Hybrid, High-Dose Dual and Bismuth Quadruple Therapies for First-Line Treatment of Helicobacter pylori Infection in Taiwan: A Multicenter, Open-Label, Randomized Trial.

INTRODUCTION: The study aimed to compare the efficacies and safety of 14-day hybrid therapy, 14-day high-dose dual therapy, and 10-day bismuth quadruple therapy in the first-line treatment of Helicobacter pylori infections. METHODS: In this multicenter, open-label, randomized trial, we recruited adult H. pylori -infected patients from 9 centers in Taiwan. Subjects were randomly assigned (1:1:1) to 14-day hybrid therapy, 14-day high-dose dual therapy, or 10-day bismuth quadruple therapy. Eradication status was determined by the 13 C-urea breath test. The primary outcome was the eradication rate of H. pylori assessed in the intention-to-treat population. RESULTS: Between August 1, 2018, and December 2021, 918 patients were randomly assigned in this study. The intention-to-treat eradication rates were 91.5% (280/306; 95% confidence interval [CI] 88.4%-94.6%) for 14-day hybrid therapy, 83.3% (255/306; 95% CI 87.8%-95.0%) for 14-day high-dose dual therapy, and 90.2% (276/306; 95% CI 87.8%-95.0%) for 10-day bismuth quadruple therapy. Both hybrid therapy (difference 8.2%; 95% CI 4.5%-11.9%; P = 0.002) and bismuth quadruple therapy (difference 6.9%; 95% CI 1.6%-12.2%; P = 0.012) were superior to high-dose dual therapy and were similar to one another. The frequency of adverse events was 27% (81/303) with 14-day hybrid therapy, 13% (40/305) with 14-day high-dose dual therapy, and 32% (96/303) with 10-day bismuth quadruple therapy. Patients receiving high-dose dual therapy had the fewest adverse events (both P < 0.001). DISCUSSION: Fourteen-day hybrid therapy and 10-day bismuth quadruple therapy are more effective than 14-day high-dose dual therapy in the first-line treatment of H. pylori infection in Taiwan. However, high-dose dual therapy has fewer adverse effects than hybrid bismuth quadruple therapies.

REAP-HP survey 2020: Comparing the real-world practice and expectation in Helicobacter pylori eradication of the Taiwanese gastroenterologists in 2015 and 2020.

BACKGROUND: REAP-HP study (Real-world practice and Expectation of Asia-Pacific physicians and patients in Helicobacter Pylori eradication) was the pioneer study investigating the expectation and preference of physicians across Asia-Pacific in H. pylori eradication in 2015. This study is the first follow-up study of REAP-HP in Taiwan. AIMS: (1) To investigate the preference in regimens for the first-line anti-H. pylori therapy of Taiwanese gastroenterologist in 2020, (2) To survey the factor that cause the most concern when prescribing anti-H. pylori regimens in clinical practice, and (3) to compare REAP-HP survey data in 2020 and those surveyed in 2015 regarding the abovementioned end-points. METHODS: A questionnaire for H. pylori eradication survey of physicians was distributed to the gastroenterologists who attended the Taiwan Digestive Disease Week 2020. Data of most commonly used first-line anti-H. pylori regimens and concerned factors when prescribing anti-H. pylori regimens between 2015 and 2020 were compared. RESULTS: A total of 258 physicians from different districts of Taiwan participated in the REAP-HP Survey in 2020. The top three most commonly used anti-H. pylori regimens in Taiwan in 2020 were 14-day standard triple therapy (36.8%; 95% confidence interval [CI]: 30.9%-42.7%), 7-day standard triple therapy (17.8%; 95% CI: 13.1%-22.5%) and 14-day reverse hybrid therapy (14.7%; 95% CI: 10.4%-19.0%) respectively. The top two factors that cause the most concern during prescribing anti-H. pylori therapy were eradication rate (82.3%; 95% CI: 77.6%-87.0%) and side effect (10.4%; 95% CI: 6.7%-15.1%). In 2015, the top three most commonly used regimens in Taiwan were 7-day standard triple therapy (62%; 95% CI: 56.2%-67.8%), 14-day standard triple therapy (21%; 95% CI: 16.1%-25.9%) and 10-day sequential therapy (7%; 95% CI: 4%-10%). A remarkable difference of the most commonly used anti-H. pylori regimens between 2015 and 2020 existed (p < .001). The top two factors that cause the most concern during prescribing anti-H. pylori therapy in 2015 were eradication rate (84.1%) and side effect (7.0%). There were no differences in the factors that cause the most concern during prescribing anti-H. pylori regimens between 2015 and 2020. CONCLUSION: 14-day standard triple therapy has replaced 7-day standard triple therapy as the most commonly used first-line anti-H. pylori therapy among Taiwanese gastroenterologists in 2020. 14-day reverse hybrid therapy is on rise to the third place as the most commonly used anti-H. pylori regimen in Taiwan.

