Global Prevalence of Helicobacter pylori Infection and Incidence of Gastric Cancer Between 1980 and 2022.

BACKGROUND & AIMS: We aimed to assess the secular trend of the global prevalence of Helicobacter pylori (H pylori) infection in adults and children/adolescents and to show its relation to that of gastric cancer incidence. METHODS: We performed a systematic review and meta-analysis to calculate overall prevalence, adjusted by multivariate meta-regression analysis. The incidence rates of gastric cancer were derived from the Global Burden of Disease Study and Cancer Incidence in Five Continents. RESULTS: Of the 16,976 articles screened, 1748 articles from 111 countries were eligible for analysis. The crude global prevalence of H pylori has reduced from 52.6% (95% confidence interval [CI], 49.6%-55.6%) before 1990 to 43.9% (95% CI, 42.3%-45.5%) in adults during 2015 through 2022, but was as still as high as 35.1% (95% CI, 30.5%-40.1%) in children and adolescents during 2015 through 2022. Secular trend and multivariate regression analyses showed that the global prevalence of H pylori has declined by 15.9% (95% CI, -20.5% to -11.3%) over the last 3 decades in adults, but not in children and adolescents. Significant reduction of H pylori prevalence was observed in adults in the Western Pacific, Southeast Asian, and African regions. However, H pylori prevalence was not significantly reduced in children and adolescents in any World Health Organization regions. The incidence of gastric cancer has decreased globally and in various countries where the prevalence of H pylori infection has declined. CONCLUSIONS: The global prevalence of H pylori infection has declined during the last 3 decades in adults, but not in children and adolescents. The results raised the hypothesis that the public health drive to reduce the prevalence of H pylori as a strategy to reduce the incidence of gastric cancer in the population should be confirmed in large-scale clinical trials.

Serum cytokine profiles predict outcomes of chronic hepatitis B patients discontinuing entecavir or tenofovir therapy.

BACKGROUND/PURPOSE: Distinct hepatitis relapse has been observed after discontinuing entecavir (ETV) or tenofovir disoproxil fumarate (TDF) therapy in chronic hepatitis B (CHB) patients. End-of-therapy (EOT) serum cytokines were compared and used for outcome prediction. METHODS: A total of 80 non-cirrhotic CHB patients in a tertiary medical center in Taiwan who discontinued ETV (n = 51) or TDF (n = 29) therapy after fulfilling the APASL guidelines were prospectively enrolled. Serum cytokines were measured at EOT and 3rd month afterwards. Multivariable analysis was performed to predict virological relapse (VR, HBV DNA >2000 IU/mL), clinical relapse (CR, VR and alanine aminotransferase > 2-fold upper limit of normal) and hepatitis B surface antigen (HBsAg) seroclearance. RESULTS: Compared with TDF group, ETV stoppers had greater interleukin 5 (IL-5), IL-12 p70, IL-13, IL-17 A and tumor necrosis factor alpha (TNF-alpha) (all P < 0.05) at EOT. Older age, TDF use, higher EOT HBsAg and IL-18 (Hazard ratio [HR], 1.01; 95% CI, 1.00-1.02) levels at EOT predicted VR, while older age, higher EOT HBsAg and IL-7 (HR, 1.25; 95% CI, 1.00-1.56) levels predicted CR. In TDF stoppers, higher IL-7 (HR, 1.29; 95% CI, 1.05-1.60) and IL-18 (HR, 1.02; 95% CI, 1.00-1.04) levels predicted VR, while IL-7 (HR, 1.34; 95% CI, 1.08-1.65) and interferon-gamma (IFN-gamma) (HR, 1.08; 95% CI, 1.02-1.14) levels predicted CR. A lower EOT HBsAg level was associated with HBsAg seroclearance. CONCLUSION: Distinct cytokine profiles were observed after stopping ETV or TDF. Higher EOT IL-7, IL-18, and IFN-gamma could be probable predictors for VR and CR in patients discontinuing NA therapies.

