Núcleo Hpylori
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Trabalhos Publicados em Setembro / 2017

RECORD 1

Effectiveness of Helicobacter pylori eradication in the prevention of primary gastric cancer in healthy asymptomatic people: A systematic review and meta-analysis comparing risk ratio with risk differenceSeta T. Takahashi Y. Noguchi Y. Shikata S. Sakai T. Sakai K. Yamashita Y. Nakayama T.PLoS ONE (2017) 12:8 Article Number: e0183321. Date of Publication: 1 Aug 2017Background: Helicobacter pylori infection is strongly associated with gastric cancer occurrence. However, it is unclear whether eradication therapy reduces the risk of gastric cancer occurrence. We evaluated whether H. pylori eradication reduces the risk of primary gastric cancer by using both risk ratio (RR) and risk difference (RD). Methods: Searches of PubMed, EMBASE, Google scholar, the Cochrane Library, and the Japan Medical Abstracts Society as well as those registered in databases of the Cochrane Central Register of Controlled Trials, metaRegister of Controlled Trials, ClinicalTrials.gov, controlled-trials.com, UMIN-CTR, JMACCT-CTR, and JAPIC-CTI between January 1965 and March 2017, supplemented with manual screening. Randomized controlled trials (RCTs) in which eradication therapy were implemented for the interventional group but not for the control group, and assessed the subsequent occurrence of primary gastric cancer as the main outcome. Two authors independently reviewed articles and extracted data. Integrated results for all data were presented as RR and RD. Results: Seven studies met inclusion criteria. The reductions in risk of primary gastric cancer occurrence in terms of overall RR and RD were 0.67 (95% CI: 0.48 to 0.95) and -0.00 ([95% CI: -0.01 to 0.00]; number needed to treat: 125.5 [95% CI: 70.0 to 800.9]), respectively. Conclusions: The effectiveness of H. pylori eradication therapy in suppressing the occurrence of primary gastric cancer was significant and comparable to that of previous studies in terms of the estimated RR. However, the estimated RD was slight and not statistically significant.

 

RECORD 2

Helicobacter pylori infection in childrenKalach N. Bontems P. Raymond J.Helicobacter (2017) 22 Supplement 1 Article Number: e12414. Date of Publication: 1 Sep 2017Helicobacter pylori infection in children differs from that in adults, from the point of view of epidemiology, host response, clinical features, related diseases, and diagnosis, as well as treatment strategies. The prevalence of H. pylori infection, in both children and adults, is decreasing in the Western World as well as in some developing countries, which contrasts with the increase in childhood asthma and allergic diseases. Recurrent abdominal pain is not specific during H. pylori infection in children. The role of H. pylori infection and failure to thrive, children's growth, type I diabetes mellitus (T1DM) and celiac disease remains controversial. The main initial diagnosis is based on upper digestive endoscopy with biopsy-based methods. Nodular gastritis may be a pathognomonic endoscopic finding of childhood H. pylori infection. The infection eradication control is based on validated noninvasive tests. The main cause of treatment failure of H. pylori infection is its clarithromycin resistance. We recommend standard antibiotic susceptibility testing of H. pylori in pediatric patients prior to the initiation of eradication therapy. H. pylori treatment in children should be based on an evaluation of the rate of eradication in the local population, a systematic use of a treatment adapted to the susceptibility profile and a treatment compliance greater than 90%. The last meta-analysis in children did not show an advantage for sequential therapy when compared to a 14-day triple therapy. Finally, the high rate of antibiotic resistance responsible for therapy failure in recent years justifies the necessity of a novel vaccine to prevent H. pylori infection in children.

 

ECORD 3

Treatment of Helicobacter pylori infection 2017O'Connor A. Lamarque D. Gisbert J.P. O'Morain C.Helicobacter (2017) 22 Supplement 1 Article Number: e12410. Date of Publication: 1 Sep 2017This review summarizes important studies regarding Helicobacter pylori therapy published from April 2016 to April 2017. The main themes that emerge involve studies assessing the efficacy of bismuth and nonbismuth quadruple regimens. While in recent years, much of the emphasis on the use of bismuth has focussed on its utility in a second-line setting, an increasing number of studies this year have shown excellent efficacy in first-line therapy. The efficacy of bismuth as a second-line after sequential and concomitant therapy was particularly noteworthy. Antibiotic resistance was more intensely studied this year than for a long time, and definite trends are presented regarding an increase in resistance, including the fact that clarithromycin resistance in particular is now at a level where the continued use of clarithromycin triple therapy first-line as a mainstream treatment is not recommended. Another exciting trend to emerge this year is the utility of vonoprazan as an alternative to PPI therapy, especially in resistant and difficult-to-treat groups.

 

RECORD 4

Other Helicobacters, gastric and gut microbiotaPéré-Védrenne C. Flahou B. Loke M.F. Ménard A. Vadivelu J.Helicobacter (2017) 22 Supplement 1 Article Number: e12407. Date of Publication: 1 Sep 2017The current article is a review of the most important and relevant literature published in 2016 and early 2017 on non-Helicobacter pylori Helicobacter infections in humans and animals, as well as interactions between H. pylori and the microbiota of the stomach and other organs. Some putative new Helicobacter species were identified in sea otters, wild boars, dogs, and mice. Many cases of Helicobacter fennelliae and Helicobacter cinaedi infection have been reported in humans, mostly in immunocompromised patients. Mouse models have been used frequently as a model to investigate human Helicobacter infection, although some studies have investigated the pathogenesis of Helicobacters in their natural host, as was the case for Helicobacter suis infection in pigs. Our understanding of both the gastric and gut microbiome has made progress and, in addition, interactions between H. pylori and the microbiome were demonstrated to go beyond the stomach. Some new approaches of preventing Helicobacter infection or its related pathologies were investigated and, in this respect, the probiotic properties of Saccharomyces, Lactobacillus and Bifidobacterium spp. were confirmed.

 

RECORD 5

Role of caspase-3/E-cadherin in helicobacter pylori-induced apoptosis of gastric epithelial cellsYang Y. Du J. Liu F. Wang X. Li X. Li Y.Oncotarget (2017) 8:35 (59204-59216). Date of Publication: 2017This study was designed to investigate the role of caspase-3/E-cadherin in Helicobacter pylori (H. pylori) -induced gastric epithelial apoptosis in cells, animal models and clinical gastritis patients. In cultured gastric mucosal epithelial cells, gastric glandular epithelial cells and C57BL/6 mice, H. pylori infection significantly induced apoptosis of gastric epithelial cells, down-regulated full-length E-cadherin and Bcl-2 expression, and up-regulated cleaved-caspase-3, E-cadherin/carboxyterminal fragment 3 and Bax expression. Z-DEVD-FMK, an inhibitor of caspase-3, attenuated the effect of H. pylori. E-cadherin overexpression significantly inhibited the apoptosis of GES-1 and SGC-7901 cells induced by the H. pylori. The results from clinical studies also showed down-regulation of E-cadherin, up-regulation of cleavedcaspase- 3 expression and increased apoptosis in gastric tissues from gastritis patients with H. pylori infection. These results suggest that the caspase-3/E-cadherin pathway is involved in the apoptosis of gastric epithelial cells induced by H. pylori.

 

RECORD 6

Correlation between virulence markers of helicobacter pylori in the oral cavity and gastric biopsiesMedina M.L. Medina M.G. Merino L.A.Arquivos de Gastroenterologia (2017) 54:3 (217-221). Date of Publication: 1 Jul 2017Background – The clinical outcome of Helicobacter pylori infection has been associated with virulence factors. The presence of these factors is useful as molecular markers in the identification of the high risk for developing severe gastric pathologies. Objective – To correlate the presence of virulence markers cagA and bab2A of H. pylori in oral and gastric biopsy samples. Methods – An observational, prospective, descriptive, and cross-sectional study was carried out between September 2011 and September 2012. Patients suffering dyspepsia with indication for upper gastrointestinal video endoscopy who attended the Gastroenterology Service of the Hospital Dr. Julio C. Perrando were included. Epidemiological investigation was completed. To detect the bacteria and their virulence genes, samples of saliva, dental plaque and gastric biopsy were taken and processed by PCR. Results – Sixty-one patients were selected for this study (30 women and 31 men). H. pylori was detected in 31 gastric biopsies and 31 oral samples. Significant difference between oral and gastric samples was found in cagA genotype. Agreement between oral and gastric genotypes was found in 38.7% of samples from the same patient. Conclusion – This study is the first in provide information about the genotypes of the Argentinean Northeast H. pylori strains. Despite the high prevalence of H. pylori infection, the most of patients had less virulent genotypes in oral cavity and gastric tissue. The cagA/babA2 combination was not frequent in the samples studied. There was not a statistical correlation between the virulence genes and gastroduodenal or oral diseases. Although in some patients the same genotype was found both in oral and gastric samples, it cannot be ensure that they corresponding to the same strain because a DNA sequencing was not performed.

 

RECORD 7

Efficacy and safety of probiotic-supplemented triple therapy for eradication of Helicobacter pylori in children: a systematic review and network meta-analysisFeng J.-R. Wang F. Qiu X. McFarland L.V. Chen P.-F. Zhou R. Liu J. Zhao Q. Li J.European Journal of Clinical Pharmacology (2017) 73:10 (1199-1208). Date of Publication: 1 Oct 2017Aim: The aim of this study was to identify the best probiotic supplementation in triple therapy for pediatric population with Helicobacter pylori infection. Methods: Eligible trials were identified by comprehensive searches. Relative risks with 95% confidence intervals and relative ranks with P scores were assessed. Results: Twenty-nine trials (3122 participants) involving 17 probiotic regimens were identified. Compared with placebo, probiotic-supplemented triple therapy significantly increased H. pylori eradication rates (relative ratio (RR) 1.19, 95% CI 1.13–1.25) and reduced the incidence of total side effects (RR 0.49, 95% CI 0.38–0.65). Furthermore, to supplemented triple therapy, Lactobacillus casei was identified the best for H. pylori eradication rates (P score = 0.84), and multi-strain of Lactobacillus acidophilus and Lactobacillus rhamnosus for total side effects (P score = 0.93). As for the subtypes of side effects, multi-strain of Bifidobacterium infantis, Bifidobacterium longum, L. acidophilus, L. casei, Lactobacillus plantarum, Lactobacillus reuteri, L. rhamnosus, Lactobacillus salivarius, Lactobacillus sporogenes, and Streptococcus thermophilus was the best to reduce the incidence of diarrhea; multi-strain of Bacillus mesentericus, Clostridium butyricum, and Streptococcus faecalis for loss of appetite; multi-strain of B. longum, Lactobacillus bulgaricus, and S. thermophilus for constipation; multi-strain of Bifidobacterium bifidum, B. infantis, L. acidophilus, L. bulgaricus, L. casei, L. reuteri, and Streptococcus for taste disturbance; Saccharomyces boulardii for bloating; and multi-strain of Bifidobacterium breve, B. infantis, L. acidophilus, L. bulgaricus, L. casei, L. rhamnosus, and S. thermophilus for nausea/vomiting. Conclusions: Probiotics are recommended to supplement triple therapy in pediatrics, and the effectiveness of triple therapy is associated with specific probiotic supplementation.

 

RECORD 8

Helicobacter pylori serological biomarkers of gastric cancer risk in the MCC-Spain case-control StudyFernández de Larrea-Baz N. Pérez-Gómez B. Michel A. Romero B. Lope V. Pawlita M. Fernández-Villa T. Moreno V. Martín V. Willhauck-Fleckenstein M. López-Abente G. Castilla J. Fernández-Tardón G. Dierssen-Sotos T. Santibáñez M. Peiró R. Jiménez-Moleón J.J. Navarro C. Castaño-Vinyals G. Kogevinas M. Pollán M. de Sanjosé S. del Campo R. Waterboer T. Aragonés N.Cancer Epidemiology (2017) 50 (76-84). Date of Publication: 1 Oct 2017Background Helicobacter pylori infection is one of the main risk factors for non-cardia gastric cancer. However, only a minority of infected persons develop the disease. This study aims at identifying H. pylori related serological biomarkers of risk for gastric cancer. Methods Incident gastric cancer cases and population controls (age, sex and region frequency-matched) from the MCC-Spain multicase-control Study were included. Seroreactivities against 16 H. pylori proteins were determined using multiplex serology. Infection was defined as seropositivity against ≥ 4 proteins. Relation of serological results to non-cardia and cardia gastric cancer was assessed using multivariable mixed logistic regression and principal components analysis. Results Seroprevalence was 88% among 2071 controls, 95% among 202 non-cardia gastric cancer cases (OR = 1.9 (95% CI: 1.0–3.6)) and 85% among 62 cardia cancer cases (OR = 0.5 (95% CI: 0.3–1.1)). In infected subjects, seropositivity for UreA, HP231, NapA and Cagδ was associated with lower non-cardia gastric cancer risk, while seropositivity for CagA and VacA was associated with higher risk. Seropositivity for CagA and seronegativity for Cagδ maintained the association after additional adjustment by serostatus of significant proteins. We identified two antibody reactivity patterns: the “virulent-pattern”, related to a threefold higher risk of non-cardia gastric cancer and the “non-virulent pattern”, related to a 60% decreased risk (4th vs. first quartile). Conclusions In our population, people seropositive for H. pylori were characterized by two patterns of antibody reactivity against H. pylori proteins: 1) Combined high seroreactivity against several proteins, associated with a lower non-cardia gastric cancer risk, and 2) High seroreactivity against CagA and VacA, associated with an increased risk.

 

RECORD 9

Effect on Helicobacter pylori eradication therapy against gastric cancer in JapanTsuda M. Asaka M. Kato M. Matsushima R. Fujimori K. Akino K. Kikuchi S. Lin Y. Sakamoto N.Helicobacter (2017) 22:5 Article Number: e12415. Date of Publication: 1 Oct 2017Background: In Japan, there have been approximately 50 000 deaths from gastric cancer annually for over 40 years with little variation. It has been reported that most gastric cancers in Japan are caused by Helicobacter pylori infection. H. pylori eradication therapy was approved for patients with chronic gastritis by the Japanese national health insurance scheme in February 2013 for patients with an endoscopic diagnosis of chronic gastritis is positive for H. pylori. We examined the effect on gastric cancer death rate 4 years after expansion of health insurance coverage. Aim: We conducted an epidemiological study and analyzed trends in prescription for H. pylori eradication therapy. We used the electronic medical claims database from Hokkaido, Japan to evaluate the impact of expansion of national health insurance coverage for H. pylori eradication therapy on deaths from gastric cancer. Methods: Data on deaths from gastric cancer were obtained from the Japanese Ministry of Health, Labour and Welfare and the Cancer Statistics in Japan (2015). Analysis of electronic claims records was performed using the National Database, mainly focusing on Hokkaido. Prescriptions for H. pylori eradication therapy and the number of patients treated for gastric cancer were also extracted from the Hokkaido database. Results: Approximately 1.5 million prescriptions for H. pylori eradication therapy were written annually. Gastric cancer deaths fell each year: 48 427 in 2013, 47 903 in 2014, 46 659 in 2015, and 45 509 in 2016, showing a significant decrease after expansion of insurance coverage for H. pylori eradication therapy (P<.0001). Conclusions: Prescriptions for H. pylori eradication therapy increased markedly after approval of the gastritis indication by the national health insurance scheme and was associated with a significant decrease in gastric cancer deaths.

 

RECORD 10

Helicobacter: Inflammation, immunology and vaccinesRobinson K. Kaneko K. Andersen L.P.Helicobacter (2017) 22 Supplement 1 Article Number: e12406. Date of Publication: 1 Sep 2017Helicobacter pylori is usually acquired in early childhood and the infection persists lifelong without causing symptoms. In a small of cases, the infection leads to gastric or duodenal ulcer disease, or gastric cancer. Why disease occurs in these individuals remains unclear, however the host response is known to play a very important part. Understanding the mechanisms involved in maintaining control over the immune and inflammatory response is therefore extremely important. Vaccines against H. pylori have remained elusive but are desperately needed for the prevention of gastric carcinogenesis. This review focuses on research findings which may prove useful in the development of prognostic tests for gastric cancer development, therapeutic agents to control immunopathology, and effective vaccines.

