in Japanese FemalesChinda D. Shimoyama T. Iino C. Matsuzaka M. Nakaji S. Fukuda S.Digestion (2017) (103-109). Date of Publication: 9 Aug 2017Background: The primary cause of osteoporosis in women is increased bone resorption and decreased bone density associated with reduced estrogen secretion. Several studies have demonstrated a relationship between Helicobacter pylori infection and osteoporosis regardless of estrogen levels. This study examined the relationship between H. pylori infection and osteopenia together with estrogen levels, calcium intake, and several lifestyle factors. Methods: This study included 473 healthy women who underwent a general health examination. Multivariate analysis was performed, with age, body mass index (BMI), smoking habit, drinking habit, exercise habit, schooling duration, estradiol levels, birth history, calcium intake, schooling duration, smoking habit, drinking habit, exercise habit, and H. pylori infection as independent variables and the presence of osteopenia as a dependent variable. Results: The adjusted OR for osteopenia with H. pylori infection was 0.95 (95% CI 0.55-1.63, p = 0.84). In contrast, osteopenia was significantly associated with age, low BMI, lesser schooling period, low estradiol levels, and low calcium intake. Conclusions:H. pylori infection was not a significant risk for osteopenia by the multivariate analysis, which included the primary confounding factors. Significant factors, such as estradiol and calcium intake, should be assessed together to study the association of H. pylori infection and osteopenia.

 

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cag Pathogenicity island-dependent upregulation of matrix metalloproteinase-7 in infected patients with Helicobacter pyloriSadeghiani M. Bagheri N. Shahi H. Reiisi S. Rahimian G. Rashidi R. Mahsa M. Shafigh M. Salimi E. Rafieian-kopaei M. Hashemzadeh-chaleshtori M. Shirzad H.Journal of Immunoassay and Immunochemistry (2017) (1-13). Date of Publication: 9 Aug 2017Helicobacter pylori (H. pylori) infection has been involved in the pathogenesis of most important gastroduodenal diseases. Matrix metalloproteinases (MMPs) are a large family of zincendopeptidases which play important roles in degradation of extracellular matrix (ECM) and various inflammatory diseases. Therefore, we examined MMP-7 mRNA levels in the gastric mucosa of patients with H. pylori infection and evaluated the effects of virulence factors, such as vacA (vacuolating cytotoxin A) and cagA (cytotoxin-associated gene), in H. pylori-infected patients upon the MMP-7 mRNA mucosal levels. We also determined the correlation between mucosal MMP-7 mRNA levels and the types of disease. Total RNA was extracted from gastric biopsies of 50 H. pylori-infected patients and 50 uninfected individuals. Mucosal MMP-7 mRNA expression level in H. pylori-infected and non-infected gastric biopsies was determined by real-time polymerase chain reaction (PCR). The presences of cagA and vacA virulence factors was evaluated using PCR. MMP-7 expression was significantly higher in biopsies of patients infected with H .pylori compared to uninfected individuals. In addition, mucosal MMP-7 mRNA expression in H. pylori-infected patients significantly associated with the cagA status and the types of disease. Our results suggest that MMP-7 might be involved in the pathogenesis of H. pylori. Peptic ulcer was associated with cag pathogenicity island-dependent MMP-7 upregulation.

 

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Second-line therapy for Helicobacter pylori eradication causing antibiotic-associated hemorrhagic colitisTanaka K. Fujiya M. Sakatani A. Fujibayashi S. Nomura Y. Ueno N. Kashima S. Goto T. Sasajima J. Moriichi K. Okumura T.Annals of Clinical Microbiology and Antimicrobials (2017) 16:1 Article Number: 54. Date of Publication: 14 Aug 2017Objective: Helicobacter pylori (H. pylori) eradication rarely develops into antibiotic-associated hemorrhagic colitis (AAHC), in which the etiology of colitis remains unclear. We herein report a rare case of AAHC caused by second-line therapy for H. pylori eradication. Results: A 65-year-old female was administered second-line therapy for H. pylori composed of 1500 mg of amoxicillin, 500 mg of metronidazole and 40 mg of vonoprazan for 7 days because of first-line therapy failure. A day after completing second-line therapy, she complained of abdominal pain and hematochezia. Colonoscopy revealed a hemorrhage and edematous mucosa with no transparent vascular pattern in the transverse colon. A bacterial culture detected Klebsiella oxytoca (K. oxytoca), but no other pathogenic bacteria. A drug-induced lymphocyte stimulation test (DLST) showed positive reactions for both amoxicillin and metronidazole. According to these findings, the patient was diagnosed with AAHC. Bowel rest for 6 days relieved her abdominal pain and hematochezia. Conclusions: The present case developed AAHC caused by second-line therapy for H. pylori eradication. The pathogenesis is considered to be associated with microbial substitution as well as a delayed-type allergy to antibiotics, suggesting that AAHC is a potential adverse event of second-line therapy for H. pylori eradication.

 

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Expressions of the CagA protein and CagA-signaling molecules predict Helicobacter pylori dependence of early-stage gastric DLBCLKuo S.-H. Chen L.-T. Lin C.-W. Yeh K.-H. Shun C.-T. Tzeng Y.-S. Liou J.-M. Wu M.-S. Hsu P.-N. Cheng A.-L.Blood (2017) 129:2 (188-198). Date of Publication: 12 Jan 2017We previously reported that early-stage gastric diffuse large B-cell lymphomas (DLBCLs), including DLBCLs with mucosa-associated lymphoid tissue (DLBCL[MALT]) and without ("pure" DLBCL) the features of MALT lymphomas, can achieve long-term complete remission after frontline Helicobacter pylori (HP) eradication (HPE). We recently reported that expression of cytotoxin-associated gene A (CagA) and CagA-signaling molecules (phospho-Src homology-2 domain-containing phosphatase [p-SHP2] and phospho-extracellular signal-regulated kinase [p-ERK]) is associated with HP dependence of gastric MALT lymphoma. However, the significance of CagA and CagA-signaling molecules in gastric DLBCL remains unexplored. The association between expression of CagA, p-SHP-2, and p-ERK in malignant B cells and tumor response to HPE was evaluated in 63 patients with stage IE/IIE1 HP-positive gastric DLBCL who received HPE as frontline treatment. We detected CagA expression in 20 of 42 DLBCL (MALT) cases (47.6%) and in 13 of 21 "pure" DLBCL cases (61.9%). CagA expression was higher in HP-dependent tumors than in HP-independent tumors (74.3% [26 of 35] vs 25.0% [7 of 28]). Patients with CagA expression responded to HPE quicker than those without expression (median time to complete remission, 4.0 months vs 5.0 months). The expression of CagA was closely associated with p-SHP-2 and p-ERK expression. Combined CagA, p-SHP-2, and p-ERK expression showed an increased positive predictive value (81.8% vs 75.9%) and an increased specificity (84.0% vs 75.0%) for HP dependence compared with CagA expression alone. Our results indicated that CagA and its signaling molecules can be detected in the malignant B cells of gastric DLBCL, and the expression of these molecules is clinically and biologically associated with HP dependence.

 

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Helicobacter pylori is associated with decrease serum level of the thyroid hormonal in healthy elderly populationSuwarni S. Risya C. Indarto D. SuradiBangladesh Journal of Medical Science (2017) 16:4 (515-520). Date of Publication: 2017Background: Helicobacter pylori infection is the most prevalence infectious disease as it affects more than half of the world population and causes chronic cellular inflammatory response in the gastric mucosa. Helicobacter pylori infection has been epidemiologically proven to be linked to extra-digestive conditions and disease. It has been speculated that H.pylori infection may be responsible for various endocrine disorders. The thyroid may be one of the targets of Helicobacter pylori chronic inflammation. Here we sought too investigate whether H.pylori infections were associated with decrease level of the thyroid hormonal. Methods: This study involved elderly aged 50-90 years who had visited a health promotion center for elderly. A total 101 euthyroid subjects were been enrolled in this cross-sectional study. Diagnosed of Helicobacter.pylori infections by ELISA of Ig G antibodies of Helicobacter pylori. We examine serum T3 level and serum TSH level by ELEXIS. For statistical method we use Pearson bivariat analysis to determine the association of two variable,and linier regression to determine which variable is more influented by Helicobacter pylori. Results: Fourty-two (41,6 %) subjects had been diagnosed with H. pylori infections. Pearson bivariat analysis showed that Helicobacter pylori infection was significantly associated with decreased serum T3 level (correlations coefficient r = -0,66,p< 0,001). The prevalence of Helicobacter pylori infection showed a increasing trend as serum TSH level decreased (correlations coefficient r = -0,53, p < 0,001). Linier regression analysis showed that Helicobacter pylori infection was significantly associated with the risk of decreased thyroid hormonal fuction (B = -0,272. R(2) = 0,676. P < 0.001). Conclusion: Our results suggested that H.pylori infections were significantly associated with the decreased serum level of T3 and TSH serum level in the healthy elderly population, whose thyroid functions were in the reference range.

