Impact of glucose-containing fluid on acute pancreatitis outcomes: A multicenter retrospective analysis.

INTRODUCTION: Fluid resuscitation reduces mortality and morbidity in acute pancreatitis (AP); however, whether glucose-containing fluids negatively impact AP remains uncertain. We aimed to examine the association between glucose-containing fluids and AP outcomes. METHODS: This multicenter retrospective cohort study included patients diagnosed with AP between January 2015 and December 2018. Glucose density was defined as total glucose content divided by total fluid volume (g/dl) on day 1, and was considered high if the level exceeded the median. Endpoints were early organ failure (OF), including cardiovascular, renal, or respiratory system failure within 7 days; 30-day OF; ICU admission; and AP-related 90-day mortality. Logistic regression models, restricted cubic spline curves, and Cox proportional hazards models were used for statistical analysis. RESULTS: From the database, 1,146 patients with AP were included. Early OF occurred in 8.8% of patients within 7 days. The high glucose-density group (>5 g/dl) had increased risk of early OF (9.7% vs. 8.2%; adjusted odds ratio [aOR], 1.69; 95% confidence interval [CI], 1.03-2.80; P = 0.039), respiratory failure (8.0% vs. 6.2%; aOR, 1.88; 95% CI, 1.09-3.24; P = 0.024), cardiovascular failure (3.4% vs. 2.4%; aOR, 3.59; 95% CI, 1.28-10.0; P = 0.015), and ICU admission (6.8% vs. 5.8%; aOR, 2.06; 95% CI, 1.08-3.94; P = 0.029), with a dose-response effect observed for cardiovascular failure and ICU admission. A significant increase 30-day OF risk (adjusted hazard ratio [aHR], 1.70; 95% CI, 1.19-2.45) was also noted. CONCLUSION: Excess glucose-containing fluid was associated with increased risks of overall, respiratory, and cardiovascular OF and ICU admission in AP.

Declining trends of prevalence of Helicobacter pylori infection and incidence of gastric cancer in Taiwan: An updated cross-sectional survey and meta-analysis.

BACKGROUND: We aimed to assess the latest prevalence and secular trend of Helicobacter pylori infection and its association with the incidence and mortality of gastric cancer in Taiwan. MATERIALS AND METHODS: Adults naive to H. pylori eradication received 13 C-urea breath test (13 C-UBT), H. pylori stool antigen test, and serology test during 2019-2020 in this prospective screening program. Children and adolescent aged between 7 and 19 years received 13 C-UBT for H. pylori screening. We also conducted a systematic review and meta-analysis to assess the secular trend of prevalence of H. pylori from 1990 to 2020 in Taiwan. The secular trends of age-standardized incidence and mortality of gastric cancer were obtained from the Taiwan Cancer Registry. RESULTS: A total of 1494 participants were enrolled, including 294 children or adolescents and 1200 adults. The overall prevalence of active H. pylori infection by 13 C-UBT was 26.6% (397/1494), which was 30.8% in adults and 9.5% in adolescents/children. The age-standardized prevalence of active H. pylori infection was 32.3% in adults after adjustment of the population structure in Taiwan. Of the 29 studies including 38,597 subjects eligible for the meta-analysis, the pooled prevalence of H. pylori infection decreased from 63.8% (95% CI: 55.9%-71%) in 1990-2000 to 28.2% (95% CI:21.8%-35.6%) in 2016-2020. The age-standardized incidence and mortality of gastric cancer have also declined from 15.2 to 10.75 per 100,000, respectively, in 1999 to 9.29 and 5.4 per 100,000, respectively, in 2019. CONCLUSIONS: The prevalence of H. pylori infection has declined in Taiwan, which correlates with the declining trends of age-standardized incidence and mortality of gastric cancer in Taiwan.

The efficacy of Lactobacillus acidophilus and rhamnosus in the reduction of bacterial load of Helicobacter pylori and modification of gut microbiota-a double-blind, placebo-controlled, randomized trial.