 

RECORD 11

Helicobacter pylori, gastric cancer and other gastrointestinal malignanciesVenerito M. Vasapolli R. Rokkas T. Delchier J.-C. Malfertheiner P.Helicobacter (2017) 22 Supplement 1 Article Number: e12413. Date of Publication: 1 Sep 2017In a retrospective study performed in California, U.S.A., ca. 3% of patients with gastric intestinal metaplasia (GIM) developed gastric cancer (GC) within a median time period of 4.6 years after diagnosis of GIM. This observation stresses the importance of targeted surveillance even in regions with a low GC prevalence. Patients with alcoholic liver disease as well as survivors of colorectal and lobular breast cancer were found to be at increased risk of secondary GC. A population-based Chinese study confirmed “serologic biopsy” as a useful screening tool for stratifying the individual risk of developing GC. Concerning GC therapy, a post hoc analysis of the MAGIC trial reported that regression of lymph node metastases, but not the tumor regression itself, predicts overall survival. Furthermore, in patients with high microsatellite instable tumors, perioperative chemotherapy leads to an increased risk of mortality. Two studies confirmed that eradication therapy is worthwhile as an initial treatment for gastric mucosa-associated lymphoid tissue (MALT) lymphoma irrespective of the H. pylori infection status and stage. An increased risk of a second primary malignancy including GC was observed in these patients treated with immuno/chemotherapy but not in patients treated solely with an H. pylori eradication treatment. With respect to gastrointestinal malignancies other than GC, discrepant data have been published regarding the association of H. pylori with pancreatic cancer whereas no association has been reported with esophageal squamous cell carcinoma. The majority of published studies still support an association of H. pylori with colon neoplasms.

 

RECORD 12

Is There a Link Between H. Pylori and the Epidemiology of Crohn’s Disease?Shah A. Talley N.J. Walker M. Koloski N. Morrison M. Burger D. Andrews J.M. McGuckin M. Jones M. Holtmann G.Digestive Diseases and Sciences (2017) 62:9 (2472-2480). Date of Publication: 1 Sep 2017Introduction: Case control studies suggest an inverse association between Helicobacter pylori (H. pylori) and Crohn’s disease (CD). It is possible this could be accounted for by confounders such as antibiotic therapy. Analyzing the geographic distribution of H. pylori and the links with the incidence and prevalence of CD would be an alternative approach to circumvent these confounders. Methods: The literature was searched for studies published between 1990 and 2016 that reported incidence or prevalence data for CD in random population samples in developed countries (GDP per capita >20,000 USD/year). Corresponding prevalence studies for H. pylori in these same regions were then sought matched to the same time period (±6 years). The association between the incidence and prevalence of CD and H. pylori prevalence rates were assessed before and after adjusting for GDP and life expectancy. Results: A total of 19 CD prevalence and 22 CD incidence studies from 10 European countries, Japan, USA, and Australia with date-matched H. pylori prevalence data were identified. The mean H. pylori prevalence rate was 43.4% (range 15.5–85%), and the mean rates for incidence and prevalence for CD were 6.9 and 91.0/100,000 respectively. The incidence (r = −0.469, p < 0.03) and prevalence (r = −0.527, p = 0.02) of CD was inversely and significantly associated with prevalence of H. pylori infection. Conclusions: Our data demonstrate a significant inverse association between geographic distribution of H. pylori and CD. Thus, it is highly unlikely that the findings of previous case control studies were simply due to confounding factors such as concomitant antibiotic use in CD patients.

 

RECORD 13

Association of Helicobacter pylori and Crohn’s Disease Incidence: An Inversion Reaction?Bartels L.E. Dahlerup J.F.Digestive Diseases and Sciences (2017) 62:9 (2217-2219). Date of Publication: 1 Sep 2017

 

RECORD 14

Management of Helicobacter pylori InfectionKavitt R.T. Cifu A.S.JAMA (2017) 317:15 (1572-1573). Date of Publication: 18 Apr 2017

 

RECORD 15

Usefulness of detection of clarithromycin-resistant Helicobacter pylori from fecal specimens for young adults treated with eradication therapyOsaki T. Mabe K. Zaman C. Yonezawa H. Okuda M. Amagai K. Fujieda S. Goto M. Shibata W. Kato M. Kamiya S.Helicobacter (2017) 22:5 Article Number: e12396. Date of Publication: 1 Oct 2017Background: To prevent Helicobacter pylori infection in the younger generation, it is necessary to investigate the prevalence of antibiotic-resistant H. pylori. Objective: The aim of this study was to evaluate the method of PCR-based sequencing to detect clarithromycin (CAM) resistance-associated mutations using fecal samples as a noninvasive method. Methods: DNA extracted from fecal specimens and isolates from gastric biopsy specimens were collected from patients with H. pylori infection. Antibiotic resistance to CAM was analyzed by molecular and culture methods. The detection rates of CAM resistance-associated mutations (A2142C or A2143G) were compared before and after eradication therapy. Results: With CAM resistance of H. pylori evaluated by antibiotic susceptibility test as a gold standard, the sensitivity and the specificity of gene mutation detection from fecal DNA were 80% and 84.8%, respectively. In contrast, using DNA of isolated strains, the sensitivity and the specificity were 80% and 100%. Of the seven cases in which eradication was unsuccessful by triple therapy including CAM, CAM-resistant H. pylori, and resistance-associated mutations were detected in three cases, CAM-resistant H. pylori without the mutation was detected in two patients, and resistance-associated mutation was only detected in one patient. Conclusion: PCR-based sequencing to detect CAM resistance-associated mutations using isolates or fecal samples was useful for finding antibiotic-resistant H. pylori infection. Although the specificity of the detection from fecal samples compared with antibiotic susceptibility testing was lower than that from isolates, this fecal detection method is suitable especially for asymptomatic subjects including children. Further improvement is needed before clinical application.

 

RECORD 16

Advances in diagnosis and treatment of helicobacter pylori infectionRanjbar R. Behzadi P. Farshad S.Acta Microbiologica et Immunologica Hungarica (2017) 64:3 (273-292). Date of Publication: 1 Sep 2017Helicobacter pylori is a Gram-negative motile bacterium causative agent of acute and chronic digestive and extra-digestive human infections. According to different reports worldwide, H. pylori symptomatic and asymptomatic infections are a global problem. The statistical investigations show a percentage of 50 for people who are involved in H. pylori acute/chronic digestive and/or extra-digestive infections around the world. This review focuses on digestive and extra-digestive diseases caused by H. pylori, the related virulence factors, diagnostic techniques including noninvasive and invasive diagnostics and treatment. There is an abundance of diagnostics for detection and identification of H. pylori. The availability, cost, and the condition of test performance may differ from place to place. To increase the level of reliability in association with diagnostic tools for detecting H. pylori, several techniques must be applied at once as multi-diagnostic technique. Furthermore, there are several pharmacotherapies which can be used for complete eradication of H. pylori infection.

 

RECORD 17

30th anniversary of the European helicobacter & microbiota study group!Mégraud F.Helicobacter (2017) 22 Supplement 1 Article Number: e12422. Date of Publication: 1 Sep 2017

 

RECORD 18

Randomized controlled study of a novel triple nitazoxanide (NTZ)-containing therapeutic regimen versus the traditional regimen for eradication of Helicobacter pylori infectionShehata M.A.H. Talaat R. Soliman S. Elmesseri H. Soliman S. Abd-Elsalam S.Helicobacter (2017) 22:5 Article Number: e12395. Date of Publication: 1 Oct 2017Background: Helicobacter pylori infection has become more and more resistant to conventional first-line treatment regimens. So, there is a considerable interest in evaluating new antibiotic combinations and regimens. Nitazoxanide is an anti-infective drug with demonstrated activity against protozoa and anaerobic bacteria including H. pylori. This work is designed to evaluate the efficacy and safety of a unique triple nitazoxanide-containing regimen as a treatment regimen in Egyptian patients with H. pylori infection. Methods: Two hundred and 24 patients with upper gastrointestinal tract (GIT) dyspeptic symptoms in whom H. pylori -induced GIT disease was confirmed were included in the study. They have been randomized to receive either nitazoxanide 500 mg b.i.d., clarithromycin 500 mg b.i.d., and omeprazole 40 mg twice daily for 14 days or metronidazole 500 mg b.i.d., clarithromycin 500 mg b.i.d., and omeprazole 40 mg twice daily for 14 days. Laboratory evaluation for H. pylori antigen within the stool was performed 6 weeks after cessation of H. pylori treatment regimens to assess the response. Results: The response to treatment was significantly higher in group 1 of nitazoxanide treatment regimen than group 2 of traditional treatment regimen. One hundred and six cases (94.6%) of 112 patients who completed the study in group 1 showed complete cure, while only 63 cases (60.6%) of 104 patients who completed the study in group 2 showed the same response according to per-protocol (PP) analysis (P<.001). The regimen was well tolerated by all the patients enrolled in the study. Conclusion: Nitazoxanide-containing triple therapy is a promising therapy for the first-line eradication of H. pylori. (ClinicalTrials.gov Identifier: NCT02422706).

 

RECORD 19

Diagnosis of Helicobacter pylori infectionBessède E. Arantes V. Mégraud F. Coelho L.G.Helicobacter (2017) 22 Supplement 1 Article Number: e12404. Date of Publication: 1 Sep 2017Important progress is being made in endoscopic methods which allow clinicians to predict the presence of Helicobacter pylori based on characteristics of gastric mucosa and to obtain targeted biopsies. There are also important developments in molecular methods with various techniques derived from standard PCR, applied both on gastric biopsies and stool specimens. Progress is being made in microfluidic systems to get a reliable diagnosis in a very short time. The interest of the (13)C urea breath test has been confirmed as well as stool antigen tests. Attempts are being made to find biological markers of premalignant conditions by serology, other than pepsinogens.

 

RECORD 20

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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Helicobacter pylori infection and nonmalignant diseasesSjomina O. Heluwaert F. Moussata D. Leja M.Helicobacter (2017) 22 Supplement 1 Article Number: e12408. Date of Publication: 1 Sep 2017A substantial decrease in Helicobacter pylori-associated peptic ulcer disease has been observed during the last decades. Drug-related ulcers as well as idiopathic ulcers are becoming predominant and are more refractory to treatment; however, H. pylori infection still plays an important role in ulcer bleeding and recurrence after therapy. The effect of H. pylori eradication upon functional dyspepsia symptoms has been reviewed in this article and generally confirms the results of previous meta-analyses. Additional evidence suggests a lack of impact upon the quality of life, in spite of improvement in symptoms. The association of H. pylori with gastroesophageal reflux disease and Barrett's esophagus remains controversial with a majority of published studies showing a negative association. Furthermore, a strong inverse relationship between the presence of H. pylori and the esophageal eosinophilia was also reported. Several studies and a review addressed the role of H. pylori in autoimmune gastritis and pernicious anemia. The association of the above still remains controversial. Finally, the necessity of routine endoscopy and H. pylori eradication before bariatric surgery is discussed. Several studies suggest the rationale of preoperative upper endoscopy and H. pylori eradication prior to surgery. However, the prevalence of H. pylori infection prior to surgery in these studies generally reflects the overall prevalence of the infection in the particular geographic area. In addition, results on the role of H. pylori in developing postoperative complications remain controversial.

 

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Helicobacter Pylory infection in patients with esophageal squamous cell carcinomaPoyrazoglu O.B. Dulger A.C. Gultepe B.S.Clinics (Sao Paulo, Brazil) (2017) 72:3 (150-153). Date of Publication: 1 Mar 2017OBJECTIVE:: Esophageal squamous cell carcinoma is one of the most common esophageal diseases in the developing world, but the relationship between esophageal squamous cell carcinoma and Helicobacter pylori infection remains a neglected topic. The primary objective of this study was to determine the association between Helicobacter pylori infection and esophageal squamous cell carcinoma. A second purpose was to determine the incidence and factors associated with Helicobacter pylori infection following esophagectomy.METHOD:: The microorganism was identified by testing the gastric biopsy materials from 95 esophageal squamous cell carcinoma patients (66 females; 39 were esophagectomized) for urease activity in a medium containing urea and a power of hydrogen detection reagent and comparing the results with those from a healthy population. Differences in patient characteristics were assessed with chi-square tests and t-tests for categorical and continuous factors, respectively.RESULTS:: The patients with esophageal squamous cell carcinoma had a significantly lower prevalence of Helicobacter pylori compared with the healthy population (p<0.001). The naive and esophagectomized patients, in contrast, showed no significant differences in Helicobacter pylori infection (p>0.005). Patients with esophageal squamous cell carcinoma showed a significant association between leukocytosis and hypoglobulinemia and the presence of Helicobacter pylori infection (p=0.023 and p=0.045, respectively).CONCLUSION:: These results suggest that Helicobacter pylori is not an etiological factor in patients with esophageal squamous cell carcinoma. We found a statistically significant negative correlation between esophageal squamous cell cancer and Helicobacter pylori infection. These findings may guide new strategies for esophageal squamous cell carcinoma therapy.

 

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Etiopathogenesis of rosacea: A prospective study with a three-year follow-upAgnoletti A.F. De Col E. Parodi A. Schiavetti I. Savarino V. Rebora A. Paolino S. Cozzani E. Drago F.Giornale Italiano di Dermatologia e Venereologia (2017) 152:5 (418-423). Date of Publication: 1 Oct 2017BACKGROUND: The aim of this study was to investigate the role of Demodex folliculorum (DF), Helicobacter pylori (HP), and small intestine bacterial overgrowth (SIBO) in the development of rosacea. METHODS: A case-control study including 60 patients with rosacea and 40 healthy controls was performed. All the patients underwent standardized skin surface biopsy to investigate DF, urea breath test for HP and lactulose breath test and glucose breath test for SIBO. Etiological therapy was started in the following order: Acaricidal treatment, antibiotics for SIBO and HP. These exams were repeated after 3 years. Statistical analysis was performed. RESULT S: As regards the 88 patients who completed the entire follow-up, DF positivity was found in 47.7% of the patients, SIBO in 25.0%, and HP in 21.6%. SIBO significantly prevailed in papulopustular rosacea, while HP in erythrosis. At the 6-month follow up, the 61% of patients were in remission. After 3 years, 18% of patients dropped out, while the remaining patients repeated all the investigations. The majority of patients were still in remission and negative for HP while only 5 were positive for DF and 4 for SIBO. CONCLUSIONS: SIBO was the most relevant factor in papulopustular rosacea. Its treatment was crucial in improvement and in maintaining the clinical remission.

 

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Review: Prevalence and dynamics of Helicobacter pylori infection during childhoodZabala Torrres B. Lucero Y. Lagomarcino A.J. Orellana-Manzano A. George S. Torres J.P. O'Ryan M.Helicobacter (2017) 22:5 Article Number: e12399. Date of Publication: 1 Oct 2017Introduction: Long-term persistent Helicobacter pylori infection has been associated with ulceropeptic disease and gastric cancer. Although H. pylori is predominantly acquired early in life, a clear understanding of infection dynamics during childhood has been obfuscated by the diversity of populations evaluated, study designs, and methods used. Aim: Update understanding of true prevalence of H. pylori infection during childhood, based on a critical analysis of the literature published in the past 5 years. Methods: Comprehensive review and meta-analysis of original studies published from 2011 to 2016. Results: A MEDLINE(®)/PubMed(®) search on May 1, 2016, using the terms pylori and children, and subsequent exclusion, based on abstract review using predefined criteria, resulted in 261 citations. An Embase(®) search with the same criteria added an additional 8 citations. In healthy children, meta-analysis estimated an overall seroprevalence rate of 33% (95% CI: 27%-38%). Seven healthy cohort studies using noninvasive direct detection methods showed infection prevalence estimates ranging from 20% to 50% in children ≤5 and 38% to 79% in children >5 years. The probability of infection persistence after a first positive sample ranged from 49% to 95%. Model estimates of cross-sectional direct detection studies in asymptomatic children indicated a prevalence of 37% (95% CI: 30%-44%). Seroprevalence, but not direct detection rates increased with age; both decreased with increasing income. The model estimate based on cross-sectional studies in symptomatic children was 39% (95% CI: 35%-43%). Conclusions: The prevalence of H. pylori infection varied widely in the studies included here; nevertheless, model estimates by detection type were similar, suggesting that overall, one-third of children worldwide are or have been infected. The few cohort and longitudinal studies available show variability, but most studies, show infection rates over 30%. Rather surprisingly, overall infection prevalence in symptomatic children was only slightly higher, around 40%. Studies including only one positive stool sample should be interpreted with caution as spontaneous clearance can occur.

 

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Octyl gallate, a food additive with potential beneficial properties to treat Helicobacter pylori infectionWolf V.G. Bonacorsi C. Raddi M.S.G. da Fonseca L.M. Ximenes V.F.Food & function (2017) 8:7 (2500-2511). Date of Publication: 19 Jul 2017Helicobacter pylori infection is marked by intense production of reactive oxygen species (ROS) through the activation of neutrophils that are constantly attracted to the infected gastric mucosa. Here, gallic acid and its alkyl esters were evaluated as compounds able to act as antimicrobial agents and inhibitors of ROS released by H. pylori-activated neutrophils simultaneously. We found that the higher hydrophobicity caused by esterification of gallic acid led to a significant increase in its ability as a cytotoxic agent against H. pylori, a scavenger of ROS and an inhibitor of NADPH oxidase in neutrophils. Octyl gallate, a widely used food additive, showed the highest antimicrobial activity against H. pylori, with a minimum inhibitory concentration (MIC) value of 125 μg mL-1, whereas gallic acid had a MIC value higher than 1000 μg mL-1. The production of superoxide anion radicals was almost 100% abolished by the addition of 10 μM (2.82 μg mL-1) octyl gallate, whereas gallic acid inhibited around 20%. A similar tendency was also found when measuring the production of hypochlorous acid. The protective effect of the esters was cytochemically confirmed. In conclusion, this study showed that hydrophobicity is a crucial factor to obtain a significant anti-ROS and anti-H. pylori activity. Finally, it highlights octyl gallate, a food additive widely used in the food industry, as a promising molecule in the treatment of H. pylori infection.