Management of Helicobacter pylori infection: the Maastricht VI/Florence consensus report.

Helicobacter pyloriInfection is formally recognised as an infectious disease, an entity that is now included in the International Classification of Diseases 11th Revision. This in principle leads to the recommendation that all infected patients should receive treatment. In the context of the wide clinical spectrum associated with Helicobacter pylori gastritis, specific issues persist and require regular updates for optimised management.The identification of distinct clinical scenarios, proper testing and adoption of effective strategies for prevention of gastric cancer and other complications are addressed. H. pylori treatment is challenged by the continuously rising antibiotic resistance and demands for susceptibility testing with consideration of novel molecular technologies and careful selection of first line and rescue therapies. The role of H. pylori and antibiotic therapies and their impact on the gut microbiota are also considered.Progress made in the management of H. pylori infection is covered in the present sixth edition of the Maastricht/Florence 2021 Consensus Report, key aspects related to the clinical role of H. pylori infection were re-evaluated and updated. Forty-one experts from 29 countries representing a global community, examined the new data related to H. pylori infection in five working groups: (1) indications/associations, (2) diagnosis, (3) treatment, (4) prevention/gastric cancer and (5) H. pylori and the gut microbiota. The results of the individual working groups were presented for a final consensus voting that included all participants. Recommendations are provided on the basis of the best available evidence and relevance to the management of H. pylori infection in various clinical fields.

Primer for Development of Guidelines for Helicobacter pylori Therapy Using Antimicrobial Stewardship.

We provide a primer to assist in the difficult transition of Helicobacter pylori therapy guidelines to those that adhere to the principles of antimicrobial stewardship. This transition will entail abandonment of many of the principles that heretofore formed the basis of treatment guidelines and recommendations. The goals of antimicrobial stewardship include optimization of the use of antibiotics while reducing antimicrobial resistance. The critical outcome measure is absolute cure rate which largely restricts comparative trials to those which reliably produce high cure rates (eg, ∼95%). Therapies that fail to achieve at least a 90% cure rate should be abandoned as unacceptable. Because only optimized therapies should be prescribed, guidance on the principles and practices of optimization will we required. Therapies that contain antibiotics which do not contribute to outcome should be eliminated. Surveillance, one of the fundamental elements of antimicrobial stewardship, must be done to provide ongoing assurance that the recommended therapies remain effective. It is yet not widely recognized when utilizing otherwise highly successful therapies, the routine test of cure data is an indirect, surrogate method for susceptibility testing. To systematically guide therapy, test of cure data should be collected, shared and integrated into local antimicrobial stewardship programs to provide guidance regarding best practices to both prescribers and public health individuals. Treatment recommendations should be compatible with those of the American Society of Infectious Disease white paper on the conduct of superiority and organism-specific clinical trials of antibacterial agents for the treatment of infections caused by drug-resistant bacterial pathogens which include criteria for ethical active-controlled superiority studies of antibacterial agents.

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.

Bismuth salts with versus without acid suppression for Helicobacter pylori infection: A transmission electron microscope study.

