Induction of cyclooxygenase-2 overexpression in human gastric epithelial cells by Helicobacter pylori involves TLR2/TLR9 and c-Srcdependent nuclear factor-

ABSTRACT Gastric epithelial cells were incubated with a panel of clinical isolates of Helicobacter pylori, including nonulcer dyspepsia with gastritis (HS, n ϭ 20), gastric ulcer (HU, n ϭ 20), duodenal ulcer (HD, n ϭ 21), and gastric cancer (HC, n ϭ 20). HC strains induced a higher cyclooxygenase-2 (COX-2) expression than those from HS, HD, and HU. The bacterial virulence factors and the host cellular pathways were investigated. Virulence genes of iceA, vacA, babA2, cagA 3Ј repeat region, and hrgA failed to show any association with the disease status and COX-2 expression. Methylation-specific polymerase chain reaction revealed HC strains not affecting the methylation status of COX-2 promoter. Nuclear factor (NF)-B, NF-interleukin 6, and cAMP response element were found to be involved in COX-2 induction. We explored a novel NF-B activation pathway. The mutants of TLR2 and TLR9, but not TLR4, inhibited H. pyloriinduced COX-2 promoter activity, and neutralizing antibodies for TLR2 and TLR9 abolished H. pylori-induced COX-2 expression

Consensus on Control of Risky Nonvariceal Upper Gastrointestinal Bleeding in Taiwan with National Health Insurance

Background and Aims. To compose upper gastrointestinal bleeding (UGIB) consensus from a nationwide scale to improve the control of UGIB, especially for the high-risk comorbidity group. Methods. The steering committee defined the consensus scope to cover preendoscopy, endoscopy, postendoscopy, and overview from Taiwan National Health Insurance Research Database (NHIRD) assessments for UGIB. The expert group comprised thirty-two Taiwan experts of UGIB to conduct the consensus conference by a modified Delphi process through two separate iterations to modify the draft statements and to vote anonymously to reach consensus with an agreement ≥80% for each statement and to set the recommendation grade. Results. The consensus included 17 statements to highlight that patients with comorbidities, including liver cirrhosis, end-stage renal disease, probable chronic obstructive pulmonary disease, and diabetes, are at high risk of peptic ulcer bleeding and rebleeding. Special considerations are recommended for such risky patients, including raising hematocrit to 30% in uremia or acute myocardial infarction, aggressive acid secretory control in high Rockall scores, monitoring delayed rebleeding in uremia or cirrhosis, considering cycloxygenase-2 inhibitors plus PPI for pain control, and early resumption of antiplatelets plus PPI in coronary artery disease or stroke. Conclusions. The consensus comprises recommendations to improve care of UGIB, especially for high-risk comorbidities

Humoral Immunity against Capsule Polysaccharide Protects the Host from magA+ Klebsiella pneumoniae-Induced Lethal Disease by Evading Toll-Like Receptor 4 Signaling ▿

Klebsiella pneumoniae magA (for mucoviscosity-associated gene A) is linked to the pathogenesis of primary pyogenic liver abscess, but the underlying mechanism by which magA increases pathogenicity is not well elucidated. In this study, we investigated the role of the capsular polysaccharides (CPS) in the pathogenesis of magA+ K. pneumoniae by comparing host immunity to magA+ K. pneumoniae and a ΔmagA mutant. We found that Toll-like receptor 4 recognition by magA+ K. pneumoniae was hampered by the mucoviscosity of the magA+ K. pneumoniae CPS. Interestingly, monoclonal antibodies (MAbs) against magA+ K. pneumoniae CPS recognized all of the K1 strains tested but not the ΔmagA and non-K1 strains. Moreover, the anti-CPS MAbs protected mice from magA+ K. pneumoniae-induced liver abscess formation and lethality. This indicates that the K1 epitope is a promising target for vaccine development, and anti-CPS MAbs has great potential to protect host from K1 strain-induced mortality and morbidity in diabetic and other immunocompromised patients in the future

Consensus of gastroesophageal reflux disease in Taiwan with endoscopy-based approach covered by National Health Insurance