 

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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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In Haitian women and preschool children, iron absorption from wheat flour-based meals fortified with sodium iron EDTA is higher than that from meals fortified with ferrous fumarate, and is not affected by Helicobacter pylori infection in childrenHerter-Aeberli I. Eliancy K. Rathon Y. Loechl C.U. Marhône Pierre J. Zimmermann M.B.The British journal of nutrition (2017) 118:4 (273-279). Date of Publication: 1 Aug 2017Fe fortification of wheat flour was proposed in Haiti to combat Fe deficiency, but Fe bioavailability from fortificants has never been investigated in Haitian women or preschool children, two key target groups. We aimed to investigate the bioavailability of ferrous fumarate (FeFum), NaFeEDTA and their combination from fortified wheat flour. We recruited twenty-two healthy mother-child pairs in Port au Prince, Haiti, for an Fe-absorption study. We administered stable Fe isotopes as FeFum or NaFeEDTA individually in low-extraction wheat flour bread rolls consumed by all participants in a randomised, cross-over design. In a final, identical meal, consumed only by the women, FeFum+NaFeEDTA was administered. We measured Fe absorption by using erythrocyte incorporation of stable isotopes 14 d after consumption of each meal, and determined Fe status, inflammatory markers and Helicobacter pylori infection. Fe absorption (geometric mean was 9·24 (95 % CI 6·35, 13·44) and 9·26 (95 % CI 7·00, 12·31) from FeFum and 13·06 (95 % CI 9·23, 19·10) and 12·99 (95 % CI 9·18, 18·39) from NaFeEDTA in mothers and children, respectively (P<0·05 between compounds). Fe absorption from FeFum+NaFeEDTA was 11·09 (95 % CI 7·45, 17·34) and did not differ from the other two meals. H. pylori infection did not influence Fe absorption in children. In conclusion, in Haitian women and children, Fe absorption from NaFeEDTA was 40 % higher than from FeFum, and the combination FeFum+NaFeEDTA did not significantly increase Fe absorption compared with FeFum alone. In the context of Haiti, where the high costs of NaFeEDTA may not be affordable, the use of FeFum at 60 mg Fe/kg flour may be a preferable, cost-effective fortification strategy.

 

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Link between Serum Pepsinogen Concentrations and Upper Gastrointestinal Endoscopic FindingsLee S.P. Lee S.Y. Kim J.H. Sung I.K. Park H.S. Shim C.S.Journal of Korean medical science (2017) 32:5 (796-802). Date of Publication: 1 May 2017The serum pepsinogen (PG) assay findings are correlated with the status of Helicobacter pylori infection, but there are controversies on the link with upper gastrointestinal (UGI) endoscopic findings. The aim of this study was to determine the significance of a serum PG assay for correlating with endoscopic findings in H. pylori-seroprevalent adult population. Korean adults who visited for a health check-up were included consecutively. Subjects after gastrectomy or H. pylori eradication were excluded. After completing the serum PG assay and anti-H. pylori immunoglobulin G (IgG) titer on the same day of UGI endoscopy, subjects with equivocal serology test finding or gastric neoplasm were excluded. Of the 4,830 included subjects, 3,116 (64.5%) were seropositive for H. pylori. Seropositive finding was related to high serum PG I (P < 0.001) and PG II (P < 0.001) concentrations, low PG I/II ratio (P < 0.001), old age (P < 0.001), and male gender (P = 0.006). After adjusting age and gender, the serum PG I and II concentrations were positively correlated with the presence of nodular gastritis (NG) (all P = 0.003). The serum PG I was positively correlated with gastric ulcer (P = 0.003), and it was correlated with duodenal ulcer in seropositive subjects (P = 0.008). The PG I/II ratio was positively correlated with erosive esophagitis, while it was inversely related to chronic atrophic gastritis and metaplastic gastritis (all P < 0.001). Our findings suggest that the serum PG assay finding correlates well with the UGI endoscopic finding. A higher serum PG concentration in subjects with NG and peptic ulcer disease suggests that endoscopic findings reflect gastric secreting ability.

 

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Cloning of Helicobacter suis cholesterol α-glucosyltransferase and production of an antibody capable of detecting it in formalin-fixed, paraffin-embedded gastric tissue sectionsKawakubo M. Horiuchi K. Komura H. Sato Y. Kato M. Ikeyama M. Fukushima M. Yamada S. Ishizone S. Matsumoto T. Ota H. Sagara J. Nakayama J.Histochemistry and Cell Biology (2017) 148:4 (463-471). Date of Publication: 1 Oct 2017Helicobacter suis (H. suis), formerly called Helicobacter heilmannii type 1 (H. heilmannii), is a gram-negative bacterium of the Helicobacter species. This pathogen infects the stomach of humans and animals such as dogs, cats, pigs, and rodents, the latter giving rise to zoonotic infection. Here, we generated a H. suis-specific antibody useful for immunohistochemistry with formalin-fixed, paraffin-embedded tissue sections. To do so, we began by cloning the gene encoding H. suis cholesterol α-glucosyltransferase (αCgT). αCgT is the key enzyme responsible for biosynthesis of cholesteryl α-d-glucopyranoside (CGL), a major cell wall component of Helicobacter species including H. suis. The deduced amino acid sequence of H. suis αCgT had 56% identity with the corresponding Helicobacter pylori (H. pylori). We then developed a polyclonal antibody (anti-Hh-I205R) by immunizing rabbits with a 205 amino acid H. suis αCgT fragment. Immunohistochemistry with the anti-Hh-I205R antibody could differentiate H. suis from H. pylori in gastric mucosa sections derived from mice infected with either pathogen. We then probed formalin-fixed, paraffin-embedded sections of human gastric mucosa positive for H. suis infection with the anti-Hh-I205R antibody and detected positive staining. These results indicate that anti-Hh-I205R antibody is specific for H. suis αCgT and useful to detect H. suis in gastric specimens routinely analyzed in pathological examinations.

 

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Epidemiology of Helicobacter pylori infectionBurucoa C. Axon A.Helicobacter (2017) 22 Supplement 1 Article Number: e12403. Date of Publication: 1 Sep 2017The study of Helicobacter pylori genetic variability brought us interesting data on the history of mankind. Based on multilocus sequence typing and more recently on whole-genome sequencing, paleomicrobiology still attracts the attention of global researchers in relation to its ancestor roots and coexistence with humans. Three studies determining the prevalence of virulence factors illustrates the controversial results obtained since 30 years by studies trying to associate prevalence of different virulence markers and clinical outcomes of H. pylori infection. Three articles analyzed the prevalence and risk of multiple (genetically distinct isolates) and mixed (susceptible and resistant isolates) infections. A number of studies confirm that H. pylori prevalence is falling worldwide especially in the developed world and in children but that the level of infection is higher in certain ethnic minorities and in Migrants. There is little new in identifying the mode of H. pylori transmission though intrafamilial spread appears to be important. There have, however, been some interesting papers on the presence of the organism in food, water, and the oral cavity.

 

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Pathogenesis of Helicobacter pylori infectionCamilo V. Sugiyama T. Touati E.Helicobacter (2017) 22 Supplement 1 Article Number: e12405. Date of Publication: 1 Sep 2017Helicobacter pylori is responsible for the most commonly found infection in the world's population. It is the major risk factor for gastric cancer development. Numerous studies published over the last year provide new insights into the strategies employed by H. pylori to adapt to the extreme acidic conditions of the gastric environment, to establish persistent infection and to deregulate host functions, leading to gastric pathogenesis and cancer. In this review, we report recent data on the mechanisms involved in chemotaxis, on the essential role of nickel in acid resistance and gastric colonization, on the importance of adhesins and Hop proteins and on the role of CagPAI-components and CagA. Among the host functions, a special focus has been made on the escape from immune response, the ability of bacteria to induce genetic instability and modulate telomeres, the mechanism of autophagy and the deregulation of micro RNAs.

 

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Helicobacter pylori infection and extragastric diseases in 2017de Korwin J.-D. Ianiro G. Gibiino G. Gasbarrini A.Helicobacter (2017) 22 Supplement 1 Article Number: e12411. Date of Publication: 1 Sep 2017The huge variety of extragastric diseases linked to Helicobacter pylori infection is widely known, and new studies are conducted every year on this topic. Neurological disorders and metabolic syndrome are some of the main issues debated in the most recent literature. Articles on the association of H. pylori with skin diseases, inflammatory bowel diseases, immunologic impairment, kidney dysfunction, allergic asthma, and respiratory diseases have been published as well. In this perspective, eradication therapy for this infection could become a mandatory measure in prevention strategy.

 

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Prevalence of Helicobacter pylori prevalence and upper gastrointestinal endoscopy in HIV/AIDS patients with gastrointestinal symptoms in the University Teaching Hospitals in CameroonAndoulo F.A. Kowo M. Ngatcha G. Ndam A.N. Awouoyiegnigni B. Sida M.B. Tzeuton C. Ndjitoyap Ndam E.C.Medecine et sante tropicales (2016) 26:3 (278-282). Date of Publication: 1 Aug 2016

 

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Yes, research mattersShinohara M.L.PLoS Pathogens (2017) 13:8 Article Number: e1006420. Date of Publication: 1 Aug 2017My father was diagnosed with stomach cancer recently. Luckily, it was still at an early stage, and endoscopic surgery successfully took care of it. My father was fortunate; since people with stomach cancer do not show clear symptoms in the early stages, the disease is often not diagnosed until it becomes advanced. In his case, the diagnosis started from a suggestion by his doctor to check whether he had a gastric infection with Helicobacter pylori, a bacterial species found in the digestive tract. In Japan, where he lives, a majority of gastric cancer patients (more than 99%) have been infected with H. pylori [1], and the causative role of this bacterial species in promoting gastric cancer is very well established. Now, scientific understanding connecting gastric cancer to H. pylori is saving the lives of many people, including my father. Thinking about this recent personal experience, I wonder if the connection between bacteria and cancer might have been considered a crazy idea decades ago. Research makes it possible to connect seemingly unrelated matters. My laboratory works on seemingly unrelated research topics, such as fungal infections and autoimmunity. However, my question is the same whatever the topic: How do leukocytes elicit and regulate inflammation when they detect infections or endogenous signals? In fact, host receptors detecting pathogens can induce autoimmunity, and autoimmunity alters host sensitivity to pathogens due to the imbalance in the immune system. We are beginning to gain some insight into this question, as revealed by some of our recent studies. For example, the NLR family, pyrin domain containing 3 (NLRP3) inflammasome, which is known to sense a wide variety of pathogens, can also change the course of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). In particular, our study suggested that disease treatment approaches need to be changed based on the activation status of the NLRP3 inflammasome [2]. Another recent study from our laboratory demonstrated that a protein, termed osteopontin (OPN), skews the balance of population sizes between myeloid cells (i.e., innate immunity) and lymphoid cells (i.e., adaptive immunity) during infections and other biological insults [3]. An intracellular isoform of OPN (iOPN) negatively regulates emergency myelopoiesis. Thus, OPN attenuates host resistance by limiting neutrophil supply at the early stage of systemic Candida infection. In contrast, a secreted OPN (sOPN) isoform positively regulates the expansion of T lymphocytes and ends up triggering autoimmune colitis. I am an immunologist but obtained my PhD in mycology. Nevertheless, it took some time for me to appreciate that research enables us to connect the dots placed far apart. This is a truly exciting time to connect seemingly unrelated biological phenomena, because scientists are exponentially increasing our understanding of nature. This is particularly true in innate immunity, which is not only the central alarming system in host–microbe interactions but also relates to almost any human disease we can imagine. However, we are facing a dark age for science and research, in which certain interests wrongfully discredit some research fields. There are things that can be achieved only by research. I am always ready to tell anyone, “Yes, research matters!”.

 

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Does Helicobacter pylori eradication play a role in immune thrombocytopenia?Llovet V. Rada G.Medwave (2016) 16 Supplement 3 (e6528). Date of Publication: 5 Sep 2016

 

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Does Helicobacter pylori infection increase the risk of adult-onset asthma?Ribaldone D.G. Saracco G. Pellicano R.European Journal of Clinical Microbiology and Infectious Diseases (2017) 36:10 (1995-1996). Date of Publication: 1 Oct 2017

 

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Tablet and oral liquid L-thyroxine formulation in the treatment of naïve hypothyroid patients with Helicobacter pylori infectionRibichini D. Fiorini G. Repaci A. Castelli V. Gatta L. Vaira D. Pasquali R.Endocrine (2017) 57:3 (394-401). Date of Publication: 1 Sep 2017To compare the clinical efficacy of tablet and oral liquid L-thyroxine (LT4) formulation in naïve hypothyroid subjects with Helicobacter pylori infection. Forty-seven adult naïve hypothyroid subjects with dyspeptic symptoms were investigated with upper endoscopy and divided into: 28 patients with Helicobacter pylori infection (Group A); 15 patients without gastric alterations (group B); 4 patients with autoimmune gastritis were excluded from the study. Subjects were randomly treated with a same dose of LT4 tablet (TAB) or oral liquid formulation (SOL), for 9 months on group A and 6 months on group B. Helicobacter pylori infection was eradicated after 3 months of LT4 treatment. On group A, after 3 months (before Helicobacter pylori eradication), subjects treated with SOL showed a greater thyroid-stimulating hormone reduction (ΔTSH(3–0): TAB = −4.1 ± 4.6 mU/L; SOL = −7.7 ± 2.5 mU/L; p = 0.029) and a greater homogeneity in the thyroid-stimulating hormone values (TSH(3mo): TAB = 5.7 ± 4.9 mU/L; SOL = 4.1 ± 2.0 mU/L; p = 0.025), compared to LT4 tablet. At 9 months (after 6 months of Helicobacter pylori eradication) mean thyroid-stimulating hormone values were lower in subjects treated with LT4 tablet (TSH(9mo): TAB = 1.8 ± 1.2 mU/L; SOL = 3.2 ± 1.7 mU/L; p = 0.006). On group B no difference were observed, at each time point, in the mean thyroid-stimulating hormone values and thyroid-stimulating hormone variations between two LT4 formulations. LT4 liquid formulation may produce a better clinical response compared to the tablet formulation in hypothyroid subjects with Helicobacter pylori infection.

 

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H. pylori seroprevalence and risk of diabetes: An ancillary case–control study nested in the diabetes prevention programAlzahrani S. Nelson J. Moss S.F. Paulus J.K. Knowler W.C. Pittas A.G.Journal of Diabetes and its Complications (2017) 31:10 (1515-1520). Date of Publication: 1 Oct 2017Objective To determine the association between H. pylori infection and risk of incident diabetes in adults at high risk for diabetes who participated in the Diabetes Prevention Program (DPP) study. Methods In a nested case–control study conducted among 421 adults with newly diagnosed diabetes and 421 matched controls, we examined the association between serological status of H. pylori at baseline and risk of incident diabetes over a mean follow-up period of 2.6 years. Using data from the baseline visit of the DPP, we also examined the cross-sectional association between presence of H. pylori antibodies and insulin sensitivity, insulin secretion and the disposition index-like measure after a 75-g oral glucose tolerance test (OGTT). Results At baseline, H. pylori antibodies were present in 40% of participants who developed diabetes and 39% of controls. After adjusting for matching factors, there was no association between exposure to H. pylori and incident diabetes (odds ratio [OR] of 1.04 (95% CI, 0.77 to 1.40). In cross-sectional analyses, H. pylori status was not significantly associated with insulin sensitivity and disposition index-like measure from OGTT. Conclusions In adults at high risk for diabetes, H. pylori seropositivity was not associated with risk of developing diabetes.