 

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Limited effectiveness with a 10-day bismuth-containing quadruple therapy (Pylera(®)) in third-line recue treatment for Helicobacter pylori infection. A real-life multicenter studyRodríguez de Santiago E. Martín de Argila de Prados C. Marcos Prieto H.M. Jorge Turrión M.A. Barreiro Alonso E. Flores de Miguel A. de la Coba Ortiz C. Rodríguez Escaja C. Pérez Álvarez G. Ferre Aracil C. Aguilera Castro L. García García de Paredes A. Rodríguez Pérez A. Albillos Martínez A.Helicobacter (2017). Date of Publication: 2017Background: Helicobacter pylori antibiotic resistance is an increasing problem worldwide. Pylera(®) may be an option as salvage therapy. Aim: To assess the effectiveness, safety, and tolerance of Pylera(®) as a third-line in clinical practice. Materials and Methods: This was a multicenter, observational, prospective database study in four Spanish hospitals. Consecutive H. pylori-infected individuals treated with Pylera(®) and a proton-pump inhibitor (PPI) were invited to participate if they had failed to respond to PPI-clarithromycin-amoxicillin as first-line and to levofloxacin-amoxicillin-PPI as second-line therapy. Eradication was tested 4-8 weeks after Pylera(®) using a C(13)-urea breath test. Treatment-related adverse effects (TRAEs) were assessed through a questionnaire and by reviewing databases. A questionnaire on patient satisfaction was completed in the last visit. Results: Of 103 subjects fulfilling the selection criteria, 101 were included in the intention-to-treat (ITT) analysis and 97 in the per-protocol (PP) analysis. A 10 day course was prescribed in all patients. Esomeprazole 40 mg b.i.d. was the most used PPI regimen (ITT=94.1%). Ninety-seven individuals (ITT=96.04%) completed more than 90% of the treatment. Overall eradication rates were ITT=80.2% (95% confidence interval [CI]: 72.3%-88.1%) and PP=84.4% (95% CI: 76.8%-91.8%). One or more TRAEs were experienced by 67.3% (95% CI: 57.7%-75.7%), all mild or moderate. TRAEs and the number of pills were the main complaints. Conclusion: In an area of high antibiotic resistance to H. pylori, 10-day Pylera(®) plus double-dose PPI emerged as an alternative as third-line therapy, although not achieving optimal eradication rates. TRAEs were common but were neither severe nor did they condition compliance.

 

 

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Dynamics of Helicobacter pylori infection as a determinant of progression of gastric precancerous lesions: 16-year follow-up of an eradication trialMera R.M. Bravo L.E. Camargo M.C. Bravo J.C. Delgado A.G. Romero-Gallo J. Yepez M.C. Realpe J.L. Schneider B.G. Morgan D.R. Peek R.M. Correa P. Wilson K.T. Piazuelo M.B.Gut (2017). Date of Publication: 24 Jun 2017Objective: To evaluate the long-term effect of cumulative time exposed to Helicobacter pylori infection on the progression of gastric lesions.Design: 795 adults with precancerous gastric lesions were randomised to receive anti-H. pylori treatment at baseline. Gastric biopsies were obtained at baseline and at 3, 6, 12 and 16 years. A total of 456 individuals attended the 16-year visit. Cumulative time of H. pylori exposure was calculated as the number of years infected during follow-up. Multivariable logistic regression models were used to estimate the risk of progression to a more advanced diagnosis (versus no change/regression) as well as gastric cancer risk by intestinal metaplasia (IM) subtype. For a more detailed analysis of progression, we also used a histopathology score assessing both severity and extension of the gastric lesions (range 1-6). The score difference between baseline and 16 years was modelled by generalised linear models.Results: Individuals who were continuously infected with H. pylori for 16 years had a higher probability of progression to a more advanced diagnosis than those who cleared the infection and remained negative after baseline (p=0.001). Incomplete-type IM was associated with higher risk of progression to cancer than complete-type (OR, 11.3; 95% CI 1.4 to 91.4). The average histopathology score increased by 0.20 units/year (95% CI 0.12 to 0.28) among individuals continuously infected with H. pylori. The effect of cumulative time of infection on progression in the histopathology score was significantly higher for individuals with atrophy (without IM) than for individuals with IM (p<0.001).Conclusions: Long-term exposure to H. pylori infection was associated with progression of precancerous lesions. Individuals infected with H. pylori with these lesions may benefit from eradication, particularly those with atrophic gastritis without IM. Incomplete-type IM may be a useful marker for the identification of individuals at higher risk for cancer.

 

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Helicobacter pylori infection and atherosclerosis: is there a causal relationship?Xu Z. Li J. Wang H. Xu G.European Journal of Clinical Microbiology and Infectious Diseases (2017) (1-9). Date of Publication: 27 Jul 2017For many years, the coexistence of Helicobacter pylori (H. pylori) infection and atherosclerotic diseases in a disproportional number of patients has inspired the presumption that a causal relationship exists between the conditions. This presumption was evidenced by the simultaneously declining epidemics of duodenal ulcer and coronary artery diseases in the United States in the past 40 years, and was further evidenced by the detection of H. pylori and their DNA in atherosclerotic plaques. Suggested mechanisms underlying this possible causality include intensified inflammatory stress, dyslipidemia, abnormal glucose metabolism, arterial stiffness, increased blood pressure and malnutrition. However, a causal relationship was disproved by results from other studies, which indicated that common risk factors shared by H. pylori infection and atherosclerosis, such as aging, cigarette smoking, disadvantageous socioeconomic status and high salt intake, may predestine their coexistence. Understanding the nature of the relationship between H. pylori infection and atherosclerosis is of vital importance, because a causality may indicate a possible strategy for preventing and treating atherosclerosis by eradicating H. pylori infection in selected individuals. This review assessed current evidence for and against a causal relationship between H. pylori infection and atherosclerosis.

 

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Helicobacter pylori outer inflammatory protein A (OipA) suppresses apoptosis of AGS gastric cells in vitroAl-Maleki A.R. Loke M.F. Lui S.Y. Ramli N.S.K. Khosravi Y. Ng C.G. Venkatraman G. Goh K.-L. Ho B. Vadivelu J.Cellular Microbiology (2017). Date of Publication: 2017Outer inflammatory protein A (OipA) is an important virulence factor associated with gastric cancer and ulcer development; however, the results have not been well established and turned out to be controversial. This study aims to elucidate the role of OipA in Helicobacter pylori infection using clinical strains harbouring oipA "on" and "off" motifs. Proteomics analysis was performed on AGS cell pre-infection and postinfection with H. pylori oipA "on" and "off" strains, using liquid chromatography/mass spectrometry. AGS apoptosis and cell cycle assays were performed. Moreover, expression of vacuolating cytotoxin A (VacA) was screened using Western blotting. AGS proteins that have been suggested previously to play a role or associated with gastric disease were down-regulated postinfection with oipA "off" strains comparing to oipA "on" strains. Furthermore, oipA "off" and ΔoipA cause higher level of AGS cells apoptosis and G0/G1 cell-cycle arrest than oipA "on" strains. Interestingly, deletion of oipA increased bacterial VacA production. The capability of H. pylori to induce apoptosis and suppress expression of proteins having roles in human disease in the absence of oipA suggests that strains not expressing OipA may be less virulent or may even be protective against carcinogenesis compared those expressing OipA. This potentially explains the higher incidence of gastric cancer in East Asia where oipA "on" strains predominates.

 

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Safety of one-week, first-line, standard triple therapy for Helicobacter pylori eradication in a Japanese populationHori K. Takagawa T. Hida N. Nakamura S.Current Drug Safety (2017) 12:2 (103-109). Date of Publication: 1 Jul 2017Background: Standard triple therapy with the proton pump inhibitors, clarithromycin and amoxicillin for Helicobacter pylori infection is considered to be safe; however, the development of significant adverse events (AEs), such as skin rashes, has been reported. Objective: To reconfirm the safety of this treatment. Methods: This was a retrospective cohort study. After the exclusion of patients allergic to penicillin, 322 consecutive patients, consisting of 305 outpatients and 17 inpatients, had received the first-line eradication treatment with lansoprazole (30 mg), clarithromycin (200 mg), and amoxicillin (750 mg) twice daily for 7 days. Their medical charts were reviewed, and data were collected. Results: Three patients discontinued the treatment because of the development of a skin rash, mild diarrhea, and heat sensation, respectively. The main AE observed was mild diarrhea in 50 patients. One patient had frequent diarrhea, but it was readily resolved by a probiotic treatment. On the second or third day after the conclusion of the treatment, a skin rash also occurred in six patients (2%). Two of these patients and one patient who discontinued the treatment were administered steroids as outpatients. They recovered within 1 month. Conclusion: Most AEs that developed were mild, except for some cases of a rash. Rashes developed in spite of the exclusion of penicillin-allergic patients and mainly after the completion of the one-week treatment. As a consequence of little previous exposure to penicillin in the Japanese population, the development of delayed rashes after this exclusion may represent first sensitization to penicillin.