BACKGROUND: Probiotics may alter the gut microbiota and may reduce antibiotic-related dysbiosis after H. pylori eradication. However, whether probiotics are effective in reducing the bacterial load of H. pylori and modifying the gut microbiota remains unknown. We aimed to assess the efficacy of Lactobacillus acidophilus and Lactobacillus rhamnosus in reducing the bacterial load of H. pylori and modifying the gut microbiota. MATERIALS AND METHODS: In this double-blind, randomized, placebo-controlled trial, we recruited 40 adult subjects with moderate to high bacterial loads of H. pylori, defined as a mean delta over baseline (DOB) value of the 13 C-urea breath test (13 C-UBT) of 10 or greater every 4 days 6 times. Eligible subjects were randomized in a 1:1 ratio to receive either probiotics containing Lactobacillus acidophilus and Lactobacillus rhamnosus or placebo twice daily for 4 weeks. 13 C-UBT was measured weekly from the beginning of treatment to 2 weeks after treatment. Amplification of the V3 and V4 hypervariable regions of the 16S rRNA was performed for fecal microbiota. RESULTS: A total of 40 subjects were randomized to receive probiotics or placebo. The DOB value was significantly lower in the probiotic group than in the placebo group after 4 weeks of treatment (26.0 vs. 18.5, p = .045). The DOB value was significantly reduced compared to that at baseline in the probiotic group (18.5 vs. 26.7, p = .001) but not in the placebo group (26.0 vs. 25.0, p = .648). However, the eradication rate for H. pylori was 0% in both groups. There was no significant difference in the DOB values between the two groups 1 and 2 weeks after discontinuation of the probiotics. There were also no significant changes observed in the α-diversity and ß-diversity at week 4 compared to baseline in the probiotic group (p = .77 and 0.91) and the placebo group (p = .26 and 0.67). CONCLUSIONS: Although the use of Lactobacillus acidophilus and Lactobacillus rhamnosus may reduce the bacterial load of H. pylori, there were no significant changes in the composition of gut microbiota. This trial is registered with ClinicalTrials.gov, NCT02725138.

Application of Helicobacter pylori stool antigen test to survey the updated prevalence of Helicobacter pylori infection in Taiwan.

BACKGROUND AND AIM: The reported prevalence of Helicobacter pylori infection in Taiwan was 54.4% in 1992. An updated prevalence of H. pylori infection in asymptomatic adults is lacking in Taiwan. We aimed to assess the updated age-standardized prevalence of H. pylori infection in asymptomatic subjects and in patients with dyspepsia and to assess the accuracy of H. pylori stool antigen (HpSA) test for screening of H. pylori in Chinese population. METHODS: Asymptomatic adult subjects (N = 189) were screened for H. pylori infection using HpSA, serology, and 13 C-urea breath test (13 C-UBT) in 2016-2017. Adult patients with dyspepsia (N = 145) were screened for H. pylori using 13 C-UBT, HpSA, serology, rapid urease test, and histology during 2016-2018. Two types of HpSA, including the Diagnostec HpSA ELISA Kit (HpSA ELISA) and Rapid Test Kit (HpSA Rapid), were used in this study. Sensitivity, specificity, and accuracy of the HpSA tests were calculated using the 13 C-UBT as golden standard test. RESULTS: The unadjusted prevalence of H. pylori was 21.2% in asymptomatic adults and 37.9% in patients with dyspepsia (P < 0.001). The age-standardized prevalence of H. pylori was 28.9% in asymptomatic adults in Taiwan. Of the 334 patients included for analysis, the area under the curve of HpSA ELISA test was 0.978, and the optimal cutoff value of optical density was 0.03. The sensitivity, specificity, and accuracy of the HpSA ELISA were 0.929, 0.983, and 0.967, respectively. The sensitivity, specificity, and accuracy of the HpSA Rapid were 0.929, 0.958, and 0.949, respectively. CONCLUSIONS: The prevalence of H. pylori infection has decreased in Taiwan. HpSA test is an accurate tool for screening of H. pylori in Chinese population.

Comparison of DNA stabilizers and storage conditions on preserving fecal microbiota profiles.

BACKGROUND/PURPOSE: Appropriate storage of fecal samples is a critical step for the unbiased analysis of microbial communities in metagenomic studies. Rapid freezing at -80 °C is usually considered to be best practice, but this approach is challenging. DNA stabilizing kits may provide a more convenient method to preserve and store clinical samples. We evaluated the reliability of two collection kits (Stratec stool collection tube with stabilizer, #1038111200 and OMNIgene.GUT OMR-200) on preserving fecal microbiota. METHODS: Samples were collected from two locations of the fecal specimen, in four healthy volunteers. The samples were sub-aliquoted and stored in a -80 °C freezer, in Stratec and OMNIgene.GUT (incubation at ambient temperature for 0, 3, or 7 days). The fecal microbial composition was assessed by 16S rRNA sequencing. RESULTS: We found that alpha diversity was not significantly affected by storage conditions. Samples stored in DNA stabilizers were still representative of the original microbial community after 7 days at ambient temperature. Individual differences were found to have a greater contribution to the differences in microbial community composition than storage conditions or sampling location. Samples subjected to stabilizers displayed microbial community shifts compared with immediately frozen samples. A linear discriminant analysis effect size (LEfSe) analysis showed that the relative abundances of Faecalibacterium were significantly higher in samples stored in Stratec kits. CONCLUSION: Our study reveals that both Stratec and OMNIgene.GUT kits provide good microbiome preservation for up to 7 days in ambient temperature and would represent good options for fecal sample collection in large scale, population-based studies.