 

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Management of gastric cancer in Indian populationIbrahim M. Gilbert K.Translational Gastroenterology and Hepatology (2017) 2017:AUG Article Number: 64. Date of Publication: 1 Aug 2017Adenocarcinoma stands the most common malignancies in the gastric carcinomas and holds a significant mortality and morbidity rates annually, due to the early vague symptoms among the population and hence the delayed presentation at advanced stages of cancer. In India the screening programs for gastric cancer has been a setback due to various logistics reasons and the data available from reporting is also not content. Our study is a review article featuring the management of gastric cancer in the Indian population. The lifestyle of India population is varied right from its southern region to its northern counterparts, which is due to its diversified culture within the country. Studies have concluded that the northern population tends to have a higher incidence comparatively and the various risk factors associated with the disease has been discussed. Management of the gastric cancer in India remains the same compared to the outside world, though the availability of endoscopic ultrasound and other technical advancements remain sparse in the field of diagnostics and staging of the disease. D2 gastrectomy remains the mainstay of surgery among the Indian population though significant number of patients are deemed inoperable on table. Neo adjuvant Chemotherapy, Radiotherapy and Targeted therapy is yet to be efficiently used across the country according to our study as there is lack of data in our registries. The incidence is decreasing in developing nations and more proximal cancers are reported. However, in India the major population-based cancer registries report an incidence decline only in Mumbai and Chennai. A shift from distal to proximal as the site of disease has not been reported from India. The contribution of the Indian scientific fraternity to the world medical literature for gastric cancer is sparse and it is clear that a lot more is to be done; the possible reason may be a busy clinical schedule or lack of initiatives. There is an urgent need for research in various aspects of gastric cancer from India including epidemiological and therapeutic areas.

 

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Hepatocyte growth factor in physiology and infectious diseasesImamura R. Matsumoto K.Cytokine (2017) 98 (97-106). Date of Publication: 1 Oct 2017Hepatocyte growth factor (HGF) is a pleiotropic cytokine composed of an α-chain and a β-chain, and these chains contain four kringle domains and a serine protease-like structure, respectively. The receptor for HGF was identified as the c-met proto-oncogene product of transmembrane receptor tyrosine kinase. HGF-induced signaling through the receptor Met provokes dynamic biological responses that support morphogenesis, regeneration, and the survival of various cells and tissues, which includes hepatocytes, renal tubular cells, and neurons. Characterization of tissue-specific Met knockout mice has further indicated that the HGF–Met system modulates immune cell functions and also plays an inhibitory role in the progression of chronic inflammation and fibrosis. However, the biological actions that are driven by the HGF–Met pathway all play a role in the acquisition of the malignant characteristics in tumor cells, such as invasion, metastasis, and drug resistance in the tumor microenvironment. Even though oncogenic Met signaling remains the major research focus, the HGF–Met axis has also been implicated in infectious diseases. Many pathogens try to utilize host HGF–Met system to establish comfortable environment for infection. Their strategies are not only simply change the expression level of HGF or Met, but also actively hijack HGF–Met system and deregulating Met signaling using their pathogenic factors. Consequently, the monitoring of HGF and Met expression, along with real-time detection of Met activation, can be a beneficial biomarker of these infectious diseases. Preclinical studies designed to address the therapeutic significance of HGF have been performed on injury/disease models, including acute tissue injury, chronic fibrosis, and cardiovascular and neurodegenerative diseases. Likewise, manipulating the HGF–Met system with complete control will lead to a tailor made treatment for those infectious diseases.

 

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Complementary and alternative medicine: A world to be exploredDamião A.O.M.C.Arquivos de Gastroenterologia (2017) 54:3 (175-176). Date of Publication: 1 Jul 2017

 

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Letter: bleeding in cirrhotics receiving coronary stenting and antiplatelet therapyPonzetto A. Figura N.Alimentary Pharmacology and Therapeutics (2017) 46:7 (709). Date of Publication: 1 Oct 2017

 

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Significance of duodenal mucosal lesions: Can they be a clue to a systemic disease?Lee S.W.Korean Journal of Internal Medicine (2017) 32:5 (813-815). Date of Publication: 2017

 

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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.Ã. 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) 22:5 Article Number: e12423. Date of Publication: 1 Oct 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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Fourteen-day high-dose esomeprazole, amoxicillin and metronidazole as third-line treatment for Helicobacter pylori infectionPuig I. González-Santiago J.M. Molina-Infante J. Barrio J. Herranz M.T. Algaba A. Castro M. Gisbert J.P. Calvet X.International Journal of Clinical Practice (2017) 71:9 Article Number: e13004. Date of Publication: 1 Sep 2017Introduction: The efficacy of currently recommended third-line therapies for Helicobacter pylori is suboptimal, even that of culture-guided treatments. Resistance to multiple antibiotics is the major factor related to treatment failure. The aim of this study was to evaluate the effectiveness and safety of a 14-day therapy using high-dose of amoxicillin, metronidazole and esomeprazole. Material and methods: Multicenter open-label study as a register in routine clinical practice in patients with two previous failures of eradication therapy. A triple therapy with esomeprazole 40 mg b.d., amoxicillin 1 g t.d.s and metronidazole 500 mg t.d.s for 2 weeks was administered as a third-line therapy after a first treatment including clarithromycin and a second treatment including a quinolone. Helicobacter pylori status was determined by either histology or (13)C-UBT both before and after treatment. Results: A total of 68 patients were included in this study. An interim analysis showed that only three out of eight patients who had received metronidazole in previous eradication regimens were cured (37%, 95% CI 8-75); as a result, after this interim analysis only metronidazole-naïve patients were included. The ITT eradication rate in metronidazole-naive patients was 64% (95% CI 51-76). Adverse events occurred in 58% of patients, all of them mild-to-moderate. Two patients (3%) did not complete >90% of the treatment because of side effects. No severe adverse events occurred. Conclusion: Cure rates of this 14-day schedule using high-dose esomeprazole, amoxicillin and metronidazole as a third-line eradication regimen were suboptimal, especially in patients who had received metronidazole in previous failed eradication regimens.

 

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Prevalence of Helicobacter Pylori infection and stress, anxiety or depression in functional dyspepsia and outcome after appropriate interventionKabeer K.K. Ananthakrishnan N. Anand C. Balasundaram S.Journal of Clinical and Diagnostic Research (2017) 11:8 (VC11-VC15). Date of Publication: 1 Aug 2017Introduction: The association between psychological factors and non-ulcer dyspepsia remains controversial. Aim: To determine the prevalence of Helicobacter pylori (HP) and Stress/Anxiety/Depression (SAD) in patients with Functional Dyspepsia (FD) and assess the outcome at three months after appropriate intervention. Materials and Methods: This prospective non-randomized interventional study was conducted on 120 patients with FD. Initial workup included upper gastrointestinal endoscopy to confirm HP infection with either of two tests, the urease test or histopathology. Patient Health Questionnaire-9 scale (PHQ-9) was used to assess depression, General Anxiety Disorder-7 scale (GAD-7) for anxiety and Perceived Stress Scale (PSS) for stress. Patients were considered positive when they had significant scores on one or more of the questionnaires (SAD+). The subjects were then classified into four groups: Group A (positive for HP and SAD, n=35), Group B (positive for HP and negative for SAD, n=31), Group C (negative for HP and positive for SAD, n=33) and Group D (negative for HP and SAD, n=21). The groups were then treated as follows: Group A: HP eradication plus psychiatric intervention, Group B: HP eradication alone, Group C: psychiatric intervention alone and Group D: proton pump inhibitors. Modified Glasgow Dyspepsia Symptom Score (Mod. GDSS) was used to assess the severity of dyspepsia at baseline and to monitor the change in score over three months. Statistical analysis was done using the Statistical Package for the Social Sciences version 16.0. Non-parametric data like proportions of response in different groups to treatment was analysed using the Chi square test and quantitative data using ANOVA. Gender wise distribution and response to treatment was calculated using the z-test and unpaired t-test. Results: Overall 120 patients were recruited across four groups. A 55% of the subjects were positive for HP and 56.7% for SAD and 29.2% for both. In all three groups, females exceeded males in a proportion of 3:1. Mod. GDSS was not significantly different at baseline between HP+ and HP-patients (p=0.1278) except when HP positivity was also associated with SAD (p<0.001), whereas SAD positivity alone significantly increased the baseline Mod. GDSS (p=0.006). Mod. GDSS declined in all four groups at three months. When a fall of four or more was considered as an indicator of significant response to intervention, it was seen that overall 74.2% responded to intervention with the best response in Group B and the poorest was in Group C. Conclusion: There is a significant prevalence of HP and SAD in FD. Appropriate intervention is beneficial except in those who are HP negative and SAD positive. This latter group requires further investigation and or drug intervention for SAD.

 

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Ten-Day Quadruple Therapy Comprising Proton Pump Inhibitor, Bismuth, Tetracycline, and Levofloxacin is More Effective than Standard Levofloxacin Triple Therapy in the Second-Line Treatment of Helicobacter pylori Infection: A Randomized Controlled TrialHsu P.-I. Tsai F.-W. Kao S.-S. Hsu W.-H. Cheng J.-S. Peng N.-J. Tsai K.-W. Hu H.-M. Wang Y.-K. Chuah S.-K. Chen A. Wu D.-C.American Journal of Gastroenterology (2017) 112:9 (1374-1381). Date of Publication: 1 Sep 2017Objectives:Proton pump inhibitor (PPI)-amoxicillin-fluoroquinolone triple therapy is recommended as a second-line treatment of Helicobacter pylori infection in the Maastricht V/Florence Consensus Report. However, the eradication rate of this standard salvage treatment is suboptimal. The objective of this study is to compare the efficacy of esomeprazole-bismuth-tetracycline-levofloxacin therapy (TL quadruple therapy) and esomeprazole-amoxicillin-levofloxacin triple therapy (AL triple therapy) in rescue treatment for H. pylori infection.Methods:Consecutive H. pylori-infected subjects after failure of first-line therapies were randomly allocated to receive either TL quadruple therapy (esomeprazole 40 mg b.d., bismuth 120 mg q.d.s., tetracycline 500 mg q.d.s., and levofloxacin 500 mg o.d.) or AL triple therapy (esomeprazole 40 mg b.d., amoxicillin 500 mg q.d.s., and levofloxacin 500 mg o.d.) for 10 days. H. pylori status was assessed 6 weeks after the end of treatment.Results:The study was stopped after an interim analysis. Of 50 patients in the TL quadruple therapy, 49 (98.0%) had successful eradication of H. pylori infection. Cure of H. pylori infection was achieved in 36 of 52 patients (69.2%) receiving AL triple therapy. Intention-to-treat analysis demonstrated that TL quadruple therapy achieved a markedly higher eradication rate than AL triple therapy (difference: 28.8%; 95% confidence interval: 15.7% to 41.9%; P<0.001). Per-protocol analysis yielded a similar result (97.8% vs. 68.6%; P<0.001). The two treatment groups exhibited comparable frequencies of overall adverse events (22.0% vs. 11.5%) and drug compliance (90.0% vs. 98.1%). The subgroup analysis showed that TL quadruple therapy was superior to AL triple therapy in patients with failure of either standard triple therapy (100% vs. 75.0%; P=0.010) or non-bismuth quadruple therapy (95.0% vs. 52.6%; P=0.003).Conclusions:Ten-day PPI-bismuth-tetracycline-levofloxacin quadruple therapy is a good option for rescue treatment of H. pylori infection following failure of standard triple or non-bismuth quadruple therapy.

 

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Helicobacter pylori infection and serum level of pepsinogen are associated with the risk of metachronous gastric neoplasm after endoscopic resectionKwon Y. Jeon S. Nam S. Shin I.Alimentary Pharmacology and Therapeutics (2017) 46:8 (758-767). Date of Publication: 1 Oct 2017Background: Patients who have undergone endoscopic resection of early gastric cancers (EGCs) are at risk for metachronous gastric neoplasm. Aim: To determine whether serum level of pepsinogen (PG), a marker of gastric atrophy, can determine which patients who have undergone endoscopic submucosal dissection for EGC are at risk for metachronous gastric neoplasm. We also investigated the effects of Helicobacter pylori eradication on metachronous gastric neoplasm incidence. Methods: We performed a retrospective study of 590 consecutive patients who underwent endoscopic submucosal dissection for EGC, from January 2008 to May 2013 at a tertiary centre in South Korea; serum levels of PG were measured at the time of endoscopic submucosal dissection and H. pylori infection status were recorded. In case of proven presence of current H. pylori infection, eradication treatment was provided. Patients underwent follow-up endoscopies at 3 months, 9 months, and each year after the procedure to detect neoplasms and were tested for H. pylori infection; serum levels of PG were measured at these time points from 442 of the patients. The main and sub-cohorts were assessed for baseline characteristics, H. pylori infection, serum level of PG, and metachronous gastric neoplasm lesions. Results: During a median follow-up period of 47.7 months, 64 patients developed metachronous gastric neoplasms. In multivariate analysis of the main cohort (n = 590), risk factors for metachronous gastric neoplasm included persistent H. pylori infection (hazard ratio [HR], 2.532; P =.022) and serum ratio of PGI:PGII of three or less at the time of endoscopic submucosal dissection (HR, 1.881; P =.018). Among patients with serum PG measurements, persistent H. pylori infection (odds ratio [OR], 4.404; P =.009) and persistent decrease in mean serum ratio of PGI:PGII to 3 or less were associated with increased risk of metachronous gastric neoplasm (OR, 2.141; P =.039). Conclusions: In a retrospective analysis of patients who underwent endoscopic resection of EGCs, eradication of H. pylori infection reduced risk for metachronous gastric neoplasm. Serum ratio of PGI:PGII of 3 or less also increase risk of metachronous gastric neoplasm after endoscopic submucosal dissection. ClinicalTrials.gov. registry number, NCT02682446.

 

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Effects of Helicobacter pylori treatment on rosacea: A single-arm clinical trial studySaleh P. Naghavi-Behzad M. Herizchi H. Mokhtari F. Mirza-Aghazadeh-Attari M. Piri R.Journal of Dermatology (2017) 44:9 (1033-1037). Date of Publication: 1 Sep 2017Rosacea is a chronic dermatological disease. Helicobacter pylori has been discussed as one of its causative factors. In this clinical trial study, we attempted to evaluate the effect of H. pylori standard eradication protocol on the rosacea clinical course. In this single-arm clinical trial, patients ascertained to have H. pylori infection based on serological studies were assessed to examine existence of rosacea. Patients with concurrent rosacea and H. pylori infection were included in the study and underwent standard H. pylori eradication therapy. Rosacea was evaluated using the Duluth rosacea grading score at the beginning, 2 months later and at the end of the trial (day 180). Of 872 patients positive for H. pylori, 167 patients (19.15%) manifested the clinical features of rosacea. The patients with concurrent rosacea were younger (P < 0.001) and with a female sex predominance (P = 0.03) when compared with rosacea-free patients. Of 167 patients, 150 received H. pylori eradication therapy, demonstrating a 92% (138/150) cure rate. The rosacea Duluth score grading on day 0, 60 and 180 among 138 patients significantly decreased in most of the criteria except for telangiectasias (P = 0.712), phymatous changes (P = 0.535) and the existence of peripheral involvement (P = 0.431). The present study concluded that H. pylori eradication leads to improvement of rosacea.

 

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Changes with aging in gastric biomarkers levels and in biochemical factors associated with Helicobacter pylori infection in asymptomatic Chinese populationShan J.-H. Bai X.-J. Han L.-L. Yuan Y. Sun X.-F.World Journal of Gastroenterology (2017) 23:32 (5945-5953). Date of Publication: 28 Aug 2017AIM To observe changes in gastric biomarker levels with age and effects of Helicobacter pylori (H. pylori ) infection in a healthy population, and explore factors associated with gastric biomarkers. METHODS Three hundred and ninety-five subjects were selected and underwent physical examinations, biochemical tests, and measurement of serum pepsinogen (PG) I and II, gastrin-17 (G-17) and H. pylori antibody levels. Analyses were made by Student's t-Test, ANOVA, Pearson's correlation and multiple linear regressions. RESULTS PGII levels were higher in the ≥ 65-years-old age group (P < 0.05) and PGI/PGII were lower in the ≥ 75-years-old age group (P = 0.035) compared to the 35-44-years-old age group. Levels of low-density lipoprotein cholesterol (LDL-C) were higher (P = 0.009) in H. pylori-infected subjects that were male. LDL-C levels were higher in 55-74-years-old age group (P < 0.05) for H. pylori-infected subjects and 45-64-yearsold age group (P < 0.05) for non-infected subjects compared to 35-44-years-old age group. Hp-IgG level positively correlated with PGI, PGII and G-17 (P < 0.001, P < 0.001, P = 0.006), and negatively correlated with PGI/PGII (P < 0.001). Creatinine positively correlated with PGI, PGII and G-17 (P < 0.001, P < 0.001, P < 0.001). Fasting blood glucose (FBG) positively correlated with PGI/PGII and G-17 (P < 0.001, P = 0.037). Age positively correlated with PGII and G-17 (P = 0.005, P = 0.026). CONCLUSION PGII levels increased while PGI/PGII declined with age in a healthy population. H. pylori infection had an effect on raising LDL-C levels to increase the risk of atherosclerosis in males, especially those of elderly age. Age, H. pylori infection, levels of renal function and FBG were associated with levels of pepsinogens and gastrin.