Fourteen-day sequential therapy is superior to 7-day triple therapy as first-line regimen for Helicobacter pylori infected children.

BACKGROUND/PURPOSE: Helicobacter pylori infection is one of the most common causes of peptic ulcer disease among children. This study is aimed to investigate the eradication rate of 14-day sequential therapy and the antibiotic resistance of H. pylori in children. METHODS: Eighty-seven treatment-naïve children (55 males; median age, 13.5 years) with H. pylori infection from January 2009 to August 2019 were recruited in this study. The status of H. pylori infection was confirmed by culture or histology with the aid of urea rapid test or C-13 urea breathe test. Patients treated with either triple therapy for 7 days or 14 days, or sequential therapy for 14 days was analyzed retrospectively. RESULTS: Thirty-eight (43.7%) patients received 14-day sequential therapy, 24 (27.6%) patients received 14-day triple therapy and the remaining 25 (28.7%) patients received 7-day triple therapy. The eradication rate of 14-day sequential therapy was significantly superior to 7-day triple therapy (97.4% vs. 80%, p = 0.032), and tended to be better than 14-day triple therapy (83%, p = 0.07). Of the 54 patients with available antibiotic resistance data, the resistant rate of clarithromycin, metronidazole, levofloxacin, and amoxicillin were 22.2%, 16.7%, 9.1% and 2.2%, respectively. Clarithromycin resistance demonstrated an inverse association with eradication success (Odds ratio = 0.017, p < 0.001). CONCLUSION: In treatment-naïve children with H. pylori infection, 14-day sequential therapy is superior to triple therapy, and achieve a high eradication rate (above 90%) in an area of high clarithromycin resistance.

Helicobacter pylori Antimicrobial Susceptibility Testing-Guided Salvage Therapy in the USA: A Real Life Experience.

BACKGROUND: The current practice guidelines recommend that Helicobacter pylori (H. pylori) culture and antimicrobial susceptibility testing (AST) be considered after patients failed the second course of H. pylori eradication therapy. AIMS: Here we report the real life experience of following this recommendation in the USA. METHODS: We established an in-house H. pylori culture protocol for AST and identified retrospectively patients who previously failed ≥ 2 courses of anti-H. pylori therapy and underwent esophagogastroduodenoscopy with AST at University of Michigan from 2010 to 2017. We determined the rate of H. pylori antibiotic resistance, the success rates of AST-guided tailored therapy, and the risk factors associated with treatment failure. RESULTS: Forty-seven patients were identified and 34 (72.3%) had successful cultures and AST. The most common antibiotic resistance was to metronidazole (79.4%), followed by clarithromycin (70.6%) and ciprofloxacin (42.9%). None of the patients were resistant to amoxicillin or tetracycline. The overall success rate of AST-guided tailored therapy was low (44.4%, 12/27). In patients infected with metronidazole-resistant H. pylori, bismuth quadruple therapy appears to be superior compared to non-bismuth quadruple therapy (6/8 or 75.0% vs. 3/14 or 21.4%, P = 0.03). High body mass index was significantly associated with tailored therapy failure (OR 1.24, 95% CI 1.00-1.54, P = 0.049). CONCLUSIONS: The success rate of AST-guided salvage therapy in the USA is low particularly in those with high BMI. Bismuth-based therapy appears to be better than non-bismuth-based regimens.

Real-world practice and Expectation of Asia-Pacific physicians and patients in Helicobacter Pylori eradication (REAP-HP Survey).