 

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Rare gastric lesions associated with Helicobacter Pylori infection: A histopathological reviewJoo M.Journal of Pathology and Translational Medicine (2017) 51:4 (341-351). Date of Publication: 1 Jul 2017Helicobacter pylori infection is associated with chronic gastritis, peptic ulcer disease, gastric adenocarcinoma, and mucosa-associated lymphoid tissue lymphoma. However, some rare gastric lesions exhibiting distinctive histological features may also be associated with H. pylori infection, including lymphocytic gastritis, granulomatous gastritis, Russell body gastritis, or crystal-storing histiocytosis. Although diverse factors can contribute to their development, there is convincing evidence that H. pylori infection may play a pathogenic role. These findings are mainly based on studies in patients with these lesions who exhibited clinical and histological improvements after H. pylori eradication therapy. Thus, H. pylori eradication therapy might be indicated in patients with no other underlying disease, particularly in countries with a high prevalence of H. pylori infection. This review describes the characteristic histological features of these rare lesions and evaluates the evidence regarding a causative role for H. pylori infection in their pathogenesis.

 

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TLR2 Arg677Trp but not TLR2 -196 to -174 ins/del and Arg753Gln polymorphism alter the risk of peptic ulcer in north of IranHabibzadeh M. Tourani M. Shokri-Shirvani J. Mostafazadeh A. Khafri S. Nouri H.R.Journal of the Chinese Medical Association (2017). Date of Publication: 2017Background: Most polymorphisms that occur in TLR-2 are associated with gastrointestinal disorders such as peptic ulcer disease (PUD). Hence, in current study, association between TLR2-196 to -174 ins/del, Arg753Gln and Arg677Trp polymorphisms and risk of PUD development in north of Iran was evaluated. Methods: This case-control study included 50 patients with PUD as cases and 50 people without peptic ulcer as control group. Blood and endoscopic biopsies were collected. Helicobacter pylori infection was screened by rapid urease test, specific IgG measurement and specific PCR for glmM gene. Then, TLR2-196 to -174 ins/del polymorphism was assessed by using allele-specific PCR. The Arg753Gln and Arg677Trp polymorphism in TLR2 gene were analyzed by the PCR-restriction fragment length polymorphism (RFLP). Results: There was no significant difference in the allele and genotype frequencies of polymorphisms in the TLR2-196 to -174 ins/ins and Arg753Gln genes between controls and patients, respectively. However, an association with increased risk for PUD was observed for polymorphism TLR-2 Arg677Trp (odds ratio [OR] = 7.9; 95% confidence interval [CI] = 0.94-67.5). Further analysis showed that H. pylori infection was associated with a significant difference in genotype and allele frequencies of TLR2-196 to -174 ins/ins and Arg753Gln polymorphism, respectively. Furthermore, there was no association between variant haplotypes and PUD development in H. pylori infected subjects. However, no association was detected between gender and genotypic frequencies of all polymorphisms in TLR2. Conclusion: Our findings showed that TLR2 Arg677Trp polymorphism and H. pylori infection may play crucial roles in peptic ulcer development respectively in north of Iran.

 

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Determining the IgM and IgG antibody titer against CMV and helicobacter pylori in the serum of multiple sclerosis patients comparing to the control group in HamadanSalim M.A. Eftekharian M.M. Taheri M. Yousef Alikhani M.Human Antibodies (2017) 26:1 (23-28). Date of Publication: 2017BACKGROUND: Multiple sclerosis (MS) is a chronic autoimmune disease that disables central nervous system (CNS) system. Cytomegalovirus (CMV) probably has an important role in the MS pathology. The infection with helicobacter pylori also is recognized as a protective agent against MS in female. METHODS: Serum samples were isolated and frozen at -70°C. The earlier mentioned anti-virus antibodies and antibacterial antibodies were quantified by Elisa kit. RESULTS: The results showed that IgG antibody average value against cytomegalovirus in the blood of multiple sclerosis patients not only decreased but also was significant statistically (p< 0.05). IgM and IgG antibodies average value in the blood of multiple sclerosis patients against helicobacter pylori shown a statistically significant decrease (p< 0.05). CONCLUSION: Therefore it may be considered that probably helicobacter pylori presence in the individuals especially in female can alleviate MS signs. CMV infection can intensify the symptoms in multiple sclerosis patients.

 

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Subversion of host kinases: a key network in cellular signaling hijacked by Helicobacter pylori CagATegtmeyer N. Neddermann M. Asche C.I. Backert S.Molecular Microbiology (2017) 105:3 (358-372). Date of Publication: 1 Aug 2017Helicobacter pylori is a paradigm of persistent pathogens and major risk factor for developing severe diseases including adenocarcinoma in the human stomach. An important bacterial factor linked to gastric disease progression is the cag pathogenicity island-encoded type-IV secretion system (T4SS) effector protein CagA. Translocated CagA undergoes tyrosine phosphorylation at EPIYA-motifs and then activates or inactivates multiple host signaling proteins in a phosphorylation-dependent and phosphorylation-independent fashion. In this way, intracellular CagA acts as a ‘masterkey’ or ‘picklock’, which evolved during evolution to hijack key host cell signal transduction functions. Crucial targets of CagA represent a variety of serine/threonine and tyrosine kinases, which control major checkpoints of eukaryotic signaling. Here we review the signal transmission by translocated CagA on multiple receptor kinases (c-Met and EGFR) and non-receptor kinases (Src, Abl, Csk, aPKC, Par1, PI3K, Akt, FAK, GSK-3, JAK, PAK1, PAK2 and MAP kinases), manipulating a selection of fundamental processes in the human gastric epithelium such as cell adhesion, polarity, proliferation, motility, receptor endocytosis, cytoskeletal rearrangements, apoptosis, inflammation and cell cycle progression. This enormous complexity generates a highly remarkable and puzzling scenario during H. pylori infection. The contribution of these signaling pathways to bacterial survival, persistence and gastric pathogenesis is discussed.

 

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Modifiable factors and esophageal cancer: a systematic review of published meta-analysesCastro C. Peleteiro B. Lunet N.Journal of Gastroenterology (2017) (1-15). Date of Publication: 18 Aug 2017There are marked differences in the etiology of the major histological types of esophageal cancer (EC)—squamous cell carcinomas (ESCC) and adenocarcinomas (EAC). This study aimed to summarize the current scientific knowledge on modifiable risk factors for EC, by histological type, through a systematic review of meta-analyses referenced in PubMed and ISI Web of Knowledge. We identified 100 meta-analyses on risk factors for ESCC (n = 54), EAC (n = 43), or EC (n = 51). ESCC risk significantly increased with alcohol and maté drinking, smoking, red and processed meat consumption and human papillomavirus infection, while it was negatively associated with body mass index and consumption of fruit, vegetables, white meat, folate, and some carotenoids. Cessation of drinking and smoking significantly reduced ESCC risk. For EAC, an increased risk was reported for smoking, body mass index, and red and processed meat consumption, while risk decreased with Helicobacter pylori infection, low/moderate alcohol drinking, physical activity, and consumption of fruit, vegetables, folate, fiber, beta-carotene, and vitamin C. Differences in results between meta-analyses and mechanisms underlying some of the associations found are discussed. This work reinforces the importance of a separate assessment of EC subtypes to allow for a proper evaluation of incidence trends and planning of prevention/control interventions.

 

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Up-regulation of transient receptor potential vanilloid (TRPV) and down-regulation of brain-derived neurotrophic factor (BDNF) expression in patients with functional dyspepsia (FD)Cheung C.K.Y. Lan L.L. Kyaw M. Mak A.D.P. Chan A. Chan Y. Wu J.C.Y.Neurogastroenterology and Motility (2017). Date of Publication: 2017Background: The role of immune activation in Functional Dyspepsia (FD) patients without previous infection is unclear. We compare the gastric and circulating brain-derived neurotropic factor (BDNF), receptor potential vanilloid type (TRPV) families and various cytokines in FD patients. Methods: Consecutive adult FD patients (Rome III) with no recent history of gastroenteritis and asymptomatic healthy controls were recruited for upper endoscopy. Subjects with GERD and IBS as predominant symptoms, diabetes mellitus, current or previous Helicobacter pylori infection, psychiatric illness and recent use of NSAID or PPI were excluded. Corpus biopsies and serum samples were collected. Key Results: Forty three [M:F=8:35, mean age: 35.0 (9.3)] FD patients were compared with 23 healthy controls [M:F=8:15, mean age: 36.6 (10.2)]. FD patients had postprandial distress syndrome (PDS) as predominant sub-type (PDS: 36, EPS: 2). There was no significant difference in the median inflammation score (FD:0 (0-1) vs Control:0 (0-1), P=.79). However, FD patients had significantly higher mRNA expression of TRPV1 (FD:0.014±0.007, Control:0.003±0.001, 4.6 fold, P=.02) and TRPV2 (FD:0.012±0.006, Control:0.003±0.001, 4 fold, P=.02) compared to controls. The serum (FD:258.0±12.3 ng ml(-1), Control:319.7±18.1 ng ml(-1), P<.01) and gastric BDNF mRNA (FD:0.06±0.008, Control:0.092±0.01, 0.65 fold, P=.02)levels significantly lower in FD patients. Secretion of cytokines (IL-4, IL-5, IL-6, IL-8, IL-10, G-CSF, TGF-β2, MCP-1)was also highly correlated with dyspeptic symptoms in patients with FD. Conclusions & Inferences: Despite lacking gastric mucosal inflammation, up-regulation of TRPV1 and TRPV2, down-regulation of BDNF were observed in FD patients. These suggest that immune alteration may contribute to the pathogenesis of FD without any previous infection.