BACKGROUND: Bismuth oxychloride produced by interaction of bismuth compounds with gastric acid is believed to damage Helicobacter pylori. The effect of bismuth salts on H. pylori in the presence of strong acid suppression is unknown. This randomized trial aimed to determine effects of bismuth subcitrate on H. pylori with and without acid suppression. METHODS: H. pylori -positive participants were allocated (1:1:1) to receive (a) no treatment (control), (b) colloidal bismuth subcitrate (CBS, 125 mg/tab), or (c) CBS plus high-dose proton-pump inhibitor (PPI), esomeprazole 40 mg q.i.d. for 3 days. In the treatment groups, CBS was given: 1 dose, 1 hour before endoscopy, 1 dose, 4 hours before endoscopy, or q.i.d. 24 hours before endoscopy. The study end-points were evaluated using transmission electron microscopy to observe the morphological changes of H. pylori in antral and corpus biopsies. RESULTS: Twenty-seven H. pylori carriers were enrolled in this trial with qualitative end-points. In the no treatment group, active budding and replication of H. pylori were observed. In the CBS group, cellular swelling, vacuolization, structural degradation, and cell wall eruption of H. pylori were observed, with no apparent association with when the CBS was given. Among those receiving high-dose PPI-plus CBS or CBS only, there were no differences in number of H. pylori present or severity of bacterial damage whether CBS was given 1, 4, or 24 hours before endoscopy. CONCLUSIONS: Based on direct morphological evaluation, the toxic effect of CBS treatment on H. pylori was demonstrated independent of acid suppression with PPI.

Changes of serum pepsinogen level and ABC classification after bariatric surgery.

BACKGROUND: Very few studies have explored the changes of serum pepsinogen after bariatric surgery and no research has evaluated the feasibility of ABC classification to predict gastric cancer risk after bariatric surgery. METHODS: We enrolled 94 obese subjects that received bariatric surgery, including 41 sleeve gastrectomy (SG) and 53 Roux-en-Y gastric bypass (RYGB). The serum pepsinogen I (PGI), pepsinogen II (PGII), PGI/II ratio and seropositivity of Helicobacter pylori ( H. pylori ) were measured before and one year after surgery. Patients were classified according to ABC classification and post-operative change was evaluated. RESULTS: Preoperatively, four (4.2%) patients were classified into high risk group (classification C and D) for gastric cancer. Significant reduction of PGI, PGII and decrease of PGI/II ratio were noted after bariatric surgery. H. pylori seropositive patients had a greater postoperative change of PGI (-38.6µg/L vs -22.1µg/L, p=0.003) and PGII (-8.0µg/L vs -2.5µg/L, p <0.001) but a less postoperative change of PGI/II ratio (-0.6 vs -2.1, p =0.04) than H. pylori seronegative patients. One year after surgery, the portion of high risk group of ABC classification for gastric cancer increased markedly from 4.2% to 23.7%. CONCLUSION: Both of SG and RYGB resulted in significant reduction of serum PGI and PGII after bariatric surgery, and significantly influenced the ABC classification. The application of ABC classification for gastric cancer screening was limited after bariatric surgery.

Screening and eradication of Helicobacter pylori for gastric cancer prevention: the Taipei global consensus.

OBJECTIVE: A global consensus meeting was held to review current evidence and knowledge gaps and propose collaborative studies on population-wide screening and eradication of Helicobacter pylori for prevention of gastric cancer (GC). METHODS: 28 experts from 11 countries reviewed the evidence and modified the statements using the Delphi method, with consensus level predefined as ≥80% of agreement on each statement. The Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach was followed. RESULTS: Consensus was reached in 26 statements. At an individual level, eradication of H. pylori reduces the risk of GC in asymptomatic subjects and is recommended unless there are competing considerations. In cohorts of vulnerable subjects (eg, first-degree relatives of patients with GC), a screen-and-treat strategy is also beneficial. H. pylori eradication in patients with early GC after curative endoscopic resection reduces the risk of metachronous cancer and calls for a re-examination on the hypothesis of 'the point of no return'. At the general population level, the strategy of screen-and-treat for H. pylori infection is most cost-effective in young adults in regions with a high incidence of GC and is recommended preferably before the development of atrophic gastritis and intestinal metaplasia. However, such a strategy may still be effective in people aged over 50, and may be integrated or included into national healthcare priorities, such as colorectal cancer screening programmes, to optimise the resources. Reliable locally effective regimens based on the principles of antibiotic stewardship are recommended. Subjects at higher risk of GC, such as those with advanced gastric atrophy or intestinal metaplasia, should receive surveillance endoscopy after eradication of H. pylori. CONCLUSION: Evidence supports the proposal that eradication therapy should be offered to all individuals infected with H. pylori. Vulnerable subjects should be tested, and treated if the test is positive. Mass screening and eradication of H. pylori should be considered in populations at higher risk of GC.