OBJECTIVE: The aims of the study were: 1, to survey the most popular anti-H. pylori regimens in Asia-Pacific region and the real-world effectiveness of these regimens; and 2, to investigate the expectation gaps of eradication rate between physicians and patients. DESIGN: A questionnaire was distributed to Asia-Pacific physicians who attended the Asia-Pacific Digestive Week 2015 meeting. Reported eradication rates from the literatures were compared with real-world rates of surveyed popular regimens within the region. In addition, a questionnaire was distributed to H. pylori-infected patients in three regions of Taiwan. RESULTS: A total of 691 physicians and 539 patients participated in the survey. The top five most commonly used regimens were 7-day clarithromycin-based standard triple therapy (50.4%), 14-day clarithromycin-based standard triple therapy (31.0%), 10-day sequential therapy (6.1%), 14-day bismuth quadruple therapy (3.9%), and 14-day hybrid therapy (3.6%). All countries except for China had a significant gap between the expectation of physicians on anti-H. pylori therapy and the real-world eradication rate of most commonly adopted regimens (all P value <.05). The expectation on minimal eradication rate among patients was higher than that of physicians (91.4% vs 86.5%, P<.001). CONCLUSIONS: It is time for physicians in Asia-Pacific countries to adopt newer and more efficacious anti-H. pylori regimens to meet the Kyoto consensus recommendation and their patients' expectations.

The C-terminal disulfide bonds of Helicobacter pylori GroES are critical for IL-8 secretion via the TLR4-dependent pathway in gastric epithelial cells.

Helicobacter pylori GroES (HpGroES), a potent immunogen, is a secreted virulence factor that stimulates production of proinflammatory cytokines and may contribute to gastric carcinogenesis. HpGroES is larger than other bacterial orthologs because of an additional C-terminal region, known as domain B. We found that the HpGroES-induced IL-8 release by human gastric epithelial cells was dependent on activation of the MAPK and NF-κB pathways. HpGroES lacking domain B was unable to induce IL-8 release. Additionally, a TLR4 inhibitor significantly inhibited IL-8 secretion and reduced HpGroES-induced activation of MAPKs. Furthermore, HpGroES-induced IL-8 release by primary gastric epithelial cells from TLR4(-/-) mice was significantly lower than from wild-type mice. We also found that HpGroES bound to TLR4 in cell lysates and colocalized with TLR4 on the cell membrane only when domain B was present. We then constructed two deletion mutants lacking C-terminal regions and mutants with point mutations of two of the four cysteine residues, C111 and C112, in domain B and found that the deletion mutants and a double mutant lacking the C94-C111 and C95-C112 disulfide bonds were unable to interact with TLR4 or induce IL-8 release. We conclude that HpGroES, in which a unique conformational structure, domain B, is generated by these two disulfide bonds, induces IL-8 secretion via a TLR4-dependent mechanism.

High-dose dual therapy is superior to standard first-line or rescue therapy for Helicobacter pylori infection.

BACKGROUND & AIMS: The efficacy of treatment of Helicobacter pylori infection has decreased steadily because of increasing resistance to clarithromycin, metronidazole, and levofloxacin. Resistance to amoxicillin is generally low, and high intragastric pH increases the efficacy of amoxicillin, so we investigated whether a combination of a high-dose proton pump inhibitor and amoxicillin (dual therapy) was more effective than standard first-line or rescue therapies in eradicating H pylori. METHODS: We performed a large-scale multihospital trial to compare the efficacy of a high-dose dual therapy (HDDT) with that of standard therapies in treatment-naive (n = 450) or treatment-experienced (n = 168) patients with H pylori infection. Treatment-naive patients were randomly assigned to groups given HDDT (rabeprazole 20 mg and amoxicillin 750 mg, 4 times/day for 14 days, group A1), sequential therapy for 10 days (group B1), or clarithromycin-containing triple therapy for 7 days (group C1). Treatment-experienced patients were randomly assigned to groups given HDDT for 14 days (group A2), sequential therapy for 10 days (B2), or levofloxacin-containing triple therapy for 7 days (C2). H pylori infection was detected by using the (13)C-urea breath test. We evaluated factors associated with treatment outcomes. RESULTS: In the intention-to-treat analysis, H pylori was eradicated in 95.3% of patients in group A1 (95% confidence interval [CI], 91.9%-98.8%), 85.3% in B1 (95% CI, 79.6%-91.1%), and 80.7% in group C1 (95% CI, 74.3%-87.1%). Infection was eradicated in 89.3% of patients in group A2 (95% CI, 80.9%-97.6%), 51.8% in group B2 (95% CI, 38.3%-65.3%), and 78.6% (95% CI, 67.5%-89.7%) in group C2. The efficacy of HDDT was significantly higher than that of currently recommended regimens, irrespective of CYP2C19 genotype. Bacterial resistance to drugs was associated with treatment failure. There were no significant differences between groups in adverse events or patient adherence. CONCLUSIONS: HDDT is superior to standard regimens as empirical first-line or rescue therapy for H pylori infection, with similar safety profiles and tolerability. ClinicalTrials.gov number: NCT01163435.

