Chun-Chao Chang

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

Objective 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. Methods 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. Results 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. Conclusions 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.

Sequential therapy for 10 days versus triple therapy for 14 days in the eradication of Helicobacter pylori in the community and hospital populations: a randomised trial

Objective Significant heterogeneity was observed in previous trials that assessed the efficacies of sequential therapy for 10u2005days (S10) versus triple therapy for 14u2005days (T14) in the first-line treatment of Helicobacter pylori. We aimed to compare the efficacy of S10 and T14 and assess the factors affecting their efficacies. Design We conducted this open-label randomised multicentre trial in eight hospitals and one community in Taiwan. 1300 adult subjects with H pylori infection naïve to treatment were randomised (1:1) to receive S10 (lansoprazole and amoxicillin for the first 5u2005days, followed by lansoprazole, clarithromycin and metronidazole for another 5u2005days) or T14 (lansoprazole, amoxicillin and clarithromycin for 14u2005days). All drugs were given twice daily. Successful eradication was defined as negative 13C-urea breath test at least 6u2005weeks after treatment. Our primary outcome was the eradication rate by intention-to-treat (ITT) and per-protocol (PP) analyses. Antibiotic resistance was determined by agar dilution test. Results The eradication rates of S10 and T14 were 87.2% (567/650, 95% CI 84.4% to 89.6%) and 85.7% (557/650, 95% CI 82.8% to 88.2%) in the ITT analysis, respectively, and were 91.6% (556/607, 95% CI 89.1% to 93.4%) and 91.0% (548/602, 95% CI 88.5% to 93.1%) in the PP analysis, respectively. There were no differences in compliance or adverse effects. The eradication rates in strains susceptible and resistant to clarithromycin were 90.7% and 62.2%, respectively, for S10, and were 91.5% and 44.4%, respectively, for T14. The efficacy of T14, but not S10, was affected by CYP2C19 polymorphism. Conclusions S10 was not superior to T14 in areas with low clarithromycin resistance. Trial registration number NCT01607918.

Endoscopic Submucosal Dissection for Gastric Epithelial Tumors: A Multicenter Study in Taiwan

BACKGROUND/PURPOSEnEndoscopic submucosal dissection (ESD) is an advanced endoscopic procedure to resect early gastric cancer (EGC). The purpose of this study was to determine the effectiveness and complications of ESD for gastric epithelial tumors in Taiwan.nnnMETHODSnWe retrospectively analyzed the efficacy and outcome of ESD in patients who received ESD for gastric epithelial tumors between June 2004 and August 2007.nnnRESULTSnA total of 70 patients with gastric epithelial tumors were treated by ESD. The mean age was 66.5 +/- 12.9 years (range, 35-84 years). The mean size of the gastric epithelial tumors was 1.85 +/- 0.81 cm. The mean size of resected specimens was 3.26 +/- 1.39 cm. The one-piece resection rate was 91.4% (64/70). The median operation time was 92.4 minutes. The complicating bleeding and perforation rates were 5.7% (4/70) and 4.3% (3/70), respectively. Emergency surgery was performed for three patients with perforations. The local recurrence rate of gastric cancer was 2.8%. Except for one patient who died of congestive heart failure and another who died of stroke, the remaining 68 patients (97.1%) survived.nnnCONCLUSIONnESD is a promising local curative treatment option for EGC in Taiwan but it still carries risks of perforation and bleeding. The education and learning curve of endoscopists will improve the outcome of this procedure.

Faecal ribosomal protein L19 is a genetic prognostic factor for survival in colorectal cancer.

Ribosomal proteins are encoded by a gene family, members of which are overexpressed in human cancers. Many of them have been found, using oligonucleotide microarray hybridization, to be differentially expressed in the faeces of patients with various stages of col‐orectal cancer (CRC). The gene encoding ribosomal protein L19 (RPL19), a prognostic marker for human prostate cancer, is differentially expressed in CRC patients. Measurement of faecal RPL19 mRNA might improve prognostic prediction for CRC patients. Using quantitative real‐time reverse transcription PCR, levels of RPL19 mRNA were detected in samples of colonic tissues from 44 CRC patients, in the faeces of 54 CRC patients and 15 controls, and in 11 colonic cell lines. Seven of 24 patients with late‐stage CRC (Dukes stages C and D) expressed over 2‐fold more RPL19 in colonic tumour tissues than in corresponding normal tissues (P= 0.038). The mean faecal RPL19 mRNA levels of late‐staged patients were higher than those of controls (P= 0.003) and early‐staged patients (P= 0.008). Patients with both high serum levels of carcinoembryonic antigen (CEA; >5 ng/mL) and high‐faecal RPL19 mRNA (≥0.0069) had higher risk (odds ratio, 8.0; P= 0.015) and lower overall 48‐month survival (33.8 ± 13.7%, P= 0.013). Oligonucleotide microarray hybridization analysis of faecal molecules identified gene transcripts differentially present in faeces. In conclusion, faecal RPL19 expression is associated with advanced tumour stages and addictive to serum CEA in predicting prognosis of CRC patients.