Accuracy of rapid Helicobacter pylori antigen tests for the surveillance of the updated prevalence of H. pylori in Taiwan.

BACKGROUND: The updated prevalence of Helicobacter pylori (H. pylori) is lacking in Taiwan. We aimed to assess the accuracy of Vstrip® H. pylori Stool Antigen Rapid Test (Vstrip®HpSA) in the detection and surveillance of the updated prevalence of H. pylori in Taiwan. METHODS: A total of 347 adult subjects including 152 volunteers and 195 symptomatic patients were recruited. Stool samples were collected for detection of H. pylori using Vstrip® HpSA, ImmunoCard STAT!® HpSA and Premier Platinum HpSA® PLUS. All subjects who have completed the stool sample collections were included in the ITT analysis. The sensitivity, specificity, and accuracy of Vstrip® HpSA were calculated compared to gold standard test with 13C-Urea breath test. RESULTS: The un-adjusted prevalence of H. pylori infection was 22.5% (95% CI: 18.3-27%) in 2018. The age-standardized prevalence of H. pylori was 21.8% in asymptomatic adults in Taiwan. The sensitivity, specificity, and accuracy of the Vstrip® HpSA, and ImmunoCard STAT!® HpSA tests were 91% (95% CI: 82-96%) versus 76.9% (95% CI: 66-86%), 97% (95% CI: 94.1-98.6%) versus 97% (95% CI: 94.1-98.6%), and 95.7% (95% CI: 92-97%) versus 92.5% (95% CI: 89-95%), respectively. CONCLUSION: The age-standardized prevalence of H. pylori infection in Taiwan was 21.8% in asymptomatic adults in 2018. The Vstrip® HpSA had equivalent performance as the ImmunoCard STAT!® HpSA, and can be used in future mass screening of H. pylori infection for gastric cancer prevention.

Efficacies of Genotypic Resistance-Guided vs Empirical Therapy for Refractory Helicobacter pylori Infection.

BACKGROUND & AIMS: We aimed to compare the efficacy of genotypic resistance-guided therapy vs empirical therapy for eradication of refractory Helicobacter pylori infection in randomized controlled trials. METHODS: We performed 2 multicenter, open-label trials of patients with H pylori infection (20 years or older) failed by 2 or more previous treatment regimens, from October 2012 through September 2017 in Taiwan. The patients were randomly assigned to groups given genotypic resistance-guided therapy for 14 days (n = 21 in trial 1, n = 205 in trial 2) or empirical therapy according to medication history for 14 days (n = 20 in trial 1, n = 205 in trial 2). Patients received sequential therapy containing esomeprazole and amoxicillin for the first 7 days, followed by esomeprazole and metronidazole, with levofloxacin, clarithromycin, or tetracycline (doxycycline in trial 1, tetracycline in trial 2) for another 7 days (all given twice daily) based on genotype markers of resistance determined from gastric biopsy specimens (group A) or empirical therapy according to medication history. Resistance-associated mutations in 23S ribosomal RNA or gyrase A were identified by polymerase chain reaction with direct sequencing. Eradication status was determined by 13C-urea breath test. The primary outcome was eradication rate. RESULTS: H pylori infection was eradicated in 17 of 21 (81%) patients receiving genotype resistance-guided therapy and 12 of 20 (60%) patients receiving empirical therapy (P = .181) in trial 1. This trial was terminated ahead of schedule due to the low rate of eradication in patients given doxycycline sequential therapy (15 of 26 [57.7%]). In trial 2, H pylori infection was eradicated in 160 of 205 (78%) patients receiving genotype resistance-guided therapy and 148 of 205 (72.2%) patients receiving empirical therapy (P = .170), according to intent to treat analysis. The frequencies of adverse effects and compliance did not differ significantly between groups. CONCLUSIONS: Properly designed empirical therapy, based on medication history, is an acceptable alternative to genotypic resistance-guided therapy for eradication of refractory H pylori infection after consideration of accessibility, cost, and patient preference. ClinicalTrials.gov ID: NCT01725906.

Paritaprevir/ritonavir, ombitasvir plus dasabuvir for East Asian non-cirrhotic hepatitis C virus genotype 1b patients receiving hemodialysis.