Independent Risk Factors Predicting Eradication Failure of Hybrid Therapy for the First-Line Treatment of Helicobacter pylori Infection.

Hybrid therapy is a recommended first-line anti-H. pylori treatment option in the American College of Gastroenterology guidelines, the Bangkok Consensus Report on H. pylori management, and the Taiwan H. pylori Consensus Report. However, the cure rates of eradication therapy in some countries are suboptimal, and the factors affecting the treatment efficacy of hybrid therapy remain unclear. The aim of this study is to identify the independent risk factors predicting eradication failure of hybrid therapy in the first-line treatment of H. pylori infection. A retrospective cohort study was conducted on 589 H. pylori-infected patients who received 14-day hybrid therapy between September 2008 and December 2021 in ten hospitals in Taiwan. The patients received a hybrid therapy containing a dual regimen with a proton pump inhibitor (PPI) plus amoxicillin for an initial 7 days and a quadruple regimen with a PPI plus amoxicillin, metronidazole and clarithromycin for a final 7 days. Post-treatment H. pylori status was assessed at least 4 weeks after completion of treatment. The relationships between eradication rate and 13 host and bacterial factors were investigated via univariate and multivariate analyses. In total, 589 patients infected with H. pylori infection were included in the study. The eradication rates of hybrid therapy were determined as 93.0% (95% confidence interval (CI): 90.9-95.1%), 94.4% (95% CI: 93.8-97.2%) and 95.5%% (95% CI: 93.8-97.2%) by intention-to-treat, modified intention-to-treat and per-protocol analyses, respectively. Univariate analysis showed that the eradication rate of clarithromycin-resistant strains was lower than that of clarithromcyin-susceptible strains (83.3% (45/54) vs. 97.6%% (280/287); p < 0.001). Subjects with poor drug adherence had a lower cure rate than those with good adherence (73.3% (11/15) vs. 95.5% (534/559); p = 0.005). Other factors such as smoking, alcohol drinking, coffee consumption, tea consumption and type of PPI were not significantly associated with cure rate. Multivariate analysis revealed that clarithromcyin resistance of H. pylori and poor drug adherence were independent risk factors related to eradication failure of hybrid therapy with odds ratios of 4.8 (95% CI: 1.5 to 16.1; p = 0.009) and 8.2 (95% CI: 1.5 to 43.5; p = 0.013), respectively. A 14-day hybrid therapy has a high eradication rate for H. pylori infection in Taiwan, while clarithromycin resistance of H. pylori and poor drug adherence are independent risk factors predicting eradication failure of hybrid therapy.

Quality of life and its associated factors in patients with hepatocellular carcinoma receiving one course of transarterial chemoembolization treatment: a longitudinal study.

OBJECTIVE: To (a) explore changes in physical and psychological distress and quality of life (QOL) and (b) identify the significant pre- and postdischarge factors related to changes in physical and mental domains of QOL over a period of 2 months in patients with hepatocellular carcinoma receiving one course of transarterial chemoembolization (TACE) treatment. METHODS: A longitudinal prospective design was used, with participants recruited from a teaching hospital in Northern Taiwan. Data were collected three times: within 3 days prior to discharge (T0) and at the fourth (T1) and eighth (T2) weeks after discharge. A set of structured questionnaires was used to assess participants' QOL, symptom distress, anxiety, and depression. Changes in QOL and associated factors were examined using generalized estimating equations. RESULTS: Eighty-nine patients were included in this study. Fatigue was reported to be the most distressful symptom after treatment. Overall QOL improved monthly after discharge. Change in physical QOL 2 months after TACE treatment was associated with age, diagnosis status, level of symptom distress, and depression after discharge. Change in mental QOL was significantly associated with gender, diagnosis status, and anxiety and depression after discharge. CONCLUSIONS: Health care providers should pay special attention to patients of older age, those who are male, and those who have higher levels of depression and anxiety after discharge. Designing personalized education programs before discharge for patients with newly diagnosed cancer versus those who have recurrent disease is suggested to help patients maintain a better QOL after discharge.