Nanostructured silicon surface modifications for as a selective matrix-free laser desorption/ionization mass spectrometry

Matrix-assisted laser desorption/ionization mass spectrometry is an established soft ionization method that is widely applied to analyze biomolecules. The UV-absorbing organic matrix is essential for biomolecule ionization; however, it also creates matrix background interference, which results in problematic analyses of biomolecules of less than 700 Da. Therefore, this study investigates hydrophilic, hydrophobic cationic, anionic and immobilized metal ion surface chemical modifications to advance nanostructured silicon mass spectrometry performance (nSi-MS). This investigation provides information required for a possible novel mass spectroscopy that combines surface-enhanced and nanostructured silicon surface-assisted laser desorption/ionization mass spectrometry for the selective detection of specific compounds of a mixture.

Trends in Irritable Bowel Syndrome Incidence among Taiwanese Adults during 2003-2013: A Population-Based Study of Sex and Age Differences.

Background No population-based irritable bowel syndrome (IBS) incidence data among Taiwanese adults are available. Whether IBS is associated with risk of organic colonic diseases remains unanswered. We investigated 1) the sex- and age-stratified trends in the annual incidence of IBS, and 2) the risk of selected organic diseases in patients with IBS compared with those without IBS among Taiwanese adults during 2003–2013. Methods Medical claims data for 1 million randomly selected beneficiaries were obtained and analyzed. Patients with IBS were considered eligible for enrollment if they aged between 20 and 100 and had at least two medical encounters with IBS codes within 1 year. To test whether there was a linear secular trend in IBS incidence over time, multivariate Poisson regression with generalized estimating equation model was conducted. The risk of selected organic diseases associated with IBS was examined using multivariate Cox proportional hazard regression. Results From 2003 to 2013, the incidence of IBS significantly decreased over time [adjusted incidence rate ratio (IRR) = 0.97, p< 0.001]; the incidence of IBS significantly increased with age (adjusted IRR = 1.03, p < 0.001) and was significantly higher in women than in men (adjusted IRR = 1.14, p< 0.001). IBS significantly associated with increased risk of microscopic colitis, inflammatory bowel disease, and colorectal cancer during a 10-year follow-up period. Conclusions The incidence of IBS increased with age and was slightly higher in women than in men among Taiwanese adults. During 2003–2013, IBS incidence gradually decreased over time. IBS may increase risk of several colonic organic diseases.

14 day sequential therapy versus 10 day bismuth quadruple therapy containing high-dose esomeprazole in the first-line and second-line treatment of Helicobacter pylori: a multicentre, non-inferiority, randomized trial

BackgroundnWhether extending the treatment length and the use of high-dose esomeprazole may optimize the efficacy of Helicobacter pylori eradication remains unknown.nnnObjectivesnTo compare the efficacy and tolerability of optimized 14u2009day sequential therapy and 10u2009day bismuth quadruple therapy containing high-dose esomeprazole in first-line therapy.nnnMethodsnWe recruited 620 adult patients (≥20u2009years of age) with H. pylori infection naive to treatment in this multicentre, open-label, randomized trial. Patients were randomly assigned to receive 14u2009day sequential therapy or 10u2009day bismuth quadruple therapy, both containing esomeprazole 40u2009mg twice daily. Those who failed after 14u2009day sequential therapy received rescue therapy with 10u2009day bismuth quadruple therapy and vice versa. Our primary outcome was the eradication rate in the first-line therapy. Antibiotic susceptibility was determined. ClinicalTrials.gov: NCT03156855.nnnResultsnThe eradication rates of 14u2009day sequential therapy and 10u2009day bismuth quadruple therapy were 91.3% (283 of 310, 95% CI 87.4%-94.1%) and 91.6% (284 of 310, 95% CI 87.8%-94.3%) in the ITT analysis, respectively (difference -0.3%, 95% CI -4.7% to 4.4%, Pu2009=u20090.886). However, the frequencies of adverse effects were significantly higher in patients treated with 10u2009day bismuth quadruple therapy than those treated with 14u2009day sequential therapy (74.4% versus 36.7% Pu2009<u20090.0001). The eradication rate of 14u2009day sequential therapy in strains with and without 23S ribosomal RNA mutation was 80% (24 of 30) and 99% (193 of 195), respectively (Pu2009<u20090.0001).nnnConclusionsnOptimized 14u2009day sequential therapy was non-inferior to, but better tolerated than 10u2009day bismuth quadruple therapy and both may be used in first-line treatment in populations with low to intermediate clarithromycin resistance.