BACKGROUND AND AIM: Data regarding the efficacy and safety of paritaprevir/ritonavir, ombitasvir plus dasabuvir (PrOD) for East Asian non-cirrhotic hepatitis C virus genotype 1b (HCV GT1b) patients receiving hemodialysis were limited. METHODS: Forty-six HCV GT1b non-cirrhotic patients receiving hemodialysis who received PrOD for 12 weeks were prospectively enrolled in seven academic centers in Taiwan. The primary efficacy endpoint was sustained virologic response 12 weeks off-therapy (SVR12 ). Patients' baseline characteristics, early virokinetics, and HCV resistance-associated substitutions (RASs) potentially related to SVR12 were analyzed. The safety profiles were also assessed. RESULTS: The SVR12 rate was 100% (46 of 46 patients). Patients' baseline characteristics, on-treatment viral decline, and baseline HCV resistance-associated substitutions did not affect SVR12 . All patients tolerated treatment well. One patient with folliculitis temporarily discontinued treatment, and another two patients had serious adverse events (SAEs), which were considered not related to PrOD treatment. The common adverse events were pruritus (19.6%), fatigue (15.2%), and upper respiratory tract infection (6.5%). Twelve (19.6%) and one (2.2%) patients had hemoglobin levels < 10 and 8.5 g/dL, respectively, which were related to renal impairment. Five (10.9%) patients had on-treatment total bilirubin level of 1.5-3.0 mg/dL, but none developed hepatic decompensation. The bilirubin levels peaked at week 1 of treatment and then declined with continuous treatment. CONCLUSION: Treatment with PrOD for 12 weeks is efficacious and well-tolerated for East Asian non-cirrhotic HCV GT1b patients receiving hemodialysis.

Real-world effectiveness and safety of glecaprevir/pibrentasvir in Asian patients with chronic hepatitis C.

BACKGROUND: Glecaprevir/pibrentasvir (GLE/PIB) is a pangenotypic direct-acting antiviral agent for the treatment of chronic hepatitis C virus (HCV) infection. Real-world data of GLE/PIB in Asian patients other than Japanese are limited. We thus investigated the effectiveness and safety profile of GLE/PIB in Taiwanese patients with chronic hepatitis C (CHC). METHODS: CHC patients who received 8, 12, or 16 weeks of GLE/PIB between August and October of 2018 were consecutively enrolled. The treatment duration was determined according to drug label. The hepatic fibrosis was staged according to liver histology, transient elastography, fibrosis index based on 4 factors (FIB-4), or findings of ultrasonography/endoscopy. The primary endpoint was sustained virological response at week 12 off therapy (SVR12). The safety profiles were also assessed. RESULTS: A total of 110 CHC patients with 51% of males were enrolled. The median age was 70 years. A majority (82%) of patients were infected with HCV genotype 2. Forty-six (42%) and 64 (58%) patients had advanced hepatic fibrosis and compensated cirrhosis, respectively. Forty-five (41%) non-cirrhotic patients were treated for 8 weeks. The overall SVR12 rates were 100%, regardless of baseline clinical characteristics. The common adverse events (AEs) were pruritus (12%), anorexia (6%), and fatigue (5%). Nine (8%) serious AEs unrelated to GLE/PIB occurred. Three (2%) patients had Grade 3 elevation of total bilirubin level. None had premature treatment termination, hepatic decompensation, or death. CONCLUSION: Interferon-free GLE/PIB regimen is highly effective and safe for Asian chronic hepatitis C patients with advanced hepatic fibrosis or compensated cirrhosis.

Systematic Review with Meta-Analysis: Concomitant Therapy vs. Triple Therapy for the First-Line Treatment of Helicobacter pylori Infection.

BACKGROUND: Whether concomitant therapy is superior to triple therapy of various treatment lengths for the first-line treatment of H. pylori remains controversial. The objective of this study is to compare the efficacy of concomitant therapy and triple therapy given for 5-14 days. METHODS: Randomized control trials (RCTs) comparing the efficacy of concomitant therapy for 5-14 days and proton pump inhibitor-amoxicillin-clarithromycin (PAC)-based triple therapy for 5-14 days in the first-line treatment of adult patients with H. pylori infection published from 1990 to January 2018 were searched from the PubMed, Cochrane Library, and Embase. Abstracts from international annual conferences were also searched. The primary and secondary outcomes were the eradication rate according to the intention-to-treat analysis and the adverse effects, respectively. Subgroup analyses were also performed according to treatment length. This study is registered with PROSPERO, number CRD42017081328. RESULTS: Of the 639 articles identified, 23 RCTs including 3305 patients in the concomitant therapy group and 3327 patients in the triple therapy group were eligible. Overall, concomitant therapy was superior to triple therapy [risk ratio (RR): 1.15; 95% confidence interval (CI): 1.09-1.21; p < 0.001]. However, there were significant heterogeneity (I2 = 74.0%, p < 0.001). In the subgroup analysis, 5-day concomitant therapy was superior to 5-day triple therapy (RR: 1.30; 95% CI: 1.04-1.62; p = 0.02), 5- or 7-day concomitant therapy was superior to 7-day triple therapy (RR: 1.16; 95% CI: 1.12-1.21; p < 0.001), and 5- or 7-, or 10- or 14-day concomitant therapy was superior to 10-day triple therapy (RR: 1.15; 95% CI: 1.08-1.23; p < 0.001). However, 5- or 10-day concomitant therapy was not superior to 14-day triple therapy (RR: 1.02; 95% CI: 0.89-1.16; p = 0.796). The frequency of adverse effects was significantly higher in concomitant therapy than triple therapy (RR: 1.19; 95% CI: 1.06-1.34; P = 0.004). CONCLUSIONS: Concomitant therapy given for 5 or 10 days was superior to 5- or 7-, or 10-day PAC-based triple therapy, but was not superior to 14-day triple therapy.