Interaction between Red Yeast Rice and CYP450 Enzymes/P-Glycoprotein and Its Implication for the Clinical Pharmacokinetics of Lovastatin.

Red yeast rice (RYR) can reduce cholesterol through its active component, lovastatin. This study was to investigate the pharmacokinetic properties of lovastatin in RYR products and potential RYR-drug interactions. Extracts of three registered RYR products (LipoCol Forte, Cholestin, and Xuezhikang) were more effective than pure lovastatin in inhibiting the activities of cytochrome P450 enzymes and P-glycoprotein. Among CYP450 enzymes, RYR showed the highest inhibition on CYP1A2 and CYP2C19, with comparable inhibitory potencies to the corresponding typical inhibitors. In healthy volunteers taking the RYR product LipoCol Forte, the pharmacokinetic properties of lovastatin and lovastatin acid were linear in the dose range of 1 to 4 capsules taken as a single dose and no significant accumulation was observed after multiple dosing. Concomitant use of one LipoCol Forte capsule with nifedipine did not change the pharmacokinetics of nifedipine. Yet, concomitant use of gemfibrozil with LipoCol Forte resulted in a significant increase in the plasma concentration of lovastatin acid. These findings suggest that the use of RYR products may not have effects on the pharmacokinetics of concomitant comedications despite their effects to inhibit the activities of CYP450 enzymes and P-gp, whereas gemfibrozil affects the pharmacokinetics of lovastatin acid when used concomitantly with RYR products.

Differential inhibitory effects of proton pump inhibitors on the metabolism and antiplatelet activities of clopidogrel and prasugrel.

The interaction between proton pump inhibitors (PPIs) and clopidogrel/prasugrel was investigated. The IC50 values of omeprazole, esomeprazole, lansoprazole, pantoprazole and rabeprazole on the metabolic ratios of 2-oxo-clopidogrel/clopidogrel, H4 (the active metabolite of clopidogrel)/2-oxo-clopidogrel and R-138727 (the active metabolite of prasugrel)/prasugrel thiolactone in human liver microsomes were determined. The antiplatelet activities of clopidogrel and prasugrel were measured with or without PPIs. As a result, most PPIs (except for pantoprazole) inhibited the formation of 2-oxo-clopidogrel with IC50 values of 20-32 µm and inhibited the formation of H4 with IC50 values of 6-20 µm. PPIs inhibited the formation of R-138727 with IC50 values of 9-25 µm. Among the tested PPIs, omeprazole exhibited the highest inhibitory potency on the formation of H4. Omeprazole, esomeprazole and rabeprazole exhibited the highest inhibitory potencies on the formation of R-138727. For platelet aggregation, omeprazole and lansoprazole show higher inhibitory effects on the antiplatelet activity of clopidogrel. On the other hand, omeprazole, esomeprazole and rabeprazole significantly decreased the antiplatelet activity of prasugrel thiolactone. These data indicate that PPIs differ in their effects of inhibiting the metabolism and antiplatelet activities of clopidogrel and prasugrel.

Identification of 14-3-3ß in human gastric cancer cells and its potency as a diagnostic and prognostic biomarker.