 

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Optimized high-dose amoxicillin-proton-pump inhibitor dual therapies fail to achieve high cure rates in ChinaHu J.-L. Yang J. Zhou Y.-B. Li P. Han R. Fang D.-C.Saudi Journal of Gastroenterology (2017) 23:5 (275-280). Date of Publication: 1 Sep 2017Background\Aim: Quadruple daily administration of proton-pump inhibitor (PPI) therapy achieves potent acid inhibition, and combined with amoxicillin, with its pharmacodynamic and pharmacokinetic characteristics, may be efficient for Helicobacter pylori eradication. We compared the efficacy of two optimized high-dose dual therapies with a bismuth-containing quadruple regimen for treating H. pylori infection. Rabeprazole dosages for H. pylori eradication were also evaluated. Patients and Methods: Treatment-naive and H. pylori-positive subjects were recruited and randomly apportioned to three treatment groups: Group A (n = 87), rabeprazole 10 mg plus amoxicillin 750 mg (4 times/day for 14 days); Group B (n = 87), rabeprazole 20 mg plus amoxicillin 750 mg (4 times/day for 14 days); and Group C (n = 89), bismuth-containing quadruple regimen consisting of rabeprazole 20 mg, bismuth 220 mg, amoxicillin 1000 mg, and clarithromycin 500 mg (2 times/day for 14 days). Four weeks after treatment discontinuation, patients were examined for H. pylori infection by (13)C-urea breath test. The rates of adverse effects, compliance, and eradication were evaluated. Results: Eradication rates in groups A, B, and C were 78.1, 81.6, and 84.3%, respectively, based on intention-To-Treat analysis, or 79.1, 83.5, and 86.2%, according to per-protocol analysis. Rates of adverse events and compliance of the three groups were similar. Conclusion: For treating H. pylori infection, optimized high-dose amoxicillin-PPI dual therapies failed to achieve high cure rates in China and held no advantage over a bismuth-containing quadruple regimen.

 

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Meta-analysis: Association of Helicobacter pylori infection with Parkinson's diseasesShen X. Yang H. Wu Y. Zhang D. Jiang H.Helicobacter (2017) 22:5 Article Number: e12398. Date of Publication: 1 Oct 2017Background: The results from observational studies on the relationship between helicobacter pylori (H. pylori) infection and Parkinson's disease remain controversial. A meta-analysis was conducted to evaluate the association between helicobacter pylori infection and Parkinson's disease. Methods: A comprehensive literature search was performed on relevant studies published from January 1983 to January 2017 in PubMed, Web of Science and EMBASE databases. The fixed or random effects model was used to pool the odds ratio with 95% confidence interval from individual studies. Publication bias was estimated by Egger's test and the funnel plot. Results: Eight eligible studies involving 33 125 participants were included in this meta-analysis. Compared with the no helicobacter pylori infected person, the pooled odds ratio of Parkinson's disease in helicobacter pylori infected person was 1.59 (95% confidence interval: 1.37-1.85). In subgroup analyzes, the combined odds ratios were 1.96 (1.23-3.12) in Asia, 1.55 (1.32-1.82) in Europe, 1.59 (1.35-1.88) in case-control studies, 1.56 (1.01-2.39) in cross-sectional studies, 1.56 (1.32-1.85) in studies with confounders adjusted, and 1.71 (1.21-2.43) in studies with no confounder adjusted, respectively. Conclusions: This meta-analysis indicated that H. pylori infection might be associated with the risk of Parkinson's disease.

 

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A significant increase in the pepsinogen I/II ratio is a reliable biomarker for successful Helicobacter pylori eradicationOsumi H. Fujisaki J. Suganuma T. Horiuchi Y. Omae M. Yoshio T. Ishiyama A. Tsuchida T. Miki K.PLoS ONE (2017) 12:8 Article Number: e0183980. Date of Publication: 1 Aug 2017Background: Helicobacter pylori (H. pylori) eradication is usually assessed using the (13)C-urea breath test (UBT), anti-H. pylori antibody and the H. pylori stool antigen test. However, a few reports have used pepsinogen (PG), in particular, the percentage change in the PG I/II ratio. Here, we evaluated the usefulness of the percentage changes in serum PG I/II ratios for determining the success of eradication therapy for H. pylori. Materials and methods: In total, 650 patients received eradication therapy from October 2008 to March 2013 in our Cancer Institute Hospital. We evaluated the relationship between H. pylori eradication and percentage changes in serum PG I/II ratios before and 3 months after treatment with CLEIA® (FUJIREBIO Inc, Tokyo, Japan). The gold standard of H. pylori eradication was defined as negative by the UBT performed 3 months after completion of eradication treatment. Cut-off values for percentage changes in serum PG I/II ratios were set as +40, +25 and +10% when the serum PG I/II ratio before treatment was below 3.0, above 3.0 but below 5.0 and 5.0 or above, respectively. Results: Serum PG I and PG II levels were measured in 562 patients with H. pylori infection before and after eradication therapy. Eradication of H. pylori was achieved in 433 patients studied (77.0%). The ratios of first, second, third-line and penicillin allergy eradication treatment were 73.8% (317/429), 88.3% (99/112), 75% (12/16) and 100% (5/5), respectively. An increasing percentage in the serum levels of the PG I/II ratios after treatment compared with the values before treatment clearly distinguished success from failure of eradication (108.2 ±57.2 vs. 6.8±30.7, p<0.05). Using the above cut-off values, the sensitivity, specificity and validity for determination of H. pylori were 93.1, 93.8 and 93.2%, respectively. Conclusion: In conclusion, the percentage changes in serum PG I/II ratios are useful as evaluation criteria for assessing the success of eradication therapy for H. pylori.

 

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Probiotics in Helicobacter pylori eradication therapy: Systematic review and network meta-analysisWang F. Feng J. Chen P. Liu X. Ma M. Zhou R. Chang Y. Liu J. Li J. Zhao Q.Clinics and Research in Hepatology and Gastroenterology (2017) 41:4 (466-475). Date of Publication: 1 Sep 2017Background Several probiotics were effective in the eradication treatment for Helicobacter pylori (Hp), but their comparative efficacy was unknown. Aim To compare the efficacy of different probiotics when supplemented in Hp eradication therapy. Methods A comprehensive search was conducted to identify all relevant studies in multiple databases and previous meta-analyses. Bayesian network meta-analysis was performed to combine direct and indirect evidence and estimate the relative effects. Results One hundred and forty studies (44 English and 96 Chinese) were identified with a total of 20,215 patients, and more than 10 probiotic strategies were supplemented in Hp eradication therapy. The rates of eradication and adverse events were 84.1 and 14.4% in probiotic group, while 70.5 and 30.1% in the control group. In general, supplementary probiotics were effective in improving the efficacy of Hp eradication and decreasing the incidence of adverse events, despite of few ineffective subtypes. In triple eradication therapy, there was no significant difference among the effective probiotics, and combined probiotics did not show a better efficacy and tolerance than single use. In triple therapy of 7 days and 14 days, Lactobacillus acidopilus was a slightly better choice, while Saccharomyces boulardii was more applicable for 10-day triple therapy. Conclusions Compared to placebo, most probiotic strategies were effective when supplemented in Hp eradication therapy. In triple eradication therapy, no probiotic showed a superior efficacy to the others. Compared to single use, combined probiotics could not improve the efficacy or tolerance significantly.

 

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Curcumin in combination with triple therapy regimes ameliorates oxidative stress and histopathologic changes in chronic gastritis– associated helicobacter pylori infectionJudaki A. Rahmani A. Feizi J. Asadollahi K. Hafezi Ahmadi M.R.Arquivos de Gastroenterologia (2017) 54:3 (177-182). Date of Publication: 1 Jul 2017Background – Helicobacter pylori (H. pylori) gastric infection is a main cause of inflammatory changes and gastric cancers. Objective – The aim of this study was finding the effects of curcumin on oxidative stress and histological changes in chronic gastritis associated with H. pylori. Methods – In a randomized clinical trial, patients were divided into two groups: a standard triple therapy group and triple therapy with curcumin group. Endoscopic and histological examinations were measured for all patients before and after 8 weeks. Results – Triple therapy with curcumin treatment group significantly decreased malondialdehyde markers, glutathione peroxides and increased total antioxidant capacity of the gastric mucosa at the end of study compared to baseline and triple regimen groups. In addition, the oxidative damage to DNA was significantly decreased in triple therapy with curcumin group at the end of study compared to baseline and compared to triple therapy (P<0.05 for both). Triple therapy group in combination with Curcumin significantly decreased all active, chronic and endoscopic inflammation scores of patients compared to the baseline and triple therapy group (P<0.05 for both). The eradication rate by triple therapy + curcumin was significantly increased compared to triple therapy alone (P<0.05). Conclusion – Curcumin can be a useful supplement to improve chronic inflammation and prevention of carcinogenic changes in patients with chronic gastritis associated by H. pylori.

 

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Investigation of IgG and IgM seroprevalence of Helicobacter pylori infections and their relation toil-6 and some risk factors among dyspeptic patients in Al-Qasim city of Babylon provinceAbbas A.F. Al-Saadi A.G.M. Fazaa S.A.Research Journal of Pharmaceutical, Biological and Chemical Sciences (2017) 8:5 (255-261). Date of Publication: 2017We aimed to explore the predominance of H. pylori infections in dyspeptic patients by detection specific IgG and IgM and their relationship to IL-6 and some risk factors. A total of 250 blood specimens were collected from patients with dyspeptic symptoms. ELISA technique was utilized to detect specific anti-H. pylori IgG and IgM, and IL-6 concentration. Results showed high IL-6 concentrations in seropositive compared with seronegative dyspeptic patients group at probability level (P ≤ 0.005). 201 (80.4%) of the sera specimens were positive to H. pylori(IgG), 115 (46%) were positive to H. pylori (IgM),95 (38%) were positive to both IgG and IgM, and 29 ( 11.6%) were negative to both .The prevalence rates of IgG and IgM were higher in male 87.4% (97/111) and 53.2%(59/111) than female 74.8 (104/139) and 40.3% (56/139) respectively. Additionally, the age of 51-60 years had the highest (93.8%) H. pylori-IgG prevalence rate, while H. pylori-IgM (62.9%) was predominant among patients in the age group 41-50 years. H. pylori IgG and IgM prevalence rates were 93.9% (92/98) and 64.3 %(63/98) respectively among smokers. In conclusion, the high infection rate of H. pylori in dyspeptic patients was significantly associated with IL-6, and prevalence rate of H.pylori infection strongly correlates with gender, age, smoking and presence of H.pylori-infected family members.

 

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Characteristics of gastric cancer in negative test of serum anti-Helicobacter pylori antibody and pepsinogen test: a multicenter studyKiso M. Yoshihara M. Ito M. Inoue K. Kato K. Nakajima S. Mabe K. Kobayashi M. Uemura N. Yada T. Oka M. Kawai T. Boda T. Kotachi T. Masuda K. Tanaka S. Chayama K.Gastric Cancer (2017) 20:5 (764-771). Date of Publication: 1 Sep 2017Background and aim: The serological risk prediction system combines the pepsinogen test and anti-Helicobacter pylori (H. pylori) antibody determination. In this system, chronic atrophic gastritis (CAG) is diagnosed using the pepsinogen test. Patients who are H. pylori negative and pepsinogen negative are classified into group A, are assumed to be H. pylori uninfected, and are at an extremely low risk for gastric cancer. However, gastric cancers are detected in this group. The aim of this study is to clarify the clinicopathological status of group A patients with gastric cancer. Methods: A total of 109 gastric cancer patients classified as group A were enrolled in a multicenter study. Group A patients were divided into two subgroups: group AN (H. pylori uninfected) and group AP (H. pylori infected). They were compared to 183 H. pylori-infected gastric cancer patients who were not in group A. Results: Of the 109 patients, only 7 were classified as group AN; the other 102 were classified as group AP. The clinicopathological features of group AP included older age, predominantly differentiated type cancer, endoscopically visualized CAG, and pepsinogen (PG) I/II ratio lower than that of group AN. In group AN, the depressed type was dominant, and the PG I/II ratio was higher than in those gastric cancer patients who were infected with H. pylori. Conclusion: Patients in group AP had CAG, and their gastric cancers were similar to those of H. pylori-eradicated patients. Concerning the recent ABC classification system, advanced decision criteria should be proposed to decrease the false-negative evaluation of gastric cancer risk.

 

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Combination of Interleukin 1 Polymorphism and Helicobacter pylori Infection: an Increased Risk of Gastric Cancer in Pakistani PopulationRaza Y. Khan A. Khan A.I. Khan S. Akhter S. Mubarak M. Ahmed A. Kazmi S.U.Pathology and Oncology Research (2017) 23:4 (873-880). Date of Publication: 1 Oct 2017Helicobacter pylori is one of the major risk factors involved in the development ofgastritis and gastric cancer (GC). H. pylori infection leads to increased production of pro-inflammatory cytokines by the host. Carriage of specific polymorphisms in cytokine genes may be associated with host susceptibility to the development of GC. We investigated the role of host genetic factors including polymorphisms of IL-1B and IL-1RN in correlation with gastritis and GC in H. pylori infected Pakistani population. A total of 230 gastritis cases and 100 GC cases were genotyped for IL 1B-511 and IL-1RN penta-allelic variable number of tandem repeats (VNTRs). A combination of IL-1B-511*T and IL-1RN*2 alleles (OR 19.064; 95% CI 2.319–156.7; p = 0.001) in H. pylori infected individuals had markedly increased risk of GC development. In Pakistani population, an increased risk of GC development is associated with the carriage of IL-1B-511*T and IL-1RN*2 alleles. Synergistic effect of H. pylori infection and IL-1B-511*T/IL-1RN*2 genotypes was also observed in association with significantly higher risk of developing GC. Further prospective and large scale studies are needed to establish the clinical impact of these findings.

 

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Helicobacter pylori-not a lonely player in gastric carcinogenesisVrancianu A.-M. Costache D.-A. Harsan P.-B. Zurac S.A. Mateescu B.R. Popp C.G. Micu V.G.Virchows Archiv (2017) 471:1 Supplement 1 (S183). Date of Publication: 1 Sep 2017Objective: Helicobacter pylori(HP) is considered the most important factor that triggers and maintains the evolution towards gastric adenocarcinoma in patients with chronic gastritis. This study evaluates correlations between Helicobacter pylori (HP) infection and pre-malignant changes of gastric epithelium. Method: We present a retrospective study including 153 cases of chronic gastritis with associated dysplasia, 62 males and 91 females, aged 25 to 92, with no previous anti-HP treatment. In 85 cases (55.56 %), patients presented HP infection with different density levels (62.74 % - low, 24.18 % - medium, 13.08 % - high). Results: Only 16.34 % of the non-infected patients presented both atrophy and metaplasia, while 24.18 % of the infected ones had those histopathologic changes. Most cases without HP had inactive gastritis, while 69.93 % of the infected had highly active gastritis. Only 10 patients with intestinal type gastric adenocarcinoma, all infected. High-grade dysplasia (including globoid type) was less associated with atrophy and metaplasia, but more with their absence in gastritis with HP. Conclusion: HP is not the only factor involved in the development of intestinal type gastric adenocarcinoma. Other factors are inducing similar pre-malignant changes and only HP-eradication is not sufficient to cease carcinogenesis cascade.

 

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Modulation of Galectin-3 and Galectin 9 in gastric mucosa of patients with chronic gastritis and positive Helicobacter pylori infectionEstevam R.B. Wood da Silva N.M.J. Wood da Silva X. Fonseca F.M. Oliveira A.G.D. Nogueira X. Pereira S.A.D.L. Pereira T.L. Adad S.J. Rodrigues V.J. Rodrigues D.B.R.Pathology Research and Practice (2017). Date of Publication: 2017Objectives: Galectins are mediators that play an important role in the inflammatory response and in this study we analyzed the expression of Galectins (Gal) -1, -3 and -9 in biopsies of the gastric antrum of patients with upper gastrointestinal symptoms. Methodology: 44 patients with upper digestive tract symptoms were evaluated, and underwent Upper Digestive Endoscopy examination. Sections of the gastric antrum were fixed in buffered formaldehyde at 4% in order to perform the anatomopathological examination and immunohistochemical analysis for Galectins-1, -3 and -9 expression. Fresh sections of gastric antrum were used for DNA extraction and evaluation of Helicobacter pylori (H. pylori). P values. <. 0.05 were considered statistically significant. Results: Gal-1 was significantly more expressed on stroma than epithelium (p. <. 0.0001), whereas Gal-3 and Gal-9 were more expressed on epithelium (p. <. 0.0001). Gal-3 was found to be significantly higher in the stroma of patients with H. pylori infection, mainly on Cag-A positive H. pylori (p. <. 0.0001). Gal-9 was down modulated in stroma of patients with chronic gastritis. Conclusion: Up modulation of Gal-3 expression was associated with H. pylori infection and down modulation of Gal-9 with the inflammatory process of chronic gastritis.