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.

Background: Whether extending the treatment length and the use of high-dose esomeprazole may optimize the efficacy of Helicobacter pylori eradication remains unknown. Objectives: To compare the efficacy and tolerability of optimized 14 day sequential therapy and 10 day bismuth quadruple therapy containing high-dose esomeprazole in first-line therapy. Methods: We recruited 620 adult patients (≥20 years of age) with H. pylori infection naive to treatment in this multicentre, open-label, randomized trial. Patients were randomly assigned to receive 14 day sequential therapy or 10 day bismuth quadruple therapy, both containing esomeprazole 40 mg twice daily. Those who failed after 14 day sequential therapy received rescue therapy with 10 day 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. Results: The eradication rates of 14 day sequential therapy and 10 day 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%, P = 0.886). However, the frequencies of adverse effects were significantly higher in patients treated with 10 day bismuth quadruple therapy than those treated with 14 day sequential therapy (74.4% versus 36.7% P < 0.0001). The eradication rate of 14 day sequential therapy in strains with and without 23S ribosomal RNA mutation was 80% (24 of 30) and 99% (193 of 195), respectively (P < 0.0001). Conclusions: Optimized 14 day sequential therapy was non-inferior to, but better tolerated than 10 day bismuth quadruple therapy and both may be used in first-line treatment in populations with low to intermediate clarithromycin resistance.

Concomitant, bismuth quadruple, and 14-day triple therapy in the first-line treatment of Helicobacter pylori: a multicentre, open-label, randomised trial.

BACKGROUND: Whether concomitant therapy is superior to bismuth quadruple therapy or 14-day triple therapy for the first-line treatment of Helicobacter pylori infection remains poorly understood. We aimed to compare the efficacy and safety of 10-day concomitant therapy, 10-day bismuth quadruple therapy, and 14-day triple therapy in the first-line treatment of H pylori. METHODS: In this multicentre, open-label, randomised trial, we recruited adult patients (aged >20 years) with H pylori infection from nine medical centres in Taiwan. Patients who had at least two positive tests from the rapid urease test, histology, culture, or serology or who had a single positive 13C-urea breath test for gastric cancer screening were eligible for enrolment. Patients were randomly assigned (1:1:1) to either concomitant therapy (lansoprazole 30 mg, amoxicillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg, all given twice daily) for 10 days; bismuth quadruple therapy (bismuth tripotassium dicitrate 300 mg four times a day, lansoprazole 30 mg twice daily, tetracycline 500 mg four times a day, and metronidazole 500 mg three times a day) for 10 days; or triple therapy (lansoprazole 30 mg, amoxicillin 1 g, and clarithromycin 500 mg, all given twice daily) for 14 days. A computer-generated permuted block randomisation sequence with a block size of 6 was used for randomisation, and the sequence was concealed in an opaque envelope until the intervention was assigned. Investigators were masked to treatment allocation. The primary outcome was the eradication frequency of H pylori with first-line therapy assessed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01906879. FINDINGS: Between July 17, 2013, and April 20, 2016, 5454 patients were screened for eligibility. Of these, 1620 patients were randomly assigned in this study. The eradication frequencies were 90·4% (488/540 [95% CI 87·6-92·6]) for 10-day bismuth quadruple therapy, 85·9% (464/540 [82·7-88·6]) for 10-day concomitant therapy, and 83·7% (452/540 [80·4-86·6]) for 14-day triple therapy in the intention-to-treat analysis. 10-day bismuth quadruple therapy was superior to 14-day triple therapy (difference 6·7% [95% CI 2·7-10·7, p=0·001), but not 10-day concomitant therapy. 10-day concomitant therapy was not superior to 14-day triple therapy. The frequency of adverse events was 67% (358/533) in patients treated with 10-day bismuth quadruple therapy, 58% (309/535) in patients treated with 10-day concomitant therapy, and 47% (252/535) in patients treated with 14-day triple therapy. INTERPRETATION: Bismuth quadruple therapy is preferable to 14-day triple therapy in the first-line treatment in the face of rising prevalence of clarithromycin resistance. Concomitant therapy given for 10 days might not be optimum and a longer treatment length should be considered. FUNDING: National Taiwan University Hospital and Ministry of Science and Technology of Taiwan.