Gastric cancer is the second most common cause of cancer deaths worldwide and due to its poor prognosis, it is important that specific biomarkers are identified to enable its early detection. Through 2-D gel electrophoresis and MALDI-TOF-TOF-based proteomics approaches, we found that 14-3-3ß, which was one of the proteins that were differentially expressed by 5-fluorouracil-treated gastric cancer SC-M1 cells, was upregulated in gastric cancer cells. 14-3-3ß levels in tissues and serum were further validated in gastric cancer patients and controls. The results showed that 14-3-3ß levels were elevated in tumor tissues (n=40) in comparison to normal tissues (n=40; p<0.01), and serum 14-3-3ß levels in cancer patients (n=145) were also significantly higher than those in controls (n=63; p<0.0001). Elevated serum 14-3-3ß levels highly correlated with the number of lymph node metastases, tumor size and a reduced survival rate. Moreover, overexpression of 14-3-3ß enhanced the growth, invasiveness and migratory activities of tumor cells. Twenty-eight proteins involved in anti-apoptosis and tumor progression were also found to be differentially expressed in 14-3-3ß-overexpressing gastric cancer cells. Overall, these results highlight the significance of 14-3-3ß in gastric cancer cell progression and suggest that it has the potential to be used as a diagnostic and prognostic biomarker in gastric cancer.

Silicon-containing water intake confers antioxidant effect, gastrointestinal protection, and gut microbiota modulation in the rodents.

We explored the effects of silicon-containing water (BT) intake on gastrointestinal function and gut microbiota. BT was obtained by pressuring tap water through silicon minerals (mullite, Al6Si2O13) column. BT decreased H2O2 chemiluminescence counts, indicating its antioxidant activity. Four weeks of BT drinking increased H2O2 scavenging activity and glutathione peroxidase activity of plasma. BT drinking did not affect the body weight but significantly reduced the weight of feces and gastrointestinal motility. BT drinking significantly suppressed pylorus ligation enhanced gastric juice secretion, gastric reactive oxygen species amount, erythrocyte extravasation, IL-1ß production by infiltrating leukocyte, and lipid peroxidation within gastric mucosa. Data from 16S rRNA sequencing revealed BT drinking significantly increased beneficial flora including Ruminococcaceae UCG-005, Prevotellaceae NK3B31, Weissella paramesenteroides, Lactobacillus reuteri, and Lactobacillus murinus and decreased harmful flora including Mucispirillum, Rodentibacter, and Staphylococcus aureus. This study pioneerly provided scientific evidences for the potential effects of water-soluble forms of silicon intake on antioxidant activity, gastrointestinal function, and gut microbiota modulation.

Residence Time-Extended Nanoparticles by Magnetic Field Improve the Eradication Efficiency of Helicobacter pylori.

Helicobacter pylori infection is one of the leading causes of several gastroduodenal diseases, such as gastritis, peptic ulcer, and gastric cancer. In fact, H. pylori eradication provides a preventive effect against the incidence of gastric cancer. Amoxicillin is a commonly used antibiotic for H. pylori eradication. However, due to its easy degradation by gastric acid, it is necessary to administer it in a large dosage and to combine it with other antibiotics. This complexity and the strong side effects of H. pylori eradication therapy often lead to treatment failure. In this study, the chitosan/poly (acrylic acid) particles co-loaded with superparamagnetic iron oxide nanoparticles and amoxicillin (SPIO/AMO@PAA/CHI) are used as drug nano-carriers for H. pylori eradication therapy. In vitro and in vivo results show that the designed SPIO/AMO@PAA/CHI nanoparticles are biocompatible and could retain the biofilm inhibition and the bactericidal effect of amoxicillin against H. pylori. Moreover, the mucoadhesive property of chitosan allows SPIO/AMO@PAA/CHI nanoparticles to adhere to the gastric mucus layer and rapidly pass through the mucus layer after exposure to a magnetic field. When PAA is added, it competes with amoxicillin for chitosan, so that amoxicillin is quickly and continuously released between the mucus layer and the gastric epithelium and directly acts on H. pylori. Consequently, the use of this nano-carrier can extend the drug residence time in the stomach, reducing the drug dose and treatment period of H. pylori eradication therapy.

Efficacy of second-line regimens for Helicobacter pylori eradication treatment: a systemic review and network meta-analysis.