 

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Osteopontin polymorphism increases gastric precancerous intestinal metaplasia susceptibility in Helicobacter pylori infected maleChang W.-L. Lin M.-Y. Kuo H.-Y. Yang H.-B. Cheng H.-C. Lu C.-C. Sheu B.-S.Future Oncology (2017) 13:16 Article Number: 0006. Date of Publication: 1 Jul 2017Aim: Whether genetic polymorphisms of osteopontin (OPN) coding gene, SPP1, determine the risk of gastric precancerous intestinal metaplasia (IM) in Helicobacter pylori infected patients. Patients & methods: Helicobacter pylori infected patients (100 with and 210 without IM) were recruited to evaluate the associations of SPP1 promoter polymorphisms with gastric IM and adjusted for age, sex and smoking. Gastric OPN expression and inflammation were evaluated by immunohistochemistry, and haemotoxylin and eosin stain. Results: Only in males, but not females, carriage of both GG genotype at rs11730059 and C-G-C haplotype at rs6833161-rs2853744-rs11730582 significantly increased the IM risk (OR: 4.92; 95% CI: 1.65-14.65; p = 0.004). Nearly 87.5% of males with IM carried risky genotype or haplotype. Carriers of the risky genotype or haplotype also had increased gastric OPN expression (p = 0.038) and inflammation (p = 0.007). Conclusion: SPP1 polymorphisms predispose to IM development in H. pylori infected males.

 

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Serum IL-10, MMP-7, MMP-9 levels in Helicobacter pylori infection and correlation with degree of gastritisSiregar G. Halim S. Sitepu R.Open Access Macedonian Journal of Medical Sciences (2016) 4:3 (359-363). Date of Publication: 15 Sep 2016AIM: Helicobacter pylori causes gastric mucosal inflammation and immune reaction. However, the increase of IL-10, MMP-7, and MMP-7 levels in the serum is still controversial. The objective of this study was to investigate the serum levels of IL-10, MMP-7 & MMP-9 in gastritis patients with H. pylori infection. MATERIALS AND METHODS: A cross-sectional study was done on seventy gastritis patients that consecutive admitted to endoscopy units. The diagnosis of gastritis was made based on histopathology and diagnosis of H. pylori infection was based on rapid urease test. Serum samples were obtained to determine to circulate IL-10, MMP-7, and MMP-9 level. Univariate and bivariate analysis were done by SPSS version 22. RESULTS: Forthy percentages of the patients were infected with H. pylori. The IL-10 level was significantly higher in H. pylori-infected patients compared to non-infected patients. However, there were no differences between serum levels of MMP-7 and MMP-9 in infected and non-infected H. pylori patients. CONCLUSIONS: The immune response to H. pylori promotes systemic inflammation, which was reflected by the increased levels of serum IL-10. However, there were no significant differences in MMP-7 and MMP-9 serum levels between positive and negative infected H. pylori patients.

 

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Rapid urine antibody test for Helicobacter pylori infection in adolescentsOkuda M. Mabe K. Lin Y. Chaochen W. Taniguchi Y. Kato M. Kikuchi S.Pediatrics International (2017) 59:7 (798-802). Date of Publication: 1 Jul 2017Background: Helicobacter pylori infection is associated with gastric cancer; thus, early diagnosis and treatment are crucial. Given that H. pylori infection in adolescents or young adults has few symptoms, screening tests are necessary for this population. In this study, the accuracy of the rapid urine H. pylori antibody (u-HpAb) test was evaluated and compared with that of urine and serum H. pylori enzyme-linked immunosorbent assay (u-HpELISA and s-HpELISA, respectively) in junior high school students. Methods: All 1,225 students attending the junior high schools in Sasayama City were invited to participate in this study. Urine and blood samples were assayed for anti-H. pylori immunoglobulin G antibodies, and rapid u-HpAb was performed by three investigators independently. When all investigators were in agreement, the test was confirmed as positive or negative. Non-concordance was defined as undetermined. Results: In total, 187 students participated in this study and provided both urine and blood samples. Three students had undetermined rapid u-HpAb. Excluding these results, the positivity rate of rapid u-HpAb was 3.3% (6/184), whereas that for u-HpELISA and s-HpELISA was 4.8% (10/187) and 5.9% (11/187), respectively. Using s-HpELISA and u-HpELISA as the standards, the sensitivity, specificity, positive predictive value, and negative predictive value of rapid u-HpAb were 85.7%, 100%, 100%, and 99.4%, respectively, excluding the undetermined rapid u-HpAb results. Conclusions: Rapid urine-HpAb test had excellent specificity but relatively low sensitivity.

 

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TLR5 Polymorphisms rs2072493, rs5744174, and rs5744168 Are Not Genetic Risk Factors for Chronic Helicobacter pylori Infection in Indian TamilsGoda V. Jayaraman M. Loganathan R. Nazeer M. Ali M. Karunakaran P. Devaraju P.Immunological Investigations (2017) 46:6 (537-543). Date of Publication: 18 Aug 2017The incidence of Helicobacter pylori (H. pylori) infection and gastric cancer is on the rise in India, and the genetic factors influencing the increased susceptibility in Indian population remain obscure. Toll-like receptors (TLRs) play a major role in innate immune system and genetic polymorphisms affecting their function were reported to enhance the risk for H. pylori infection. Seventy-seven patients (n = 77) diagnosed with H. pylori infection and 230 healthy subjects were recruited in this study. The rs2072493, rs5744174, and rs5744168 polymorphisms within TLR5 gene were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and Tetra-ARMS PCR genotyping techniques. Present study revealed that these studied polymorphisms are less frequent in south Indian Tamils and thus failed to confer a significant risk to develop chronic H. pylori infections. The distribution of ancestral allele of rs2072493 polymorphism conferred resistance to develop chronic H. pylori infection in our population (p = 0.024; OR = 0.53; 95% CI: 0.3–0.91). The lesser incidence of polymorphic alleles suggests that the TLR5 gene is under genetic selection pressure to withstand the prevailing endemic infections among south Indian Tamils.

 

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A comparative study of magnifying blue laser imaging and magnifying narrow-band imaging system for endoscopic diagnosis of Helicobacter pylori infectionTahara T. Takahama K. Horiguchi N. Yoshida D. Kawamura T. Okubo M. Ishizuka T. Nagasaka M. Nakagawa Y. Shibata T. Ohmiya N.Biomedical Reports (2017) 7:3 (236-240). Date of Publication: 2017Helicobacter pylori (Hp) infection is a major cause of gastric cancer. The use of proton-pump inhibitors, anti-platelet and anti-coagulant has become widespread in the clinic. Thus, it would be clinically useful to distinguish Hp-positive stomachs by endoscopic findings alone. Blue laser imaging (BLI) is a new image-enhanced endoscopy technique that utilizes a laser light source developed for narrow-band light observation. We investigated the diagnostic ability of magnifying BLI endoscopy to distinguish Hp-positive stomach in cancer free subjects. The data were also compared to the diagnostic ability of magnifying narrow-band imaging (NBI) endoscopy. In total, 215 participants were randomly assigned to the NBI (n=112) and BLI (n=113) groups. The greater curvature of the gastric middle and upper corpus were carefully evaluated with magnifying NBI or BLI. Small, round pits, accompanied with regular honeycomb-like subepithelial capillary networks (SECNs), being regularly interspersed with collecting venules were considered as Hp infection negative, while enlarged or elongated pits with unclear SECNs or dense fine irregular vessels were considered as Hp infection positive. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for the diagnosis of Hp infection for the NBI group was 0.97, 0.81, 0.87 and 0.95, respectively. Sensitivity, specificity, PPV and NPV for the BLI group was 0.98, 0.92, 0.93 and 0.98, respectively. There was no significant difference among the values for the NBI and BLI groups (all P>0.2). In conclusion, the diagnostic ability of magnifying BLI is acceptable, since it is similar to that of magnifying NBI.

 

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Cytokine expression associated with Helicobacter pylori and Epstein-Barr virus infection in gastric carcinogenesisKim J.Y. Bae B.-N. Kang G. Kim H.-J. Park K.APMIS (2017) 125:9 (808-815). Date of Publication: 1 Sep 2017Helicobacter pylori and Epstein-Barr virus (EBV) infection, and associated cytokines are involved in gastric carcinogenesis. We investigated the expression of these cytokines and their relationship with clinicopathological characteristics. The study included specimens from 207 patients with gastric adenocarcinoma, 56 with chronic gastritis, 32 with metaplasia, and 30 with low-grade epithelial dysplasia. Tissue microarrays were constructed and immunohistochemical staining for IL-1β, IL-6, IL-10, IL-17, p16, p21, TNF-α, and TNFR1 was performed. EBV and H. pylori infection status was determined. IL-1β, IL-6, IL-17, p16, and p21 protein expression was significantly higher in adenocarcinoma cases than in the other cases (p < 0.05). EBV was only noted in adenocarcinoma (13 cases, 6.3%). The H. pylori infection rate in adenocarcinoma was significantly higher than that in the other cases (p < 0.005). IL-6 expression was associated with improved survival (p < 0.05), whereas IL-17 expression was associated with decreased survival (p < 0.05). IL-6 expression was inversely associated with angioinvasion, and disease stage (p < 0.05), whereas IL-17 expression was associated with disease stage (p < 0.05). IL-10 expression was correlated with IL-1β and TNF-α expression, and p16 expression was correlated with IL-17 and EBV status. Our results indicate that IL-6 and IL-17 are associated with gastric carcinogenesis and may be considered prognostic factors.