Impact of amoxicillin resistance on the efficacy of amoxicillin-containing regimens for Helicobacter pylori eradication: analysis of five randomized trials.

BACKGROUND: The impact of amoxicillin resistance on the efficacy of regimens containing amoxicillin for Helicobacter pylori eradication remains unknown. OBJECTIVES: To investigate whether the efficacy of an amoxicillin-containing regimen is affected by amoxicillin resistance and to identify the optimal breakpoint for amoxicillin resistance. METHODS: This was a pooled analysis of five randomized trials conducted in Taiwan from 2007 to 2016. Patients who received amoxicillin-containing regimens were recruited. MICs were determined by agar dilution testing. Meta-analysis was performed to assess the risk ratio of eradication failure in amoxicillin-resistant strains compared with susceptible strains of seven different regimens. We performed further the pooled analysis and logistic regression in patients treated with clarithromycin triple therapy to identify the optimal breakpoint for amoxicillin resistance. RESULTS: A total of 2339 patients with available amoxicillin MICs were enrolled. Meta-analysis showed that the presence of amoxicillin resistance was consistently associated with increased risk of treatment failure of amoxicillin-containing regimens at different breakpoints (risk ratio: 1.41, 95% CI 1.12-1.78, P = 0.004 when the cut-off was 0.5 mg/L). The heterogeneity was low (I2 = 0%, P = 0.615). Pooled analysis also showed that amoxicillin resistance was an independent risk factor for treatment failure of clarithromycin triple therapy at different breakpoints. The best correlation was observed when the breakpoint of amoxicillin resistance was ≥0.125 mg/L (kappa coefficient 0.298), at which the resistance rate was 11.1% (110 of 990). CONCLUSIONS: The efficacies of amoxicillin-containing regimens are affected by amoxicillin resistance and the optimal breakpoint MIC is ≥ 0.125 mg/L.

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 10 days (S10) versus triple therapy for 14 days (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 5 days, followed by lansoprazole, clarithromycin and metronidazole for another 5 days) or T14 (lansoprazole, amoxicillin and clarithromycin for 14 days). All drugs were given twice daily. Successful eradication was defined as negative 13C-urea breath test at least 6 weeks 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.

Association Between Serum Level of Hepatitis B Surface Antigen at End of Entecavir Therapy and Risk of Relapse in E Antigen-Negative Patients.

BACKGROUND & AIMS: This study investigated whether serum level of hepatitis B surface antigen (HBsAg) at the end of entecavir treatment was associated with risk of relapse. METHODS: We performed a prospective multicenter study of 161 consecutive patients with chronic hepatitis B in whom the hepatitis B virus was no longer detected after 3 years or more of entecavir therapy. Treatment ended between July 1, 2011 and July 1, 2015. Patients were monitored for clinical relapse (hepatitis B virus DNA >2000 IU/mL and level of alanine aminotransferase more than 2-fold the upper limit of normal) and virologic relapse (hepatitis B virus DNA >2000 IU/mL). Outcomes were calculated using the Kaplan-Meier method and risk factors were identified by Cox proportional hazards modeling. RESULTS: Two years after therapy ended, 49.2% of patients in the entire cohort had a clinical relapse (95% confidence interval [CI], 40.9%-58.1%) and 81.7% had a virologic relapse (95% CI, 74.3%-88.0%). Among patients who were hepatitis B e antigen-negative at the end of therapy, 39.2% had a clinical relapse (95% CI, 30.3%-49.6%) and 77.4% had a virologic relapse (95% CI, 68.6%-85.2%). Serum level of HBsAg was associated with relapse in the hepatitis B e antigen-negative patients (Ptrend = .006 for clinical relapse; Ptrend = .0001 for virologic relapse). In multivariate Cox regression analysis, the hazard ratio (per log IU/mL increment) for clinical relapse was 2.47 (95% CI, 1.45-4.23) and for virologic relapse was 1.80 (95% CI, 1.33-2.45). The 11 (9%) patients with levels of HBsAg <10 IU/mL did not relapse. CONCLUSIONS: Serum level of HBsAg is associated with risk of relapse in patients who are hepatitis B e antigen-negative after treatment with entecavir. A low titer of HBsAg might be used to identify patients at low risk for relapse after treatment.

Levofloxacin Sequential Therapy vs Levofloxacin Triple Therapy in the Second-Line Treatment of Helicobacter pylori: A Randomized Trial.