Treatment of Helicobacter pylori infection and its long-term impacts on gut microbiota.

The rising prevalence of antibiotic resistance and the long-term safety following eradication therapy are important issues in the management of Helicobacter pylori infection. The prevalence of clarithromycin, levofloxacin, and metronidazole resistance of H. pylori has increased to 21%, 27%, and 45%, respectively, in the Asia-Pacific region. Personalized treatment guided by susceptibility testing may provide a reliably excellent eradication rate in the first-line treatment but is costly and not widely available. Population-specific empirical therapy according to the local prevalence of antibiotic resistance may be an alternative strategy. Levofloxacin-based therapy and bismuth quadruple therapy are the recommended second-line rescue therapy. Susceptibility testing or genotypic resistance-guided therapy is the preferred treatment for refractory H. pylori infection, but empirical therapy may be an acceptable alternative. Eradication of H. pylori leads to short-term perturbation of gut microbiota. The diversity of gut microbiota can be restored months after eradication therapy, but the speed of recovery varies with regimens. The short-term increases of antibiotic resistance of Escherichia coli and Klebsiella pneumoniae may be restored to basal states months after H. pylori eradication. Future studies that apply in-depth sequencing, such as shotgun metagenomics sequencing, are needed to clarify whether the compositions of gut microbiota at the species level are fully restored.

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.

Endoscopic submucosal dissection comparing with surgical resection in patients with early gastric cancer - A single center experience in Taiwan.

BACKGROUND/PURPOSE: The choice of endoscopic submucosal dissection (ESD) as first line treatment for selected early gastric cancer (EGC) patients was proved as effective as surgical treatment in studies over many countries. Yet there is no such cohort comparison in Taiwan. This study is aimed to describe our experience in ESD treated EGC and to compare the outcomes with those underwent surgical treatment. METHODS: This was a retrospective cohort study reviewing the patients with EGC underwent ESD and surgical treatments in a single tertiary referral center in Taiwan. The primary endpoint was disease specific survival. Recurrence free survival and length of hospital stay were also compared. RESULTS: The disease specific survival between indicated ESD and surgery showed no significant difference (cumulative survival 100% vs. 97.03%, p = 0.39), so as the recurrence free survival (cumulative survival 92.31% vs. 94.06%, p = 0.60). In subgroup analyses of ESD treated patients, a non-significant recurrence rate difference between indicated and non-indicated ESD was found (cumulative recurrence 7.69% vs. 20%, p = 0.39) and a higher recurrence rate in patients with non-R0 resection compared with R0 resection (cumulative recurrence 0% vs. 40%, p < 0.01). However, the shorter duration of hospital stay in ESD group was noted in comparison to surgery (mean 5.67 days vs. 15.75 days, p < 0.01). The ESD patients have minor complications including bleeding, perforation and fever than surgery. CONCLUSION: ESD is a reasonable first line treatment in selected early gastric cancer in additional to surgery. Pre-treatment evaluation and post-ESD review of curability is crucial to further surveillance program or definite therapy including surgery.

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.

Altered gut microbiota and inflammatory cytokine responses in patients with Parkinson's disease.