Background and aims: Gastroesophageal reflux disease (GERD) is emerging as a clinical complication in the Orient. The consensus comprises recommendations to GERD control under the advantage of endoscopy-based approach covered by the Taiwan National Health Insurance. Methods: The steering committee defined the consensus scope to cover diagnostic, therapeutic, unresolved, controversial, or long-term proton pump inhibitor-related issues to GERD. The literature review emphasized domestic data, after which the draft statements and statement evidence levels were defined. Thirty-five experts of GERD in Taiwan formed the expert group to conduct the consensus conference by a modified Delphi process to vote anonymously to reach a consensus, defined by an agreement of ≥ 80% for each statement, and to set the recommendation grade. Results: The consensus included 22 statements, including seven on diagnostic approach, seven on therapeutic suggestion, and eight on unresolved, controversial, or long-term proton pump inhibitor-related issues to GERD. The consensus highlighted that the endoscopy approach to GERD can define the disease spectrum and exclude malignant potential. The questionnaire survey can not only define GERD, but also monitor treatment response and quality of life. The consensus addressed suggestions for the unresolved issues related to extraesophageal presentation and adverse concerns of GERD after long-term use of proton pump inhibitors. In the endemic area of upper gastrointestinal cancers, Helicobacter pylori eradication is suggested to reduce progression of gastric precancerous lesions, and endoscopic surveillance of Barrett’s esophagus with dysplasia deserves prospective research. Conclusion: The consensus comprises recommendations for the management of GERD in a high upper gastrointestinal cancer area with a national coverage of endoscopic approach

Survey of the adherence to the consensus of gastroesophageal reflux disease before and after the implementation course

Background/Purpose: The prevalence of Gastroesophageal reflux disease (GERD) is increasing worldwide, including Asia. Although several consensus reports have been published, little is known regarding the adherence of the physicians on the consensus of GERD. We aimed to survey the agreements and adherence of physicians to the Taiwan GERD consensus before and after the continual medical education (CME) courses. Methods: Two-hundred and twenty-seven physicians, including 81 fellows of gastroenterology, 135 qualified gastroenterologists, and 11 non-gastroenterologist attending physicians were invited to the CME course. Their agreements and adherence to the statements before and after the CME course were assessed by the pre-defined questionnaire with the aid of electronic keypads. The adherence rate before and after the CME course were compared by the McNemar test to indicate the changes in their willingness to follow the statements in clinical practice. Results: The rates of agreement of the 227 participating physicians were uniformly greater than 80% for all of the 22 statements. However, the adherence rates were lower than 80% in 16 statements before the CME intervention. The adherence rates were significantly (p < 0.05) increased in 15 of these 16 statements after the CME intervention. The adherence rate can be improved to greater than 80% for those statements with high level of evidence. Conclusion: Although physicians agreed with the statements, the pre-CME survey disclosed limited adherence rates to the statements. The education intervention through the CME courses can improve the adherence of consensus statement, especially for those with higher level of evidence. Keywords: Adherence, Consensus, Barrier, Gastroesophageal reflux disease, Educatio

The Primary Resistance of Helicobacter pylori in Taiwan after the National Policy to Restrict Antibiotic Consumption and Its Relation to Virulence Factors-A Nationwide Study.

The Taiwan Government issued a policy to restrict antimicrobial usage since 2001. We aimed to assess the changes in the antibiotic consumption and the primary resistance of H. pylori after this policy and the impact of virulence factors on resistance.The defined daily dose (DDD) of antibiotics was analyzed using the Taiwan National Health Insurance (NHI) research database. H. pylori strains isolated from treatment naïve (N=1395) and failure from prior eradication therapies (N=360) from 9 hospitals between 2000 and 2012 were used for analysis. The minimum inhibitory concentration was determined by agar dilution test. Genotyping for CagA and VacA was determined by PCR method.The DDD per 1000 persons per day of macrolides reduced from 1.12 in 1997 to 0.19 in 2008, whereas that of fluoroquinolones increased from 0.12 in 1997 to 0.35 in 2008. The primary resistance of amoxicillin, clarithromycin, metronidazole, and tetracycline remained as low as 2.2%, 7.9%, 23.7%, and 1.9% respectively. However, the primary levofloxacin resistance rose from 4.9% in 2000-2007 to 8.3% in 2008-2010 and 13.4% in 2011-2012 (p=0.001). The primary resistance of metronidazole was higher in females than males (33.1% vs. 18.8%, p<0.001), which was probably attributed to the higher consumption of nitroimidazole. Neither CagA nor VacA was associated with antibiotic resistance.The low primary clarithromycin and metronidazole resistance of H. pylori in Taiwan might be attributed to the reduced consumption of macrolides and nitroimidazole after the national policy to restrict antimicrobial usage. Yet, further strategies are needed to restrict the consumption of fluoroquinolones in the face of rising levofloxacin resistance