OBJECTIVES: The efficacy of levofloxacin triple therapy has fallen below 80% in the second-line treatment of Helicobacter pylori (H. pylori). We aimed to assess whether the levofloxacin sequential therapy is more effective than levofloxacin triple therapy in the second-line treatment. METHODS: This open-label, randomized, multicenter trial was conducted between 2012 and 2015. H. pylori-infected subjects who failed from clarithromycin-based regimens (N=600) were randomized (1:1) to receive levofloxacin sequential therapy (LS: lansoprazole and amoxicillin for the first 5 days, followed by lansoprazole, levofloxacin, and metronidazole for another 5 days) or levofloxacin triple therapy (LT: lansoprazole, amoxicillin, and levofloxacin for 10 days). Successful eradication was defined as negative (13)C-urea breath test at least 6 weeks 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 prevalence of clarithromycin, levofloxacin, and metronidazole resistance was 60, 17.6, and 36.9%, respectively. The eradication rates of LS and LT were 84.3% (253/300) and 75.3% (226/300), respectively, in the ITT analysis (P=0.006) and 86.3% (253/293) and 78.8% (223/283), respectively, in the PP analysis (P=0.021). The efficacies of both LS and LT were affected by levofloxacin resistance. The secondary resistance of levofloxacin was 66.7 and 73.9% after LS and LT, respectively. The efficacies of LS and LT were not affected by the CYP2C19 polymorphism. CONCLUSIONS: Levofloxacin sequential therapy was more effective than levofloxacin triple therapy, and it is recommended in the second-line treatment for H. pylori ( TRIAL REGISTRATION NUMBER: NCT01537055).

Distinct aetiopathogenesis in subgroups of functional dyspepsia according to the Rome III criteria.

BACKGROUND AND OBJECTIVE: Whether there is distinct pathogenesis in subgroups of functional dyspepsia (FD), the postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS) remains controversial. We aimed to identify the risk factors of FD and its subgroups in the Chinese population. METHODS: Patients with dyspepsia and healthy subjects who underwent gastric cancer screening were enrolled in this multicentre study from 2010 to 2012. All patients were evaluated by questionnaire, oesophagoduodenoscopy, histological examination and Helicobacter pylori tests. Subgroups of FD were classified according to the Rome III criteria. Psychiatric stress was assessed by the short form Brief Symptom Rating Scale. CagA and VacA genotypes were determined by PCR. RESULTS: Of 2378 patients screened for eligibility, 771 and 491 fulfilled the diagnostic criteria of uninvestigated dyspepsia and FD, respectively. 298 (60.7%) and 353 (71.9%) individuals were diagnosed with EPS and PDS, respectively, whereas 169 (34.4%) had the overlap syndrome. As compared with 1031 healthy controls, PDS and EPS shared some common risk factors, including younger age (OR 0.95; 99.5% CI 0.93 to 0.98), non-steroidal anti-inflammatory drugs (OR 6.60; 99.5% CI 3.13 to 13.90), anxiety (OR 3.41; 99.5% CI 2.01 to 5.77) and concomitant IBS (OR 6.89; 99.5% CI 3.41 to 13.94). By contrast, H. pylori (OR 1.86; 99.5% CI 1.01 to 3.45), unmarried status (OR 4.22; 99.5% CI 2.02 to 8.81), sleep disturbance (OR 2.56; 99.5% CI 1.29 to 5.07) and depression (OR 2.34; 99.5% CI 1.04 to 5.36) were associated with PDS. Moderate to severe antral atrophy and CagA positive strains were also more prevalent in PDS. CONCLUSIONS: Different risk factors exist among FD subgroups based on the Rome III criteria, indicating distinct aetiopathogenesis of the subdivisions that may necessitate different therapeutic strategies.

Sequential versus triple therapy for the first-line treatment of Helicobacter pylori: a multicentre, open-label, randomised trial.

BACKGROUND: Whether sequential treatment can replace triple therapy as the standard treatment for Helicobacter pylori infection is unknown. We compared the efficacy of sequential treatment for 10 days and 14 days with triple therapy for 14 days in first-line treatment. METHODS: For this multicentre, open-label, randomised trial, we recruited patients (≥20 years of age) with H pylori infection from six centres in Taiwan. Using a computer-generated randomisation sequence, we randomly allocated patients (1:1:1; block sizes of six) to either sequential treatment (lansoprazole 30 mg and amoxicillin 1 g for the first 7 days, followed by lansoprazole 30 mg, clarithromycin 500 mg, and metronidazole 500 mg for another 7 days; with all drugs given twice daily) for either 10 days (S-10) or 14 days (S-14), of 14 days of triple therapy (T-14; lansoprazole 30 mg, amoxicillin 1 g, and clarithromycin 500 mg for 14 days; with all drugs given twice daily). Investigators were masked to treatment allocation. Our primary outcome was the eradication rate in first-line treatment by intention-to-treat (ITT) and per-protocol (PP) analyses. This trial is registered with ClinicalTrials.gov, number NCT01042184. FINDINGS: Between Dec 28, 2009, and Sept 24, 2011, we enrolled 900 patients: 300 to each group. The eradication rate was 90·7% (95% CI 87·4-94·0; 272 of 300 patients) in the S-14 group, 87·0% (83·2-90·8; 261 of 300 patients) in the S-10 group, and 82·3% (78·0-86·6; 247 of 300 patients) in the T-14 group. Treatment efficacy was better in the S-14 group than it was in the T-14 group in both the ITT analysis (number needed to treat of 12·0 [95% CI 7·2-34·5]; p=0·003) and PP analyses (13·7 [8·3-40], p=0·003). We recorded no significant difference in the occurrence of adverse effects or in compliance between the three groups. INTERPRETATION: Our findings lend support to the use of sequential treatment as the standard first-line treatment for H pylori infection. FUNDING: National Taiwan University Hospital and National Science Council.