 

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Relationship between helicobacter pylori infection and colorectal cancer: A meta-analysis of observational studiesWang X. Wang G. Zhang L.International Journal of Clinical and Experimental Medicine (2017) 10:8 (11402-11408). Date of Publication: 2017Helicobacter pylori infection has been proposed to be associated with bowel cancers. The purpose of this meta-analysis was to evaluate the association between H. pylori infection and CRC. In this study, all case-control studies up to January, 2017 were identified by searching PubMed and Cochrane library. In absence of significant heterogeneity fixed-effects model (Mantel-Haenszel method) was used otherwise random effects (Der Simonian-Laird method) model was used. Subgroup analysis was performed to assess the sources of heterogeneity (CRC subtype, geographic area, and study design type). 6 case-control studies, and 4 cross-sectional studies with a total of 16,857 participants and more than 3300 incident cases of CRC were included in our meta-analysis. In overall meta-analysis, pooled analysis of 10 observational studies imply that there is an increased risk of CRC in patients with history of H. pylori infection. But, pooling high quality studies showed that there was no significant association between H. pylori infection and risk of CRC. In subgroup analysis, association between H. pylori infection and CRC was observed only in cross-sectional studies but not in case-control studies. Both colon and rectal cancer did not show any significant association with H. pylori infection. Studies conducted in Asia showed a significant positive association of risk of CRC and H. pylori infection. Our meta-analysis suggests that there is no conclusive evidence to show the association between risk of CRC and H. pylori infection, and the heterogeneity present in the existing evidence which was neglected in many of the previous meta-analysis while deriving conclusions.

 

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Accuracy of the Ultra-Rapid Urease Test for diagnosis of Helicobacter pylori infectionMcNicholl A.G. Ducons J. Barrio J. Bujanda L. Forné-Bardera M. Aparcero R. Ponce J. Rivera R. Dedeu-Cuso J.M. Garcia-Iglesias P. Montoro M. Bejerano A. Ber-Nieto Y. Madrigal B. Zapata E. Loras-Alastruey C. Castro M. Nevarez A. Mendez I. Bory-Ros F. Miquel-Planas M. Vera I. Nyssen O.P. Gisbert J.P.Gastroenterologia y Hepatologia (2017). Date of Publication: 2017Background: Rapid Urease Test (RUT) is a simple, cheap and relatively fast method for diagnosing Helicobacter pylori infection. It is therefore the preferred method used for patients undergoing gastroscopy. Most kits require 24. h to give results. The new Ultra-Rapid Urease Test (URUT) kit by Biohit® requires less than 1. h. Objective: To determine URUT's diagnostic accuracy. Method: Prospective, blind, multi-centre study involving dyspeptic patients. One corpus biopsy and three antral biopsies were obtained during gastroscopy for standard histological analysis, RUT and URUT. The URUT result was checked after 1. min, 5. min, 30. min and 60. min and the RUT was checked over the course of 24. h. Histology was used as the gold standard test. Results: 144 patients were included, 68% female, with a mean age of 49 years old; 50% were H. pylori positive. RUT and URUT diagnoses were correct in 85.9% and 90% of the cases, respectively. The mean waiting time for a positive RUT result was 6. h. The sensitivity, specificity, and positive and negative predictive values for RUT were, respectively, 82%, 90%, 89% and 84%. The URUT's results were similar (85%, 94%, 94% and 87%). These figures improved when patients taking PPIs were excluded (RUT: 86%, 91%, 93% and 83%; URUT: 91%, 94%, 96% and 89%). No statistically significant differences were found when comparing RUT and URUT distributions of correct diagnoses (McNemar's Test, p = 0.3) but there was a tendency towards better results with the URUT. Conclusion: The URUT is equivalent to (or slightly better than) the traditional RUT in diagnosing H. pylori infection, and provides results in less than an hour.

 

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TIFA signaling in gastric epithelial cells initiates the cag type 4 secretion system-dependent innate immune response to helicobacter pylori infectionGall A. Gaudet R.G. Gray-Owen S.D. Salama N.R.mBio (2017) 8:4 Article Number: e01168-17. Date of Publication: 1 Jul 2017Helicobacter pylori is a bacterial pathogen that colonizes the human stomach, causing inflammation which, in some cases, leads to gastric ulcers and cancer. The clinical outcome of infection depends on a complex interplay of bacterial, host genetic, and environmental factors. Although H. pylori is recognized by both the innate and adaptive immune systems, this rarely results in bacterial clearance. Gastric epithelial cells are the first line of defense against H. pylori and alert the immune system to bacterial presence. Cytosolic delivery of proinflammatory bacterial factors through the cag type 4 secretion system (cag-T4SS) has long been appreciated as the major mechanism by which gastric epithelial cells detect H. pylori. Classically attributed to the peptidoglycan sensor NOD1, recent work has highlighted the role of NOD1-independent pathways in detecting H. pylori; however, the bacterial and host factors involved have remained unknown. Here, we show that bacterially derived heptose-1,7-bisphosphate (HBP), a metabolic precursor in lipopolysaccharide (LPS) biosynthesis, is delivered to the host cytosol through the cag-T4SS, where it activates the host tumor necrosis factor receptor-associated factor (TRAF)-interacting protein with forkhead-associated domain (TIFA)-dependent cytosolic surveillance pathway. This response, which is independent of NOD1, drives robust NF-κB-dependent inflammation within hours of infection and precedes NOD1 activation. We also found that the CagA toxin contributes to the NF-κB-driven response subsequent to TIFA and NOD1 activation. Taken together, our results indicate that the sequential activation of TIFA, NOD1, and CagA delivery drives the initial inflammatory response in gastric epithelial cells, orchestrating the subsequent recruitment of immune cells and leading to chronic gastritis. IMPORTANCE H. pylori is a globally prevalent cause of gastric and duodenal ulcers and cancer. H. pylori antibiotic resistance is rapidly increasing, and a vaccine remains elusive. The earliest immune response to H. pylori is initiated by gastric epithelial cells and sets the stage for the subsequent immunopathogenesis. This study revealed that host TIFA and H. pylori-derived HBP are critical effectors of innate immune signaling that account for much of the inflammatory response to H. pylori in gastric epithelial cells. HBP is delivered to the host cell via the cag-T4SS at a time point that precedes activation of the previously described NOD1 and CagA inflammatory pathways. Manipulation of the TIFA-driven immune response in the host and/or targeting of ADP-heptose biosynthesis enzymes in H. pylori may therefore provide novel strategies that may be therapeutically harnessed to achieve bacterial clearance.

 

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Increased risk of chronic obstructive pulmonary disease among patients with Helicobacter pylori infection: a population-based cohort studyPeng Y.-H. Chen C.-K. Su C.-H. Liao W.-C. Muo C.-H. Hsia T.-C. Sung F.-C. Lai C.-H. Kao C.-H.Clinical Respiratory Journal (2017) 11:5 (558-565). Date of Publication: 1 Sep 2017Background: Increasing evidence suggests that Helicobacter pylori infection (HPI) may have extragastric manifestations, including the respiratory system. This study investigated the role of HPI in increasing the subsequent risk of chronic obstructive pulmonary disease (COPD) in a nationwide population. Methods: We conducted this retrospective cohort study using data from the Longitudinal Health Insurance Database, which is derived from the Taiwanese National Health Insurance Research Database. A total of 5941 adults who were newly diagnosed with HPI between 2005 and 2006 were selected. Healthy patients without HPI were selected from the general population and frequency matched as a ratio of 4:1, according to age, sex, and index years. Both cohorts were followed up from the index date to the end of 2011 to measure the incidence of COPD. Cox proportional hazard regression analysis was used to assess the hazard ratio (HR) of COPD between the HPI cohort and non-HPI cohorts. Results: The overall HR of COPD was 1.84 (95% confidence intervals = 1.57–2.17) for the HPI cohort, compared with the non-HPI cohort, after adjusting for age, sex, and comorbidities. Although the incidence of COPD was substantially higher in the elderly participants (age, ≥ 65 years) than that in younger participants, the highest HR (4.05, 95% confidence intervals = 1.39–11.8) of COPD was observed in the youngest (age, 20–49 years) participants. Conclusion: In this study, the patients with HPI exhibited a significantly higher risk of COPD than those without HPI did.

 

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Decline in prevalence and risk of helicobacter pylori in kidney transplant recipients: A systematic review and meta-analysisCheungpasitporn W. Thongprayoon C. Wijarnpreecha K. Mitema D.G. Mao M.A. Nissaisorakarn P. Podboy A. Kittanamongkolchai W. Sakhuja A. Erickson S.B.Journal of Evidence-Based Medicine (2017) 10:3 (171-176). Date of Publication: 1 Aug 2017Objective: The study's aims were (1) to investigate the prevalence and (2) to assess the risk of Helicobacter pylori (H. pylori) infection in kidney transplant recipients. Methods: A comprehensive literature search was performed from inception until September 2016. Studies that reported prevalence, relative risks, odd ratios, or hazard ratios of H. pylori among kidney transplant recipients were included. Pooled risk ratios and 95% CI were calculated using a random-effect model. Results: Eleven observational studies with 2545 kidney transplant recipients were enrolled. Between year 1990 and 2000, the estimated prevalence of H. pylori among people with kidney transplant was 50% (95% CI: 31% to 68%), with a prevalence of 46% (95% CI: 23% to 70%) in high-income countries and 55% (95% CI: 22% to 86%) in middle-income countries, respectively. From year 2000 to 2016, the estimated prevalence of H. pylori among people with kidney transplant was 35% (95% CI: 26% to 45%), with a prevalence of 28% (95% CI: 19% to 37%) in high-income countries and 45% (95% CI: 38% to 51%) in middle-income countries. Data regarding prevalence of H. pylori infection in low-income countries were limited. The pooled RR of H. pylori in kidney transplant recipients was 0.57 (95% CI: 0.33 to 1.00) when compared to people with non-transplant. Conclusions: There has been a decline in prevalence of H. pylori in kidney transplant recipients with the overall estimated prevalence of H. pylori in kidney transplant recipients of 35%, particularly in both high-income and middle-income countries. Also, our meta-analysis demonstrates a potential decreased risk of H. pylori infection in kidney transplant recipients compared with non-transplant populations.

 

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Interleukin-17C in human Helicobacter pylori gastritisTanaka S. Nagashima H. Cruz M. Uchida T. Uotani T. Abreu J.A.J. Mahachai V. Vilaichone R. Ratanachu-ek T. Tshering L. Graham D.Y. Yamaoka Y.Infection and Immunity (2017) 85:10 Article Number: e00389-17. Date of Publication: 2017The interleukin-17 (IL-17) family of cytokines (IL-17A to IL-17F) is involved in many inflammatory diseases. Although IL-17A is recognized as being involved in the pathophysiology of Helicobacter pylori-associated diseases, the role of other IL-17 cytokine family members remains unclear. Microarray analysis of IL-17 family cytokines was performed in H. pylori-infected and uninfected gastric biopsy specimens. IL-17C mRNA was upregulated approximately 4.5-fold in H. pylori-infected gastric biopsy specimens. This was confirmed by quantitative reverse transcriptase PCR in infected and uninfected gastric mucosa obtained from Bhutan and from the Dominican Republic. Immunohistochemical analysis showed that IL-17C expression in H. pylori-infected gastric biopsy specimens was predominantly localized to epithelial and chromogranin A-positive endocrine cells. IL-17C mRNA levels were also significantly greater among cagA-positive than cagA-negative H. pylori infections (P = 0.012). In vitro studies confirmed an increase in IL-17C mRNA and protein levels in cells infected with cagA-positive infections compared to cells infected with either cagA-negative or cag pathogenicity island (PAI) mutant. Chemical inhibition of IκB kinase (IKK), mitogen-activated protein extracellular signal-regulated kinase (MEK), and Jun N-terminal kinase (JNK) inhibited induction of IL-17C proteins in infected cells, whereas p38 inhibition had no effect on IL-17C protein secretion. In conclusion, H. pylori infection was associated with a significant increase in IL-17C expression in human gastric mucosa. The role of IL-17C in the pathogenesis of H. pyloriinduced diseases remains to be determined.

 

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Erythromycin encapsulation in nanoemulsion-based delivery systems for treatment of Helicobacter pylori infection: Protection and synergyTran L.T.C. Gueutin C. Frebourg G. Burucoa C. Faivre V.Biochemical and Biophysical Research Communications (2017). Date of Publication: 2017Poorly water-soluble and unstable compounds are difficult to develop as drug products using conventional formulation techniques. The aim of the present study was to develop and evaluate a nanoformulation prepared by a hot high-pressure homogenization method, which was a scalable and solvent-free process. We successfully prepared stable nanodispersions to protect a labile antibiotic, erythromycin. The mean diameter of the dispersed droplets was approximately 150 nm, and size distribution was unimodal. Dispersion was physically stable at room temperature for over six months. Using erythromycin as a model compound, we studied its antimicrobial activity in vitro on Helicobacter pylori. Results showed that drug encapsulation improves API stability in an acidic environment and is conducive to a synergistic effect between the drug and the formulation.

 

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Characteristics and risk factors for sporadic non-ampullary duodenal adenocarcinomaKakushima N. Ono H. Yoshida M. Takizawa K. Tanaka M. Kawata N. Ito S. Imai K. Hotta K. Ishiwatari H. Matsubayashi H.Scandinavian Journal of Gastroenterology (2017) 52:11 (1253-1257). Date of Publication: 2 Nov 2017Objectives: Despite the gradual increase in the incidence of non-ampullary duodenal adenocarcinoma (NADAC), the associated characteristics and risk factors remain poorly understood. The aim of this study was to clarify the clinical characteristics and risk factors of sporadic NADAC. Materials and methods: In this retrospective case-control study, we enrolled 156 Japanese NADAC patients with 160 lesions from our hospital’s cancer registry over 13 years. The patient demographics and clinical findings were compared to 468 age- and sex-matched controls selected from our medical health checkup recipients. Results: The ratio of men to women among the NADAC patients was 2:1, the median age was 64 years (range 31 to 90 years), the majority of the lesions were located in the second portion of the duodenum, and well-differentiated adenocarcinoma was the dominant histology. A univariate analysis revealed that smoking was a common risk factor for both men and women, whereas Helicobacter pylori (HP) infection and a history of colorectal cancer (CRC) were risk factors for the men. The multivariate analysis revealed that smoking, a history of CRC, and HP positivity were also individual risk factors for NADAC. Conclusions: Smoking, a history of CRC, and HP positivity were identified as risk factors for NADAC.

 

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Associations of Helicobacter pylori infection and peptic disease with diabetic mellitus: Results from a large population-based studyHaj S. Chodick G. Refaeli R. Goren S. Shalev V. Muhsen K.PLoS ONE (2017) 12:8 Article Number: e0183687. Date of Publication: 1 Aug 2017Background: Evidence is conflicting regarding the association between Helicobacter pylori infection and diabetes mellitus. The study objective was to examine associations of H. pylori infection, gastric ulcers and duodenal ulcers, with diabetes mellitus. Methods: This cross-sectional study was undertaken using coded data from the computerized database of Maccabi Health Services in Israel, on 147,936 individuals aged 25–95 years who underwent the urea breath test during 2002–2012. Multiple logistic regression models were conducted, while adjusting for known risk factors for diabetes mellitus. Results: A H. pylori positive test was recorded for 76,992 (52.0%) individuals and diabetes for 12,207 (8.3%). The prevalence of diabetes was similar in individuals with and without H. pylori infection, but this association was modified (P for heterogeneity 0.049) by body mass index (BMI): adjusted odds ratio (aOR) 1.16 (95% confidence intervals (CI) 1.04–1.29) in persons with BMI<25 kg/m(2) versus aOR 1.03 (95% CI 0.98–1.08) in persons with BMI≥25 kg/m(2). Diabetes mellitus prevalence was higher in persons with gastric (aOR 1.20 (95% CI 1.06–1.34)) and duodenal ulcers (aOR 1.20 (95% CI 1.12–1.28)) compared to persons without these diagnoses. Conclusions: In this large population-based study, we demonstrated significant positive associations, albeit of small magnitude, of H. pylori infection and peptic disease with diabetes. The long-term gastric inflammation and associated-damage to the gastric mucosa might play a role in such associations.

 

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Helicobacter pylori infection perturbs iron homeostasis in gastric epithelial cellsFlores S.E. Aitchison A. Day A.S. Keenan J.I.PLoS ONE (2017) 12:9 Article Number: e0184026. Date of Publication: 1 Sep 2017The iron deficiency anaemia that often accompanies infection with Helicobacter pylori may reflect increased uptake of iron into gastric epithelial cells. Here we show an infection-associated increase in total intracellular iron levels was associated with the redistribution of the transferrin receptor from the cell cytosol to the cell surface, and with increased levels of ferritin, an intracellular iron storage protein that corresponded with a significant increase in lysosomal stores of labile iron. In contrast, the pool of cytosolic labile iron was significantly decreased in infected cells. These changes in intracellular iron distribution were associated with the uptake and trafficking of H. pylori through the cells, and enhanced in strains capable of expressing the cagA virulence gene. We speculate that degradation of lysosomal ferritin may facilitate H. pylori pathogenesis, in addition to contributing to bacterial persistence in the human stomach.