Correction: Aminoazo dye-protein-adduct enhances inhibitory effect on digestibility and damages to gastro-duodenal-hepatic axis (PLoS ONE (2017) 12: 4 (e0170555) DOI: 10.1371/journal.pone.0170555)

[This corrects the article DOI: 10.1371/journal.pone.0170555.].

Evaluation of Overexpressed Cannabinoid 1 Receptor in Liver Fibrosis Tissues via Detecting CB1R Antagonist, AM251, by MALDI-TOF MS in Vitro

Background: Liver fibrosis leads to liver cirrhosis and even cancer progressively, but can be prevented through early detection. A reliable tissue biomarker is desirable in order to design a non-invasive diagnosing tool to complement invasive liver biopsy. Presently many studies have reported that the cannabinoid 1 receptor (CB1R) is associated with liver fibrosis, and therefore it is possible to measure the expression of CB1R for detecting the stages of liver fibrosis. The aim of this study was to measure the protein expression of CB1R via detecting its antagonist, AM251, utilizing biomedical techniques and matrix assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometer in vitro. Methods: The rats were treated with/without 0.04% thioacetamide to induce each stage of liver fibrosis (F0-F4) which was determined by hematoxylin and eosin (H&E) staining according to METAVIR Classification. Immunohistochemistry was used to detect the expression and position of CB1R. Fluorescent microscopy was used to observe the binding capacity of tocriflour 1117 (T1117), a fluorescent analogue of AM251, to CB1R. MALDI-TOF MS was used to measure the amount of AM251 after incubating with liver fibrosis tissue sections. Results: CB1R overexpressed in the liver fibrosis tissues and increased from F0 to F4 stage. T1117 binding assay showed that AM251 could interact with CB1R specifically. Moreover, the quantification analysis of MALDITOF MS indicated that AM251 could present the amount of CB1R in each stage of liver fibrosis with increase from F0 to F4 (p＜0.05). Conclusion: We showed that CB1R overexpressed in liver fibrosis tissues as a reliable biomarker. The data imply that in vitro measurement of CB1R antagonist, AM251, may help distinguish the stages of liver fibrosis. Furthermore, we suggest that AM251 may be used as a detecting ligand and applied in nuclear imaging technique for diagnosing liver fibrosis.

Predictors of Mortality in Patients with Pyogenic Liver Abscess Requiring Intensive Care

Background: Despite progress in the diagnosis and management of pyogenic liver abscess, the mortality rate remains high in critically ill patients. There have been limited studies on patients with pyogenic liver abscess requiring intensive care. The aim of this study was to assess the risk factors of mortality among patients with pyogenic liver abscess treated in intensive care unit (ICU). Methods: Thirty-five patients with pyogenic liver abscess admitted to ICU, between January 2003 and June 2009, were studied retrospectively. Parameters including general characteristics, clinical presentations, Acute Physiology and Chronic Health Evaluation (APACHE) Ⅱ scores, features of liver abscess and laboratory data were reviewed. The main outcome measure was survival. Univariate and subsequent multivariate logistic regression analyses were performed to assess the risk factors for mortality. The best cut-off for each identified independent risk factor for mortality was then investigated. Results: Univariate analysis implicated APACHE Ⅱ scores on admission, abscess size and gas formation as prognostic factors of mortality. Multivariate analysis showed higher APACHE Ⅱ scores on ICU admission (OR=1.387; 95% CI=1.106-1.739) and size of the liver abscess (OR=2.986; 95% CI=1.060-3.723) as independent prognostic factors for mortality. Finally, APACHE Ⅱ scores≥17 and the diameter of liver abscess≥5 cm were found to be relatively more accurate in predicting mortality in the study population. Conclusion: In patients with pyogenic liver abscess requiring intensive care, APACHE Ⅱ scores≥17 and the diameter of liver abscess≥5 cm were accurate predictors of mortality.