BACKGROUND: Current guidelines recommend bismuth-containing quadruple therapy (BQT) and quinolone-containing therapy after failure of first-line Helicobacter pylori eradication therapy. However, the optimum regimen of second-line eradication therapy remains elusive. We conducted a network meta-analysis to compare the relative efficacy of 16 second-line H. pylori eradication regimens. METHODS: Three major bibliographic databases were reviewed to enrol relevant randomised controlled trials between January 2000 and September 2018. Network meta-analysis was conducted by STATA software and we performed subgroup analysis in countries with high clarithromycin resistance and high levofloxacin resistance, and in patients with documented failure of first-line triple therapy. RESULTS: Fifty-four studies totalling 8752 participants who received 16 regimens were eligible for analysis. Compared with a 7-day BQT, use of probiotic add-on therapy during, before, and after second-line antibiotic regimens, quinolone-based sequential therapy for 10-14 days, quinolone-based bismuth quadruple therapy for 10-14 days, bismuth quadruple therapy for 10-14 days, and quinolone-based triple therapy for 10-14 days were significantly superior to the other regimens. Subgroup analysis of countries with high clarithromycin resistance and high levofloxacin resistance revealed that the ranking of second-line eradication regimens was distributed similarly in each group, as well as in patients with failure of first-line triple therapy. CONCLUSION: We conducted a detailed comparison of second-line H. pylori regimens according to different antibiotic resistance rates and the results suggest alternative treatment choices with potential benefits beyond those that could be achieved using salvage therapies recommended by guidelines.

Synergistic effect of imp/ostA and msbA in hydrophobic drug resistance of Helicobacter pylori.

BACKGROUND: Contamination of endoscopy equipment by Helicobacter pylori (H. pylori) frequently occurs after endoscopic examination of H. pylori-infected patients. In the hospital, manual pre-cleaning and soaking in glutaraldehyde is an important process to disinfect endoscopes. However, this might not be sufficient to remove H. pylori completely, and some glutaraldehyde-resistant bacteria might survive and be passed to the next patient undergoing endoscopic examination through unidentified mechanisms. We identified an Imp/OstA protein associated with glutaraldehyde resistance in a clinical strain, NTUH-C1, from our previous study. To better understand and manage the problem of glutaraldehyde resistance, we further investigated its mechanism. RESULTS: The minimal inhibitory concentrations (MICs) of glutaraldehyde andexpression of imp/ostA RNA in 11 clinical isolates from the National Taiwan University Hospital were determined. After glutaraldehyde treatment, RNA expression in the strains with the MICs of 4-10 microg/ml was higher than that in strains with the MICs of 1-3 microg/ml. We examined the full-genome expression of strain NTUH-S1 after glutaraldehyde treatment using a microarray and found that 40 genes were upregulated and 31 genes were downregulated. Among the upregulated genes, imp/ostA and msbA, two putative lipopolysaccharide biogenesis genes, were selected for further characterization. The sensitivity to glutaraldehyde or hydrophobic drugs increased in both of imp/ostA and msbA single mutants. The imp/ostA and msbA double mutant was also hypersensitive to these chemicals. The lipopolysaccharide contents decreased in individual imp/ostA and msbA mutants and dramatically reduced in the imp/ostA and msbA double mutant. Outer membrane permeability assay demonstrated that the imp/ostA and msbA double mutation resulted in the increase of outer membrane permeability. Ethidium bromide accumulation assay demonstrated that MsbA was involved in efflux of hydrophobic drugs. CONCLUSION: The expression levels of imp/ostA and msbA were correlated with glutaraldehyde resistance in clinical isolates after glutaraldehyde treatment. Imp/OstA and MsbA play a synergistic role in hydrophobic drugs resistance and lipopolysaccharide biogenesis in H. pylori.

Pharmacokinetic- pharmacodynamic analysis of the role of CYP2C19 genotypes in short-term rabeprazole-based triple therapy against Helicobacter pylori.