 

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Why should pathologist always report glandular atrophy in helicobacter pylori gastritis?Roxana-Zoia B. Micu G.-V. Popp C.-G. Voiosu T. Zurac S.-A.Virchows Archiv (2017) 471:1 Supplement 1 (S180). Date of Publication: 1 Sep 2017Objective: Gastric dysplasia is the last step in Helicobacter pylori (HP) induced carcinogenesis, after glandular atrophy (GA) and intestinal metaplasia (IM). This study evaluates the significance of GA and IM for patients' outcome. Method: We designed a case-control study including endoscopic gastric biopsies from 72 patients with similar demographic data (two groups: 36 patients with gastritis and dysplasia and 36 patients with gastritis without dysplasia). Results: HP infection rate was higher in patients with dysplasia (91 % vs 52 %; p = 0.073). GA and GA-IM association were more frequent in dysplasia group (p = 0.034, respectively p = 0.038). No significant correlation between IM and dysplasia were found. In patients with dysplasia, minimal GA was associated with a higher density of HP (33.33 % vs. 5.55 %), whereas severe GA was linked to low density HP (2.77 % vs. 30.00 %). Conclusion: There is a strong connection between HP status and subsequent premalignant changes. GA is the most significant indicator of evolution towards intraepithelial and invasive malignancy, so it is mandatory to be always evaluated and reported, in order to conceive a special management plan for patients with persistent atrophy after HP gastritis.

 

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Tissue-based in situ detection of the clarithromycin resistance for the personalised Helicobacter pylori eradication therapyKocsmár É. Szirtes I. Kramer Z. Kramer M. Szijártó A. Buzás G.M. Bene L. Kocsmár I. Karczub J. Katona L. Kiss A. Schaff Z. Lotz G.Virchows Archiv (2017) 471:1 Supplement 1 (S191). Date of Publication: 1 Sep 2017Objective: Clarithromycin-resistance (Cla-res) is the leading cause of treatment failure of Helicobacter pylori (HP) infections. Our aim was to examine the prevalence of clarithromycin-resistant HP-infection and its connection to gender and age in a monocentric cohort. Method: 4744 HP-positive adults were examined (2708 females; 57.1 %, 2036 males; 42.9 %). HP-positive gastric mucosal tissue slides were investigated by a bacterial rRNA-targeted FISH-test (BactFISH Helicobacter Combi Kit) detecting the clarithromycin-sensitive and - resistant HP-bacteria. HP eradication-related and -independent antibiotic consumption anamneses of these patients were collected in cooperation with the Hungarian National Health Insurance Fund. Results: Overall Cla-res rate was 17.2 %. Females showed significantly (p < 0.0001) higher Cla-res rate (19.8 %) than males (13.7 %). Low Cla-res prevalence (12.9 %) was found in the age group 70+. Cla-res rate reached 20 % in females aged under 70, while it was less than 15 % in males except ages 30-39 (15.3 %). Cla-res prevalence was significantly lower (5.52 %) in macrolide-naive patients than in the macrolide-treated group (30.5 %; p < 0.001). No significant difference was found between macrolide-naive females and males (6.4 % vs. 4.6 %; p = 0.057). Conclusion: Gender and age distribution of clarithromycin-resistance should be considered for HP-eradication treatments. Our results suggest that higher prevalence of clarithromycin-resistance in females is related to increased exposition to macrolide antibiotics.

 

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Does Helicobacter pylori infection play a role in iron deficiency anemia in hemodialysis patients?El-Said H. Attallah A.H.B. Ali-Eldin Z.A.Clinical Nephrology (2017) 88:4 (177-180). Date of Publication: 2017Background: Among the disorders that may affect patients with endstage renal disease (ESRD), anemia is the most responsive to treatment; any reversible cause should be identified, and the most common reversible cause is iron deficiency. We investigated the relationship between Helicobacter pylori infection and iron deficiency anemia in a hemodialysis population. Materials and methods: This cross-sectional study included 90 adult patients with ESRD on maintenance hemodialysis. Iron deficiency anemia (IDA) was determined by hemoglobin, serum iron, ferritin, and transferrin saturation (TSAT) values. H. pylori diagnosis was done by detection of H. pylori antigen in stool. Results: It was found that H. pylori stool antigen was positive in 50 patients (55.6%), while 40 patients were negative for H. pylori (44.4%). 71% of patients had anemia (Hb < 10 g/dL), and 63% of patients had iron deficiency anemia (TSAT < 30%). No significant differences were found between H. pylori-positive and -negative groups in any of the variables analyzed: hemoglobin (8.96 ± 1.8 vs.9.76 ± 1.4 g/dL), serum iron (86 ± 17.5 vs. 87 ± 18.2 pg/dL), ferritin (284.8 ± 60.5 vs. 301.4 ± 50.1 ng/dL), or TSAT index (26.79 ± 18.42% vs. 29.83 ± 18. 01% μg/dL). Conclusion: H. pylori infection has a nonsignificant effect on iron deficiency anemia in hemodialysis patients. We recommend that routine screening for H. pylori is not needed among dialysis patients with iron deficiency anemia.

 

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Gastric Cancer as Preventable DiseaseRugge M. Genta R.M. Di Mario F. El-Omar E.M. El-Serag H.B. Fassan M. Hunt R.H. Kuipers E.J. Malfertheiner P. Sugano K. Graham D.Y.Clinical Gastroenterology and Hepatology (2017). Date of Publication: 2017Gastric cancer, 1 of the 5 most common causes of cancer death, is associated with a 5-year overall survival rate less than 30%. A minority of cancers occurs as part of syndromic diseases; more than 90% of adenocarcinomas are considered as the ultimate consequence of a longstanding mucosal inflammation. Helicobacter pylori infection is the leading etiology of non-self-limiting gastritis, which may result in atrophy of the gastric mucosa and impaired acid secretion. Gastric atrophy establishes a field of cancerization prone to further molecular and phenotypic changes, possibly resulting in cancer growth. This well-understood natural history provides the clinicopathologic rationale for primary and secondary cancer prevention strategies. A large body of evidence demonstrates that combined primary (H pylori eradication) and secondary (mainly endoscopy) prevention efforts may prevent or limit the progression of gastric oncogenesis. This approach, which is tailored to different country-specific gastric cancer incidence, socioeconomic, and cultural factors, requires that the complementary competences of gastroenterologists, oncologists, and pathologists be amalgamated into a common strategy of health policy.

 

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Helicobacter pylori infection is associated with type 2 diabetes, not type 1 diabetes: An updated meta-analysisLi J.-Z. Li J.-Y. Wu T.-F. Xu J.-H. Huang C.-Z. Cheng D. Chen Q.-K. Yu T.Gastroenterology Research and Practice (2017) 2017 Article Number: 5715403. Date of Publication: 2017Background. Extragastric manifestations of Helicobacter pylori (H. pylori) infection have been reported in many diseases. However, there are still controversies about whether H. pylori infection is associated with diabetes mellitus (DM). This study was aimed at answering the question. Methods. A systematic search of the literature from January 1996 to January 2016 was conducted in PubMed, Embase databases, Cochrane Library, Google Scholar, Wanfang Data, China national knowledge database, and SinoMed. Published studies reporting H. pylori infection in both DM and non-DM individuals were recruited. Results. 79 studies with 57,397 individuals were included in this meta-analysis. The prevalence of H. pylori infection in DM group (54.9%) was significantly higher than that (47.5%) in non-DM group (OR = 1.69, P<0.001). The difference was significant in comparison between type 2 DM group and non-DM group (OR = 2.05), but not in that between type 1 DM group and non-DM group (OR = 1.23, 95% CI: 0.77-1.96, P=0.38). Conclusion. Our meta-analysis suggested that there is significantly higher prevalence of H. pylori infection in DM patients as compared to non-DM individuals. And the difference is associated with type 2 DM but not type 1 DM.

 

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Inflammatory Bowel Diseases: Review of Known Environmental Protective and Risk Factors InvolvedVan Der Sloot K.W.J. Amini M. Peters V. Dijkstra G. Alizadeh B.Z.Inflammatory Bowel Diseases (2017) 23:9 (1499-1509). Date of Publication: 1 Sep 2017Inflammatory bowel diseases consisting of Crohn's disease and ulcerative colitis are chronic inflammatory diseases of the gastrointestinal tract. In addition to genetic susceptibility and disturbances of the microbiome, environmental exposures forming the exposome play an important role. Starting at birth, the cumulative effect of different environmental exposures combined with a predetermined genetic susceptibility is thought to cause inflammatory bowel disease. All these environmental factors are part of a Western lifestyle, suiting the high incidence rates in Europe and the United States. Whereas receiving breastfeeding, evidence of a Helicobacter pylori infection and vitamin D are important protective factors in Crohn's disease as well as ulcerative colitis, increased hygiene, experiencing a bacterial gastroenteritis in the past, urban living surroundings, air pollution, the use of antibiotics, nonsteroidal anti-inflammatory drugs, and oral contraceptives are likely to be the most important risk factors for both diseases. Current cigarette smoking yields a divergent effect by protecting against ulcerative colitis but increasing risk of Crohn's disease, whereas former smoking increases chances of both diseases. This review gives a clear overview of the current state of knowledge concerning the exposome. Future studies should focus on measuring this exposome yielding the possibility of combining all involved factors to one exposome risk score and our knowledge on genetic susceptibility.

 

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Concomitant immediate and delayed type hypersensitivity to amoxicillin in the same patient: Two case reportsSteiner-Monard V. Bircher A.J. Scherer Hofmeier K.Allergy: European Journal of Allergy and Clinical Immunology (2017) 72 Supplement 103 (702-703). Date of Publication: 1 Aug 2017Case Report: Adverse drug reactions to amoxicillin (AMX) usually present with urticaria or exanthema resulting either from type I or type lV sensitization. We present two cases showing clinical manifestations of both immediate and delayed type hypersensitivity to AMX with corresponding skin test reactivity. Patient 1: A 54-year-old female patient developed a generalized pruritic, partly maculopapular exanthema after two doses of AMX/clavulanic acid (AMX/CL) administered for an erysipelas on the abdomen. Antibiotic therapy was switched to clindamycin for 14 days. The exanthema persisted and was accentuated in the large folds, and facial angioedema occurred despite administration of antihistamines and prednisone. Subsequently, the patient showed disseminated desquamation. A diagnosis of Symmetric Drug Related Intertriginous Flexural Exanthema (SDRIFE) was retained. Skin tests with AMX and AMX/CL were positive after 20 minutes and at 24 hours. PPL and MDM were negative, benzylpenicillin and piperacillin/tazobactam were positive after 24 hours only, clindamycin was positive in the immediate reading only. Reexposure with aztreonam and cefuroxime was tolerated. SDRIFE was attributed to amoxicillin, angioedema may have been caused by clindamycin. Patient 2: A 23-year-old female patient was treated for helicobacter pylori gastritis with AMX/CL, clarithromycin and pantoprazole for 7 days. On day 8 she developed a maculopapular exanthema persisting for 3 days. Dizziness, facial swelling and dyspnea occurred at the same time for one day only. Skin tests were positive for AMX and AMX/CL after 20 minutes and persisted for more than a week. Skin tests for clarithromycin and pantoprazole were negative. Both patients had an unusual both immediate and delayed skin test reactivity to AMX. In both patients clinical manifestations represent more likely a T cell mediated mechanism, although also immediate type symptoms were present. Investigations are ongoing with basophil activation tests (BAT) and lymphocyte transformation tests (LTT) to elucidate the concomitant presence of immediate and delayed type hypersensitivity in the two patients. So far it is unclear whether one single epitope or two different determinants on the AMX molecule are responsible for this unusual concomitant sensitization pattern.

 

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Primary hepatic marginal zone lymphoma (malt-type lymphoma). A case reportAón Bertolino M.L. Cora F. Piantanida F. Ruiz M. Alposta L. Dezanzo P.Virchows Archiv (2017) 471:1 Supplement 1 (S331). Date of Publication: 1 Sep 2017Objective: The purpose of the study was to report an unusual lymphoid proliferation occurring in the liver of a 76-year-old woman without underlying chronic liver disorder or autoimmune condition. Method: The patient refered to biliary symptoms, weight loss, sweating and pruritus. Tomographic study showed hepatic right lobe image of 9 cm that was resected (partial hepatectomy). Morphological and immunohistochemical study was performed. Results: Histological sections revealed a dense population of small lymphoid cells with round nucleus and inconspicuous nucleolus, scarce large immunoblastic cells and numerous plasma cells in a stroma with sclerosis. The lymphoid proliferation showed some lymphoepithelial lesions of biliary ducts. Immunoprofile was CD20+ CD79a + BCL-2+, negative for CD3, CD5, CD23, CD45Ro and BCL-6, with a low Ki-67 index (5 %). Bone marrow biopsy was not involved and ulterior gastric biopsy had Helicobacter pylori gastritis. Conclusion: HepaticMALT-type lymphoma case studies have been rarely reported. This lymphoma is usually related with inflammatory or autoimmune diseases but there may be no underlying associations like in our patient at the time of diagnosis. Complete surgical excision in localized disease have been proposed. AlthoughMALT-type lymphoma of the liver is considered a low grade lymphoma, patients should be closely followed up for recurrence.

 

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Stromal R-spondin orchestrates gastric epithelial stem cells and gland homeostasisSigal M. Logan C.Y. Kapalczynska M. Mollenkopf H.-J. Berger H. Wiedenmann B. Nusse R. Amieva M.R. Meyer T.F.Nature (2017) 548:7668 (451-455). Date of Publication: 24 Aug 2017The constant regeneration of stomach epithelium is driven by long-lived stem cells, but the mechanism that regulates their turnover is not well understood. We have recently found that the gastric pathogen Helicobacter pylori can activate gastric stem cells and increase epithelial turnover, while Wnt signalling is known to be important for stem cell identity and epithelial regeneration in several tissues. Here we find that antral Wnt signalling, marked by the classic Wnt target gene Axin2, is limited to the base and lower isthmus of gastric glands, where the stem cells reside. Axin2 is expressed by Lgr5(+) cells, as well as adjacent, highly proliferative Lgr5(-) cells that are able to repopulate entire glands, including the base, upon depletion of the Lgr5(+) population. Expression of both Axin2 and Lgr5 requires stroma-derived R-spondin 3 produced by gastric myofibroblasts proximal to the stem cell compartment. Exogenous R-spondin administration expands and accelerates proliferation of Axin2(+)/Lgr5(-) but not Lgr5(+) cells. Consistent with these observations, H. pylori infection increases stromal R-spondin 3 expression and expands the Axin2(+) cell pool to cause hyperproliferation and gland hyperplasia. The ability of stromal niche cells to control and adapt epithelial stem cell dynamics constitutes a sophisticated mechanism that orchestrates epithelial regeneration and maintenance of tissue integrity.

 

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A safety and pharmacokinetic study in real-life practice of pylera in france: The saphary studyBlin P. Lelièvre B. Rouyer M. Zerbib F. Diquet B. Mégraud F. Tison F. Guiard E. Bignon E. Barbet V. Lassalle R. Droz-Perroteau C. Moore N.Pharmacoepidemiology and Drug Safety (2017) 26 Supplement 2 (396). Date of Publication: 1 Aug 2017Background: Pylera, a capsule-based therapy with bismuth, metronidazole, and tetracycline, is indicated in eradication of Helicobacter pylori (H. pylori). Due to the history of bismuth encephalopathy risk, the French Health Authority has requested to conduct a post-marketing program in France to observe potential changes in bismuth concentrations. Objectives: To verify the absence of bismuth accumulation in patients prescribed Pylera in a real-life setting. Methods: Minimal invasive observational study of patients treated with Pylera for H. pylori infection, included and followed by gastroenterologists (GE) and general practitioners (GP) with 3 visits: at inclusion, at end of treatment (EOT) i.e. 10 days, and at 28 days after the EOT. A blood sample was obtained before the 1st Pylera intake and 24h after the last Pylera intake for a bismuth dosage by a centralized referral laboratory, and a 3rd sample in case of whole blood bismuth concentration >50 μg/L at 2nd sample. Results: Among 202 patients included from 13 Mar 2014 to 2 Dec 2015 by 34 physicians (80% GE and 20% GP), 190 took at least one dose of Pylera (Safety population) and 2 required blood samples were obtained from 167 (Per protocol population). Among Safety population, 46% were men and median age was 54 years. The Pylera duration treatment was 10 days for 85% of patients. These characteristics were close to those of Per protocol population. Among these latter, the median bismuth concentration at the EOT was 15.4 μg/L (95%CI: [15.6; 18.3]). Two patients had a concentration >50 μg/L: 56.0 μg/L for a 83 years old woman with low weight (45 kg) associated with non-serious memory impairment during treatment, reversible after treatment discontinuation, and 50.9 μg/L for a 82 years old man without neurological AE. For Safety population, neurological AEs occurred for 20% of patients during treatment period, all nonserious, and 95% as related to Pylera by investigators. Non-neurological AEs were observed for 25% of patients, mainly digestive disorders (19%), all non-serious, and 88% as related to Pylera. No serious AE were reported during the study period. The eradication of H. pylori infection was confirmed in 71% of cases, treatment failure in 5%, while 24% were undetermined due to missing data for diagnostic test. Conclusions: The SAPHARY study shows few cases (2 patients) of bismuth concentration >50 μg/L without severe neurology AE with Pylera. The effectiveness and safety profiles in a real-life setting seem to be close to those found in the literature.