 

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Helicobacter pylori infection, atrophic gastritis, and pancreatic cancer riskLiu H. Chen Y.-T. Wang R. Chen X.-Z.Medicine (United States) (2017) 96:33 Article Number: e7811. Date of Publication: 1 Aug 2017Background: To investigate the associations of Helicobacter pylori (Hp) infection and atrophic gastritis (AG) with pancreatic cancer risk. Methods: A literature search in PubMed was performed up to July 2017. Only prospective cohort and nested case-control studies enrolling cancer-free participants were eligible. Incident pancreatic cancer cases were ascertained during the follow-up. The risks of pancreatic cancer were compared between persons infected and noninfected with Hp, or between those with and without AG status at baseline. Odds ratios (ORs) or hazard ratios were combined. Subgroup and sensitivity analyses were performed, and publication bias was estimated. Results: Three cohort studies and 6 nested case-control studies, including 65,155 observations, were analyzed. The meta-analyses did not confirm the association between pancreatic cancer risk and Hp infection (OR = 1.09, 95% confidence interval [CI] = 0.81-1.47) or AG status (OR = 1.18, 95% CI = 0.80-1.72). However, particular subpopulations potentially had increased risks of pancreatic cancer. Cytotoxin-associated gene A (CagA)-negative strains of Hp might be a causative factor of pancreatic cancer (OR = 1.30, 95% CI = 1.05-1.62), but a sensitivity analysis by leave-one-out method did not fully warrant it (OR = 1.20, 95% CI = 0.93-1.56). In 1 nested case-control study, AG at stomach corpus in Hp-negative subpopulation might have increased risk of pancreatic cancer, but with a poor test power = 0.56. Publication biases were nonsignificant in the present meta-analysis. Conclusion: Based on current prospective epidemiologic studies, the linkage of pancreatic cancer to Hp infection or AG status was not warranted on the whole. Nevertheless, prospective studies only focusing on those specific subpopulations are further required to obtain better power.

 

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Helicobacter pylori infection and severity of coronary atherosclerosis in patients with chronic coronary artery diseaseJukic A. Bozic D. Kardum D. Becic T. Luksic B. Vrsalovic M. Ljubkovic M. Fabijanic D.Therapeutics and Clinical Risk Management (2017) 13 (933-938). Date of Publication: 27 Jul 2017Aim: Controversy exists concerning the relation between Helicobacter pylori (HP) infection and coronary artery disease (CAD). We aimed to examine the relationship between HP infection and severity of coronary atherosclerosis in patients with chronic CAD. Patients and methods: A total of 150 patients (109 [73%] men; mean age 62.61±10.23 years) scheduled for coronary artery bypass grafting surgery were consecutively enrolled in the cross-sectional study. According to rapid urease test and/or gastric biopsy samples stained with hematoxylin and eosin and according to Giemsa, patients were classified as HP positive (n=87; 58%) or HP negative (n=63; 42%). Coronary angiograms were scored by quantitative assessment, using multiple angiographic scoring system: 1) vessel score (number of coronary arteries stenosed ≥50%), 2) Gensini score (assigning a severity score to each coronary stenosis according to the degree of luminal narrowing and its topographic importance) and 3) angiographic severity score (number of coronary artery segments stenosed ≥50%). Results: In comparison to HP-negative patients, HP-positive patients were more frequently hypertensive (P=0.014), had higher values of systolic (P=0.043) and diastolic (P=0.005) blood pressure and total cholesterol (P=0.013) and had lower values of high-density lipoprotein-cholesterol (HDL-C; P=0.010). There were no significant differences between the groups in the severity of coronary atherosclerosis: vessel score (P=0.152), Gensini score (P=0.870) and angiographic severity score (P=0.734). Conclusion: It is likely that HP infection is not a risk factor for the severity of coronary atherosclerosis in chronic CAD patients.

 

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Reply to the Letter to the Editor on “Helicobacter Pylori Does Not Affect Postoperative Outcomes after Sleeve Gastrectomy”Shanti H. Almajali N. Al-Shamaileh T. Samarah W. Mismar A. Obeidat F.Obesity Surgery (2017) 27:9 (2466). Date of Publication: 1 Sep 2017

 

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Hematologic disorder: A manifestation of helicobacter pylori infectionZamani M. Masrour-Roudsari J. Zamani V.Caspian Journal of Internal Medicine (2017) 8:2 (133-134). Date of Publication: 2017

 

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Barrett’s Oesophagus and Oesophageal Carcinogenesis Following Obesity Surgery: Helicobacter Pylori Must Be Eradicated?Kassir R. Lointier P. Phelip J.-M. denneval A. Williet N. Tiffet O.Obesity Surgery (2017) 27:9 (2464-2465). Date of Publication: 1 Sep 2017

 

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Anemia and iron deficiency related to inflammation, helicobacter pylori infection and adiposity in reproductive-age cuban womenPita-Rodríguez G.M. Basabe-Tuero B. Díaz-Sánchez M.E. Gómez-Álvarez A.M. Campos-Hernández D. Arocha-Oriol C. Díaz-Fuentes Y. Puentes-Márquez I. Herrera-Javier D. Llera-Abreu E.MEDICC Review (2017) 19:2-3 (10-17). Date of Publication: 1 Apr 2017INTRODUCTION: Iron deficiency is the main cause of anemia, but infections, inflammation and other factors also play a role. Anemia in women of childbearing age is a risk for pregnancy, childbirth and childhood development during the first two years of life. In Cuba, per WHO definition, anemia is a moderate public health problem in the third trimester of pregnancy and in preschoolers, with a prevalence of 21.6%, in both cases. OBJECTIVE: Estimate prevalence of anemia and iron deficiency in women of childbearing age and assess its relation to inflammation, overweight, central adiposity, H. pylori infection and ingestion of iron-rich foods and enhancers of iron absorption. METHODS: A cross-sectional, analytical study was performed in 391 women aged 18-40 years in four municipalities of Havana, Cuba, from February through June 2014. Variables (indicators in parentheses) were anemia (hemoglobin), iron deficiency (ferritin), nutritional status (body mass index and waist circumference), inflammation (C-reactive protein, acid alpha 1-glycoprotein and interleukin 6), H. pylori infection and ingestion of iron-rich foods. SPSS 20.0 and Epi Info 7.1.2.0 were used for statistical analysis. RESULTS: Anemia prevalence was 24.6% (96/391); iron deficiency, 68% (266/391); H. pylori infection, 47.1% (184/391); inflammation detected by C-reactive protein, 8.4 % (33/391) and by alpha-1-gly-coprotein, 19.9% (78/391). Limited results are included for interleukin 6, which was determined in fewer cases (96). Excess body weight was found in 38.7% (150/388) and increased central adiposity in 26.7% (101/378). Iron deficiency was the main cause of anemia (OR 2.68). Central adiposity, excess body weight, and iron deficiency were positively associated with inflammation (OR of 1.77, 1.23 and 1.72, respectively), whereas H. pylori infection was negatively associated with iron deficiency and anemia (OR 0.75 and 0.94, respectively). Low consumption of meat (OR 1.17) and vegetables (OR 1.36) showed discrete limited positive associations with iron deficiency, as well as low consumption of eggs (OR 1.69) and vegetables (OR 1.56) with anemia. CONCLUSIONS: Anemia is a moderate public health problem in the studied group, but with iron deficiency present in two thirds of the population and associated with anemia. Risk factors for anemia and iron deficiency, such as menorrhagia and bacterial or viral infections, should be assessed in women of childbearing age, to support interventions needed to reduce risks in pregnancy and childbirth.

 

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Epidemiologic characteristics of gastric malignancies among Jordan University hospital patientsAwad H.A. Hajeer M.H. Abulihya M.W. Al-Chalabi M.A. Al Khader A.A.Saudi Medical Journal (2017) 38:9 (965-967). Date of Publication: 2017Objectives: To discover the epidemiologic distribution of gastric malignancies among Jordan University Hospital patients and to compare this distribution with the neighboring Arab countries. Methods: Retrospective study covering the period between January 2006, and May 2016, in Jordan University Hospital, Amman, Jordan. All cases were retrieved from the computer system and analyzed using IBM SPSS version 23 software. Results: One hundred sixty-five cases were analyzed. Male-to-female ratio was 1.2:1. The mean age was 58.6 with 32.1% of patients aged 50 or younger. Primary adenocarcinoma was the most common tumor, half of which were diffuse type, followed by carcinoid tumors (15.2 %), lymphomas (10.3%), and gastrointestinal stromal tumors (8.5%). Proximally located tumors accounted for 15.4%. Helicobacter pylori were present in approximately half of the cases and 34.6% of cases contained intestinal metaplasia. Conclusion: Jordan is a low-risk area for gastric cancer, but carcinoma occurs at a young age and is associated with gastritis, Helicobacter pylori infection, and intestinal metaplasia in a large proportion of cases. Better strategic health planning and early detection is needed, especially in young patients suffering from gastritis.