AIMS: The aim was to explore the role of CYP2C19 polymorphism in short-term rabeprazole-based triple therapy against Helicobacter pylori infection. METHODS: Patients with H. pylori infection were tested for CYP2C19 genotype as poor metabolizers (PMs) or extensive metabolizers (EMs, homozygous EM or heterozygous EM) and given rabeprazole for 7 days. Antibiotics (clarithromycin and amoxicillin) were given on days 1-4, days 4-7, or days 1-7. A direct link model with an effect compartment was used in the population pharmacokinetic-pharmacodynamic analysis. The status of H. pylori infection was evaluated. RESULTS: Rabeprazole clearance was lower in CYP2C19 PMs than in EMs (with average values of 10.7 vs. 16.8 l h(-1) in PMs and EMs, respectively), resulting in higher plasma levels in the former group. The values of EC(50) and k(eo) of gastrin response increased with multiple doses of rabeprazole. The k(eo) values were lower in CYP2C19 PMs than in EMs on day 1 (0.012 vs. 0.017 x 10(-4) l min(-1)), and higher than in EMs on day 4 (0.804 vs. 0.169 x 10(-4) l min(-1)) of rabeprazole treatment. The predicted gastrin-time profile showed a higher response in CYP2C19 PMs than in EMs on days 4 and 7. Helicobacter pylori was eradicated in all CYP2C19 PMs except in one patient infected by a resistant strain. In contrast, in CYP2C19 EMs the eradication rates ranged from 58 to 85%. CONCLUSIONS: CYP2C19 genotypes play a role in H. pylori eradication therapy. Rabeprazole-based short-term triple therapy may be applicable in CYP2C19 PMs for H. pylori eradication.

Effective prevention and treatment of Helicobacter pylori infection using a combination of catechins and sialic acid in AGS cells and BALB/c mice.

The increasing emergence of Helicobacter pylori strains resistant to antibiotics may cause unsuccessful treatment. An alternative agent or mixture with anti-H. pylori effect is urgently required to reduce H. pylori infection. We explored the preventive and therapeutic potential of a combination of catechins and sialic acid on H. pylori-infected human gastric cells in vitro and in mice in vivo. We evaluated the anti-H. pylori activity of catechins and/or sialic acid using the agar dilution and checkerboard methods. The effect of catechins and/or sialic acid on H. pylori infection-induced oxidative stress and apoptosis/autophagy in cell culture was explored using an ultrasensitive chemiluminescence analyzer, immunocytochemistry, and Western blotting. Specific pathogen-free BALB/c mice were divided into uninfected control, infected control, pretreated, and post-treated groups. The effects of catechins/sialic acid were determined by histology and immunocytochemistry. The combination of catechins and sialic acid showed synergistic or additive anti-H. pylori activity and significantly reduced inducible nitric oxide synthase expression and Bax/Bcl-2-mediated apoptosis but enhanced Beclin-1-mediated autophagy. All mice infected with H. pylori displayed gastritis and accumulation of 3-nitrotyrosine and 4-hydroxynonenal. Pretreatment with catechins/sialic acid completely prevented H. pylori infection and resulted in normal histology. Post-treatment with catechins/sialic acid decreased the bacterial load and gastritis score and eradicated up to 60% of H. pylori infections in a dose-dependent manner. This is the first demonstration to our knowledge of a nonprobiotic, nonantibiotic treatment that is 100% effective in preventing and has promising possibilities for treating H. pylori infection. Further studies are needed to confirm this result in humans.

Change of Uncertainty in Illness and Unmet Care Needs in Patients With Recurrent Hepatocellular Carcinoma During Active Treatment.

BACKGROUND: Uncertainty about or related to cancer-related treatment and prognosis is commonly experienced by patients with hepatocellular carcinoma and might be associated with unmet care needs. However, their dynamic associations have not been examined in this population. OBJECTIVE: The aim of this study was to explore change in unmet care needs and uncertainty under different levels of uncertainty (low vs high) before discharge and the significant factors related to change of uncertainty in patients with recurrent hepatocellular carcinoma after treatment. METHODS: A set of questionnaires was used to collect data including symptom distress, supportive care needs, and uncertainty of illness before discharge (T0), 1 month after discharge (T1), and 2 months after discharge (T2). The significant factors related to uncertainty were identified by generalized estimating equations. RESULTS: The patients with high uncertainty, who were younger in age, had significantly higher levels of symptom distress and unmet care needs. Before discharge, the patients' highest levels of unmet needs were psychological in the high-uncertainty group. Patients with jobs, higher unmet care needs, and high uncertainty before discharge had higher levels of uncertainty over time. CONCLUSIONS: The changes in uncertainty were significantly associated with unmet care needs over time, and the baseline level of uncertainty was a significant factor related to the change of uncertainty. IMPLICATIONS FOR PRACTICE: Healthcare providers should take into account each individual's age, levels of psychological need, and symptom distress and should offer personalized information related to psychological needs and symptom management to decrease levels of uncertainty before discharge.