Assessment of Narrow-Band Imaging Algorithm for Video Capsule Endoscopy Based on Decorrelated Color Space for Esophageal Cancer: Part II, Detection and Classification of Esophageal Cancer.

Esophageal carcinoma (EC) is a prominent contributor to cancer-related mortality since it lacks discernible features in its first phases. Multiple studies have shown that narrow-band imaging (NBI) has superior accuracy, sensitivity, and specificity in detecting EC compared to white light imaging (WLI). Thus, this study innovatively employs a color space linked to décor to transform WLIs into NBIs, offering a novel approach to enhance the detection capabilities of EC in its early stages. In this study a total of 3415 WLI along with the corresponding 3415 simulated NBI images were used for analysis combined with the YOLOv5 algorithm to train the WLI images and the NBI images individually showcasing the adaptability of advanced object detection techniques in the context of medical image analysis. The evaluation of the model's performance was based on the produced confusion matrix and five key metrics: precision, recall, specificity, accuracy, and F1-score of the trained model. The model underwent training to accurately identify three specific manifestations of EC, namely dysplasia, squamous cell carcinoma (SCC), and polyps demonstrates a nuanced and targeted analysis, addressing diverse aspects of EC pathology for a more comprehensive understanding. The NBI model effectively enhanced both its recall and accuracy rates in detecting dysplasia cancer, a pre-cancerous stage that might improve the overall five-year survival rate. Conversely, the SCC category decreased its accuracy and recall rate, although the NBI and WLI models performed similarly in recognizing the polyp. The NBI model demonstrated an accuracy of 0.60, 0.81, and 0.66 in the dysplasia, SCC, and polyp categories, respectively. Additionally, it attained a recall rate of 0.40, 0.73, and 0.76 in the same categories. The WLI model demonstrated an accuracy of 0.56, 0.99, and 0.65 in the dysplasia, SCC, and polyp categories, respectively. Additionally, it obtained a recall rate of 0.39, 0.86, and 0.78 in the same categories, respectively. The limited number of training photos is the reason for the suboptimal performance of the NBI model which can be improved by increasing the dataset.

Hepatitis B core-related antigen dynamics and risk of subsequent clinical relapses after nucleos(t)ide analog cessation.

BACKGROUND/AIMS: Finite nucleos(t)ide analog (NA) therapy has been proposed as an alternative treatment strategy for chronic hepatitis B (CHB), but biomarkers for post-treatment monitoring are limited. We investigated whether measuring hepatitis B core-related antigen (HBcrAg) after NA cessation may stratify the risk of subsequent clinical relapse (CR). METHODS: This retrospective multicenter analysis enrolled adults with CHB who were prospectively monitored after discontinuing entecavir or tenofovir with negative HBeAg and undetectable HBV DNA at the end of treatment (EOT). Patients with cirrhosis or malignancy were excluded. CR was defined as serum alanine aminotransferase > two times the upper limit of normal with recurrent viremia. We applied time-dependent Cox proportional hazard models to clarify the association between HBcrAg levels and subsequent CR. RESULTS: The cohort included 203 patients (median age, 49.8 years; 76.8% male; 60.6% entecavir) who had been treated for a median of 36.9 months (interquartile range [IQR], 36.5-40.1). During a median post-treatment follow-up of 31.7 months (IQR, 16.7-67.1), CR occurred in 104 patients with a 5-year cumulative incidence of 54.8% (95% confidence interval [CI], 47.1-62.4%). Time-varying HBcrAg level was a significant risk factor for subsequent CR (adjusted hazard ratio [aHR], 1.53 per log U/mL; 95% CI, 1.12-2.08) with adjustment for EOT HBsAg, EOT anti-HBe, EOT HBcrAg and time-varying HBsAg. During follow-up, HBcrAg <1,000 U/mL predicted a lower risk of CR (aHR, 0.41; 95% CI, 0.21-0.81). CONCLUSION: Dynamic measurement of HBcrAg after NA cessation is predictive of subsequent CR and may be useful to guide post-treatment monitoring.