 

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Research progress of microRNAs in gastric cancerShen B. Lu J.-W. Zhang Y. Wu Y. Yuan Y. Feng J.-F.Journal of International Translational Medicine (2017) 5:2 (71-79). Date of Publication: 21 Jun 2017MicroRNAs (miRNAs) are a class of short highly-conserved non-coding endogenous RNA molecules of 18-25 nucleotides in length. By incompletely or completely complementary to 3'-untranslated region (3'-UTR) of mRNAs, miRNAs can suppress the transcription of target genes, and degrade mRNA. This article mainly reviewed the relevant research progress of miRNAs in gastric cancer. Abnormal miRNAs regulated by epigenetics participate in the proliferation, apoptosis, metastases and invasion of gastric cancer cells by regulating different target genes. In the meantime, NF-kB and AKT signal pathways highly associated with gastric cancer progression might be activated or inhibited by miRNAs. miRNAs involving in change of drug resistance of tumor cells can provide new targets for the treatment of gastric cancer. Abnormal expression of miRNAs in the blood provides new biological markers for noninvasive diagnosis of gastric cancer. Moreover, miRNAs also participate in carcinogenic process of gastric cancer caused by helicobacter pylori (HP) infection. In conclusion, miRNAs play important roles in the occurrence, progression, diagnosis, treatment and prognosis of gastric cancer, which provides new insight into gene therapy for gastric cancer.

 

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Serum antibodies against Helicobacter pylori neutrophil activating protein in carriers of IL-4 C-590T genetic polymorphism amplify the risk of gastritis and gastric cancerTalebkhan Y. Doozbakhshan M. Saberi S. Esmaeili M. Karami N. Mohajerani N. Abdirad A. Hosseini M.E. Nahvijou A. Mohagheghi M.A. Mohammadi M.Iranian Biomedical Journal (2017) 21:5 (321-329). Date of Publication: 1 Sep 2017Background: 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.

 

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Synergistic effect of hyperglycemia and Helicobacter pylori infection status on colorectal adenoma riskHu K.-C. Wu M.-S. Chu C.-H. Wang H.-Y. Lin S.-C. Liu S.-C. Liu C.-C. Su T.-H. Chen C.-L. Liu C.-J. Shih S.-C.Journal of Clinical Endocrinology and Metabolism (2017) 102:8 (2744-2750). Date of Publication: 1 Aug 2017Context: Both Helicobacter pylori and type 2 diabetes mellitus are possible risk factors for colon adenoma. Objective: The purpose of this study was to assess the interaction between H. pylori and hyperglycemia status on the risk of colon adenoma. Design, Setting, and Participants: This was a cross-sectional, retrospective study conducted at the MacKay Memorial Hospital, Taiwan. The study included 3943 subjects aged >40 years undergoing bidirectional gastrointestinal endoscopy on the same day between July 2006 and June 2015. All subjects had a gastric biopsy specimen tested for H. pylori. Main Outcome Measure: Colon adenoma with and without H. pylori infection at different hemoglobin A1c (HbA1c) levels. Results: The prevalence of colorectal adenomas in patients who were H. pylori-positive and H. pylori-negative was 37.3% and 27.29%, respectively. Multivariate logistic regression analysis identified male sex, age, body mass index, H. pylori infection, and HbA1c≥6.5% as independent risk factors for adenoma; use of hypoglycemic agents decreased this risk. The prevalence of adenoma was increased with elevated HbA1c levels regardless of H. pylori status. The odds ratio (OR) for adenoma was 1.44 (95% confidence interval [CI], 1.20 to 1.73) if H. pylori was present or 1.68 (95% CI, 1.05 to 2.70) in patients who were H. pylori-negative but had HbA1c ≥7.0%. If both conditions were present, the OR was 4.79 (95% CI, 2.92 to 7.84). A 1%increase in HbA1c was associated with an increased prevalence of adenoma by 42.4% in H. pylori-positive subjects. Conclusions: The combination of H. pylori infection and elevated HbA1c is associated with an increased risk of colon adenoma.

 

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Global Prevalence of Helicobacter pylori Infection: Systematic Review and Meta-AnalysisHooi J.K.Y. Lai W.Y. Ng W.K. Suen M.M.Y. Underwood F.E. Tanyingoh D. Malfertheiner P. Graham D.Y. Wong V.W.S. Wu J.C.Y. Chan F.K.L. Sung J.J.Y. Kaplan G.G. Ng S.C.Gastroenterology (2017) 153:2 (420-429). Date of Publication: 1 Aug 2017Background & Aims The epidemiology of Helicobacter pylori infection has changed with improvements in sanitation and methods of eradication. We performed a systematic review and meta-analysis to evaluate changes in the global prevalence of H pylori infection. Methods We performed a systematic search of the MEDLINE and EMBASE databases for studies of the prevalence of H pylori infection published from January 1, 1970 through January 1, 2016. We analyzed data based on United Nations geoscheme regions and individual countries. We used a random effects model to calculate pooled prevalence estimates with 95% confidence intervals (CIs), weighted by study size. We extrapolated 2015 prevalence estimates to obtain the estimated number of individuals with H pylori infection. Results Among 14,006 reports screened, we identified 263 full-text articles on the prevalence of H pylori infection; 184 were included in the final analysis, comprising data from 62 countries. Africa had the highest pooled prevalence of H pylori infection (70.1%; 95% CI, 62.6−77.7), whereas Oceania had the lowest prevalence (24.4%; 95% CI, 18.5−30.4). Among individual countries, the prevalence of H pylori infection varied from as low as 18.9% in Switzerland (95% CI, 13.1−24.7) to 87.7% in Nigeria (95% CI, 83.1−92.2). Based on regional prevalence estimates, there were approximately 4.4 billion individuals with H pylori infection worldwide in 2015. Conclusions In a systematic review and meta-analysis to assess the prevalence of H pylori infection worldwide, we observed large amounts of variation among regions—more than half the world's population is infected. These data can be used in development of customized strategies for the global eradication.

 

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The potential value of serum pepsinogen for the diagnosis of atrophic gastritis among the health check-up populations in China: A diagnostic clinical researchTong Y. Wu Y. Song Z. Yu Y. Yu X.BMC Gastroenterology (2017) 17:1 Article Number: 88. Date of Publication: 20 Jul 2017Background: The aim of this study is to assess the validity of the measurement of pepsinogen as a screening test for chronic atrophic gastritis (AG) in health check-up populations in China. Methods: Patients from consecutive regular health check-up were enrolled from January 2014 to June 2015. Endoscopy, combined with monitoring the Helicobacter pylori (Hp) infections, and measuring the serum pepsinogen (PG) were used to determine the diagnostic accuracy of PG for the screening of atrophic gastritis. Histopathology was assessed by the Operative Link on Gastritis Assessment (OLGA) system. Statistical analysis was performed using SPSS statistical software. Results: The total Hp infection rate was 40%. Based on pathology, the 996 participants were divided into three groups: non-atrophic (NAG), mild-moderate atrophic (MAG): stage I and II of the OLGA classification, and severe atrophic (SAG): stage III and IV of the OLGA classification. Compared with NAG and MAG groups, PGR decreased significantly in SAG group (p < 0.05). PGI and PGII levels were significantly elevated in Hp-positive group, while the PGR was markedly decreased (p < 0.01). When MAG and SAG groups were combined and compared with NAG group, the best cutoff value for atrophy diagnosis was PGI ≤50.3 ng/ml; the cutoff value in Hp-negative group was absolutely higher than in Hp-positive group. When NAG and MAG groups were combined and compared with the SAG group, the best cutoff value for diagnosis of severe atrophy was at PGR ≤4.28. The cutoff values in Hp-negative and Hp-positive groups were calculated at PGR ≤6.28 and ≤4.28, respectively. Conclusions: Pepsinogens play an important role in the identification of patients with atrophic gastritis and severe AG. Use of different cutoff values of PG for Hp-negative and Hp-positive groups may offer greater efficacy in the diagnosis of AG.

 

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The impact of host's genetic susceptibility on Helicobacter pylori infection in childrenMǎrginean M.O. Mǎrginean C.O. Meliţ L.E. Voidǎzan S. Moldovan V. Bǎnescu C.Medicine (United States) (2017) 96:30 Article Number: e7612. Date of Publication: 2017The aim of our study was to investigate the impact of interleukin (IL)-6 190C/T, IL-6 174G/C, IL-6 572G/C, tumor necrosis factoralpha (TNF-α) 308G/A, and angiotensin-converting enzyme (ACE) I/D gene polymorphisms on Helicobacter pylori (H. pylori) infection in children. A cross-sectional study was performed on 126 children (57 children with H. pylori infection and 69 children without H. pylori infection) aged between 3 and 18 years presenting to a Pediatrics Tertiary Hospital from Romania. Children were assessed clinically, endoscopically, histopathologically, and genetically. In our study, we found that the presence of the CT and CT+TT genotypes of IL-6 190C/T (P<.002 and P=.04), allele G of IL-6 572 G/C polymorphism (P=.01), genotypes GA and AA of TNF-α 308G/A polymorphism (P=.04, P=.01), and genotype II of ACE I/D polymorphism (P=.02) were associated with H. pylori infection, while the CC genotype of IL-6 174G/C polymorphism was scarcely encountered in children with H. pylori infection [P=.02, odds ratio (OR)=0.06; 95% confidence interval (95% CI): 0.003-0.128]. Taking under consideration the 4 variant genotypes (IL-6 572G/C, IL-6 190C/T, TNF-α 308G/A, and ACE I/D), we noticed a 2 times higher incidence of H. pylori infection (OR=6.34; 95% CI: 2.15-25.8). We may consider that the IL-6 190C/T, IL-6 174G/C, IL-6 572G/C, TNF-α 308G/A, and ACE I/D gene polymorphisms may increase the children's susceptibility for acquiring H. pylori infection; therefore, they may contribute to the pathogenesis of H. pylori gastritis.