 

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Human helicobacter heilmannii-like organisms infectionOstahi I.A. Villanacci V. Crisafulli V. Dumbrava M.E. Diculescu M. Gheorghe C. Becheanu G.Virchows Archiv (2017) 471:1 Supplement 1 (S181). Date of Publication: 1 Sep 2017Objective: Helicobacter Heilmannii (HHLO) is a bacterial agent with a rare occurence in humans (0.1-2 %) and colonizes especially the antrum. Method: We present a retrospective analysis of a series of 62 cases with HHLO gastric infection, registered at Fundeni Clinical Institute and at Brescia Civil Hospital, compared with 62 Helicobacter Pylori gastritis cases (HP). Results: HHLO was found more frequently in young patients (less than 50 years of age), with a slight predominance in males (70.97 % HHLO, compared to 59.68 % HP). All patients presented chronic active gastritis. HHLO seemed to determine less intensity of chronic inflammation (80.65 % moderate and 19.35 % mild HHLO, respectively 88.71 % moderate and 11.29 mild HP). Severe activity was found in 3 of the 62 HHLO cases, compared with 17 HP cases. Mild activity was observed in 26 HHLO and in only 13 HP cases. 4 of the HHLO cases had glandular atrophy, while 6 of the HP ones had. Intestinal metaplasia was observed in 3 HHLO and in 17 HP cases. Only 3 HHLO cases had follicular gastritis compared with 15 HP cases. There was one case with associated HHLO and HP infection. Conclusion: This is a large series of HHLO infection in humans. It predominates in males and younger patients, and determines a less severe inflamamation than HP. Atrophy is similarly diagnosed, but intestinal metaplasia is rarely observed in HHLO infection. Follicular gastritis is more frequently associated with HP infection.

 

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Practical Approach to the Flattened Duodenal BiopsySmyrk T.C.Surgical Pathology Clinics (2017). Date of Publication: 2017Celiac disease features duodenal intraepithelial lymphocytosis with or without villous atrophy. Lymphocytosis without villous atrophy will be proven to represent celiac disease in 10% to 20% of cases. The differential diagnosis is broad: Helicobacter pylori gastritis, NSAID injury and bacterial overgrowth are considerations. Lymphocytosis with villous atrophy is very likely to be celiac disease, but there are mimics to consider, including collagenous sprue, tropical sprue, drug injury, and common variable immunodeficiency. Histologic clues to a diagnosis other than celiac disease include paucity of plasma cells, excess of neutrophils, granulomas, and relative paucity of intraepithelial lymphocytes.

 

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Drug usage patterns of pylera in France using the national claims databaseBlin P. Rouyer M. Guiard E. Zerbib F. Diquet B. Mégraud F. Tison F. Abouelfath A. Lassalle R. Droz-Perroteau C. Moore N.Pharmacoepidemiology and Drug Safety (2017) 26 Supplement 2 (341). Date of Publication: 1 Aug 2017Background: Pylera, a capsule-based therapy with bismuth, metronidazole, and tetracycline, is prescribed for eradication of Helicobacter pylori (H. pylori). Due to the history of bismuth encephalopathy risk, the French Health Authority requested a postmarketing program in France including a drug utilization study. Objectives: To describe the usage patterns of Pylera in a real-life setting. Methods: Cohort study of patients with a 1st dispensing of Pylera between April 2013 and April 2014, identified in a representative national French reimbursement database, the Echantillon Généraliste des Bénéficiaires (EGB), which is a 1/97th sample of the nationwide French claims and hospitalisation database (66 million persons, SNIIRAM). Patients had a 12-month clinical history and follow-up from the index date. Misuse (main criterion) was defined as a dispensing of more than one pack of Pylera at index date or a dispensing not preceded by diagnostic test in 12- month before 1st dispensing. Results: 540 patients with a first dispensing of Pylera were included. Their main characteristics were: mean age of 53 years, 44% of men and 18% previously treated for the eradication of H. pylori in 12-month before index date. The main prescribers were gastroenterologists or hospital physicians (61%), followed by general practitioners (30%). A proton pump inhibitor was co-dispensed for 93% of patients, mainly omeprazole (65%) and esomeprazole (17%). 9 patients (2%) had a hepatic or renal impairment, and one patient was pregnant. 59 patients (11%) met the misuse criterion: 10 had more than one pack of Pylera (7 patients with 2 packs, 2 with 3 packs, and one with 4 packs), and 49 without urea breath test or endoscopy before index date. Taking also into account the serology test as a diagnostic test, the misuse criterion decreased to 51 patients (9%). Within the 1-year follow-up period, 45 patients (8%) had a new tritherapy prescription to eradicate H. pylori. Conclusions: This real-life nationwide French claims and hospitalisation database study showed a misuse of Pylera for just over 10% and mostly were misusers because of lack of diagnostic test before Pylera treatment, and two or more packs of Pylera dispensed for 2%. Some contraindications were also observed such as hepatic or renal impairment, and pregnancy. A new dispensing of a specific treatment, indication of treatment failure was given to 8% that is close to an eradication failure rate of H. pylori infection in France between 10% and 30% as shown in the literature.

 

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Chinese Classical Formula Sijunzi Decoction and Chronic Atrophic Gastritis: Evidence for Treatment Approach?Gan D. Xu A. Du H. Ye Y.Evidence-based Complementary and Alternative Medicine (2017) 2017 Article Number: 9012929. Date of Publication: 2017Objective. This aim is to evaluate the effect of Sijunzi decoction (SJZD) treating chronic atrophic gastritis (CAG). Methods. We performed searches in seven databases. The randomized controlled trials (RCTs) comparing SJZD with standard medical care or inactive intervention for CAG were enrolled. Combined therapy of SJZD plus conventional therapies compared with conventional therapies alone was also retrieved. The primary outcome included the incidence of gastric cancer and the improvement of atrophy, intestinal metaplasia, and dysplasia based on the gastroscopy and pathology. The secondary outcomes were Helicobacter pylori clearance rate, quality of life, and adverse event/adverse drug reaction. Results. Six RCTs met the inclusion criteria. The research quality was low in the trials. For the overall effect rate, pooled analysis from 4 trials showed that modified SJZD plus conventional medications exhibited a significant improvement (OR = 4.86; 95% CI: 2.80 to 8.44; P < 0.00001) and without significant heterogeneity compared with the conventional medications alone. None reported the adverse effect. Conclusions. Modified SJZD combined with conventional western medicines appears to have benefits for CAG. Due to the limited number and methodological flaw, the beneficial and harmful effects of SJZD for CAG could not be identified. More high-quality clinical trials are needed to confirm the results.

 

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Amoxicillin-clavulanic acid desensitization: Clinical report and schedule employedGarcia-Nunez I. Algaba-Marmol M. Suarez-Vergara M. De Sola-Romero M. Barasona-Villarejo M. Waeyenbergh D. Ignacio-Garcia J.Allergy: European Journal of Allergy and Clinical Immunology (2017) 72 Supplement 103 (634). Date of Publication: 1 Aug 2017Case report: Background: Betalactam allergy is a very common consultation problem in our Allergy Departments, and there are commercialized several alternatives in order to recommend in patients with a positive result in the allergological study. The problem begins when these patients need an antibiotic because the alternative treatment isn't enough to erase the culprit bacteria. Our aim was to show a desensitization protocol with amoxicillin-clavulanic acid in a patient with a confirmed diagnosis of betalactam allergy. Patients and methods: A 35 years old female patient came to our Allergy Department referring general pruritus without urticaria or angioedema one hour after the first amoxicillin-clavulanic dose intake prescribed for tonsillitis, and needing amoxicillin-clavulanic acid in order to treat a resistant Helicobacter Pylori infection to alternative treatments. A clinical report focused in other allergies and pathologies was performed and an in vivo study (including a Drug Provocation Test with amoxicillin-clavulanic acid) was performed too, with a positive result of DPT after one hour (general pruritus and mild urticaria). We performed a desensitization following the protocol showed in table 1 in order to offer this treatment to erase the infection. Results: Our patient tolerated the desensitization protocol with only mild pruritus after an accumulated dose of 525 mg, being well controlled with conventional treatment (without adrenaline). She followed with the treatment at home without any problems Conclusion: We present a patient with a confirmed amoxicillin-clavulanic acid sensitization and a desensitization protocol to this drug. In a future, a reduction of this schedule may be studied in order to improve this treatment method. (Table Presented).

 

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SNP rs3202538 in 3'UTR region of ErbB3 regulated by miR-204 and miR-211 promote gastric cancer development in Chinese populationShi Y. Chen X. Xi B. Yu X. Ouyang J. Han C. Qin Y. Wu D. Shen H.Cancer Cell International (2017) 17:1 Article Number: 81. Date of Publication: 13 Sep 2017Background/aims: ErbB3 is an oncogene which has proliferation and metastasis promotion effects by several signaling pathways. However, the individual expression difference regulated by miRNA was almost still unknown. We focused on the miRNAs associated SNPs in the 3'-UTR of ErbB3 to investigate the further relationship of the SNPs with miRNAs among Chinese gastric cancer (GC) patients. Methods: We performed case-control study including 851 GC patients and 799 cancer-free controls. Genotyping, real-time PCR assay, cell transfection, the dual luciferase reporter assay, western-blot, cell proliferation and trans-well based cell invasion assay were used to investigate the effects of the SNP on ErbB3 expression. Moreover, a 5-years-overall survival and relapse free survival were investigated between different genotypes. Results: We found that patients suffering from Helicobacter pylori (Hp.) infection indicated to be the susceptible population by comparing with controls. Besides, SNP rs3202538 (G/T) in ErbB3 3'-UTR was involved in the occurrence of GC by acting as tumor risk factors. SNP rs3202538 (G/T) could be regulated by both miR-204 and miR-211 which caused an upregulation of ErbB3 in patients. Furthermore, the carriers of T genotype was related to the significantly high expression of ErbB3, and to big tumor size, poor differentiation as well as the high probability of metastasis. Both miR-211 and miR-204 can significantly decrease cell proliferation, metastasis as well as downstream AKT activation through G but not T allele of ErbB3 3'UTR. Moreover, the SNP of G/T was associated with shorter survival of post-surgery GC patients with 5 years of follow up study. Conclusion: In conclusion, our findings have shown that the SNP rs3202538 (G/T) in ErbB3 3'-UTR acted as promotion factors in the GC development through disrupting the regulatory role of miR-204 and miR-211 in ErbB3 expression.

 

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The cytoprotective protein clusterin is overexpressed in hypergastrinemic rodent models of oxyntic preneoplasia and promotes gastric cancer cell survivalVange P. Bruland T. Doseth B. Fossmark R. Sousa M.M.L. Beisvag V. Sørdal Ø. Qvigstad G. Waldum H.L. Sandvik A.K. Bakke I.PLoS ONE (2017) 12:9 Article Number: e0184514. Date of Publication: 1 Sep 2017The cytoprotective protein clusterin is often dysregulated during tumorigenesis, and in the stomach, upregulation of clusterin marks emergence of the oxyntic atrophy (loss of acid-producing parietal cells)-associated spasmolytic polypeptide-expressing metaplasia (SPEM). The hormone gastrin is important for normal function and maturation of the gastric oxyntic mucosa and hypergastrinemia might be involved in gastric carcinogenesis. Gastrin induces expression of clusterin in adenocarcinoma cells. In the present study, we examined the expression patterns and gastrin-mediated regulation of clusterin in gastric tissue from: Humans; rats treated with proton pump (HATPase) inhibitors and/or a gastrin receptor (CCK2R) antagonist; HATPase β-subunit knockout (H/K-β KO) mice; and Mongolian gerbils infected with Helicobacter pylori and given a CCK2R antagonist. Biological function of secretory clusterin was studied in human gastric cancer cells. Clusterin was highly expressed in neuroendocrine cells in normal oxyntic mucosa of humans and rodents. In response to hypergastrinemia, expression of clusterin increased significantly and its localization shifted to basal groups of proliferative cells in the mucous neck cell-chief cell lineage in all animal models. That shift was partially inhibited by antagonizing the CCK2R in rats and gerbils. The oxyntic mucosa of H/K-β KO mice contained areas with clusterin-positive mucous cells resembling SPEM. In gastric adenocarcinomas, clusterin mRNA expression was higher in diffuse tumors containing signet ring cells compared with diffuse tumors without signet ring cells, and clusterin seemed to be secreted by tumor cells. In gastric cancer cell lines, gastrin increased secretion of clusterin, and both gastrin and secretory clusterin promoted survival after starvation- and chemotherapy-induced stress. Overall, our results indicate that clusterin is overexpressed in hypergastrinemic rodent models of oxyntic preneoplasia and stimulates gastric cancer cell survival.

 

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The phenotypic heterogeneity of Hereditary Diffuse Gastric Cancer (HDGC). Report of one family with early-onset diseaseGullo I. Garrido L. Castedo S. Baptista M. Devezas V. Ribeiro I. Ferreira R. Figueiredo C. Oliveira C. Trindade E. Carneiro F.Virchows Archiv (2017) 471:1 Supplement 1 (S34). Date of Publication: 1 Sep 2017Objective: The time-course of the development of clinically significant HDGC is unpredictable. Little is known about the progression from preclinical, indolent lesions to widely invasive, aggressive phenotypes. We report a HDGC family with a pathogenic germline CDH1-mutation (c.1901C>T) with early-onset disease, to discuss mechanisms behind morphological and clinical heterogeneity. Method: Endoscopic biopsies from the proband (18-year-old male with widely invasive, metastatic DGC) and prophylactic total gastrectomies (PTGs) from six family members were studied by morphology and immunohistochemistry for E-cadherin, Ki-67, p53, pSrc and pStat3. Helicobacter pylori (H. pylori) cagA status was also determined. Results: The aggressive DGC from the proband was characterised by pleomorphic cells, absent E-cadherin expression, high Ki-67 proliferation index, and p53, pSrc and pStat3 overexpression. The 6 PTGs contained early DGCs (n = 1-33) with typical signet-ring cells, decreased membranous E-cadherin expression and absence of p53 and Ki-67 immunoreactivity. H. pylori cag-A-positive strains were detected in all family members, except in a 14-year-old female. Conclusion: The results of this study reinforce our previous data [Adv Exp Med Biol. 2016; 908: 371] on heterogeneity of HDGC and demonstrate that the aggressive phenotype is characterised by increased proliferation and activation of oncogenic events. The role of H. pylori infection and virulence-associated genes is debatable.

 

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The relevance of gastric cancer biomarkers in prognosis and pre- and post- chemotherapy in clinical practiceAbbas M. Habib M. Naveed M. Karthik K. Dhama K. Shi M. Dingding C.Biomedicine and Pharmacotherapy (2017) 95 (1082-1090). Date of Publication: 1 Nov 2017Gastric cancer (GC) is one among the major cancer types, causing human deaths and present noticeable heterogeneity. The incidences and mortality rates are higher in males in comparison to females with a male to female ratio of 2.3:1. A lot of studies have revealed out the molecular basis, pathogenesis, invasion and metastasis related findings of gastric stomach cancer. Present review encompasses the salient information on various biomarkers for the early diagnosis, treatment and prognosis of gastric cancer elaborate the clinical importance of serum tumor markers in patients with this cancer as well as checking the growths, together with epigenetic changes and genetic polymorphisms. A deep and rigorous search was carried out in Pub Med/MEDLINE using specific key words; “gastric cancer”, with “tumor marker”. Our search yielded 4947 important reports about related topic from books and articles that were published before the end of August 2017. Conclusively, Scientists are utilizing high time and resource to salvage this nemesis which is of global importance and cause health burden. Classical and novel biomarkers are important for treatment as well as pre- and post- diagnosis of GC. Major causes for GC are cigarette smoking, infection by Helicobacter pylori, atrophic gastritis, sex/gender, and high salt intake. Early diagnoses of GC is important for the management, treatment, pathological diagnoses by stage prognosis and metastatic setting; although the treatment outcome proved to be not much fruitful following chemotherapy, and oral medication with oxaliplatin, capecitabine, cisplatin and 5- fluorouracil (5-FU). More research studies and exploring the practical usage of gastric cancer biomarkers in diagnosis, prognosis and pre- and post- chemotherapy in clinical practice for countering gastric cancers would alleviate to some extent the ill health sufferings of humans being caused by this important and common cancerous condition.

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