OBJECTIVE: Emerging evidence suggests that gut microbiome composition alterations affect neurodegeneration through neuroinflammation in the pathogenesis of Parkinson's disease (PD). Here, we evaluate gut microbiota alterations and host cytokine responses in a population of Taiwanese patients with PD. METHODS: Fecal microbiota communities from 80 patients with PD and 77 age and gender-matched controls were assessed by sequencing the V3-V4 region of the 16S ribosomal RNA gene. Diet and comorbidities were controlled in the analyses. Plasma concentrations of IL-1ß, IL-2, IL-4, IL-6, IL-13, IL-18, GM-CSF, IFNγ, and TNFα were measured by a multiplex immunoassay and relationships between microbiota, clinical characteristics, and cytokine levels were analyzed in the PD group. We further examined the cytokine changes associated with the altered gut microbiota seen in patients with PD in another independent cohort of 120 PD patients and 120 controls. RESULTS: Microbiota from patients with PD was altered relative to controls and dominated by Verrucomicrobia, Mucispirillum, Porphyromonas, Lactobacillus, and Parabacteroides. In contrast, Prevotella was more abundant in controls. The abundances of Bacteroides were more increased in patients with non-tremor PD subtype than patients with tremor subtype. Bacteroides abundance was correlated with motor symptom severity defined by UPDRS part III motor scores (rho = 0.637 [95% confidence interval 0.474 to 0.758], P < 0.01). Altered microbiota was correlated with plasma concentrations of IFNγ and TNFα. There was a correlation between Bacteroides and plasma level of TNFα (rho = 0.638 [95% CI: 0.102-0.887], P = 0.02); and a correlation between Verrucomicrobia abundance and plasma concentrations of IFNγ (rho = 0.545 [95% CI - 0.043-0.852], P = 0.05). The elevated plasma cytokine responses were confirmed in an additional independent 120 patients with PD and 120 controls (TNFα: PD vs. control 8.51 ± 4.63 pg/ml vs. 4.82 ± 2.23 pg/ml, P < 0.01; and IFNγ: PD vs. control: 38.45 ± 7.12 pg/ml vs. 32.79 ± 8.03 pg/ml, P = 0.03). CONCLUSIONS: This study reveals altered gut microbiota in PD and its correlation with clinical phenotypes and severity in our population. The altered plasma cytokine profiles associated with gut microbiome composition alterations suggest aberrant immune responses may contribute to inflammatory processes in PD.

Expressions of the CagA protein and CagA-signaling molecules predict Helicobacter pylori dependence of early-stage gastric DLBCL.

We previously reported that early-stage gastric diffuse large B-cell lymphomas (DLBCLs), including DLBCLs with mucosa-associated lymphoid tissue (DLBCL[MALT]) and without ("pure" DLBCL) the features of MALT lymphomas, can achieve long-term complete remission after frontline Helicobacter pylori (HP) eradication (HPE). We recently reported that expression of cytotoxin-associated gene A (CagA) and CagA-signaling molecules (phospho-Src homology-2 domain-containing phosphatase [p-SHP2] and phospho-extracellular signal-regulated kinase [p-ERK]) is associated with HP dependence of gastric MALT lymphoma. However, the significance of CagA and CagA-signaling molecules in gastric DLBCL remains unexplored. The association between expression of CagA, p-SHP-2, and p-ERK in malignant B cells and tumor response to HPE was evaluated in 63 patients with stage IE/IIE1 HP-positive gastric DLBCL who received HPE as frontline treatment. We detected CagA expression in 20 of 42 DLBCL (MALT) cases (47.6%) and in 13 of 21 "pure" DLBCL cases (61.9%). CagA expression was higher in HP-dependent tumors than in HP-independent tumors (74.3% [26 of 35] vs 25.0% [7 of 28]). Patients with CagA expression responded to HPE quicker than those without expression (median time to complete remission, 4.0 months vs 5.0 months). The expression of CagA was closely associated with p-SHP-2 and p-ERK expression. Combined CagA, p-SHP-2, and p-ERK expression showed an increased positive predictive value (81.8% vs 75.9%) and an increased specificity (84.0% vs 75.0%) for HP dependence compared with CagA expression alone. Our results indicated that CagA and its signaling molecules can be detected in the malignant B cells of gastric DLBCL, and the expression of these molecules is clinically and biologically associated with HP dependence.