 

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Helicobacter pylori infection increases the risk of adult-onset asthma: a nationwide cohort studyWang Y.-C. Lin T.-Y. Shang S.-T. Chen H.-J. Kao C.-H. Wu C.-C. Yang T.-Y.European Journal of Clinical Microbiology and Infectious Diseases (2017) 36:9 (1587-1594). Date of Publication: 1 Sep 2017Helicobacter pylori infection (HPI) appears to reduce risk of childhood-onset asthma, but the relationship between HPI and adult-onset asthma is inconclusive. This study explored the potential association between HPI and risk of adult-onset asthma. We conducted a national insurance retrospective cohort study using the longitudinal health insurance database (LHID 2000) in Taiwan. We enrolled the HPI group consisting of 1664 patients with HPI diagnosis between 2000 and 2007, and the non-HPI group consisting of 6,656 age- and sex-matched subjects without HPI. All study participants had been followed up from index date to the diagnostic date of asthma, withdrawal from the National Health Insurance program, or the end of 2011, which came first. We analyzed risk of adult-onset asthma with respect to sex, age, and comorbidities by using Cox models. Cigarette smoking status, which could not be obtained from the program, was adjusted indirectly by considering chronic obstructive pulmonary diseases in our statistical models because the disease is related to heavy smoking. After adjustment for sex, age, and comorbidities, HPI was significantly associated with an increased 1.38-fold risk of adult-onset asthma. Moreover, among people without comorbidities, the 1.85-fold risk of adult-onset asthma remained higher for the HPI population compared with the non-HPI population. In this study, patients with HPI exhibited a significantly higher risk of adult-onset asthma than did the subjects without HPI.

 

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Anoectochilus roxburghii: A review of its phytochemistry, pharmacology, and clinical applicationsYe S. Shao Q. Zhang A.Journal of Ethnopharmacology (2017) 209 (184-202). Date of Publication: 14 Sep 2017Ethnopharmacological relevance Anoectochilus roxburghii (Orchidaceae), also known as Jinxianlian (Simplified Chinese: ) and Jinxianlan (Simplified Chinese: ), is valued in many Asian countries, where this plant species is used for medicinal, culinary, and ornamental purposes. As a food, A. roxburghii is widely used as a treatment booster and medicine because of its various beneficial properties; these include, most notably, the curative effects of heat dissipation and cooling of blood, elimination of dampness, detoxification, and immunity enhancement. Aim of this review This review aims to provide up-to-date information on the phytochemistry, pharmacology, and clinical applications of A. roxburghii. Materials and methods Relevant information on A. roxburghii was obtained by an online search of worldwide-accepted scientific databases (Web of Science, ScienceDirect, Elsevier, Springer, NCBI, ACS Publications, CNKI, and Wanfang data). Results Phytochemical investigations have revealed that the major chemical constituents of A. roxburghii are polysaccharides, flavonoids, glycosides, organic acids, volatile compounds, steroids, triterpenes, alkaloids, and nucleosides. These compounds have been proven to be the main bioactive substances responsible for pharmacological activities such as antidiabetic, antilipemic, anti-inflammatory, antiviral, liver protective, renal protective, immunomodulatory, abirritant, sedative, and antineoplastic effects. Conclusions A variety of dosage forms of A. roxburghii are currently being applied to patients suffering from hyperuricemia, type 2 diabetes mellitus, chronic hepatitis B, Helicobacter pylori infection, cough-variant asthma, and other conditions. Nevertheless, further research is needed to clarify A. roxburghii absorption, distribution, metabolic, and excretion pathways. Moreover, the toxicology in A. roxburghii and A. formosanus are also in urgent need of research, especially long-term in vivo chronic toxicity tests need to be carried out.

 

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Organoid culture systems to study host–pathogen interactionsDutta D. Clevers H.Current Opinion in Immunology (2017) 48 (15-22). Date of Publication: 1 Oct 2017Recent advances in host–microbe interaction studies in organoid cultures have shown great promise and have laid the foundation for much more refined future studies using these systems. Modeling of Zika virus (ZIKV) infection in cerebral organoids have helped us understand its association with microcephaly. Similarly, the pathogenesis of bacterial (Helicobacter pylori, Clostridium difficile) and viral (Norovirus, Rotaviruses) infections have been precisely dissected in organoid cultures. Additionally, direct associations between microbial colonization of tissues and diseases like cancer have also been deciphered. Here we discuss the most recent and striking studies on host–microbe interactions in organoid cultures, highlighting various methods which can be used for developing microbe-organoid co-culture systems.

 

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Upper gastrointestinal complications and cardiovascular/ gastrointestinal risk calculator in patients with myocardial infarction treated with aspirinWen L.Chinese Medical Journal (2017) 130:16 (1909-1913). Date of Publication: 20 Aug 2017Background: Aspirin is widely used for the prevention of cardiovascular and cerebrovascular diseases for the past few years. However, much attention has been paid to the adverse effects associated with aspirin such as gastrointestinal bleeding. How to weigh the benefits and hazards? The current study aimed to assess the feasibility of a cardiovascular/gastrointestinal risk calculator, AsaRiskCalculator, in predicting gastrointestinal events in Chinese patients with myocardial infarction (MI), determining unique risk factor(s) for gastrointestinal events to be considered in the calculator. Methods: The MI patients who visited Shapingba District People’s Hospital between January 2012 and January 2016 were retrospectively reviewed. Based on gastroscopic data, the patients were divided into two groups: gastrointestinal and nongastrointestinal groups. Demographic and clinical data of the patients were then retrieved for statistical analysis. Univariate and multiple logistic regression analyses were used to identify independent risk factors for gastrointestinal events. The receiver operating characteristic (ROC) curves were used to assess the predictive value of AsaRiskCalculator for gastrointestinal events. Results: A total of 400 MI patients meeting the eligibility criteria were analyzed, including 94 and 306 in the gastrointestinal and nongastrointestinal groups, respectively. The data showed that age, male gender, predicted gastrointestinal events, and Helicobacter pylori (HP) infection were positively correlated with gastrointestinal events. In multiple logistic regression analysis, predicted gastrointestinal events and HP infection were identified as risk factors for actual gastrointestinal events. HP infection was highly predictive in Chinese patients; the ROC curve indicated an area under the curve of 0.822 (95% confidence interval: 0.774–0.870). The best diagnostic cutoff point of predicted gastrointestinal events was 68.0‰, yielding sensitivity and specificity of 60.6% and 93.1%, respectively, for predicting gastrointestinal events in Chinese patients with MI. Conclusions: AsaRiskCalculator had a predictive value for gastrointestinal events in Chinese patients with MI. HP infection seemed to be an independent risk factor for gastrointestinal events caused by long-term aspirin treatment in Chinese patients with MI, and it should be included in the risk calculator adapted for Chinese patients.

 

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G. lamblia and H. pylori infections among mentally challenged individuals in rehabilitation centers in Alexandria, EgyptHassanein F.I. Shehata A.I. Abdul-Ghani R.Journal of Infection in Developing Countries (2017) 11:7 (577-582). Date of Publication: 2 Aug 2017Introduction: Concomitant infections with pathogens are common, particularly when there are shared modes of infection or when one pathogen promotes the other. Residence among closed-type care institutions may pose an additional risk of such infections. Mentally challenged patients in rehabilitation centers constitute one of the special needs groups exposed to parasitic infections, including giardiasis. Several studies reported concomitant infection with G. lamblia and H. pylori worldwide and in Egypt; however, the co-existence of these two pathogens among mentally challenged individuals remains unexplored. The present study aimed to study the prevalence and association between G. lamblia and H. pylori among mentally challenged patients in rehabilitation centers in Alexandria, Egypt. Methodology: 200 individuals admitted to four mental rehabilitation centers in the period from June 2013 to January 2014, who guardians gave informed consent, were recruited. Stool samples were collected and subjected to trichrome stain for G. lamblia and to antigen detection for H. pylori. Results: The overall prevalence rates of G. lamblia and H. pylori were 8.5% and 24.0%, respectively. Monoinfection rates were 5.5% for G. lamblia and 21.0% for H. pylori, while concomitant infection with both species was detected in only 3.0% of cases. However, individuals who were H. pylori-positive were about two times more likely to be infected with G. lamblia than those who were H. pylori-negative (12.5% vs. 7.2%). Conclusions: Mentally challenged individuals in Alexandria harbouring H. pylori are about two times more likely to be exposed to G. lamblia. Large-scale studies are recommended to confirm this association.

 

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Gastric lanthanosis (lanthanum deposition) in dialysis patients treated with lanthanum carbonateShitomi Y. Nishida H. Kusaba T. Daa T. Yano S. Arakane M. Kondo Y. Nagai T. Abe T. Gamachi A. Murakami K. Etoh T. Shiraishi N. Inomata M. Yokoyama S.Pathology International (2017) 67:8 (389-397). Date of Publication: 1 Aug 2017Lanthanum carbonate (LaC) is used to prevent hyperphosphatemia in dialysis patients. It is commonly believed that there is little LaC absorption from the intestines. However, La deposition in the gastric mucosa, which we coined “gastric lanthanosis”, was recently reported. We describe here the clinicopathological features of and a possible mechanism for gastric lanthanosis. This study included 23 patients with definite gastric lanthanosis. We extracted characteristic clinicopathological features of gastric lanthanosis by computed tomography (CT) imaging and endoscopic, histologic, electron-microscopic, and element analysis examinations. The Helicobacter pylori infection rate in the lanthanosis group was much lower than that among the general population. The clinicopathological features characteristic of gastric lanthanosis were mucosal high-density linear appearance by CT, reflective bright-white spots (BWS) by gastroscopy, eosinophilic histiocytes occasionally phagocytizing foreign materials by histology, and numerous electron-dense particles in the histiocytes. The particles had burr-like skeletons resembling La crystals. Gastric lanthanosis is an under-reported, but not a rare lesion. It is characterized by endoscopic BWS and histologic eosinophilic histiocytes in dialysis patients treated with LaC. The proposed mechanism for gastric lanthanosis is that LaC is dissolved by gastric juice, crystallized within the mucosa and is phagocytized by histiocytes.

 

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Magnifying NBI Patterns of Gastric Mucosa After Helicobacter pylori Eradication and Its Potential Link to the Gastric Cancer RiskTahara T. Tahara S. Tuskamoto T. Horiguchi N. Yoshida D. Kawamura T. Okubo M. Nagasaka M. Nakagawa Y. Urano M. Kuroda M. Shibata T. Ohmiya N.Digestive Diseases and Sciences (2017) 62:9 (2421-2427). Date of Publication: 1 Sep 2017Background: Gastric cancer develops after successful H. pylori eradication in patients with severe atrophic gastritis. We classified atrophic and non-atrophic mucosa of gastric body using magnifying NBI endoscopy in patients after successful H. pylori eradication. Materials and Methods: One hundred and twenty-five patients after successful H. pylori eradication (median period after eradication: 36 months) were enrolled. Magnifying NBI patterns in the uninvolved gastric body were divided into the following: restored-small, round pits, accompanied with honeycomb-like subepithelial capillary networks; atrophic-well-demarcated oval or tubulovillous pits with clearly visible coiled or wavy vessels. The subjects were also classified into the three types: Grade 0—restored pattern is shown in all or almost the entire area of gastric body; Grade 1—mixture of restored and atrophic pattern, there is a considerable portion of the atrophic area in the lesser curvature; Grade 2—atrophic pattern is shown in all or almost the entire area of the gastric body. Results: Sensitivity and specificity for atrophic type for detection of histological intestinal metaplasia were 95.9 and 98.3%, respectively. No association was observed between the prevalence of Grades 0, 1 and 2 and duration after eradication, while grades 1 and 2 were significantly frequent in gastric cancer patients diagnosed both before (27/35: 77%) and after (23/31: 74%) eradication, compared to the cancer-free subjects (15/59: 25%) (P < 0.001). The grades 1 and 2 were also common in patients who underwent H. pylori eradication for gastric ulcer. Conclusions: Magnifying the NBI pattern well correlates with pathological status of gastric mucosa after H. pylori eradication and may predict gastric cancer occurrence.

 

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H. pylori infection increases gastric mucosal COX2 and mTOR expression in chronic gastritis: Implications for cancer progression?Badary D.M. Rahma M.Z.A.A. Ashmawy A.M. Hafez M.Z.Pathophysiology (2017) 24:3 (205-211). Date of Publication: 1 Sep 2017Background Helicobacter Pylori is a Gram-negative bacterium that infects the human stomach and plays an important role in the pathogenesis of chronic gastritis. H. pylori associated chronic gastritis affects various molecular markers related to gastric cancer development. The aim of this study to assess the effect of H. pylori infection on gastric mucosa and to explore its role in gastric carcinogenesis via COX2 and mTOR mucosal expression. Materials and methods This study comprised archival blocks from 60 dyspeptic patients who underwent gastric endoscopic biopsies for histopathological examination. The blocks were cut at 4 μm thicknesses, stained with hematoxylin and eosin to score, using updated Sydney system, and subjected to Giemsa stain to assess H. pylori infection. Then, immunohistochemical method was carried out to determine the expression of COX2 and mTOR. Results Increased H. pylori colonization was significantly correlated with increased severity of inflammation, activity, atrophy, intestinal metaplasia, and the presence of high-grade dysplasia. Also, studied molecular markers were significantly associated with increased H. pylori colonization and presence of severe metaplasia, atrophy, and dysplasia. Conclusion These findings suggest that there is a positive feedback loop between H. pylori infection and the pathogenesis of gastric mucosal changes. Also, mTOR and COX2 over expression cause premalignant changes and subsequent tumor occurrence. This may help in providing innovative approaches for the detection of patients-with a higher chance of cancer development, and in trying to introduce effective therapy preventing tumor occurrence, or even using these molecular markers as potential targets for tumors treatment strategies.

 

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Prevalence and characteristics of Epstein-Barr virus-associated gastric carcinomas in PortugalNogueira C. Mota M. Gradiz R. Cipriano M.A. Caramelo F. Cruz H. Alarcão A. E Sousa F.C. Oliveira F. Martinho F. Pereira J.M. Figueiredo P. Leitão M.Infectious Agents and Cancer (2017) 12:1 Article Number: 41. Date of Publication: 19 Jul 2017Background: Gastric cancer (GC) is one of the most common malignant tumors of the digestive tract and is the third leading cause of cancer death worldwide. Epstein-Barr virus (EBV) has been associated with approximately 10% of the total cases of gastric carcinomas. No previous study has analyzed the prevalence of EBV infection in gastric cancer of the Portuguese population. Methods: In the present study, we have analyzed 82 gastric carcinoma cases and 33 healthy individuals (control group) from Coimbra region for the presence of EBV by polymerase chain reaction (PCR) and by in situ hybridization (ISH) for EBV-encoded small RNAs (EBERs). The status of H. pylori infection was assessed by serology and by PCR. Results: EBV was detected by PCR in 90.2% of stomach cancer cases, whereas EBERs were detected in 11%. In our series, EBV-associated gastric carcinoma (EBVaGC) were significantly associated with gender and the majority of them presented lymph node metastasis. These cases were generally graded in more advanced pTNM stages and, non-surprisingly, showed worse survival. H. pylori infection was detected in 62.2% of the gastric cancers and 64.7% of these patients were CagA+. On the other hand, the H. pylori prevalence was higher in the EBV-negative gastric carcinomas (64.4%) than in those carcinoma cases with EBV+ (44.4%). Conclusions: The present study shows that prevalence of EBVaGC among Portuguese population is in accordance with the worldwide prevalence. EBV infection seems to be associated to poorer prognostic and no relation to H. pylori infection has been found. Conversely, the presence of H. pylori seems to have a favourable impact on patient's survival. Our results emphasize that geographic variation can contribute with new epidemiological data on the association of EBV with gastric cancer.

 

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Global patterns and trends in stomach cancer incidence: Age, period and birth cohort analysisLuo G. Zhang Y. Guo P. Wang L. Huang Y. Li K.International Journal of Cancer (2017) 141:7 (1333-1344). Date of Publication: 1 Oct 2017The cases of stomach cancer (SC) incidence are increasing per year and the SC burden has remained very high in some countries. We aimed to evaluate the global geographical variation in SC incidence and temporal trends from 1978 to 2007, with an emphasis on the effect of birth cohort. Joinpoint regression and age–period–cohort model were applied. From 2003 to 2007, male rate were 1.5- to 3-fold higher than female in all countries. Rates were highest in Eastern Asian and South American countries. Except for Uganda, all countries showed favorable trends. Pronounced cohort-specific increases in risk for recent birth cohorts were seen in Brazil, Colombia, Iceland, New Zealand, Norway, Uganda and US white people for males and in Australia, Brazil, Colombia, Costa Rica, Czech Republic, Ecuador, Iceland, India, Malta, New Zealand, Norway, Switzerland, United Kingdom, Uganda, US black and white people for females. The cohort-specific ratio for male significantly decreased in Japan, Malta and Spain for cohorts born since 1950 and in Austria, China, Croatia, Ecuador, Russia, Switzerland and Thailand for cohorts born since 1960 and for female in Japan for cohorts born since 1950 and in Canada, China, Croatia, Latvia, Russia and Thailand for cohorts born since 1960. Disparities in incidence and carcinogenic risk persist worldwide. The favorable trends may be due to changes in environmental exposure and lifestyle, including decreased Helicobacter pylori prevalence, increased intake of fresh fruits and vegetables, the availability of refrigeration and decreased intake of salted and preserved food and smoking prevalence.

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